Bromine Addition to Cyclohexene in Dichloromethane ; Thorpe's Synthesis of the Caged Acid, 4-Methyltricyclo[1.1.0.0[Superscript 2-4]] Butane-1,2,3-Tricarboxylic Acid

Brigham Young University BYU ScholarsArchive

Theses and Dissertations

1962-08-02

Sulfonation of chlorobenzene and the selectivity relation ; Bromine addition to cyclohexene in dichloromethane ; Thorpe's synthesis of the caged acid, 4-methyltricyclo[1.1.0.0[superscript 2-4]] butane-1,2,3-tricarboxylic acid

John A. Gurney Brigham Young University - Provo

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BYU ScholarsArchive Citation Gurney, John A., "Sulfonation of chlorobenzene and the selectivity relation ; Bromine addition to cyclohexene in dichloromethane ; Thorpe's synthesis of the caged acid, 4-methyltricyclo[1.1.0.0[superscript 2-4]] butane-1,2,3-tricarboxylic acid" (1962). Theses and Dissertations. 8218. https://scholarsarchive.byu.edu/etd/8218

This Dissertation is brought to you for free and open access by BYU ScholarsArchive. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of BYU ScholarsArchive. For more information, please contact [email protected], [email protected]. &p ~·'. - ....., (,022- -,~ :--..._ .EJg,/ SULFONA!TlON -OF OROBENZENE AND

11(_;2,; ~ THE SELECTIVITY RE · 5tION '----.-. ~- ""

BROMINE ADDITION TO CYCLOHEXENE :.

IN DICHLOROMETHANE

THORPE'S SYNTHESIS OF THE CAGED ACID,

4-METHYLTRICYCLO [1. 1. 0. 0 2- 4] BUTANE-

' 1, 2, 3-TRICARBOXYLIC ACID

A Dissertation

Submitted to the

Department t>f Chemistry

Brigham Young University

Provo, Utah

In Partial Fulfillment

of the Requirements for the Degree

Doctor of ~hilosophy

in Organic Chemistry

John A. Gurney

August, 1962 -ii-

This dissertation is accepted in its present'. form 1}Dythe

Department of Chemistry of the Brigham Young University as

satisfying the dissertation requirement for the degree of Doctor of ~hilosophy. -iii-

To the Faculty and Staff of the Chemhtry

Department who have dediciate:d thehi efforts

to the building of a gi'flat Graduate Schbol

of Chemistry. -iv-

AqKNOW LEDGM~NT S

Dr. Nelson has allowed much freedom of thought and action, given wise counsel and provided a stimulating working atmosphere. I am especially pleased with this training.

I take deep pride in acknowledging the part n:iy;. a,ble ·wifei · who was under seige from the younger members of our family during the hours of compilation and pro'ofin~, has played in supporting and encouraging my

E;fforts. We extend gratitude to our parents for assistance during many important moments.

The study of bromine addition was generously supported through two research grants (NSF grant numbers G-5414 and G-14435) from the

National Science Foundation. Thorpe 1s synthesis was kindly supported through part of one summer by Brigham Young University. I am grate- ful for this financial help.

Brigham Young University has provided much in the way of excellent equipment, fine facilities and good supplies. I particularly appreciate the fine environment of the University. -v-

TABLE OF CONTENTS

Page

Acknowledgements iv

List of Tables viii

List of Figures xii

Manuscripts for the Journal of the American Chemical Society xiv

THE SULFONATION OF CHLOROBENZENE AND THE SELECTIVITY RELATION Part I

Introduction 1

Background 6

Results and Discussion 7

Isomer Dist.ribution 7

Competitive Sulfonation 11

Experimental Section 19

:Preparation of Sodiuµi o-, m - and p-Chlorobenzene sulfonatilJ 19 i - Isomer Distribution 21

!:>reparation of Ferric·~ .. , m - and p-Toluenesulfonates 27

Oprnpetitive Sulfonation 29

Appendix 1,Derivation Check of Ingold• s Equation 38

Appendix 2, Calculation of the Chlorobenzene • B~nzene Rate ~-s:tan:t Ratio 39

Bibliography 42

BROMINE ADDITION TO CYCLOHEXENE IN DICHLOROMETHANE Part. II Sur.vey of Basic Concepts . 47 -vi-

Page

Current Mechanistic Idea,s 47

Literature Background 54

Kinetics 54

Cis Addition 57

Oxygen and Light 58

. Structural and Medium Effects • 59

Discussion of Results 64

Second-Order Addition • 65

, Zero-order Addition 67

Oxygen Photo Effect 73

· Experimental Section 76

Purification of Dichloromethane, Bromine and Cyclohexene 76

Rate· Study of Cyclobe-JEEme aruLBromine in Dichloromethane 80

. Results 85

Oxygen. Photo Effect • 89

Appendix • 91

Bibliography • . . 93

THORPE'S SYNTHESIS OF THE CAG5_D f,-CID, 4-METHYLTRICYCLO[ 1. 1. O. 0 - ] - BUTANE-I, 2, 3-TRICARBOXYLIC ACID Part Ill

Introduction • 104

Background • 105

Discussion . . 109

Ethyl Isodehydracetate • 109

, Ethyl(.3-Methylglutaconate 110

Michael Addition 115 -vii-

Page

1, 1, l-Ethanetriacetic Acid . . . . 115 1, 1, 1-Ethane-triace{yl Bromide 116

11 o(, ol', d- -TriMome-l, 1, 1-Ethanetriacetyl Bromide . . 116 , . Experimental Section 118

Ethyl Isodehydracetate . 118

Absolute Ethanol 124

Diethyl {3-Methylglutaconate • • 124 Diethyl d.-Cyano-1, 1, 1-Ethanetriacetate (Michael Addition) • • 131

1, 1, 1-Ethanetriacetic Acid 132

Recrystallization Experiments with 1, 1, 1-Ethanetriacetic Acid 134

1, 1, 1-Ethanetriacetyl Bromide 135

Ethyl ol, ol 1, cJ." -Tribromo•l, 1, 1-Ethanetriacetate 137

Infrared Spectra 139

Bibliography • • 145

Abstract 1 -viii ...

LIST OF TABLES

Table Page

1 Comparison of the Calculated Substituent Factors (o-+) of Toiuene and the Halobenzenes 4

2 Available Isomer Distribution Data of Halobenzene Sulfonation 6

3 Melting Points of S- Benzylisothiouronium 2.,-, ~ and p-Chlorobenzene- and g•Toh,1enesulfonates 8, 21

4 Isomer Distribution Recount Data for the Sulfonation of Chlorobenzene 9, 25

5 Available Isomer Distribution Data of the Sulfonation of Chlorobenzene 10

6 Hydrolysis of 2_•, ~- and p•Chlorobe;nzen@Sulfonic Acids • 11

7 The Effect of Temperature on the Yield of Ferric m -Toluenesulfinate 12

8 Competitive Sulfonation Recount Data of Toluene and Chloro benzene 14, 34

9 Isomer Distribution and Purification Data of Sodium 'O- Chlorobenzene sulfonate-s 35. 23

10 Isomer Distribution and Purification Data of Sodium m - Cblorobenzene sulfonate .. 535. 24

11 Isomer Distributicm and Purification Data of Sodium p- Chlorobenz•ene sulfonate-s35. - 25

12 Comparison of Etllpirica.1 and Experimental Counting. Deviations • 26

13 The Isomer Distribution of the Sulfonation of Chloro- benzene • 27

14 Temperature Effect on the Yield of Ferric m -Toluene- sulfonate • 29

15 Sodium,p-ToJ.uenesulfonate-s 35 Competitive and Purifkation Data • • 31 -ix-

Table Page 35 16 - Sodium p-Chlorobenzenesulfonate-s Competitive and Purification .Count Data • 32

17 Constants Used in Calculation of Partial Rate Factors • • 39

18 Comparison of Basicity and the Rate Constants of Hydrogen Chloride -and Chlorine Addition • 52

19 'Surface Catalysis of Bromine.-Ethylene Addition .56

2.0 -Effect" of Structure on Bromine Addition 63

2.1 Classes of Bromine Addition, Reactions 64

22 -Promotion of Bromine Addition to -Cyclohexene by Light • • • • 65, 81

23 Bromine Addition to Cyclohexene 65

24 Inhibition of Bromine Addition to Cyclohexene by Hydro- gen Bromide. Cyclohexene ·Distilled frorrLSodium . 66, 86

25 Inhibition of Bromine Addition to Cyclohexene by Hydro- gen Bromide. Cyclohexene from a Cuprous Chloride Adduct • • • • • • 66, 87

26 Bromine Addition to Cyclohexene Purified through a . Copper ·(I) Chloride Adduct •. Zero-Order • 67

27 _Re-activity of Various Brominating Re-agents with Allyl- trimethylammonium ,Perchlorate • • 72

28 Description of the Aurora Borealis - . 74 30 Procedure for Determination of Bromine-Cyclohexene Re-action Rates • • • • 83

31 Bromine Addition to Cyclohexene Distilled from.Sodium 86

32 Bromine Addition to Cyclohexene, Least Hydrogen Bromide Present (A) • • • 88

33 Bromine Addition to Cyclohexene, Some Hydrogen Bromide Present (B) • • • 88 ~x-

Table Page

34 Bromine Addition to Cyclohexene, Much Hydrogen Bromide Pre sent (C) 88

35 Bromine Addition to Cyclohexene, Most Hydrogen Bromide Present (D) .• 89

36 ·Pressure and Photo Effect Intensity 89

37 Pressure and the Repeats of the Photo Effect 90

38 Effect of Temperature on the Yield of Ethyl Isodehydracetate 109

39' The Relationship of Ethyl 13-Methylglutaconate Yield and Ethyl Isodehydracetate Storage 111

40 Ferric Chloride Test of Various Ethyl Isodehydracetate Samples and the Yield of Ethyl 13-Methylglutaconate 112

41 Effect of Distillation on the Physical Properties of Ethyl Isodehydracetate 112

42 Elemental Analysis of Various Ethyl Isodehydracetate Samples 113

43 Promotion of a.-Bromination of 1, 1, 1-Ethanetriacet~l Bromide 116

44 Ethyl Isodehydracetate Synthesis and Isolation Variables 121

45 Yields and Physical Constants of Ethyl Isodehydracetate • 122

46 Ferric Chlo,ride Test of Various EIDA Samples . 122

Effect of Redistillation on Physical Properties of Ethyl Isol:l.ehydracetate 123

48 Ultraviolet Spectra of Ethyl Isodehydracetate 123

49 Yields and Physical Properties of Diethyl 13.. Methyl- glutaconate 126

50 Diethyl 13--Methylglutaconate Synthesis Variables 127

51 Reagent Variation During the Synthesis of Diethyl 13-Methylglutaconate 128 -xi-

Table Page

52 -Effect of Various Metals on the·Synthesis of Diethyl /3 -Methylglutaconate • 129

53 Ethyl Is odehydracetate Reaction ,Mixture Treatment and Diethyl /3 -Methylglutaconate ·Yields • • • 130

54 The Guerbet Reaction and the Yield of Diethyl (3 -Methyl- glutaconate • • • • • • 131

55 Decarboxylation of Diethyl cl-Carboxy-1, 1, l•Ethanetri- acetic ·Ester ·Nitrile, ..Michael Addition .Product 1.32

56 Extraction of 1, 1, 1-Ethanetria.cetyl Bromide Synthesis Products • • • • • 136

57 Trace Effects on ct -Br-omination of 1, l, l•Ethanetriacetyl Bromide 138 -xii-

TABLE OF FIGURES

Figures Page

1 Variation in~ of Para Substitution in ,Cblorobenzene, Toluene and Anisole as a. Function of P 3

2 . Comparison of the Para and Meta Partial Rate-Factors for Sttbstitution •Of Toluene and Benzene 5

3 Comparison of Some-Substitution Reactions of Chloro- benzene 17 35 4 Extrapolation of Sodium _E-Chlorobenzenesulfonate-s Recrystallization Count Data 36

5 Comparison of Chlorine-and Hydrogen.Chloride Addition ·-, '• ~ with Olefin Basicity • • • 53

6 Inhibition of Bromine Addition to Cyclohexene by Hydrogen Bromide from Bromine ·Substitution of Dichloromethane 68

7 . Effect of the Reaction Medium on Bromine-Olefin Addition 60

8 Comparison of Second-Order Bromine Addition with other ·Olefin Addition. Reactions • 61

9 , Reaction. Capsule and.Pressure-Filling Pipet 82

10 Infrared Spectrum of Diethyl 0\.-cyano-l, 1, 1-Ethanetri- acetate -.

11 Intrarea 'Spectrum of the "Imido" Acid of 1, 1,1-Ethane- triacetic Acid • • • • • 140

12 Infrared Spectrum of a Non-Ether-Sample of 1, 1, 1- Ethanetriacetic Acid • • 140

13 Infrared Spectrum of an, Ether.· Sample of 1, 1, 1-Ethane- triacetic Acid • • • 141

14 Infrared, Spectrum of the Trilactone of 1, 1, 1-Ethanetri- acetic Acid • • 141 THE SULf'ONATION OF CHLOROBWZENE ANO T·HE·SELECTIVITY RELATION

Introduction

..Aromatic substitution has pr-ovided an important testing g-round and

source- of organic chemical theory. The Englis-h school of electronic theory developed by R. -R

(43, 67, 69) has been drawn from the directive effects found in aromatic

substitution, The directive power of vari-ous -s-u-bstituents- was explained qualitatively in- terms of- orbital overlap or resonance effects- and a dipole interaction or inductive effects. Quantitative efforts begun in this setting

led to silnple r$lati-onshi-p-s-between many aromati-c &ubstitution reactions

(76).

The rates of substitution at the various positions relative to benzene

found definition as the partial rate fact-ors--ortho (or), meta (mr) and para

factors (p 1). The para pq.rtial rate factor has been adopted as the measure of reagent activity and the ratio of the para and meta factors as the measure

of the selectivity of these two positions toward the reagent. The reagent

activity was found to be proportional to the selectivity (7).

(1)

Under sta.p.ding of the slope ~ in equation 1 can be obtained from an

application 'of the familiar Nernst free energy-equilibrium relation to

the rate constant equation (52).

-4F:l: = RT £n k (2)

The original Nernst relation was between free energy and the equilibrium

constant. ( 3) ..,z_ An application o.f . equation 2 similar to that of Hammett (36) has

1-(ffd. t-0 an assignment of two parameters, one related to the reagent in

use ( P) ari.d the other to a ring substituent•s ability (cr°t) to withdraw

or supJi>ly electrons to the reaction site (58), for example:

- aF P ¥ cc log pf = a- P +,,a (4)

- .6.F (5) m

If equation 4 is . substracted from 5, equation 6 is .obtained·~ .:~

( 6)

.And if eq,uation 4 · i s 0 divided by 6, the meaning of the slope of the linear

relationship between the partial rate factors at the meta and para positions

is s.eenc:in equation,_ 7 ,::.the ·.}.Iarnmett ...Brown equation. er- + log Pf = { _ ___,,_P______,._ (7) u p + - rr m +

• Many of the available data such as nitration, bromination, and fit mercuration gave linear plots whichl in equation 7; others deviated by

relatively small amounts (75). Mefa substitution in. the halol;>e.nzenes

fits reasonably.well but , para substitution varies. much more,

The variation of the substituent constant at the para position ( +) o-p

i of the halobenzenes indicates deviation of the halobenzenes from a simple

fit in the Brown-Hammett equation (Eq. 6), Table 1 and Fig. 1 (9, 62).

Plotting of the partial rate values available for the sulfonation of Ill toluene also showed a significant lack of agreement with other reactions

of toluene (Fig. 2) (7, 75).

Because the data for sulfonation of toluene and for substitution of

.the halobenzenei'S, apparently both fail to. fit . . a simple linear correla-

tion, determination of the partial rate factors of halobenzene sulfonation -3-

0.6

0.4 0

0 0 0.2 0 OQ) p-C\ 0 0 00 0 0 0 0.0 0

~ -0.2 0 0 +6 Oo p-Me 'c>

0 -0.4 0

-0.6 0 0 0 0 p-OMe Q) -0.8 0 0 0 0 0 -1.0

-7.0 -6.0 -5.0 -4.0 -3.0 -2.0 -1.0 p Fig. I Variation in <:r+of Para Substitution in Chlorobenzene, Toluene and Anisole as a Function of p. -4-

Table 1.· Comparison of the Calculated Substituent Factors (a-+) of Toluene and the Halobenzenes (9)

Solvolysis I. R. of Uncat. Uncat. Ionization of t•cumyl Sti,bs-. •Ae eto-phenone B.r2 Cl2 Nitratien of Ar2CH-OH chloride

P.a.ra

Me -0.325 -0.278 -0.365 -0.278 -0.306 -0. 311 ___,...__ F 0.081 -0. 100 0.012 -0.028 -0.073 Cl ------0.055 o. 133 0.201 o. 107 o. 114 Br 0.162 -.--~--0.074 0.152 0.091 0.150 _.,..__ ._._ I ------0.055 o. 101 o. 135 Meta Me ------0. 061 -0.087 -0.079 ------0.066 _c!:>_..,..__ F o. 406 ------0.352 Cl 0.406 ------0.470 0.422 0.399 _"""____ Br --·------0.477 ------0,405 I ----.------0.346 ------0.359

Rho (P) 12, 30 12.14 8. 06 6.22 4.74 4.54

I_lef. 48 57, 11 57, 12 68, 44 18, 17 . 9 46, 19 20 ... -5-

4,0------,

:J.O

ci ~ 2.0 .3

1.0

0.0...._ ____ ,.__ ___ --+ ______,.. __ 00 1.0 2.0 3.0

Log Pt/mf Fig.2 Comparisonof the Para and Meta PartialRate Factors for Substitution of Tolueneand Benzene. -6- is n-e-eded and should serve as ,a test of free energy relationships in aromatic substitution.

Finally, careful redetermination of values which once deviated from a simple linear plot has brought several reactions such as chloromethylation, mercuration and halogenation into agreement (7., 75).

The vast industrial application and the lack of definitive data from aromatic sulfonation indicate a need for determination of partial rate factors.

Research was carried out to provide accurate data for sulfonation of chlorobenzene.

Background

Of the four halobenzenes, the sulfonation of chlorobenzerie has received the most study. Since chlorobenzene was first sulfonated with fuming sulfuric acid (41), various reagents and conditions have been used . a-d to prepare the para isomer.

Until recent work, sulfonation of the halobenzenes was thought to provide 100% para substitution (39), The ortho and meta isomers had escaped detection.

Table 2. Available Isomer Distribution Data of Halobenzene Sulfonation

Substituent % Ortho % Meta % Para Reference Cl 1.8 .. 5.8 12. 6-16. 6 81. 6 72

Br 13 37 50 51 I 0.8 0.6 98.6 14 a. H 2so 4 .d. 1.84 (77). 0 H (10% free SO ), d. b. 2so 4 3 1. 9, < 60 (2). c. SO 3 (34). d. ClSO H, 20-25° (35, 66). 3 -7- The valaes for bromobenzeae and iodobenzene were determined by an isotopic dilution method. After reaction with sulfur trioxide-s 35 , aliquots of the isomeric sulfonation mixture were introduced into large samples of individual isomers and were then recrystalized to a constant count. The ratio of the counts revep.led the isomer distribution.

Factors other than the ratio of ortho, meta and para isomers may well affect the sample counts. Since p-chlorobenzenesulfonic acid monohydrate formed readily during recrystallization (5 6), hygroscopic salts were possible and would lower count values. The extensive displacement of a..t-butyl group from E_-di-t ...butylbenzene (88. 4% p-~t-hltyl)benzenesulfonic acid) with chlorosulfonic acid at 20-25° (55) presented the possibility of chlorq--group displacement with sulfur trioxide. Such a chloro -group displacement became likely with the observation of iodo· group displacement (51).

Results and Discussion

Isomer Distribution--The isotopic dilution technique of determining isomer and competitive rate ratios required fairly pure individual isomers.

Several compounds were made to get the individual isomers of sodium chloro- benzen:esulfonate with sufficient purity. The Sandmeyer reaction (59) provided a means of obtaining reasonably pure sodium .9.-. ~- and p-chlorobenzenesulfonates. The corresponding o-, ~ .. and p.:.chloroanilines, commercially available, were used to prepare the needed diazonium salts.

Treatment of the respective diazonium salts with sulfur dioxide in acetic acid solution and a cuprous chloride catalyst provided~-, ;,!:- and p-chlorobenzenesulfonyl chloride--90%, 73% and 74% yields, respectively.

The sulfonyl chlorides hydrolyzed readily with aqueous sodium carbonate. -8-

HCI · S02/AcOH) dCINaN02) o:ICu2Cl2

aq.Na2C03 o:I 6 > a::·

Purification during recrystallization was followed with wet tests for

chloride, sulfate and phenol until each contaminate was gone (75% product

recovery). Final purity was checked with the melting points of the S- benzylisothiouronium a:tylsulfonates.

Table 3.. M~lting Points of S•Benzylisothiouronium o-, m- and p-Chlorobenzene- and p- Tolu~nesulfonate,s (61) -

I b 0 Sodium Sulfonate M. P. I. c .. Lit. M:P., c ..

o-chlorobenzene- 159-160 160. 8 m-chlorobenzene- 138-139 ------_£~chlorobenzene- 174-174.5 174.4

g ...toluene• 182-182.5 182.2

Both !ilOdium 2."' and g-chlorobenzenesulfonate were obtained as hydrated

salts. Only the ortho isomer proved to be hygroscopic. All samples were

dried before weighing and the ortho isomer was recounted on a day of low

relative humidity. The final ortho count increased ca. 1% as the sample

hydrated and buckled toward the geiger tube window. -9- 'Equal molar amounts (0. 025 moles)a of chlorobenzene ..nd sulfur trioxide-s3 5 (40) were combined in ca. 170 ml. of refluxing sulfur dioxide.

The sulfur dioxide was removed and the mixture was neutralized with aqueous sodium carbonate.

Aliquots of the isomeric mixture were added to equal amounts of the pure isomers and recrystallized with a two-crop system. The first crop grown under slower crystallization conditions generally provided the better purity. The second crop grown more rapidly gave a comparison of the filtrate purity to that of the first crop. This method generally gave converging values in addition to the constant count of successive recrystallizations.

The convergence of values was more prominant tha'n the changes of successive

counts and allowed much shorter counting times during scanning of the various recrystallizations. Such a technique also lent confidence to the values obtained. Times given in Table 4 are for 30, 000 counts.

Table 4. Isomer Distribution Recount Data for the Sulfonation of Chlorobenzene

Isomer Recrystallization 1st Crop (mins. )· 2nd Crop (mins.)

Ortho o-15 412.30 407.67 408.01

o-17 423.73

Meta m-21 22.09 21. 77 22.08 21.94

m-23 21. 98 22.05

Para 8,99 9.16 8.82 9.26 p-13 9.11 9.21

a. Excess so is known to form an adduct with chlorobenzenesulfonic acid (83). 3 -10- Th-e coQ.nting -deviati-en was estimated with a propagation ,of random error equation (65) and compared to the actual counting deviation calculated with the widely used standard deviation equation. --Agreement occurred between the two sets of values-and indicated an adequate performance of the counting equipment. A cursory examination of the approximations made in calculating the precision range of the isomer percentages showed that these were probably maximum values. Appendix 2 may be consulted for detail ( 84).

Comparison of our isomer distri&ution values with those available

(Table 5) showed a high percentage of meta isomer and may indicate an isomerization of ortho and para isomers.

Table 5. Available Isomer Distribution Data of the Sulfonation of Chlorobenzene

Reaction Conditions %Ortho - %¥eta %Para Ref. ,...____ 238° 40.7 H2SO 4 , 59.3 7'? H so , 220° 35. 8 64.2 :n. 2 4 ----·- S0 , liq. SO , -10° 1 3 2 . 28. 8. ·10. our work H SO , H O bath 71 77 2 4 2 ------C1SO 3H, 20° to 25° ------7'2.f .35, 6:6 SO , C H c1 , -12° 3.s+2.o 14.6!2.o 81. 6 :i?, 3 2 4 2 ' -

Although direct proof is lacking for an isomerization of chlorobenzene- at. IG»w temperatures sulfonic acid in ~ unreactive mediu:i:n,everal. items support such a conclusion. Both 2,-, and p-chlorobenzenesulfonic acid changed to!!:- chlorobenzenesulfonic acid in sulfuric acid (71). Hydrolysis of each isomer of chlorobenzenesulfonic ,kid ·showed the same pattern of relative reactivity and depend~d on the pH (49, 71, 73). -11-

Table 6. Hydrolysi& of 0-, m- and p- Chlorobenzenesulf~ic Acids One Mole of Sulfonie Acid-in·--4. 5 Moles ef--Water (73)

Hydrolysis Percentage Isomer 100 Hrs., 163° 8 Hrs., 184°

ortho 49.1 30.0

meta 2.2 1.9

para 14.4 7.7

The hydrolysis equilibrium constant was only moderately temperature dependent, KP = 1. 08 - l. 22 from 220° to 500° (49).

If hydronium ion and sulfuric acid could both effect the movement of the sulfonic acid group, then chlorobenzenesulfonic acid itself might be

expected to produce isomerization. Chlorobenzenesulfonic acid probably

fits in the following order of acid strength (3):

and would be strong enough to catalyze the isomerization of the ortho and para isomers.

Oompetitive Sulfonation .. •The probable displacement of the chloro group

required the selection of a competitor molecule other. than benzene.

Because work on toluene was ,-Iready under way, it was chosen. Sodium g-toluenes.ulfonate could be separated from sodium benzenesulfonate by

recrystallization (22). The values of the toluene-benzene rate ratio and the

isomer distribution of toluene allowed calculation of the chlorobenzene-

benzene rate ratio.

Before the general synthesis of arylsulfonyl chlorides used in the·

synthesis of sodium ;2-, ~- and g-chlorobenzenesulfonates became available, ferric p-toluenesulfinate was prepared as an intermediate for the preparat1J~- - . of sodium p-toluenesulfonate. To make the. ferric sulfinate, :_p-toluidinium. sulfate was diazotized with nitrous acid at 5 to 10°. Treatment with.added sulfur dioxide and powdered copper, the Gatterman reaction, gave ·p-toluenesulfinic acid (31) which was converted to the very insoluble c artd stable ferric p-toluenesulfinate (70) in 100% yield (lit. 80% [39]).

Similar treatment of-2_ .. and ~-toluidinium sulfate gave 70 and 72% yields (lit. yield 90% for ortho [31]) of ferric o-. and ~-toluenesulfinate.

Variation of the diazotization temperature strongly affected the yield as can be seen with ferric m-toluenesulfinate.

Table 7. The Effect of Temperature on the Yield of Ferric m-Toluenesulfinate

Temperature 1°c. Result • 2 to 5 72% ferric m-toluenesulfinate

-1 to 1 only amine salt

5 to 8 only red diazo compound (80)

The o-, ~- ·and p-toluene sulfinic acids readily appeared if their ferric

salts were thoroughly mixed or warmed with dilute sulfuric acid and copper -13- powder. Crystals apparently of good purity formed on chilling the clear

solution in ice. The p-toluene.sulfinic ~cid melted at 92° (lit. m. p. 86-87°

[3j). The order of water solubility of the toluenesulfinic acids was m > p > o.

This method of preparing arylsulfinic acids was convenient in view of ready disproportionation of the arysulfinic adds.

Attempts at oxidation of the ferric~.,., ~- and g-toluenesulfinates with acidic, neutral and basic hydro:perdXide gave mix~ures of thiosulfonate esters, thiols and sulfonic acids. However, bromine water reacted smoothly and directly with the ferric salt to give p-toluenesulfonyl bromide, as suggested by experiments with arysulfinic acids (arylsulfonyl bromide yield 90%(64]).

Toluenesulfonyl bromide could be readily hydrolyzed with potassium

carbonate.

A ratio of 50 parts chlorobenzene and 25 pa:rts toluene to I. 0 of sulfur trioxide-s 35 was selected to provide enough sodium g-chlorobenzenesulf~nate 35 for purification and to allow complete consumption of sulfur trioxide-s •

Pure p-toluenesulfonate and p-chlorobenzenesulfonate were added to aliquots

of the neutralized sulfonic-s 35 acid mixture and determined the isotopic

dilution for the two para positions. These two mixtures were then rec:rys-

tallized using the two-crop system described earlier. For the isomer

distribution, this system allowed shorter counting times and by convergence

of the two-crop v~lues allowed more confidence in the final sample selection

for recounting. The converging pattern of sodium p-toluenesulfonate

showed a delayed count minimum in the second crops as compared to the

first crops. The final first crops rose in counting rate. The .minimum

counts, however, agreed as to value. Rising counts apparently indicated a -14- bulk :dens1ty greate:r· than the standard , bulk g,ehsity: : produced during sample grinding (60). Although the values ,of the two crops of sodium p- chlorobenzenesulfonate did not converge (low activity, 163 cts. /min. , prevented further recrystallization), they did approach a constant value.

The values of the two crops were extrapolated to the final value.

Table 8. Competitive Sulfonation Recount Data of Toluene and Chlorobenzene (100, 000 cts. )

Recrys. Mins. Recrys. Mins.

T-7 12.57 C-27 523.02 12.45 530.95 12.47 534.49

T-8 12.63 C-29 556.09 12.66 559.65 12.77

T-12 12.69 ,12.64

Corrections for background (16. 1 ± 1. 0 cts. /mins.) and for dilution of the sodium p-chlorobenzenesulfonate (10. 14 times) gave count v;=tlues of

sodium p-chlorobenzenesulfonate 1,176 t 21 cts. /min.

sodium g-toluenesulfonate 7,864 ! 25 cts. /min.

The derivation of Ingold 1s equation for calculating rate constant ratios (45) was extended. a If the kinetics were of the form

n = 2 for sulf onation

x = monosubstituted benzene

z = sulfur trioxide equation 9 followed regardless of the value of n, a. See .Appendix I. -15- log a/(a-x ) k /k = 0 (9) X y ) log cAc-y 00

a = aromatic x initial

c = aromatic y initial

x = aromatic x reacted at t = oo 00

y ,:: aromatic y reacted at t = oo 00

Many mono-substituted benzenes in the reaction with sulfur trioxide, including chlorobenzene (83), are first order with respect to the mono- substituted benzene (13,21,32,33,35,81). We concluded tli.at equation 7 held for sulfonation.

A derivation check similar to that used in extending Ingold's equation reaffirmed the direct relationship of rate constant ratios at the various positions (o, m and p) to the percentage of the isomers.

k /k ortho 0 X = %

k /k = % meta m X

l}i• k /k = para p X %

An evaluation of the relationship between the para and meta rate ratio constants at infinite reagent activity reproduced the -partial rate factors and the selectivity relation.

log 6 k /k = c log 2 kp/km ( 10) P PliH

( 1)

The total rate ratio was calculated with equation 9 and converted to the ortho, meta and para factors of chlorobenzene sulfonation. -16-

kPhMe/kPhCl = 8.8

of = o. 064

mf = 1.7, 4. 2, pf =

log pf = o. 63.

log p/mf = 0.69

Neither the amount of isomerization of chlorobenzenesulfonic acid nor that of chloro group displacement was determined. These possible corrections were neglected, but reasonable estimates of each did not greatly affect the partial rate £actors. A graphic comparison (Fig. 3) of the selectivity relation for sulfonation compared moderately well with Olah•s nitration,

Ferguson•s bromination and chlorination of chlorobenzene (63, 30, 74).

Other available data generally fit a line going through the origin

(4;,9, 16, 24, 53, 54, 63, 68).

The line defined by a best fit of the points of nitration, chlorinatiol}, and bromination did not run through the origin but rather above and through the log Pf axis. This evidence could indicate a linear relation with a difference of reactant randomness, activational entropy (AS*), between the halobenzene and benzene molecules. Such a difference in A st of chlorobenzene sulfonation has been observed (83).

Olah has suggested the presence of two basic centers in the halo-- benzenes (1, 63) which can interact with the elect.rophilic reagent. The basic center at the halo substituent could interact with an incoming reagent.

SuGh a reversible interaction would give a loss of reactant randomness or net decrease in the entropy of activation relative to benzene. An I r- ....I

0.5

0.0 0 Benzylation

0 Bromodeboronation

o':" O"I .3 -0.5 J~olvolysis of t-Cumyl Chloride

Destannylation0 BrominationO OegermanylationO C¾cetylation (Ferguson)

-IO BromodesilytationO

-1.5

0.0 0.5 /.0 1.5 2.0 2.5 3.0 Log pf/mf Fig. 3 Comparison of Some Substitution Reactions of Chlorobenzene. -18- int,ramolecular transfer of the reagent from the halo group to the para position of the ring, the other basic center, would require less orientational change. This would give a small difference of activational entropy between the meta and para positions.

E+- f X X 0 + E+ ) 0 > X X X X -H+ E or > or I I ¢ 0 H Q+ OE E

In the selectivity relation, the entropy terms related to the para and meta factors are, about equal and of opposite sign a n.d , essentially add on. the right side out/ leaving. an entropy of activation term on the left-hand side of equation

1 . . An additio~al entropy contribution has been examined in biphenyl and

shown to have a simple and non-linear character (76). The additional entropy contribution in chlorobenzene sulfonation may well be simple and linear. Chlorobenzene may represent the second case in which an additional entropy factor (A) appears and can be described with the selectivity relation (Eq. 11 ) .

(11)

It is possibl~ that the factor A is a constant for chlorobenzene and a variable for biphenyl. -19- E-xperim-ental Section

.Preparation .Gf Sedlum _£:-, :!!.- and p-Chlorobenzenesulfonates--The isotope

dilution technique of determining isomer distributions and competitive rate

ratios required fairly pure individual isomers, The Sandmeyer reaction

(59) provided a means of obtaining reasonably pure sodium o-, m- and

p-chlorobenzene sulfonate s.

NoN0 3 ) Cu2C12 ) QCIHCI o:IS02/AcOH Oilaq, Na 2C03> ON:+

The diazonium salt from 137. 6 g. of p-chloroaniline (Eastman, white

label, 1. 00 mole) was prepared by dropwise addition at 1-0° of sodium

nitrite solution (76. 0 g. '", 1. 10 moles, Baker and Adams, reagent grade

in 120 ml. Hz0) to g-chloroaniliniu.m chloride (1. 0 mole p-chloroaniline

in 250 ml. ether added dropwise to 340 ml. cone. HCl). If diazotized

p-chloroaniline were reacted at 10° with an acetic a~id (400 ml. Wasatch

Chem. Co., analytical reagent) solution of cupric chloride (20 ~. CuClz• 2H 0, 2 grade unknown in 25 ml. H2O} which had been saturated with sulfur dioxide (Army Surplus, grade unknown) solid p-chlorobenzenes,ulfonyl chloride

precipitated. The same procedure gave liquid~- and ~-chlorobenzenesulfonyl

chlorides from~- and :!;-chloroaniline if the diazotization temperature of

the ortho and meta isomers were kept at 12 and 15°, respectively. The

yields were para 95, ortho 73 and meta 74%. -20- The three chlorobenz~ne-sulfonyl chloride-a were wa-shed with cold water, hydrolyzed slowly by adding boiling water and small portions of sodium carbonate. The resulting sodium~-, ~--, and £-chlorobenzene- was sulfonates/ generously treated with Norit and recrystallized from neutral aqueous solutions ~• give 75% recovery of t,he respective sodium salts.

In slightly basic solution the hydration of sodium E_-chlorobenzenesulfonate increased. In an acidic solution, sodium o-chlorobenzenesulfonate did the same. Reduction of the number of required recrystallizations occurred as phenols were removed from the dry salts with ether (Merck, anh. ).

Final drying of the salts (120° at 10 mm., 48 hrs,) removed water of hydration from sodium 2- and p-chlorobenzenesulfonates. The meta salt did not hydrate. Wet tests £or chloride, sulfat~, and phenol with aqueous silver nitrate, barium acetate and ferric chloride provided criteria of purity during recrystallization.

Final purity was checked with the preparation of S-benzylisothiouronium sulfonates (70). A solution of S-benzylisothiouronium chloride (82) (1 g., batch prepared by J. Knight Expt.J 68-D) in 2 ml. of hot water was added

\ to 1. 00 g, each of sodium~-, ~, and p-chlorobenzenesulfonate (preparation

146-F, 108-F, 107-F, respectively) and sodium p-toluenesulfonate (J.

Duvall, Expt. 197-IS) in 2 ml. of hot water,

In each case a precipitate appeared on cooling and was recrystallized twice from ca. 10 ml. of ethanol-water mixture. Extensive oiling-out of

S-benzylisothiouronium ~-chlorobenzenesulfonate was overcome by adding ethyl alcohol beyond the cloud point and by scratching the beaker to induce crystallization. / -21- Table 3. Melting Points of S-Benzylisothiouronium o-, m- and p-Chlorobenzene and p- Tolu-;ne sulfonates (61) -

0 .. 0 ·t:i? Derivative m. I>•• , C .. Lit. m.p. ,, C.

o-Chloro- 159-160 160 •. a m-Chloro ... 138-139 ----- p-Chloro- 174-174.5 174.4

p•Toluene- 182-182.5 182.2

Isomer Distribution--A reaction mixture of o-, E:_-, and E_-benzenesulfonic-

s35 acids resulted as 2. 8 g. chlorobenzene (0. 025 mole, made up to 10 ml. with liq. S0 ) was added dropwise over twenty minutes to 2 g. (0. 025 mole ) 2 sulfur trioxide-s 35 in 160 ml. of liquid sulfur dioxide at reflux. The sulfur

trioxide-s 35 had been exchanged six weeks with O. 5 g. (ca, 3 me.) barium

sulfate-S 35 {14,,.40),

When the reaction solution was evaporated to dryness, neutralized with aqueous sodium carbonate and reduced in bulk to about thirty milHliters,

no sulfone could be extracted with ether. Ten-milliliter aliquots of this

solution added to equal 25. 00 g. portions each of sodium~-, ~-, and

p-chlorobenzenesulfonate determined the isotopic dilution of each isomer.

Two crystal crops (25° and o° C.) were taken during each successive

recrystallization of sodium~-, ~-, and p-chlorobenzenesulfonate before

the mother-liquor was discarded. The fir st crop grown under slower

crystallization conditions (95 to 25°, on an asbestos pad) provided the better

0 purity. The second crop grown more rapidly (25 to o , in ice) gave a

comparison of the filtrate purity to that of the first crop. Frequent

supersaturation of the meta isomer could be relieved by seeding and

a. Other values are g-ch1oro-m. p. 175 0 and p-toluene-181-182 0 (38). -22- scratching. ·Crop samples were taken from each recrystallization and then prepared for COlJnting.

Dried samples (60-120 mg., 48 hours at 120°/5mm.) from various recry_stallizations were ground 40 seconds each in 111 polystyrene,vJa~ and

3/8" ball pestles with a "Wig-L-Bug" amalgamator (Cresent Dental Mfg.

Co., Chicago, Ill., serial No. 76652). a Ground samples of an even thickness settled from ether (Merck. anh. , planchet 1 / 3 to 1 /2 full}, if they were weighed to 50! ~ 1 mg. with a Mettler balance, dispersed with a small rod having an end flattened at a right angle and swirled in an elliptical counter-clockwise motion. If the elliptical motion were smoothly reversed to a clockwise motion for one turn at the end of the swirling, uniformity of sample thickness improved. Evaporation of the ether at room temperature and storage in a vacuum desiaCator (anh. CaC1 , 5 mm.) 2 completed the sample preparation.

Tracerlab (Boston 10, Mass.) made the following equipment which was 35 used in the counting of S a thin-win~ow geigerc tube {TGC 14,ser. No.

411) and preamplifier (ser. No. 1126), an automatic sample changer (model

SC-GD, No. 550), a printer {model SC SF No. 803) and a Compu/Matic II scaler {model 5C-71 ser. No. 334). The geiger tube helium bubble rate, voltage and sensitivity were kept at L 0/sec., 1250 v. and 0. 25, respectively.

a. A technique used to prepare KBr windows for IR spectra,(29). -23-

Table 9. Isomer Distribution and Purificatio1:3fata of Sodium ~-Chlorobenzenesulfonate-S (Expt. 157-F)

Recrys. 1st Crop (mins.) 2nd Crop (mins.) No. of Cts. Date o-1 4.924 4.749 10,000 4 Sept. 161 9.93 4.80 o-3 6.952 11. 13 7.05 11.24 o-5 35.21 40.48 30,000 35.07 40.58 o-7 50.48 22.34 10,000 66.99 22.40 o-9 29.10 38.34 29.38 38.61 o-11 59.08 40.26 60.22 40.36 o-13 98.26 40.26 8 Sept. 161 97.04 40.36 o-15 1-3. 21 1-4.1--9 I ,.-00-0 28 Oct. ~-61 14. 60 14.19 14.56 13. 37 o-17 14.32 14.84 14.84 -24-

Table 10, Isomer Distribution and Purification Data of Sodium ~-Chlorobenzenesulfonate-s 35 (Expt. 157-F)

Recrys. 1st Crop (mins.) 2nd Crop {mins.) No. of Cts. D.ci.te m-1 1. 70 1. 32 10,000 7 Sept. 161 1. 65 1. 31 m-3 1. 93 1.34 1. 91 1.35 m-5 2.21 1.74 2.27 1. 75 m-7 3.23 3.00 3.16 3.04 m-9 2.87 2.69 2.95 m-11 3.59 3.01 3. 63 3.08 m-13 3. 73 3.82 m-15 7. 12 5.71 3 Oct. 161 5.87 5,66 5.82 5,63 m-17 6.02 5.83 6.01 5.87 6. 10 5.82 m-19 5.57 4.95 5.48 4.99 5.52 4.98 m-21 6. 26 6.76 6. 14 6.80 6.07 6.73 m-23 6. 15 6.06 6. 12 -25- Table 11. Isomer Distribution and Purification Data of 35 Sodium p-Chlorobenzenesulfonate-S (Expt. 157-F)

Re~rys. 1st Crop (mins.) 2nd Crop (m.ins-.) No. of Cts. Date p-1 1.88 1.93 10,000 7Sept.'61 1. 87 1. 93 p-3 2.04 1. 95 2.05 1.95 p-5 2.05 2.05 p-7 1.96 2.13 8 Sept. 161 p-9 2.20 2. 02 p-11 2.04 2. 04 p-13 2.05

Constant purity was taken at the point of agreement of counts between the two crops. In each case the last three samples were recounted on the same day (26 Oct. •61) at 30,000 cts.

Table 4. Isomer Distribution Recount Data for the Sulfonation of Chlorobenzene

Isomer . Recrys. 1st Crop {mins.) 2nd Crop (mins.)

Ortho o-15 412.30 407.67 408.01

o-17 423.73

Meta m-21 22.09 21. 77 22.08 21. 94

m-23 21. 98 22.05

Para p-11 8.99 9. 16 8.82 9.26

p-13 9. 11 9.21 -26- The countiag deviation was calculated from a propagation of random error equation (65),

C / t 2 + C / t 2) 1 / 2 ( s s b b

0-c = calc. deviation

Cs = sample count

Cb - backgroµnd count

t time for sample count s =

th = time for background count, and compared to the actual counting deviation calculated from the following standard deviation equation,

= + I I 2 ( C 5 /tts - "i}.s -

6 = {:Eis2/n)l/2

is = standard deviation of time for total count {C s + Cb) deviation from t •s = s

ts = average time for total count (Cs + Cb)

0- s = standard deviation ,_ n number of determinations.

Agreement occu'rred between the two sets of values.

Table 12. Comparison of Erripe:rical and Experimental Counting Deviations (65)

Isom~r (; C (cts. /min.) crs (cts. /min}

Ortho + 2. I fl +- 2. 6 Meta +- 8. 0 ! 8. 1 Para ": 19 +- 14 After correction for a background count of 20. 95 cts. /min., the following counts were converted to percentages. -27- Table 13. The Isomer Distribution of the Sulfo.natioa of Chlorobenzene

Isomer cts. /mir(txp: • '.161-F) Percentage 0

Ortho so. 6 + _ 2. 6 1

Meta 1, 343. + 8. 1 29

Para 3,276. + 14. 70

Thus the first attempt at determining the isomer distribution of chlorobenzene sulfonation in liquid sulfur dioxide has given the values of

1% ortho, 29% meta and 70% para substitution.

Preparation of Ferric o,.., ~- and p-toluenesulfiil.ates.-·-£efore the general synthesis of arylsulfonyl chlorides used in the synthesis of the sodium

~-, ~- and p ...chlorobenzenesulfonates became available, we made ferric p ...toluenesulfinate as an intermediate for the preparation of sodium p- toluenesulfonate. The Gatterman reaction yielded p-toluenesulfinic acid

{31) which was converted to the very insolqible and stable orange ferric p-toluenesulfinate (79). -28-

The 'p-toluidinium sulfate (10. 00 g. , 0. 094 mole of amine, Eastman,

reagent, with 30 g. cone. H 2 so 4, · 0. 31 mole ) in 200 ml. HzO gave

p-toluenediazonium sulfate after treatment with 8 g. of sodium nitrate - . (Baker and Adams, reagent 0. 12 mole) in 40 ml. 'of water at 5 to 10°.

Sulfur dioxide was bubbled into the diazonium salt solution at -2° as

25 g. of copper powder was added in 0.1 g. portions. The solid residue

of p-toluenesulfinic acid dissolved as ammoni111.m sulfanate on vigorous

mixing with four portions of 75 ml. dilute ammonium hydroxide (1: 3 vols.

of cone. NH 4 OH to H 20). The remaining copper powder was filtered

off. The combined ammonium sulfinate and reaction filtrates were

acidified and a slight! excess of concentrated ferric chloride (50%

FeCl3) was added.

The flocculant orange precipitate was filtered from the solution,

redissolved with dilute ammonium hydroxide, reprecipitated with con-

centrated ferric chloride, thoroughly washed with water, washed with

one 5-ml. portion of ethyl alcohol and dried over potassium hydroxide

(25°, 3 mm.). The yield was 16.8 g. (100% yield, lit. 80% [31]).

Similar treatment of o - and ~-toluidine gave 11. 5 and 11. 7 g.

{70 and 72%, lit. 90% for the ortho [31]) of ferric~-- and~- toluene-

sulfinate. Phosphorous pentoxide was exchanged for the potassium

hydroxide as the drying agent. Variation of the diazotization temper-

ature strongly affected the yield as can be seen with ferric m-toluene-

sulfinate. ., -29--

Table 14. Temperature Effect .on the Yield of Ferri'€: m-Toluene·sulfiinate

Temp, c 0 Result

2 to 5 11. 7 g. ferric m-toluenesulfinate

-J to 1 amine salt

5 to 8 red diazo cmpd. (80)

Each of the~-, ~-, and p-toluenesulfinic acids readily reappeared

if 0. 2 g. of each ferric toluenesulfinate was thoroughly mixed or warmed

with 0.25 ml. of 30% sulfuric acid and 0.2 g. of copper powder. W~ll-

defined crystals formed on chilling the clear solution in ice. The p-

toluenesulfinate formed plates,m.p. 92° (lit. m.p. 86-87° [31]), and

o- and m-toluenesulfinate formed thin needles. The order of water

solubility of the toluenesulfinic acids was m> p > o.

Attempts at oxidation of the ferric toluenesulfinates with acidic,

neutral and basic hydroperoxide gave mixtures of the thiosulfonate

esters, thiols and sulfonic acids. However, bromine water reacted

smoothly and directly to give p-toluenesulfonyl bromide as suggested

by experiments with the sulfinic acid (lit. yield 90% [64]). The sulfonyl

bromide could be readily hydrolyzed with potassium carbonate.

Competitive Sulfanation--Since benzenesulfonate appeared during the

sulfonation of iodobenzene (51) apparently by sulfonic acid displacement

of the iodo substituent, toluene was used as the competitor molecule in

later experiments (22). Toluene also served in the following experiment

to avoid benzenesulfonate enrichment. After sulfonation had occurred,

chloride ion was found in the resulting mixture. -3:0-

A ratio of 50 parts chlorobenzene and 25 parts of tokene to 1. 0 of sulfur trioxide-s 35 was selected to provide enough sodi~m p-chloro-

benzenesulfonate-s35 isomer for purification and to allow complete

consumption of sulfur trioxide-s 35 . Sulfur trioxide-s 35 (0. 892 g.,

1.11 x 10- 2 mole:i) in 200 ml. of liquid sulfur dioxide (Army Surplus,

grade unknown) was added over twenty minutes time to 50. 0 ml. of

chlorobenzene (City Chem. Corp., lot no. B257, b.p. 131-132°,

0. 492 mole,, under Na) and 25. 0 ml. of toluep.e (Baker reagent,

0. 235 mole :, over Na) together in the same 2.75 ml. of liquid sulfur

dioxide. - The sulfur trioxide (Sulfan-B, Allied Chemical & Dye Corp.)

was exchanged 6 weeks with 0.30 g. (ca. 1.2 me.) Bas 35 . (14,40). o4 All additions and transfers we re kept at reflux temperature with

a dry ice ...acetone cold-finger condenser and under the cover of a calcium

chloride drying tube. The sulfur dioxide was refluxed with stirring for

twenty minutes over P . Portions were distilled into a greaseless 2o 5

24/40 ',$' wash bottle and into a 500-ml. sulfonation reactor. Both

vessels were dried overnight at 120°/5 mm;·-

The crude arylsulfonic-s 35 acids deposited : on evaporating the

mixture overnight. The heterogeneous mixture was spun into a mov-

ing liquid sheet at the reactor walls to aid aspiration of the remaining

toluene and chlorobenz~ne from the mixture. The crude acid re s.idue

in 110 ml. of H2O neutralized easily with small portions of sodium. 35 carbonate. Extraction. of the sulfonate-s solution with four 10-ml.

portions of methylene chloride (no sulfone found) provided a solution

of labeled sodium O"', m•, and p•toluene-and chlorobenzene sulfonate s. Fi!ty milliliter aliquots of this solution were added to l 0. 00 g. each of sodium p•toluenesulfonate (5. 15 x 10- 2 mole) and of sodium p-

chlorobenzenesulfonate (expt. 107-F, 4.62 x 10- 2 mole) to set the isotopic dilution of each para isomer.

After two crops of crystals were taken frqm each recrystallization

(25° and o0 )a.,. . they'we;re prepared for counting· as be.fore. Dried sa~ples were treated and counted the same as de scribed for the isomer distribution.

Table 15. Sodium p-Toluenesulfonate-s 35 Competitive and Pti"rification Data (E:x:pt: l-61-F:.013)

Recrys. 1st Crop,(mins.) 2nd Crop (mins.) No. of Cts. Date

T-1 18 . 44 18 . 04 3 0 0, 0 0 0 9 Jan . ' 6 2 18.43 18.16 18.35 18.18 18.40

T-3 19.29 19.40 19.32 19.36 19.27 14.42

T-5 19.61 20.07 19.66 20.11 19.60 20.07

T-7 20.~4 20.40 20.35 20.60 20.38 20. 61

T-9 19.47 22.45 22 Jan. '62 19.53 22.51 19.60 22.34

T-11 21.68 22.74 21. 74

21. 87 20.86 21.80 20i92 22.03

a. Seep.21 -32-

Table 16. Sodium _e-Chlorobenzenesulfonate.;.s35' · Competitive and Purification Count Data- (Expt. 161-F• 13)

Recrys. 1st Crop (mins,) 2nd Crop (mins.) No. of Cts. Date

C-1 21. 19 18.95 300,000 8 Jan. 1 62 21. 15 19.01 21.13 18.83 21,. 15

C-3 20.20 16.36 20.32 16.41 20.26 16.52 20.47 16.41

C-5 24.22 17.47 24.39 17.51 24.44 17.66

C•7 27. 09 18.31 27.04 18.47 27.25 18.54

C-9 30. 15 crop too 22 Jan. '62 30.36 small to 30.40 count

C-11 35. 15 25.91 35.15 25.97' 35.33 26.05

C'-13 39.58 29.33 39.53 29.33 39.92 29.24

.9-15 46.78 26.67 46.84 26. 75 46.69 26.49

C-17 2.24 1.60 10, 000 22 Feb. 1 62 2.29 1.56 z. 31 1.57 2.36 1.64 2.45 1. 71 2.41 1. 65 -33- Table 16. continued

Recrys. 1st Crop (mins.) 2nd Crop (mins.) No. of Cts. Date

C• 19 2.75 1.70 2.78 1.. 75 2.74 1. 73 2.79 1. 79 2.81 1~ 84 2. 83; 1.83 a .;C-21 3.06 2.34 3. 11 2.36 3.11 2.35 3.17 2.32 3. 19 2.31 3.20 2.33

C-23 10.55 6.30 3,000 9 Mar. I 62 11.02 6.25

G-25 12.19 9,95 11.90 9.33

C-27 13.30 9,33 13.78 9.40

C-29 13.92 13.87

Constant purity was taken at the point of greatest count time.

Extended recounts begun on the ~ day (2 Apr. 1 62) at 100, 000 cts. with pure samples of sodium p-chlorobenzene- and p-toluenesulfonates produced the values in Table 8.

a. Sample C-21 (0. 0881 g.) was diluted with fresh sodium p-chlorobenzenesulfonate (0. 8067 g., 107-F) - -34-

Table 8. Competitive Sulfonation Recount Data of Toluene and Chlorobenzene

Recrys. Mins. Recrys. Mins.

T-7 12.57 C-27 523.02 12.45 530.95 12.47 534.49

T-8 12.63 C-29 556.09 12.66 559.65 12.77

T-12 12.69 12.64 12.74

Calculation of the total rate ratio from the raw counts above and the isomer distribution data came through values and relationships given in Appendices 1 and 2.

The partial rate factors were calculated from the total rate ratio with the following definitions (7, 44):

Pf = Partial rate factor for substitution at the para position, an. index of reagent activity.

,. ii' 1. 2 c 6 positions of benzene related to 5 of chloroben:zene

o/oP= Percent para substitution

20% = Correction for statistical substitution ~~. pa~ po S:;,'(lt 5)

kPhc:1/kPhH = Total rate ratio of chlorobenzene to benzene

mf = Partial rate factor for substitution at the meta position .35_

%M = Percent meta substitution

40% = Correction for statistical substitution (2/ 5)

Of = l. z (% O/4 0%) kPhCl/k PhH

of = Partial rate factor for substitution at the ortho position

%0 = Percent ortho substitution

pf/mf = An index of reagent selectivity between the meta and para positions.

After using corrections for the extra dilution of sodium ·p-chlorobenzenesulfonate arx:L dilution of sodium p-chlorobenzenesulfonate-s 35 and sodium p•toluenesulfonate•S 35 the total rate ratio, para and meta factors were respectively 8. B. 4. 2, and 1. 7. A graphic comparison of the logarithms of the partial rate factors for substitution at the para and, meta positions revealed a point for chloro~

1:enzene sulfonation just above the line for other reactions of chlorobenzene (Fig. 3). This difference fits as to direction with the experimental problems of purifying and counting sodium p-chlorobenzenesulfonate in the, competitive experiment and sodium ~-chlorobenzenesulfonate in the isomer distribution. (Fig. 4).

A better selection of experimental conditions based on a knowledge of purification and reaction conditions may facilitate increased accuracy in determination of the isomer distribution and partial rate factors of chlorobenzene sulfonation. Analytical factors es.pecially desired would be a determination of chloro displacement, a greater dilution for recrystallization of sodium p-chlorobenzenesulfonate in the competitive 36

5.0

4.0

Cl) Q.l 3.0 -sC ~

2.0

/.0

II 13 15 17 /9 21 23 25 27 29 31 33 35 37 3 9 4/

Recrystallizations Fig. 4 Extrapolation of Sodium p-Chlorobenzenesulfonate-S 35 Recrystallization Count Data. -37- experiment and more control of crystal size of the meta isomer in the isomer distribution study. The ratio of chlorobenzene and toluene might be further adjusted to provide more sodium p-chlorobenzenesulfonate for recrystallization in the competitive experiment. -38-

Appendix 1

Derivation Check of Ingold 1 s Equation (45, 47)

a = chlorobenzene initial

b = sulfur trioxide initial

-dy = k (c-y) (b-x-y)n C = toluene initial dt y

X = chlorobenzene at time t

y = toluene at time t

dx n = any real number = (a-x) (b~x-y)fi dy (c-y) (b-x-y)n limits

at t = 0 X = 0 y ;: 0 at t = oo X = xoo, value measured y = y oo' value measured

~-K (t)I~ = ky/ky t 1 l' Hospital's Rule (25) ky (t)I~

0 n d' (b-x-y) L n n ~/ky. = 00 a-: (b-x-y) : (b-x-y) (b-x-y)n ~od oo (c~y) at all values of x and y between t = 0, oo

log(a_:) kx/ky = 00

log(. c-yc oo ) -39-

Appendix 2 Calculation of the Chlorobenzene ... Benzene Rate Constant Ratio

Table 17. Constants used in the Calculation of .Partial Rate Factors (37)

• Compound M.W.

Chlorobenzene 112. 5 1. 107

Toluene 92. 13 0.8669

Sodium p-chlorobenzene sulfonate

Sodium p-toluenesulfonate 194.2a

Sulfur trioxide

Counting Deviation and Background

= Sample count (for 50 mg.) :cSobs • = Total count observed Cb = Background cbunt

= (Cs/ts 2 + Cb/tb 2) 1/z (65) = Emperical standard deviation

= Time for sample count

= Time for background count

CT = .(7,880- 16.1 + 25) cts./min. = 7, 864 + 25 cts. / min. .

Cc1 = (179.2 - 16. 1 + 1. 7) ct s. / min. = 163.1 + 1. 7 cts. /min. = Sodium p-toluene sulfonate-s35 constant count

= Sodium p-chlorobenzenesulfonate-s 35 constant count a. Isotopic enrichment neglected. Relative amount was small. -40-

Dilution Equation (15) mc1(Sc1W Cl - STWT )Mi +mc1ST w T(mTT - Dr) - mTSc:31Wc-ith~d1'I' .+ ~l)~T+ rrtc1mTST W TDT T = 0

aliquot moles of original Na p - MePhSO3 (· 50 ml. frlTY) 110ml.

• ST = activity per mole of Na p- MePhSO 3 (CT x -WT)

5 c1 = activity per mole of Na 'P- ClPhSO 3 (Gel x W c1)

molecular weight of Na p-MePhSO WT = 3

Wc1 = molecular weight of Na p-ClPhSO 3 \.. mT = fraction of Na p- MePhSO 3 in isomer distribution

mCl = fraction of Na p-ClPhSO3 in isomer distribution

DT = moles _of sodium p-MePhSO 3 diluent

Dc1 = moles of sodium p-ClPhSO 3 diluent T = total aliquot moles [ 5 0 ml. l l_!10 ml. (xoo + y ooj

The following approximate solution of the dilution equation above gave accuracy to four significant figures, as compared to the exact. _, answer of the usual quadratic equation solution. This approximate solution allowed the use of a slide rule.

MT • 1 .i 8 [ c1Wc1 Dc1 )- + 1 -rr.::::;- STWT m T -- ~ T ~* Cl mTTf

MT = 3. 45 X 10- 3 -41-

Total Rate Ratio (44)

. log a/ (a-x ) kPhCl/kPhMe = 00 log c/ (c-y ) 00

a = chlorobenzene initial

C = toluene initial

il-'Xoo = chlorobenzene at t 00

c-yoo = toluene at t 00 kphc1/kPhMe = 8. 77 + 0.01 kphc1/kphH = {kPhMe/ kPhH) / (kphMe/kphcl)

kphc1/kPhH · - · total rate ratio of chlorobenzene to ·benzene kph~e/:kPhH = total rate ratio of :tolttene to benzene, 8.82, (22) kphCi/lcphMe total rate ·ratio of' toluene to chlorobenzene = 1. 01± o. 02

Accuracy of Single Dilution Method (84)

im .•i So '·-· (1 + ~ ) ( _.&_s_ ) (31) m m:1 s So m S m - ' 1 s s 0 - .im m = relati:vecerror.in: amount of ra'dioactive· 'mate rial

m ::: unknown amount of radioactive material

ml = inactive diluent

so = specific activity of m specific activity at dilution with m s = 1

if m 1 >>n:i .Jm N 6s &So m s so

neglecting 6S Q so pm d:. &S m s -42-

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84. H. Weiler, Intern. l..;, Appl. Radiation and Isotopes 1~ 49 {1961). BROMINE ADDITION TO CYGLOHEXENE IN DIGHLOROME THANE

Survey of Bask Concepts

The uniqueness of. our results prompted a thorough survey of

th~ volu,mi:qous liter,ature. of' b,romine-olefin.addition {almost Z, 000

papers) (150).

As one might expect, halogen addition has

The addition of halogen to olefins was discovered by four Dutch chemists in 1794 (45). They prepared ethylene chloride (Dutch liquid) from ethylene

(olefiant gas). Since its discovery this simple reaction has received much

qualitative attention. More quantitative work began with Faraday's obser- vations of chlorine addition, substitution and light catalysis, to and ';Vith ethylene

(55). Since Balard first added brownish-red bromine to ethylene (14), most if not all students of organic chemistry have seen the color fade from

bromine-water or bromine-carbon tetrachloride solution. This is now a widely used simple test for carbon-ca;rbon unsaturatiop..

Current mechanistic ideas .. ']',he, details of the reaction pathway. stem

from careful determination of the bromination products of fumaric and

. - - - maleic acids (58, 60, 123, 124). These products were mainly~- and

mixtures of d- and~-dibromosuccinic acids.

Br-- > (meso) •48-

C02H C02H /C~H C Br2 Br Br II > + (d,I) C Br Br H · 'co 2 C02H C02H

M~so..;. ·, ·d"' ,a.ndJ~dihroino:succip.ic acid arid the products from acetylene dicarboxylic acid supported Michael's principle of trans addition (9, 128)

---the 1 addition of bromine atoms from opposite sides of the double bond.

The principle of trans'" addition was confirmed by many more examples

!:Jince Michael I s day, particularly in polar so~vents (78, 92, 105 t-g •

The two-step character of the reaction was clearly revealed in the classic experiments of Francis (62).

a. maleate and fumarate ions (94) b. · cis• and trans ...2-butene (133) c. norbornylene (154) d. 1, 4•epoxy•l, 2, 3,.4, ..tetrahydrophthalic anhydride (95) e. cis• and trans:.{!,,-·a~yl-mercatoacrylic acids (135) f. unsaturated acia~ (116) g. cyclopropene (199) Every product contained one or two brbmo groups but no product con-

tained two groups corresponding to the anions. Since van' t Hoff observed the the formation of/bromohydrin of fumaric acid (77), a reaction similar to a-g the last one above, many examples of the mixed product have been found .

. Both trans addition and two- step character were seen in the reaction of

bromine or chlorine with sodium dimethyl maleate: .. (180).

Me, /coo- "c · II C Me/ "--coo-

coo-

a. allyl alcohol, HzO (27) b. unsat' d acids, HzO (139, 147)

c. cyclohexene, pyridine (16, 71) d. aromatic, alkyl, alcohol, aldehyde and carboxylic olefins, methanol (125, 151)

e. olefins, acetic acid (33)

f. stilbene, methanol (27)

g. ally+ bromide, o 2 (30, 163) -50-

If bromine was added to y ~,&-unsaturated acids and esters) similar lactonic products appeared: ,Tl,2, 132;, 2Q0).

With trans addition, two-step character and an analogy with epoxide,

Roberts and Kimball postulated a 3-rp.embered ring, the bromonium intermediate (153).

/0"'- -c---C- -c· /~ c- / ' / '

A second.step backside displacement with a negative ion then gave trans addition. Such a cyclic intermediate was supported by the isolation of chloronium..,.. bromonium and iodoni.w:n compounds (141, 164) •

. x-

X'7. = C 1,-, Br - , r-, BF - ; 4 Other supporting evidence has come from reactions thought to involve the bromonium or chloronium intermediate. A qromide ion displacement of a protonated hydroxy group gave a product readily explained by -51-

a cyclic intermediate (206).

> EB HzO Me Me

Evidence of a chloro group migration was observed in chlorobydrih1

formation with allyl chloride-C1 36 (206). Again a bridged intermediate

was used for an explanation of the products (110).

c-c, 36 C-OH I HOCI I; C > ) c-c136 (4 9/o) II I + C C-CI

c-c136 c-c,36 f, I C-OH (36%) + c-c, (65%) .J I c-c, C-OH

By comparison the three possible intermediates fer chlorine and

hydl'ogen chloride addition and olefin basicity are similar to the bromo- niwn intermediate. These intermediates should bear a strong resemblance to one another •

Cl H ' /@"' /©"" -C---C- ' -c----c- ' / ' / '

A limit~d compadson of chlorine addition with hydrogen chloride addition rates showed not only the same response of substituents but a linear relationship to olefin basicity, Fig. 5, and Table 18.(basicity was based on Henry's law). Table IB. Comparison of Basicity and the Rate Constants of Hydrogen Chloride and Chlorine Addition (50, 70, 167, 177)

Basicity, K HCl, -78. 5°, kz Clz/HOAc, kz, ( >C,=G<) = 1 0 Z.17x 10- 3 very fast, 6 (0°) ., ' 3 1.28 X 10- ca. 8. 50

Cl . /Cl 4 ·'-ccc 7,58 X 10• ,?•75 4.4 X 10"'9

Cl '-ccc 5. 62 X 10• 4 0. 001(-46°) 2. 2 X 10•9 'c1

Cl Cl '-c=C/ 2. 56 X 10""4 0.21 1. 3 X lo- ll 'c1

, Cl Cl 'c=c/ 9. 09 x l0"" 5 0.001 (0°) very slow Cl/ 'c1 -53-

3.0

G(-46°C)

2.0 c 0 :;::: !€j - "tJ ~

0.0

0.0 0.5 1.0 1.5 Olefin Basicity, Log Krel Fig.5 Comparison of Chlorine and Hydrogen Chloride Addition with Olefin Basicity. Relative rates and basicity of tetrachloroethylene were set equal to one. -54-

-Since the relative rates of chlorine and b-rom-ine addition under similar con-

ditions are the same (112), bromine addition data should be simil-&.Tly linked

to olefin basicity.

A further study of the relationship between hydrogen .chloride and

bromine addition would shed Hght on their close linear relationship with

olefin basicity, Fig. 5. The experimental work reported hereafter includes

a preliminary study of the kinetics of bromine addition to cyclohexene at

o° C. in dichloromethane.

Literature Background

Much study of the ionic, dark, thermal or singlet bromine addition as

compared to little study of free radical, lighted, non-thermal or triplet

bromine addition covers nearly one hundred and forty years of effort. The

seeming simplicity of bromine addition hides an array of results and prob-

lems. Our work was no exception.

A survey of Chemical Abstracts gave eight hundred references that

could be linked to the mechanism of bromine addition. Although several

reviews (8, 21, 53, 106, 107, 112, 121, 122, 146, 152, 155, 161, 203) are

available, each generally relates only to portions of the -literature which

were available and which had caught the imagination of the respective

authors .. Certainly because of its scope the area is in need of a more

general view .

. Kinetics - Because bromine addition rates cover the extreme range from

inert to highly reactive olefins, much work has been done with olefins of a

moderate reactivity, such as unsaturated carboxylic acids. Extreme

reactivity has been measured through competitive reactions between two

olefins for a limited amount of bromine or chlorine (6, 9, 82,118,167). _55 ..

The rates of reactions in which a charged intermediate is produced for neutral reactants are strongly affected by changes in the polarity of reaction solvents (81). The bromonium intermediate required a charge; and the reactants, promine and olefin, were uncharged. Increases in solvent polarity may be provided by changing or mixing solvents and by adding various salts. Usually kinetic studies in water or we~ media have yielded second- order kinetics, first-order in olefin and first-order in bromine •. Some of the olefins that have been studied are stilbene (17), maleic and fumaric acids {ZS, 77), cis-cinnamic and acrylic acids (157), allyl alcohol, various fatty acids and hydrocarbons (193 ).

In non-aqueous solvents a third-order term, second-order in bromine -2 concentration, became important. It predominated above 2. 5 x 10 M in pure acetic acid {157, 197). In chloroform and chlorobenzene, a second- -2 order reaction appeared {with the third-order appeall'ing only below 2. 0 x 10

M bromine) in additions to ,allyl benzoate, cinnamic acid and ethyl cinnamate

(113, 195.). If the solvents, carbon tetrac.hloride ,and acetic acid, were mixed, kinetic chan~es also ,appeared with cyclohexene, styrene, stilbene and tri- phenylethylene. The addition of carbon tetrachloride decreased the third- order r•te constant {118). The more polar acetic acid increased the rate.

Careful studie& have ... 1s0 been pe-rformed with mixtures of carbon tetrachloride, acetic and trifluoroacetic acids (86 ). and . Surface and trace catalysis indicated a heterogeneous reaction/occurred in pure carbon tetr-a.chloride (63, 119). The following are believed to be evidence of a heter ogeneus reaction: variable rate constants (174), decreasing rate with increasing temperature (44, 202), rapid initial rate (73, 103), -56-

increasing rate with increased glass surface (157), and an additio'nal high

reaction order (about four) in very pure carbon tetrachloride (113). Early

synthetic work was also done in carbon disulfide (59, 97, 98, 99, 114, 2.07,

208 ), carbon tetrachloride and chloroform (23, 99, 114, 129, 130, 208 ).

An increasing rate with the ,kind of surface in the order pyrex <.silica,{

alumina( uncatalyzed (7) confirll) s s.u.:cfa.ce ..catalysis in carbon tetrachloride.

, Similar surface effects have appeared during bromine-ethylene addition in

the- ga-.s-ph&&e. If the walls of a reactor were coated with various materials,

the following rate constants were observed:

Table 19. Surface Catalysis of Bromine-Ethylene Addition (142, 179)

Surface k paraffin o. 0030

cetyl alcohol 0.0266

glass o. 0506

stearic 11,cid 0.0864

palmitic .-eid 100 (-COOH at reaction surface)

, Some of the catalysts of bromine addition are chlorine, iodine (73 ), pyridine (120, 189), tetramethylammonium. tribromide ·(36 ), . antimony (III)

(35 ), bismuth (W), tin (IV),, and arsenic (V) bromides (120, 189), iron (III)

(156) and mercury (II) chlorides (131, 153 ), other metal salts (lll), acids expecially hydrogen bromide (143, 153) and water (44, 172, 202). These generally polar catalysts can associate with bromine or the olefin and would aid in the formation of a charged intermediate. -57-

Cis addition - This simple reaction mode is seldom observed. Both o-,

0 1 -dinitrostilbene (145) and 1, 4-diacetoxyl-cis-2-butene (22) have given predominately cis-dibromide. Although light favored cis addition of bromine to 1, 4-epoxy-1, 2, 3, 4-tetrahydrophthalic anhydride· (24, 95 ), darkness gave almost all cis addition between cinnamic acid and chlorine in carbon tetra-ehloride {100) and 37% cis addition between cinnam-ic add and bromine (127). Light (127) or iodine (195) provided more trans addition with both chlorine and bromine. Cis addition was the main side reac ... tion in chlorine substitution of phenanthrene (109). This reaction was unaffected by oxygen or light. Generally, cis addition in the reactions above was favored by non-polar solvents. This was also true of cis- addition to benzoyl-, p-bromobenzoyl- and mesitoylacrylic acids (134).

Thus, trans addition may be dependent on small amounts of polar materials usually present. An intermediate which accounted for cis addition and third-order kinetics proposed by Waters, Caverhill and

Robertson was the intermediate,

V-Br~- 1 S+Br--Br---C--Br ! • /\

If this intermediate were combined with a possible "ii'-complex step

(47, 48 ), the following sequence could be written: -57-

Cis addition - This simple reaction mode is seldom observed. Both o-, o'-dinitrostilbene (145) and 1, 4-diacetoxyl-cis-2-butene (22) have given predominately cis-dibromide. Although light favored cis addition of bromine to 1, 4-epoxy-l, 2, 3, 4-tetrahydrophthalic anhydride (24, 95 ), darkness gave almost all cis addition between cinnamic acid and chlorine in carbon tetra-chloride {100) and 37% cis addition between cinnamic add and bromine-(127). Light (127) or iodine (195) provided more trans addition with both chlorine and bromine. Cis addition was the main side reac.;. tion in chlorine substitution of phenanthrene (109 ). This reaction was unaffected by oxygen or light. Generally, cis addition in the reactions above was favored by non-polar solvents. This was also true of cis- addition to benzoyl-, p-bromobenzoyl- and mesitoylacrylic acids (134).

Thus, trans addition may be dependent on small amounts of polar materials usually present. An intermediate which accounted for cis addition and third-order kinetics proposed by Waters, Caverhill and

Robertson was the intermediate,

V-Br~- 1 S+Br--Br---C--Br l /\

If this intermediate were combined with a possible 'Ti'-complex step

( 4 7, 48 ), the following sequence could be written: -58- \/-Bro- \cl \.!. 1 Br ll-4Br c:,-t:Br- -Br- --s=;--Br ! II 2 2 /\ > A > /\

\/_ Br \j_ Br I I + C - Br Br-/\ /\

Bromine-olefin 1i'-complexes were observed with 1, 1-diaryl- and tet;r..a- arylethylenes where the aryl groups are p-chloro, p-bromophenyl or phenyl (29) •. Such 71'-complexes were also found with 1, 2-dichloroethylenes

(190), tetrachloroethylene (15, 29) and crotonic acid (29, 36).

Oxygen and Light - While oxygen affected some addition teactions, this effect was either absent or bas gone unobserved with most olefins •. ~ygen

{19, 188, 201) or hydrogen bromide (168) retarded the reaction of bromine and cinnamic acid. This reaction was not only accelerated by benzoyl peroxide but synergistically promoted by oxygen and hydrogen bromide

(168 ). If hydrogen chloride were substituted for hydrogen bromide, this unusual effect did not appear.

Oxygen catalysis was absent with most oe,.<3-unsaturated -acids (162).

However, oxygen reacted with bromine and cyclohexene, styrene, c:A-phenylstyrene, ally! bromide ·and-allyl chloride to give ,<3-bromoper- oxides (30). Temperature and decreasing solvent polarity,. HOAc>

ArNO CC1 > ArH, promoted the extent of reaction. 2 > 4 -59-

The effect of light on various unsaturated .acids, esters (25, 26, 87,

148, 149, 174, 175, 209), nitriles (148, 149) and chloroethylenes (87, 148)

was confirmed by our observation of light promotion of bromine addition

to cyclohexene •

. Structural and .Medium, Effects - The effect of the reaction medium on the

bromine-olefin addition followed the pattern of a polar intermediate. The

substituent response at the double bond was greatest with second-order

addition in pure ·acetic add a-nd least in dichloromethane,. Fig • .7 (5, 6,

10, 118, 167)a-f •

. Cyclohexene in comparison with other olefins may be similar to~

2-butene and faster than ethylene, Table 20,. Fig. 8. Graphic comparison

-4 a. 1 x 10 M Br2 /HOAc (158)

b. HoAc (107)

c. CCl4:-P (44) 2 o5 d. Me·OH (193)

e. HOAc-HBr (107)

£. CH Cl (82) 2 2 -2 g. 1 x 10 M Br /HOAc (158) 2 h. phthaloyl peroxide (65)

i. epoxidation (178)

j. dichlorocarbene ·(18 7)

k. dibromocarbene ·(17 0)

1. bromine ,addition .in dichloromethane (82:)

m. atomic oxygen (41) 16.0

14.0 lo 0

12.0

C -~0 :a "C <{ 10.0 0 a;... 1/) .::I: -Q) 0 O'I 0::- 0 _J Q) .::: 8.0 0 -a; 0::

6.0

:r :r 0 0 0.. :r s:: :r (.Jo' (.J (.J Q. (.J (.J (.J I V I I I -~ I (.J (.J (.J <.JU (.J (.J 0 (.J C.) 0""0 uh ,, q II (.J (.J " (.J " (.J" (.J" <.JU" " ~ ... (.J y I I I I ·-.!!" u"t'U o''r s:: I\ us: s:: C.) u 0 a. a. u a. ou

Relative Rate of Atomic Oxygen Addition, Log(krel>o Fig.7 Effect of the Reaction Medium on Bromine-Olefin Addition. The relative rates of crotonic acid were set equal to one. .-I '°I

4 txm- M -Br2 /HOAc I 7.0 lo 0

6.0

5.0

c .2 .t "0 "0 4.0 <( ~ 0 f -u, .:,c. G) 0, 0 aYc-c~ 0 3.0 a:-., ...J ~ 0

:c :c o' ~ <.> I ~ <.)

2.0 u u ioo '-" .Y: (,) ~' y o.!! X'u• o'Z b'o -1.0 Relative Rate of Atomic Oxygen Addition, Log(kre1>0

Fig.8 Comparison of Second-Order Bromine Addition with Other Olefin Addition Reactions. The relative rates of ethylene were set equal to one. -62- of several addition reactions (4, 6, 10, 49, 118, 167)a, f-m revealed extensive linear relationships,. Fig. 8 •. Some ·authors of the work upon which this linear relationship depends were ·aware of, but didn't use it.

This does not include· Cvetanovic,. who has made use of linear relationships among the·alkyl substituted olefins (41) •. Excepting the higher reactivity of atomic oxygen, bromine ·addition covered the full range A substituent response,. Fig. 8 .. More determinations of various addition reactions with the less reactive olefins would-add much to this addition selectivity relationship. This would also provide-an important check on the validity of such a relationship.

Addition reactions were •also linearly related to ionization potential

(38, 79), olefin basicity (196} and possibly heats of hydrogenation (2) and spectroscopic excitation energies (165). The-addition reactions did not correlate with silver complex stability because complex formation was. apparently subject to steric influences. (186, 205 ). Other simple and non-linear relationships exist between olefin reactivity and olefin spectra (5) •. These have received some theoretical discussion (52, 138).

The directive powers of various substituents have been qualitatively explained in terms of a dipole interaction or inductive effects and "il'- · orbital overlap or resonance effects (55, 82,. 107). Most of the data in

Table 20 were well accounted for by coupling the qualitative theory above with steric hindrance in the case of the butyl group. Table 20. Effect of Structure on Bromine Addition

Substituent Reactivity Reference

Me< Me < Me < Me 6, 82, 177 2 3 4 Ph < Ph < Ph < Ph 115 4 2 3 107,,

X4 < X3 < X2 < X, X;:: F

I < Br < Cl < F (o-halocin.- · 204 namic acids) CH CN < CH Br < CH Cl < CH F 167 2 2 2 2 CC1 < CHC1 < CH Cl 167 3 2 2 5, 6, 82, 177 CO2H < CHO < CH 2OH

C=C=C=C=C=C < C=C==C < C=C 32, 93

linolenic < linoleic < oleic acids 88

trans < cis 25, 107, 157, 177,182

GH2But < 1:n.1t 25 .ro-r,.vs:5.,,1s 7.,15·9,, 177, 182 Br< CH 2Br 25,107,15~,159,177, 182 (CHzCl)2 < GH 2Cl 118

C:G < C=G 31, 158, 182

CflzN+Me < · GO H CO .. 15 7, 181, 192 3 2 < 2

. SOzMe< GOzH < Br < C = C < CH 2But < But < Bun 155, 157, 15·9, 111

p•N'O2Ph•C=G-COzH < Ph-C=G-GO 2H <·p-MePh,C:C-CO2H 155,T57n5'9 ,177.

The order reversal seen in the ~-halocinnamic acids (204) could be

explained as a steric effect until the same order appeared with the

halomethyl group ...--:halogen one carbon away from the double bond

(76). An extension (176) of Grimm's principle (76) provides an under-

standing of this order reversal and materially aids understanq.ing of

other substituents such as me thine {- C=-). -64-

The classification .of bromine -addition reactions was :made by

Robertson,and de la Mare by comparison of various catalyst effects on

different substituents, Table 21 (112, 155 ) •

Table 21. . Classes of Bromine Addition.Reactions (The inequality,> <, and equal signs designate the relative effect of various catalysts and reagents on reaction rates) Acid and Anion Unca.talyzed Anion Catalyzed Anion Catalyzed .Catalyzed, · Electrophilic . ·Electrophilic Nucleophilic Nucleophilic

1. . Cl > Br l. Cl Br 1. c1
2 2 2 2 < 2 2. . Small salt 2. Li Cl> LiBr 2 • . NaOAc Br 3. Br
·LiBr, • HBJ!>HCl> _H ClO 2 4 H SO,?HN0 2 3 5. k[Aj[BrJ[H+j

6. +I, +T, 6. .-I, +T, . C,HzCl 6. -I, -T, and conj. e.g.,. Me, Ph with basic center, . CHO~COPh .C•N~Nozso R 2

Dis cuss ion of Results

We have determined the rate of bromine-cyclohexene addition in

dichloromethane at o° C. This was done to provide-a pi.lot study for a

systematic variation of solvents at low temperatures.

Although nitrogen.flushing was used throughout our solution manipulations,

some -oxygen was allowe-d into the reaction system by back diffusion through

the pump. H c,;vever, none of our rate measurements changed with changes

in oxygen or hydroperoxide content (Tables 24 and 25). -65-

The reaction between bromine and cyclohexene in dichloromethane did

show reaction promotion by light, Table 22.

Table 22. Promotion of Brom~ne Addition to Cyclohexene by Light -2 Brz 1. 7 x 10 -~ HBr 3 x 10- 2 .M

Light Source Total Reaction Time,. Seconds

Oxygen Torch 2

Tungsten light bulb, 500 W 9. 5 ± 2

Fluorescent tube, 15 W 10. 3 t. 2

Hood pilot light, 6 W 12.. 8 ± 2

.None 14. 0 :t o. 5

After the--ambient factors of air and light were examined, we found two

differing results .

. Second-order addition - Our second-order rate constant obtained from

cyclohexene purified with sodium compared reasonably well with the

available values, Table 23.

Table 23. Bromine Addition to Cyclohexene

Reaction ..Medium . Rate· Constant . Jlef • 5 35° 20% HOAc-CC1 1. 53·X 10 119 4 1 k3 4 35° 151, 119 10% HOAc-CC1 3.35·X 10 4 k3 ·x10 4 15° 193 ·MeOH 2.7 kz HoAc 3 ,X 104 k 250 159 2 CH C1 , 6 x 10- 3 M HBr 56.7 k 00 our work 2 2 2 25° HOAc, O. 5 ·M HBr 1. 65 kz 54

. Since we determined rates at a higher bromine concentration, our constant

is one -of the most rapid yet measured with the traditional thiosulfate titration method. -6:6-

Our second-order reaction probably went by the following mechanism

(161):

Br -c---c-/@"' Both our zero:.. / and second-order " reactions were depressed by hydrogen bromide (Fig. 6, Tables 24 and 25 ).

Table 24. Inhibition of Bromine Addition to Cyclohexene by Hydrogen Bromide. Cyclohexene Distilled from Sodium. Pumping Total Reaction Time, Time, secs. )C:C

3 2.04 2.2 4.79 3 X 10-S 2.-3 6 4-5 1. 62 6. 0 2.45 5 X 10- 10

Table 25. Inhibition of Bromine Addition to Cyclohexene by Hydrogen Bromide. Cyclohexene from a Cuprous Chloride Adduct. Pump- ing Total Reaction Time, Time, secs. Brz x 10- 2M HBr x 10- 3M >C,=C

5.6 1. 89 less* 2.10 1 6

5.7 1. 27 more* 2.10 1 6

14 1. 7 3 4. 58 8 10

18 8. 9 11 4.58 1 10 *Both less than 3 x 10- 3 M. This depression was apparently due to hydrogen tribromide formation.

Thus, cyclohexene belongs to the first class of bromine addition---uncatalyzed electrophilic addition, Table 21. -67- Zero-or,der Addition -

Our results of a zero-order reaction have little precedent or par;.. allel. Only one other example of zero-order bromine addition is known.

This example was seen with ethylene (202). Walisch and Dubois obtained second-order kinetics with cyclohexene in aqueous methanol (193) and

Mathai (118) an additional third-order term in carbon tetrachloride-acetic acid mixtures, both in marked contrast to zero-order bromine addition.

Our results were obtained from cyclohexene purified through a copper{!) chloride adduct {see Fig. 6 and Table 26).

Table 26. Bromine Addition to Cyclohexene Purified through a Copper(!) Chloride Adduct. Zero-Order.

= Reaction Time, secs. 0.105N S2O3 , mls. HBr, M

0.0 1.98 less* 3.2 0,87

4.9 0.85

0.0 1. 17

3.7 0.27 4.3 0.14

0.0 1. 72 3 X 10 .. 3

7.5 0.80

9.5 0.56

0.0 0.89 1.1 X 10- 2 6.25 0.58

9.5 0.42 10.3 0.37

*Both less than 3 x 10- 3 M. ri> -.c I

/.5

q, ·S ~ ~~ cl§'l' ....~ ~ "" -~ "l:, 1.0 .;:, q, ~ !;: ~ iii :s~ '-.):s G

0.5 HydrogenBromide Content A

5.0 100 15.0 Time, seconds Fig. 6 Inhibitionof Bromine Addition to Cyclohexeneby Hydrogen Bromide from Bromine Substitutionof Dichloromethane.Zero-order Addition. Zero-order reactions, relatively rare, have usually occurred in heterogeneous systems an.dare thought to depend on a saturated surface. Exam- ples are decomposition of nitroµs oxide, ammonia and ethylene iodide and disproportionation of cyclohexene (66, 74, 75, 83). Pt >

Pt >

CH2I-CH2I CH2=CH2 6 > + I2

Pd 6 > + 0 0 0adding Such a surface control of bromine addition was checked by/ calcium hydride and increasing glass surface area. Variation of calcium rate hydride and glass surface area produced no/changes in our system.

A catalyst-controlled zero-order reaction was seen in chlorine substitution of acetic anhydride (104) and bromine substitution of excess malonic acid (13). The solvents carbon tetrachloride, acetic acid and acetyl chloride affected the rate but not the zero-order (104). Chlorine substitution of acetic anhydride was first-order in the catalysts iodine, iron(III) and tin(IV) chlorides (104). This type of catalysis presented the possibility of a low-level catalytic impurity which could control the concentration of the reactive intermediate. The following reactions

(1, 18, 20, 42, 43, 56, 89, 210) are readily obtained with cyclohexene and might provide such an impurity: -70 ...

Strong acid> 0 6

Pt >

air 21ight ➔ 2noCaH2 (OO)n 0-0H 0

02 > 0 0 6 ) O+H20 0-0H OH 0 0 -7L-

Most of the possible low-level catalysts were eliminated for various reasons. The methylcyclopentene s react with bromine more rapidly than cyclohexene and dibromo products do not usually affect further reaction (117). Gyclohexane and benzene not forming a copper(!} adduct were removed during purification. Their 'reappearance without a catalyst would be very slow. Polymerization was not observed in the samples used and along with cyclohexane and benzene would be inert during bromine addition. The somewhat polar cyclohexene hydroperoxide might serve as a catalyst. However, variation of hydroperoxide :content showed that bromine-cyclohexene addition was independent of thi~ impurity. Inactivity of

2-cyclohexenone and confirmation of the inactivity of 2-cyclohexene hydroperoxide came through a sample of cyclohexene distilled from sodium.

A second-order reaction with bromine was obtained from this olefin sample which contained cyclohexenone and hydroperoxide. Cyclohexenone and the hydroperoxide were also in cyclohexene prepared from copper(!) chloride.

Gyclohexanesulfonic acid and 2-cyclohexenol remain to be considered as possible active impurities. Their simultaneous appearance during adduction (sodium bi sulfite prevented air oxidation of cuprous chloride) and their similar reactivity with sodium prevented separation and experimental evaluation. Of these, cyclohexanesulfonic acid seemed' unlikely as a limiting catalyst . The acids HGl,04, HBr, H 2so4 , HGl and HN0 3 (9,

11, 67, 91, 111, 137, 143, 160, 184) gave only second• and third-order addition reactions with various olefins. -72-

Copper (I) may have entered the final sample through a volatile compound.

Even slight stability of a copper compound would permit traces to trans - fer because large amounts of copper (I) were present during steam distillation of cyclohexene •

. Since silver (I) ion gave a bromonium ion, Br+ , from bromine (4 6,

64), copper (I) might do the same. Bromonium ion was also prepared by adding a strong acid to hypobromous acid, giving H 0 -t Br or Br+ 2 (64, 85 ) •. The relative rates of various brominating agents with allyltrimethylammonium perchlorate suggested that bromonium ion could be very reactive and consumed as rapidly as it was produced, Table 27.

Table 27. Reactivity of Various Brominating Reagents with Allyltrimethylammonium Perchlorate (85)

Brominating. Reagent Rate, Constant, k . + 14 HtO Br 2 X 10

BrCl 5700

Br 1. 6 2

Br - 0.65 3 HOBr 0.025

In dilute solutions chloronium ions, ct or HtO + Cl, did react in a process first-order in hypochlorous acid and zero-order in olefin

(108, 110).

If the amount of bromonium ion were fixed at the beginning of and during the reaction, then the brominating reagent would go to zero- order as well .. Such was expected with copper (I) action on bromine. ·The re- peating sequence below would continue until the reactants were gone. -73-

ar ) > + at 0 O Br A less likely generation of bromonium ion might occur with cyclohexenol providing a mild basic center which could enter the repeatin~; sequence above.

Base) + 2Br Br Base Br 2 + 3

Thus our work is both unique and consistent with·a large body of information and suggestive of new avenues of approach.

Oxygen Photo Effect---Our study of bromine ·addition rates was done in total darkness. This allowed complete dilation of the eyes and the observation of an emission.of pale blue light when various mixtures of oxygen, nitrogen and air were jarred. The intensity of this effect increased with increasing oxygen content, with a lower temperature and with the presence of dichloromethane solutions of cyclohexene or ·bromine. An intensity maximum occurred at ca. 10 mm. The ·number of times the effect was repeated rela.tsi directly to the pressure. The samples could be recharged even with the safety light.

A high level laboratory effect, the Lewis-Rayleigh, was observed with nitrogen in an electric discharge tube. The Lewis-Rayleigh effect is a golden-yellow afterglow due to recombination of nitrogen atoms (84); however, it is different from our effect. Apparently we -are the first to see the oxygen photo effect in the laboratory as described above. -74-

Although we have not determined the wave length of the light emitted,

our effect may be related to natural phenomena of the atmosphere such as

St. Elmo's fire, afterglow of the night sky, and the northern ,and southern

auroras. Some of the reactions of the atmosphere have been studied with

rockets and simulated in the laboratory (68) •

. St. Elmo's fire, named by mariners of the Middle Ages who saw it

in the ship's rigging, is observed today about and in aircraft and apparently

in tornadoes .. Static electricity is generally associated with, St •. Elmo's

fire which is usually a bright blue or green color.

Night afterglow is observed in many places and is a low-level effect

(72). Blue lines were observed in the spectra of the night afterglow {28).

The spectacular northern and southern lights often contain blue either

,mixed with green or as a pure color. Blue color has been related to the

nitrogen molecule and has appeared particularly in the high atmosphere.·

Table 28. Description of the Aurora Borealis (37, 101)

Color Source Height, miles

Red (rare) 0 600

Blue NZ 600

Yellow (red plus NZ 175-150 green) Green 0 150 -160

. Scarlet N2 50 -75-

The light of the aurora is caused by collision of protons and electrons with oxygen ,nd nitrogen molecules. Auroras can be produced with•an atomic bomb . (102 ). -76-

Experimental Section

.Purification of dichloromethane, bromine and cyclohexene - In a kinetic system the impurities must be absent, inactive, or accountable in effect to allow a clear view of the reaction under study. With this in mind dichloromethane, bromine and cyclohexene were each purified and evaluated.

Distillation of dichloromethane (Eastman, b. p. 39-40° /760 mm .1 d.

1. 322/20°) from calcium hydride (City Chem. Corp., New York, no.

J357) gave a short fore-fraction at 34°/647 mm. and a general fraction (calc. ) at 36. 5° / 649 mm.,/ 41. 3° /760 mm. (lit. 41°) (80). The take-off rate through a 50-plate vacuum-jacketed column was regulated for this distillation at 1:25 with a column head having a valve magnetically operated from a distillation timer and relay (Precision Distillation Apparatus Co.,

Santa Monica, California, E-7).

Passage of dichloromethane through fresh silica gel (W.R. Grace Co., mesh size 28-200, grade 12, part no. ii-08-08-237), deoxygenation for two hours over calcium hydride with pure nitrogen (Whitmore Oxyg·en Co.,

11 p.p.m. of o 2 and 60 p.p.m. of total impurities) and storage over cal-

cium hydride packets made with filter paper completed the preparation.

A cooling curve (140) of dichloromethane which was prepared as above

revealed a line at 15. 730 ohms. All obtainable regions of the freezing curve were horizontal. The value of 15. 730 ohms was converted to a temperature value of -95.04° C. (lit. -95.14°) (51) with the aid of the Callender equation.

Leeds and Northrup provided a table of Callender equation parameters

and calibration values for the platinum resistance thermometer (Leeds and

Northrup, model no. 8163, ser. no. 1522230) and M-q.eller Bridge (Leeds -77-

and Northrup, Speedomax, G, ser. no. 59•95088-1-1) which were used to get the freezing curve.

Sudborough' s acid wash and recrystallization method of purifying bromine (174) has received a kinetic evaluation (3) and formed the basis of our purification. A pound (450 g.) of bromine (reagent grade, Baker and Adams, Allied Chemical, no. S197} was vigorously shaken in a sep- each aratory funnel ~ . with three successive portions/of 10% sodium hydroxide solution (analytical reagent, Mallinckrodt} (34, 166) and concentrated sulfuric acid _(reagent grade, Dupont, sp. gr. 1. 842), respectively. The bromine separated cleanly from the acid when the mixture was allowed to stand for three hours. The sample was distilled from 10 g. of anhydrous copper sulfate (analytical reagent, Mallinckrodt) and the fore-fraction rejected. The remainder was treated one more time with acid. Six to seven recrystallizations in a methanol-ice bath held in a Dewar flask gave at first large rhombahedral crystals and finally well-d.efined needle if!. A pair of glass-stoppered 300-ml. Erlenmeyer flasks (greaseless, 24/40 !f, dried at 120° /15 mm.) were used during the recrystallizations. The final heart-cut was sublimed twice at ca. 7 mm. Only the final mid-fraction was kept.

Cyclohexene (99. 83 +mole %, Phillips) was refluxed 30 minutes over sodium and distilled (194} at 77°/648 min. into a glass-stoppered bottle.

Evaporation of liquid nitrogen (99~ 5%) through a 1: 1: 1 mixture of pyl;"o• gallol, (N. F., Baker Chemical, lot no. 3607} potassium hydroxide J

(reagent grade Baker and Adamson) and water; cone. sulfuric acid and a drying tower containing anhydrous calcium chloride (Brothers Chem- ical Co., 8 mesh), anhydrous calcium sulfate (W .A. Hammond Drierite

Co., 8 mesh) and sodium hydroxide (reagent grade, pellets, J. T. Baker) gave an oxygen,.free atmosphere during reflux, distillation and storage under a bell-jar. Five liters of liquid nitrogen in a metal Dewar con .. tainer supplied gaseous nitrogen for ten days. A ferrox test (144), performed with acidified ferrous thiocyanate, showed no hydroperoxide in the cyclohexene after storage. The fe rrox reagent was prepared by dissolving ferrous sulfate and potassium thiocyanate in dilute hydro• chloric or sulfuric acid and decolorizing the pink solution with a minimum of zinc dust. A test with anhydrous aluminum chloride and chloroform

(171) indicated with an orange color a trace of benzene or homolog of benzene.

A cooling curve of cyclohexene prepared as above was taken with the same equipment used with dichloromethane. The cyclohexene contained

0 1 mole % of impurity and an extrapolated m.p. of 14. 806 ohms or-103. 53

C (lit. m.p. - 103. 500 + O. 015° C,) (173). Infra.red peaks due to impurity were found at 1700, lOt>0 and.95O cm -l and we re as signed to cyclohexenone (: S.adtler Curve, Index No, 19138).

A less conventional procedure of purifying cyclohexene was based on a cuprous bromide adduct method (136). The process was carried out in a one liter Erl~nmeyer flask stoppered with a polyethylene covered cork and cooled in an ice bath in a large Dewar flask, One hundred and fifty mls. (1.,48 moles) of cyclohexene (99 +mole %, Phillips) was mixed with ..,79_ a water solution conta~ning 112. 3 g. (2 .1 moles) ammonium chloride

(reagent grade, Baker & Adams), cuprous bromide (prepared from

60 g., O. 455 moles, of copper sulfate, analytical reagent, Mallinckrodt, potassium bromide and sodium bisulfite) or cuprous chloride (analytical reagent, Mallinckrodt) and 7. 5 g. of sodium bi sulfite (U.S. P., Industrial

Distributors, Inc., lot no. 1129). Enough liquid detergent (Tergitol, ca.

1. 5 ml.) was added to give a permanent emulsion. The mixture was vigorously agitated and stored in an ice bath for 12 hours. Less time .or insufficient mixing lowered the yield of a:bout 30-40%. Greater time periods gave increased amounts of 3 ...methylcyclopentene (3. 7p.) (9(6) by an acid catalized rearrangement (169, 210) and bromination of the double bond (positive Beilstein and KI/ acetone tests). The mixture proved to be light sensitive.

1 The adduct was filtered at o0 and rapidly washed three times with ice water~ After the washed solid was quickly transferred to a standard and pre .. assembled distillation set-up (250-ml. 24/40 J~R:..j: B'-" fla.sk 2.4/.40 and· 1q/·~.Q.-~,th:1:ee'7';',Va.y:.distilling head,.:etc:. );· water -wa.s.added· aria:. cyclohe.xene ·st'eam dis.tilled at ca~ 67°/ 650 mm~: A; half-degree cut was taken.

The wet hydrocarbon was salted from the water phase with sodium sulfa:1.te, separated, partly dried over anhydrous sodium S1J.lfate and com- pletely dried over calcium hydride. This product contained mainly methyl .. cyclopentene impuritie$. The olefin (still over C~H2) was chilled in a dry ice-ethanol bath as an ethanol slush was prepared. The slush was made by first chilling with dry ice to ca. -80°. This not only gave initial cooling but enough CO 2 to lower the melting 0 £reezing temperature of the -so ..

slush below the supersaturation point of the olefin. Slower crystallization could be achieved by omitting the Dry Ice treatment or by using isopropyl alcohol. The olefin in an ethanol-.CO 2 bath required at least

2-3 hours to crystallize. The supernatant liquid (1-2 ml.) was decanted, the solid melted and the process repeated three to four times. The re-

250 fractive index of the fore-fraction was 1. 4115 and that of the retained 250 250 fraction 1.4465 (lit. 1.4440 [173]). The mole fraction of impurities was estimated at ca. 0.1 mole %. The extrapolated m. p. was -103. 80 0

(lit. -103. 50 ,± o. 015° [173]). -1 Infrared peaks turned up agc!-in at 1700, 1060 and 95-0 cm as well as -1 -1 peaks at 830. 746 and 729 cm . The peaks at 8:~0, 746 .and 12·9 cm -1 were as signed to cyclohexene hydrope-roxide. The peak at 78.0' cm ··.was tentatively assigned to cyclohexenol. The infrared peaks due to impurity were detected by comparison to the spectra of fresh cyclohe.::x:ene prepared

from cyclohexanol (40, 57), m.p. 24-25° (lit. 25.15°) (183), b.p. 155.5-

155. 7° / 646 mm. (lit, 161. 1°) (183). If contact of cyclohexen.e and 85% phosphorid acid were kept to a minimum, little 3-.methylcyclopentene

appeared.

A sample of cyclohexene dried 10 months over calcium hydride in

an amber bottle (J. Knight, distilled 3/ 6/ 59) gave a solid product at 0°

(lit., cis~l-2-dibromocyclohexane m.p. 9 .. 10°, trans-m,p. -2 to-3°)

(39) with bromine (analytical reagent, Baker and Adams, Allied Chem-

ical).

Rate Study of Cyclohexene and Bromine in Dichloromethane .. Use of

various light sources confirmed the sensitivity of bromine-cyclohexene addition to light, Table 2 2..

Table 2 a. Promotion of .Bromine ·Addition to· Cyclohe:Xene by '.Light Brz 1. 7 ·x 10-2 ,M_ >c=c 4. 58 X 10-2 HBr 3;x. 10-3 M RO2H 8 x 10-3 M (Expt. No. 131-F)

l.i=ght Source Total ReaGtion time, seconds

Oxygen torch <2

Tungsten bulb, 500 W 9. 5 + 2

{ Fluorescent tube, 15 W 10. 3 + 2

Hood pilot light, 6, W 12. 8 + 2

None 14 + 0.5

A capsule with two compartments separatep. by a thin glass diaphragm

or break-seal (Fig. 9) allowed rapid combination of the reactants in the dark. It was possible to record the sound of the breaking seal and quench ..

ing of the reaction with a magnetic tape recorder (Wollensak, model T-1500,

ser. no. 151644), foot control {Wollensak TF-404) and Mylar magnetic tape

(1600 ft., 1 mil, Scotch 141 Tartan series).

Pressure-filling pipets (Fig. 9) were designed and calibrated (appen-

dix) to fill the reaction capsule with dichloromethane solutions of bromine

and cyclohexene. Since individual volumetric flasks varied in height, the pipets were mated to specific 50 ml. g. s. volumetric flasks during con-

struction and both given a common label.

Light promoted a bromine substitution of dichloromethane containing

traces of water. Forty five minutes were required for complete reaction

of O. 05 M Br 2 solution. Samples dried with either activated alumina (12 82.

'----9.Smm 10

3.5mm 1.0.

#20Syringe

n~ Picene wax

Ki---Cork

Slug

to fit flask

Actual Size 10cm l Fig. 9 Reaction Capsule and Pressure-Fi Iling Pipet. ..a3-

0 }lrs. at 185 ) or calcium hydride took several hours to react pY sub- sti.tution. So, a safety light was made from a 10 watt bulb behind a

Wratten O filter which was covered with a piece of violet spot light gelatin and the pipets and flasks were painted with several coat$ of bla·ck Testor' s Butyrate Dope {insoluble in dichloromethane). The safety light and painting allowed measurement of bromine solution volumes without detectable substitution.

Evacuation of the lower compartment of the reaction capsule gave a pressure flush of the solution intd the lower chamber. This gave rapid mixing. A syringe needle sealed with Apiezon picene wax to a length of pressure tubing and a Duoseal pump were used for evacuation.

A procedural time table held unaccounted factor.a constant and aided determination of reaction orders.

Table 30. Procedure for Determination of Bromine-Cyclohexene Reaction Rates

. Operation Temp., 0 c 'Iime Req.

1. Dry Reactors 150 overnight

2. Flush with pure N 2 (Whitmore Oxygen Co., 11 p.p.m. 0 2 ) 150--25 40 s'ecs. / chamber

3. Rapidly place rubber serum stoppers and cool 25 4 mins.

4. Add olefin sol. to the lower chamber 25 1 min.

5. Freeze with liq. N 2 -196 2 mins.

6. Evacuate lower cp.amber, 1 to 100 mm. -196 3-10 mins.

continued ..... Table 30 continued.

. Operation Temp. 0 C Time Req.

7. Add Br 2 sol. t,o upper chamber (safety light) 25 4 mins.

8. Ice bath (dark} 0 10 mins.

9. Start tape recorder

10. Break the diaphragm (t 9} 0 0.1 sec.

11. Open and quench with 40% KI sol. (ti} 0.1 sec.

12. Titrate and stop recorder (room light) 25 3 mins.

Bromine solutions were made by adding bromine (chilled to 0°) with a

1. 0-ml. tuberculin syringe to a tared and Nz flushed volumetric flask.

The amount of bromine was weighed and the flask filled to the mark with

dichloromethane. The weighed amount of bromine agreed with titrated

values of an aliquot of the dichloromethane solution if it were protected

from light.

Hydrogen bromide was introduced by exposing the solution and was

determined by difference between the titrated and weighed values. Bro-

mine was converted to iodine with a 40% potassium iodide solution for

titration to a starch end point with thiosulfate solution (90). The stability

of the potassium iodide solution improved if it were made up from distilled

water which had been saturated for a minute with pure Nz through a medium

dispersion tube. The stability of 0.10 !!_· thiosulfate so\ution also improved

if 10 mg. of mercuric iodide were added to a liter of solution. The cyclohexene solution was made up in a manner similar to the bromine solution. Direct weighing determined the concentration of the olefin solution. Cyclo,hexene hydroperoxide was introduced on exposure of cyclohexene to the air. A plot of hydroperoxide concentration as a function of time (42) was generally confirmed with direct titration (191).

The titration method given was modified by shortening the reaction time between hydroperoxide and iodide and by titrating through a blanket of nitrogen. The following improved procedure was used. A solution con• taining 4. 0 ml. of practical grade isopropyl alcohol (dried over CaH 2, blank neg.), 0. 2 ml. of glacial acetic acid and 1,. 00 ml. of sample was heated to reflux under pure nitrogen in a 50 ml. 12/ 30 J Erlenmeyer flask topped with a 12/ 30 J West condensor. One milliliter of saturated potassium iodide in isopropyl alcohol was rapidly added and the mixture immediately chilled in an ice bath. All transfers were made with syringe needles which were made from an iron alloy. Iron traces apparently cata ... lyzed the oxidation of the iodide (126, 198). Addition of 1 ml. of liquid nitrogen allowed titration under a blanket of gaseous nitrogen with 0. 005 = ~- Sz0 3 sol. This method increased the calculated concentration value of cyclohexene hydroperoxide by 35 to 40%. Comparison of oui- results with original values (191} indicated accuracy within 5%.

Results - Each point, determined independently, represents an individual experiment. Each sample was conducted separately through the pr?cedure

given in Table 13. With samples of cyclohexene distilled from sodium,

the- total reaction time remained independent of bromine, cyclohexene,

hydroperoxide concentrations and pumping time but depended on hyd:togen -86-

bromide content of the system, Table 24.

Table ZA. Inhibition of Bromine Addition to Cyclohexene by Hydrogen Bromide. Cyclohexene Di.stilled from Sodium. {E:xpt. nos. 173 .. , 179-, 180· & 181-F)

Total Pumping Reaction , : : '. Time .Time, secs. Brz.x:10· 2 M HBrx::10- 3 M >e=c

7 < 1.8 1.62 0.5 2.45 1 x 10"' 10

<"2 2.16 1.0 2.45 6::x:10- 7 4

3 2. 04 2.2 4.79 3 x 10· 5 2-3

4-5 1. 62 6.0 2.4s 5x 10· 6 10

Table 3 1. Bromine Addition to Cyclohexene Distilled from Sodium

2 2 Br 2 1. 62 x 10"" M >0:=C< 2. 45 :x: 10- M HBr 6 x 10•3 M RO H 5 x 10-6M 2 - 10 mins. pumping time {180--F)

Reaction Time, secs. O. 0504 -I!s 2O3 - , mls.

0.0 3. 19

2.0 1.90

2.5 1.83

3.5 • 1.64

Rate data taken from Table 3L, cyclohexene distilled from sodium, .., '·'- was plotted with the second order expression,

l ln · b(a-x) = kzt a--b a(b-x) 2 a = 2.45-:x: 10• M[>G=G<] 0 2 b = 1. 62 x: 10"" M[Br2] 0 x = extent of reaction at time t

k 2 = second-order rate constant -87-

and gave

With samples of cyclohexene prepared from a cuprous chloride adduct, the total reaction time was dependent on hydrogen bromide content of the system and independent of bromine, cyclohexene, hydroperoxide and pumping timie. This system also proved to be independent of calcium hydride and glass surface area, Table 25.

Table 25. Inhibition of Bromine Addition to Cyclohexene by Hydrogen Bromide Cyclohexene from a Cuprous Chloride Jrlduct (Expt. nos. 132-, 133-, 136-, 137-, 138- and 152-F)

Total Pumping Reaction Time 2 Time, secs. Brz x 10""2 M_ HBr x 10- 3 M >OC< _x10- M_R02H X: 10-~ mins.

5.6 1. 89 less* 2.10 1 6

5.7 1.27 more* 2. 10 1 6

14 1.7 3 4.58 8 10

18 8.9 11 4.58 1 10

*Both less than 3 x· 10-3 M.

Rate data plotted from Tables 31-34 revealed a zero order with a

slope related to hydrogen bromide concentration and independent of bromine, cyclohexene, hydroperoxide concentrations and pumping time,

Fig. 6. Table 32. Bromine Addition to Gyclohexene, Least Hydrogen Bromide Present (A)

l3r 1. 89:-x 10-Z M. 2 2 >G=C

Reaction Time, Secs.

o.o 1.98

3. 2. 0.87

0.85

Table 33,. Bromine Addition to Gyclohexene, Some Hydrogen Bromide Acid Present (B)

:Br 1.27 10-2 10-2 2 :x- M. >G=C<.2.lOx_ M. HBr, more* R0 H . 10- 2 M. 2 and 6 mins. pumping time (152-F)

0.105 N. - , Reaction Time, secs. s2o 3 mls.

o.o 1. 17

3.7 Q.27

4. 3 0.14

*both less than 3 x 10- 3 M,

Table 34. Bromine Addition to Gyclohexene,Much Hydrogen Bromide Present (G)

-l3r 1. 7; x 10· 2 M. >G=G<4. 58 x 10- 2 2 HBr 3 x: 10-3 M, ROzH 8x 10-Z M. and 10 m.ins. pumping time (Expt. nos. 132- and 133-F)

· Reaction Time, secs.

o.o 1.72

7.5 0.80

9.5 0.56 -89-

Table 3,5. Bromine Addition to Cyclohe.xene, Most Hydrogen Bromide Present (D)

Br 8. 9 X: 10-Z M. 2 2 )C=C<4.58x 10- M. HBr 1. b~ 10- 2 M. ROzH 1 x 10- 2 M. and 10 mins. pumping time (Expt. nos. 136-, 137.- and 138-F)

Reaction Time, secs. 0.105 N. = mls. s2o 3 '

0.0 0.89

6.25 0.58

9.5 0.42

10.3 0.37

Oxygen Photo Effect - The study of bromine reaction rates was done in total darkness. This allowed complete dilation of the eyes and the observation of an emission of pale blue light when various gas samples were jarred.

Several reaction capsules were filled with nitrogen, air, and oxygen.

Back diffusion through the pump allowed air contamination. The capsule with the most oxygen gave the greatest intensity, Table 36.

Table 36. Pressure and Photo Effect Intensity

Pressure, mms. Nz Air Oz

1 none none none

10 stronger stronger, full strongest, full tube tube

20 weak stronger weak

650 faint (very ------sharp blow) -~--- -90-

The presence of dichloromethane solutions of cyclohexene or bromine at •196°, liq. N 2 bath, increased the intensity. The number of times that the photo effect could be repeated with air was related to the pressure,

Table 3:i.

Table 37. Pressure and the Repeats of the Photo Effect

Air Pressure, mm. No. of Repeats per Sample zs0 -196° 0.30 3 5

0.65 7 6

1.0 7 7

4.3 14 19

5.0 19 20

If the air samples were kept in total darkness for one and a half hours before jarring, the light intensity decreased. The ga.s could be recharged by exposure of the samples to the safety light. The lower temperature increased the intensity. -91-

Appendix

Time amd concentration measurements were evaluated as to accuracy and prechion. A Wollensak tape recorder increased timewise less tl\an

+ o. 1%as .compared to + O. 4% for a :eell and Howell and + l. 0% for a

Concord machine. Three different tapes (1 mil.) were also compared with the fol~owing result: (u.sing the Wollensak recorder):

A. V. C. polyester + 5.0%

A. V • C. Mylar + o. 2%

Scotch Tartan No. 141 + 0.1% I' All of these measuremen~·s were taken by recording and reproducing a time signal from a Lab-Chn,n timer. The timer showed less than -3 + 2 x 10 % time change when compared during four hours to the standard time signal on station KLUB (560 kilocycles). The time signal on ktation

~LUB is comparable in accuracy to Naval Observatory time. Conversion oi recorded time intervals to a numerical value was the limiting factor and varied ca. : O. 2 sec.

The concentration variable of pipet precision was tested by calibrating

' four pipets (Fig. 9}. The value obtained averaged : 1. 0% deviation. The pipet y"Qlumes follow below:

Pipet Vol. TD, 32°, ml. CHzClz

A 2. 35.: • 029

C 2. 45 + ... 039

D 2.37 +... -021

E 2. 49 +_ • 012 -92- Solvent evaporation caused an itnportant amount of the above 'dev:iation

Hence, ! 1. CY%may be th-e smallest limit that can be obtained by using transfer pipets. -93-

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168. O. Shimamura, Bull Chem. Sac. Japan ..!:1J 274(1942) [f. A. 41, 447li(l947)}. -- ·-

169. N. J. Shuildn, Bull. acad. sci. U. R. S.S., Cla$se sci. chim. 1944, 440 [ C. A . .39 43196 (1945)):--

170. P. S. SkellandA. Y. Garner,_!. Am. Chem.~. 78, 5430(1956).

171. D. P. Stevenson, C. D. Wagner, O. Beeck and J. W. Otvos, J. Am. Chem.~ 74, 3269(1952). 172. T. D. Stewart and K. R. Edlund, J.- ----Aill~ Chem. --- Soc. 45, IO 14(1923). 173. A. J. Streiff, J. C. Zimmerman, L. F. Soule, M. T. Butt, V. A. Sedlak, C. B. Willingham and F. D. Rossini, J. Research Nat'l. ~ Standards _i!, 323( 1948) (Paper No. 1929).

174. J. S. Sudborough and J. Thomas, J. Chem.~- .J:!.,715(1910).

175. J. S. Sudborough and J. Thomas, Proc. Chem. ~- _33, 318(1906) { c. A. _!, 17307 ( 1907)} •

176. C. G. Swain and E. R. Thornton, J. ~ Chem. Soc. 84, 822(1962),

177. B. E. Swedlund and P. W. Robertson, J. Chem. ~ 1947, 630.

178. D. Swern, J. Am. Chem. ~ 68, 1692(1947).

179. B. A. Talmuq and D. L. Talmud, Acta Physicochim; U. R. ~- S. 10, 481(1939) [C.A. 33, 63655 (1939)]:--.

180. D. S. Tarbell and P. D. Bartlett, J. Am-. Chem. ~2,2, 407(1937).

18h E. M. Terry and L. Eichelb€rger, J. Am. Chem. Soc.£, 1067(1925).

182rro Rt J. Thurmaier, Doc .. Diss., State Univ. of Iowa, 1960 [I;>iss. -·-·-,Abs. ~l 1385;•fl961)]. 1.83. J. Timmermans and Mme. Hennaut-Roland, J. chim phys. 34, 693(1937) [C.A. E_, 32176(1938)]. - - -

184. I. Ting and P. W. Robertson, J. Chem. Soc. 1947, 628.

189'. I. A. I. Titov and F. L. Marklyaev,. Zhµr. Obshchei Khim. 24., 1624( 1954) [ C. A. 49, 1234lg( 1955)], 45 refs. -102~ 186 ... J .• G. Traynham and,~. F. Sehnert, J. Am .. Chem.~~, 4024 (1956).

187 .• A. F. Trotman,-Dickenson; ~ R~pts. 55f 53(1958).

188.. Y. Urushibara and M. Takebayashi, Bull. Chem. Soc. Japan~, 356(1937) [C. A. ~, 77278 (1937)]. - --

189 ... R. Venkataraman, Proc. Indian Acad. Sci. 13A, 259(.1941) [~. A. 35, 65023 (1941)]. --

190. D. Verhoogen, Bull., soc. chim. Belg. 34, 434( l 9Z5) [ C. A. 20, 24808 (1926)]. - --

191. C. D. Wagner, R. H. Smith and E. D. Peters,~• Chem. 1.2» 977(1947).

192. l. K. Walker and P. W. Robertson, J. Chem. Soc. 1939, 1515.

19.3. W. Walisch and J. E. Pubois, ~- 92, 1028(195.9}.

194. H. I. Waterman and H. A. van Weston, Rec. trav. chim. 48, 637(1929).

195. ' H. D. C. Waters, A. R. Caver hill a.md P. W. Robertson, J. Chem. Soc. 1947, 1168.

196. R. West, I.· Am. Chem. Soc • .!!_, 1614(1959).

197~ E. P. White and P. W. Robertson, J. Chem.~ 1939, 1509.

198 • .J. P. Wibaut, H. B. van Leeuwen and .B. van der Wal, Rec, trav •. cp.im. 73, 1033(1954).

199. K. B .• Wiberg and W, J •. Bartley, J, Am. Cherp. ~foe._ 8_2,. 6,375(1960,). - ~- .. -._ ' -- ,- /c

200. T. Wieland and U. Wintermeyer, ~- ~, 1721( 1957).

201. J. Willard and F. Daniels, J. ~- Chem. Soc._...f!, 2240(1935).

202. G. Williams, J. Chem. Soc. 1932, 1147.

203. G. Williams, Trans. Faraday Soc. ~ 749(1941), 114 refs.

204~ H. Willstaedt, ~ 64B, 2688( 1931).

205. S. Winstein and H. J. Lucas, J. Am. Chem. Soc. 60, 836(1938).

206. S. Winstein and H. J. Lucas, J. Am. Chem. ____,_Soc. -61, 1476(1939). 207. J. Wislicenus., Ann. 248, 283, 301, 318, 322(1888), Ann. 250, 244 (1889), 212, so; 61(1893). -103- 208 .. J .. WisUcenus and F. Seeler, ~- ~ 2693(1895).

209. N. A. Yajnik and tt;. L. Uppal, J. Indian Chem. Soc. ~. 729( 1929).

I 210. W. D. Zelinskii and Y. A. Arbuzov, Jompt .• rend. acad. sci. U. R..'S.'S. ~' 794(1939) [c.~ 34, 36965 (1940} • THORPE'S SYNTHESIS OF THE CAGED ACID, 4--METHYLTRICYCLO [1. 1. 0. o2 ...4 J BUTANE-1, 2, 3-TRICARB0XYLIC ACID

Introduction

. The concept of ions, first developed with inorganic compounds such

as sodium chloride, has provided an understanding of polar organic re•

actions such as nucleophilac- substitution ( 20) and {3-elimination(17 ).

· Organic free radicals are important as ~ :LntermediatetSc: in the other por•

tion of organic chemistry. The free radical was first discovered by Gorn- ,

berg. He prepared the unusual equilibrium mixture of hexapheny}ethane

and triphenylmethyl free radicals (13, 1~.). Similar properties of more

fleetingly available reactive intermediates; such as found in halogen sub-

stitution, helped to define free radical pathways.

An analogy to the available and structurally similar epoxide allowed

Br /0"' -c---c-/~"' -c---c- / ' / ' the postulation. of the bromonium intermediate ( 33 ). Here, a known . ·-~-.., ,. I £' product was used in describing a reaction intermediate.

A unique intermediate was proposed to explain the reaction products

of aminometh,ylcyclopropane and' nitrous acid ( 29 ) • -105-

Each dotted bond has a bond order of one-third. This peculiar structure has no verified analogs. A possible analog has been reported in the case

of the caged acid, 4•methyltricyclo [1. 1. 0. 02- 4] butane-1, 2, 3-tricarboxylic

acid. But the synthesis of this compound has

never been repeated or verified and as such has enjoyed some disrepute.

We found it possible to recreate a key step in the synthesis sequence lead-

ing to the. caged compound above.

Background

The creation of Thorpe I s classic synthesis of the caged acid originally

required eight years and five students ( 1, 2, 3, 22, 34, 35).

Generally ep.ch step in the ,sequence was pursued and reported as- a unit. I

The synthesis up to 1, 1, 1-ethanetriacetic acid has been repeated ( 19,

21, 25) and confirmed by an independent synthesis ( 9 ). Mono- ( 9 ),

bis-( 2), ):\,ndtri~~bromination){ 1, 2 ) ; of 1, 1, 1-ethanetriacetic acid has

been reported. However a more recent a-bromination attempt ( 25)

gave a product different from those reported. This product proved to be

useless for ring closure.

Thorpe reported a double closure of the a., a..'-dibromo ester of -106-

1., 1, 1-ethan~t:d-ac-etic add when it was tr:eated wfth hot conc~ntrated potas-

·sium hydroxide ( 2 ). This gave three isom_eric triacids which were assigned the following structures:

(d, I)

0 0 0 acid, m. p. 154 acid, m. p. 165 acid, m. p. 193

0 O anhydride, m,. p. 103 anhydride, m. p. 121 .t'lO anhydride

(meso-cb) (1Xace-mic) (me so-trans)

Further a.-bromination of the first two products produced brpmo esters but the third passed directly to a caged acid which contained no bromine and was the same as the tris-dehydrobrominated product of

1 ethyl a, a.' , a."-tribromo-1,1,1-ethanetriacetic add. More recently an alte;rnate explanation was devhed for the three bicyclo compounds

( 20 ). Isomeric isoprenetricarboxylic acids were prop,sed a1id sy~- thesized. Anhydride formation guided, the selection of isomers. (meso-cis) (racemic) (me so•trans)

However the behavior of these triacids toward bromi.ne and permanganate was much different than Thorpe's compounds and it was concluded that this explanation was not likely.

Since J. F. Thorpe is no longer living, R. B. Woodward (25') ):on..-1- tacted C. K. Ingold and R. M. Beesley. Ingold remembered seeing the caged compound but suggested th,at Beesley would be a better source of information. Beesley replied by a letter which is reproduced below:

Galle Heriberto Frias 931, Golonia del Valle, Mexico 12, D. F., Mexico 'J January 1950

Dr. R. B. Woodward, Department of Chemistry, Harvard University Cambridge 38, Mass. u. P· A. Dear Dr. Woodward:

Today I received your letter of the 4th inst. I fear I can be of little direct value to you. After obtaining my M. Sc. in 1913 I was employed by Prof. (later Sir) J. F. Thorpe as his paid laboratory assistant first at Sheffield University and later at the Imperial College of Science, South ·Kensington. Our association ceased in the month of August 1914 when he decided I had not the necessary academic mind and I had the urge to go off to the wars. I finally devoted myself to Petroleum Chemistry in Mex- ico with no small measure of success, thus ju_stifying Thorpe's judgement of my capacitie~.

Actually I had no idea that my name had been associated with any pub .. lications of Thorpe until in the way of business I purchased a copy of "THE PRINCIPLES OF MOTOR FUEL PREPARATION AND APPLICATION" by Nash/Howes, published by Chapman and Hall, London, 1934.

You must have obtained my name from the reports of the British Chemical Society and my address from the Register of the Royal Institute of Chemistry .. So far as I can remember at this late date the paper to which you re.fer was published in the joint names of R. M. Beesley, J. K. Ingold and J. F. Thorpe. Now Ingold certainly has the academic mind, in fact when.I visited the Imperial College of Science in 1916 I found him sport- ing the uniform of a full Lieutenant in our old laboratory whilst I was still a mere Sargent Royal Engineers after eighteen months service on the, fight- ing front. Probably we were both in our proper places.

I am sure Ingold can give you whatever information you may require since according to my latest information he is now Professor Christppher ~elk'.Ingo14, D.Sc., A.R.C.S., D.I.C-., F. R ..S., F.R.I.C., etc., ·etc.

You had better write him as follows:

Prof. C. K. Ingold % The Royal Institute of Chemistry 30 Russell Square London, W. G:. I.

In due course I should be glad to know whether or not my suggestions have been of any use in sowing your difficulties.

Yours very sincerely,

(signed)

R. M. Beesley Excepting the claim for synthesis of ethyl bicycle [1.1.,&] butane-!- carboxylate ( 38) the bicyclobutane triacids of Thorpe are the only · of known de'.rivatives /bicycilohut'ane; ' An¢!. Thorpe I S' caged:,fcid is'.the d:q:ly known example of tricyclobutane.

Discussion

Our continu~d need for a supply of 1, 1, 1-ethanetriacetic acid required several repeats of the various syntheses. From this repetition of work, information was gained about each of the steps up to and inch~ding a- bromination of 1, 1, 1-ethanetriacetic acid. Also certain working ideas were evolved.

Ethyl Isodehydracetate - The first step in the sequence began with the conversion of ethyl acetoacetate to ethyl isodehydracetate. Both an inte:rmole ... cular condensation between two ( 39) ethyl acetoacetate molecules and an intramolecular condensation of the intermediate ( 18a) woulq. give a decrease in reagent randomness, a negative entrophy of activation (-AS +). A decrease in reagent randomness is favored by lower temperatures. If the reaction equilibrium is related to the rate-determining process, then low~r temperatures should improve the yield. The yield of ethyl isodehy• dracetate was found to depend inversely on the temperature, Table 38 ..

Table 3'8. Effect .of Temperature on the Yield of Ethyl Isodehydracetate

Temp., 0 C. Yield, %

ice bath 37

5 to 8 39

- to -15 41

2 to 5 46

continued -- ...110-

Table 3 S .continued.

Temp., 0 c Yield, %

-10 to -3 50

-3 to 5 51

~15 55

-25 , 66

Ethyl 13-MethylglutacoJate - Ethyl isodehydracetate gave various yields

of ethyl {3-methylglutaconate with concentrated sodium methoxide or ethox-·

ide. Ethyl acetate was often observed during cleavage. If ethyl acetate and

isodehydracetate are the only products, then the reaction may be balanced

, by Ferguson's redox method ( 10 ). The original.description of the

NoOEt >

reaction ( 3 ) allowed a fair amount of contact with the air. We con-

structed a system which permitted synthesis under nitrogen or oxygen.

While neither affected the yield, introduction of: 03tygen into the reaction

mixture produced additional heat. A survey of the synthesis variables

of ethyl 13-methylgtutaconate showed a connection between the time of

. ethyl isodehydracetate storage at room temperature before isolation,

Table!•<). The yield of ethyl j3•methylglutaconate approached a maximum 0 111-

Table 39. The Relationship of Ethyl j3-Methyl-- glutaconate Yield and Ethyl Isodehydr- - a.cetate~Stor.c\-ge Storage at Rm. Temp. Yield,% Until Isolation, Days

0 1

2 0

12 11

26 3

29 28

31 11

51 7

72 6 + 1

81 ca. 8

at 7-8 days storage during the synthesis of ethyl isodehydracetate.

Another storage effect on the yield of ethyl (3-methylglutaconate was

observed with ethyl isodehydracetate. A portion of freshly redistilled

heterocycle was sealed in pyrex as a control and compared with a por-

tion that was exposed to the air for six months ( 18). The heat of reaction

( tJ. T) was used to follow the amount of cleavage.

0 EI.DA t:J.T, C.

sealed 14

exposed 20

A ferric chloride test( ( 32, 37) : (aq. FeC1 and HCl) with different 3

samples of ethyl isodehydracetate pointed to enolic constituents. These

constituents could be removed by distilling ethyl isodehydracetate from. .. 112.. calcium carbonate. This treatment gave no glutaconate ester during attempts at cleavage.

Table 40. Ferric Chloride Test of Various Ethyl Isodehydracetate Samples and the Yield of Ethyl r,... Methylglutaconate

Color of FeCl3 Test E 13,MGYield, %

bright green 29

dark green _;ca. 60

greenish black ca. 70

deep red 72

A rapidly distilled sample of ethyl isodehydracetate ( .. OH peaks ' -1 3500 ...3200 cm. ) changed when it was slowly redistilled (130-180 dps. / min., 94% recovery)·.

Table 41. Effect of Distillation on the Physical Properties of Ethyl Isodehydracetate

Distillation B, P. 0 c. /mm.

isolation (CaCO ) 165-190/6 to 8 3 rapid 136-143/1. 1 1.4913250 0 20 slow 109-121 / 0. 8 to 0. 7 1. 5129

Infrared spectra of the slowly redistilled sample differed from the rapid

-1 -1 sample as methyl (2950 cm. }, lactone (1650 cm. } and conjugated carbon-carbon double bond (1540 cm. -l} peaks appeared and the hydroxyl 1 (3500-3200 cm. "' } and methylene double bond (1390, 920 cm. - 1) peaks disappeared with redistillation.

a. Lit. 1. 5129 250 (4) -113-

Table 42. Elemental Analysis of Various Ethyl Isodehydracetate Samples { 3, 35 ) Found, % r Rapid Slow , C10H12O4 Cale. % Distillation Air Contact Di stillatiori

C 61.2 63,0 55.3 61.3 61.2

H 6. 1 6.2 6. 1 6.3 6.6

0 32.6 31. 3 38.6 32.4 32.3

The above data and .an;addiitional .observation are suminarizea below:

1. A relationship of ethyl j3-methylglutaconate yield with the storage

of ethyl isodehydracetate at room temperature before isolation.

2. A relationship of ethyl j3-methylglutaconate yield with the ferric

chloride test of ethyl isodehydracetate.

3. Complete cleavage of ethyl isodehydracetate with dilute sodium

ethoxide at reflux (18) ...

4. The agreement in elemental analysis of rapidly redistilled

(cleavable) and slowly redistilled heterocycle (non-cleavable.).

5. An enolic-like infrared spectra.

These features suggest a tautomeric mixture varying in composition

with synthesis conditions.

The foregbing data fit a temperature and catalyst dependant keto-enol

equilibrium a. Structures I, II, and III were assigned to possible

members of a keto-enol equilibrium.

a. Ethyl acetoacetate keto-enol equilibrium (5, 24, 27, 3D.,. 31). O◊CH3 HQ◊CH3 HO◊CH2I . ~ I C02Et C02Et h C0 2 Et CH3 CH2 CH3

I II III

The keto form {I) is the ~ost volatile and crystalline due to dipole-- dipole interactioht1:1l,dinter ...proton bonding of the enol forms II and III.

Distinction between II and III, less clearly made, gave the enol II

as the more likely. Enols II and III might yield two corresponding products (IV and V) in alkali.

CH3 I Et02C-C-C=C-C02Et

IV V

Ester IV would be expected to rearrange in basic media to the more

stable ester V, ethyl !3-methylglutaconate.

The interconvertability of the Feist acids VI and VII (equilibrium

essentially to the left) in strong base (2. S·N NaOH) ( 7 ) strengthened the possibility of enols II and III.

CH2 CH3

(d, I) < (d, I) > ~•C02H C02H H02C VI VII -115-

·Michael Addition - Addition of ethyl cyanoacetate to ethyl f3-methylglutaconate in ethyl alcohol gave diethyl a-carboxy .. 1, 1, 1-ethanetriacetic ester nitrile. This car boxy ester decarboxylated on re distillation to yield diethyl 1, 1, 1-ethanetTiacetic ester nitrile, m. p. 34-37°. This nitrile was first prepared by Beesley and Thorpe ( 2 ) and later identified by Thorpe and; Wood ( 35 ) . A third distillation apparently gave ethyl 13, 13-dimethylglutarate.

1, 1, 1-Ethanetriacetic Acid - Samples of 1, 1, 1 .. ethanetriacetic acid that had been in contact with ether and had been sufficiently recrystallized

0 melted at or above 172 ( 1, 3:ti,, 89') .. $ample.s which we:r.e carefully excluded from ether melted at a lower temperature and were more difficult to purify. An ether-free sample of 1, 1, 1--ethanetriacetic acid, m.p. 166-

1670, was treated with ethyl ether and recrystallized. This sample then melted at 171-172 0 . Our best ether sample, extensively recrystallized from dilute hydrochloric acid, melted at 173. 0-175. 8°. Titration of the two forms above gave transient ehd points. The non-ether sample began this behavior at two equivalents of base. The changes lasted from several

seconds to a few minutes. The ether sample s!llCM.edthis behavior at 2 3/ 4

equivalents. This transition change lasted a few seconds. Both samples

gave a final end point at 3 .1 equivalents. The non-ether sample showed

less intensity in the carboxyl infrared spectra region, Figs. 12 and 13.

Thus, one carboxyl group of the non-ether sample was internally bonded

and less available to base. -116-

1, 1, 1-Ethanetriacetyl Bromide .. 1, 1, 1 •Ethanetriacetic acid was readily

converted tp 1, 1, 1-ethanetriacetyl bromide with phosphorous pentabromide.

We were able to isolate this acid bromide from the reaction mixture by

soxhlet extraction with 1: 1 ligroine and methylene chloride. Phosphoryl

bromide and a small amount of the mono-anhydride of 1, 1, 1-ethanetria-

cetic acid were also isolated and identified.

a, a', a"-Tribromo-1, 1, l•Ethanetriacetyl Bromide - A number of com-

pounds occurring along the course of the synthesis of 1, 1, 1-ethanetriacetic

.acid .(synthesis relics) wer~ tried as reaction promoters.

Table 43. Promotion of a-Bromination of 1, 1, 1- Ethanetriacetyl Bromide

Synthesis Relics Result

no change NH 4 Cl

(NH 4 )2S04 no change HzO no change

cone. HCl no change

liquified mixture, no lac tones

benzoyl peroxide a trace of di;lactone

continued --- -117-

Table 43:continqed.

Synthesis Relics Results

EtOH brief bromination

vigorous action, liquified mixture, lactone s

dioxane no change

If ethyl ether was· either in the triacid sample or added to the reaction mixture, the triacetyl bromide could be 6.-brominated by adding bromine to the mixture. If ethyl ether was absent, the triacetyl bromide could not be a-brominated during •six months ti:i:ne. ·We.can now say that ethyl ether introduced during recrystallization of 1, 1, l•ethanetriacetic acid is required for a- bromination.

Ether was also found in simple beaker experiments to double the

rate of reaction with moisture in the air and with acetic acid. This co- promotion of a•bromination, the Hell-Volhard-Zelinski reaction, may be

related to the formation of an oxonium compound from ether and bromine

( 26 ) and the catalysis of certain Friedel-Crafts reactions by aluminum

bromide monomer complexes (2A1Br 3 ...Et 20) ( 36 ).

We believe the successful bromination of 1, 1, 1-ethanetriacetic

acid means an important break through toward getting Thorpe I s caged

acid. Material in hand would allow a modern determination of structure

and acceptance or rejection of the tricyclobutane derivative. -118- Experimental Section

Ethyl Is-odehydraeetate-•This synthesis r-equired an unusual equipment arrangement and deserves some description. A three-liter round- bottomed three-necked flask was fitted with·~. straight condenser, mechanically driven Tru-bore stirrer, and a fine-pore fritted dispersion tube. The glassware had the appropriate S' connections. A hydrogen chloride acid generator delivered gas to the dispersion tube through tygon tubing. Excess hydrogen chloride could be removed with a water scrubber connected to the condenser by rubber tubing. A mercury bubble counter Wc!,S placed between the generator and the disc. A calcium chloride drying tube inserted between the condenser and the scrubber protected the reaction from water.

All tubing connections were tightly wrapped with heavy rubber bands a~d painted with tygon.

Several aids to dependable and adequate ga.,s generation were developed.

Treatment periods frequently extended to 12 hours.

1. The system was gently aspirated with rapid water flow in the scrubber ..

2. The concentrated hydrochloric acid funnel was kept filled to the brbn.

3. The generator reactor flask was filled half full of concentrated sulfuric acid.

4. Generation was started before the dispersion disc was introduced into the mixture.

5. A flow of gas was maintained that would just break the surface of the mixture.

6. The capillary tube was carefully placed in a vertical position before generation was begun.

7. The mixture was stirred slowly. -119- After the a.ir was swept from the system ( 15 mins.), all the hydrogen chloride that could be generated was taken in by the reaction. The reaction mixture was cooled and vigorously stirred by bubbling air through a bath of ice and 1;>pent acids from the generator. Ordinary power-driven -stirrers usually failed during the long periods of acid treatment. Additional concentrated hydrochloric acid was required to maintaip. the desired bath temperatur~. Ice was replaced and diluted liquid removed as needed.

Temperatures to ,. H,0 could be easily reached but not easily maintained.

If methanol-ice mixtures were substituted lower temperatures could be attained and -15° was rea,dily maintained. The reaction mixture was stirred as the l;>ath and reactant mixture reached the desired temperature. While this was being done, the generator was charged and checked for operationi stirring reduced to a slow rate, the system covered and acid treatment begun •

. Two kilograms ( 15. 4 moles) of ethyl acetoacetate (reagent grade,

Matheson, Coleman and Bell, n 20 1. 4164) was treated with various amounts of hydrogen chloride at various temperatures over a period of about two weeks. Hydrogen chloride was generated by introducing concentrated hydrochloric acid (reagent grade, 37%, J. T. Baker, Lot. Nos. 6045, 6039, sp. grav. 1. 19) through a capillary tube under concentrated sulfuric acid

(Baker and Adams, 95-96%, Lot. No. B808231, sp. grav. 1. 84, [2-F, 4-F);

Lotte.·Chem. Co.',, sp. grav. 1. 275, [ 18 .. F); C. P. Reagent, DuPont, 95-

98%, sp. grav. J.:.84, [27-F) ). CQ!der temperatures gave increased rates of gas absorptiOnt other things ·being equal. Also it gave a less colored product.

At first the treatments covered two periods of time, each eight hours in length. In the week between, short bursts were used to maintain the .. 120 .. acid level in the mixture.; • This procedure was altered to give saturation.

Saturation took approximately 12 to 16 hours as would be expected from doubling the preparation s.ize.

Significant amounts of the heterocycle could be detected in the reaction mixture after 12 to 14 days. This was observed throuih small droplets on the flask walls which reflected a striking blue color.

After fourteen days, the mixture was washed with 1 to 3. 7 liters of chilled water (2 0 ) and cracked ice in 250-ml. portions. The organic phase was washed with three I-liter portions of various concentrations of sodium carbonate solution. All the washings were kept chilled below 5° by th.e addition of cracked ice. A typical washing resulted in 20 to 25 liters of solution. Hence a new method was evolved. This was done by taking advantage of the easy low temperature crystallization of crude ethyl isodehydracetate. About a kilogram ·of crude ester crystallized at 2° when crushed ice was added and thoroughly_ mixed with the organic phase. The crude ester mixed with additional crushed ice was filtered off and was melted at 3 0 by warming in the room. This process was repeated twice.

The .crude material was then washed with portions of sodium carbonate sohiti~n until the ester was neutral and dried over anhydrous Na • 2so 4 The combined wash, solution was extracted with either ether or benzene.

The. extract was dried over anhydrous sodium sulfate, combined with product and an placed in an evacuated desiccator (20-100 mm., over KOH} until hydrogen chloride evolution stopped. If this procedure were omitted. p.ydrogen chloride evolved during distillation and was accompanied by yield losses. The gas evolution could be prevented by adding calcium carbonate

(Tech. grade) to the distillation pot but calcium carbonate affected the -i21- yield in the n-ext 1tep. Very pure ester nearly colorless (118. 5° /0. 7 mm.) and

stored in a pyrex gla,ss containEfir turned yellow in a few days. This color

gradually deepened in time but could be removed by redistillation.

The variation of synthesis and isolation variables are given in Table 44.

Table 44 .. Ethyl Isodehydracetate Synthesis and Isolation Variables

:f!C:l Generation Na2co Wash Distill£d EIDA Ref. 0 3 Temp. , C Time, Hrs. HCl( 37%), ml. Liters Normality From Expt. ...___No • ice bath 19. 5 ----- 1 l ------2-F s to 8 9! 4 ----- I l -----· 4-F -to •15 37.3 2250 ...... 3 ----- .. 1-LE 6

efficient cooling ------0.75 l ---..-.-.... 4 2 to 5 31. 7 1 976 I NazCO 3 7-F -10 to -3 3810 1 CaCO 35. 6 l 3 27-F __,,_ 0 to 5 .. ------2 --..----· 25 .. 3 to 10 1 44~8 4112 1.5 CaCO 3 18-F __..,.,._ ..:.j -15 24 .. 7 ca.7400 3 5-LE 6

efficient cooling ...... ----- 0.75 l ----- 4 -15 to -40,(-25) 16. 5 1300 l I ----- 3-0 18

Apparently 1 the amounts of HGl sufficed for rec:1.ction to occur in that no

relatlon to yield was noted.

The yields and physical constants of various experiments a.re given in

Table 4,5_. ...1zz;.. Table 45. Yields and Phygical Constants of ~thyl Isodehydracetate,

EIDA Ref. 0 Yield, ,no Expt;. No • % B.P., C/mm. .---.,.

37 135-145/1. 0 to 1. 5 2-F 200 39 l08-12~il to 1. 5 1. s 122 4-F

41 165-190/19. 5 to 20. 5 - - - - - c,:, - -·- - 1-LE 6 25 42-46 132-140/2, d 1. 1619 4 139-9.5/2 1.512925° 200 46 120-152/0 to 0 1. 5126 7-F 50 165-190/6 to 8 --~------0 27-F 1 14-115 / 1. 0 1. 512424. 4 t d,25 1. 1845 _____. _____ 51 115-130/1. 5 to 2. 5 25·

51 140-16)/1 to 2.5 1. 511225. 70 18-F 55 155/ 3 (m. p. 14°~.) ------5-LE 6 63 160-190/20 ---··----- 6 65 140-160/4 28 240 66 114 ...140/1 to 2 1. 5136 3-0 18

The y,ields of ethyl isodehydracetate ( 37-66%) varied inversely with the

temperature (0 to •25q). A ferric chloride test (37) (aq. FeC1 and ,r 3 ~Cl) with diffetent samples. of ethyl isodehydracetate pointed to enolic

constituents,. Table 46.

Table 46. F~r.ric Chloride Test of Va:rjous EIDA Samples

Test Color EiDA Expt. No. bright green 3-0 dark green 5-LE

greenish black ~-0-A dark req 4-F-6-D-l -123-

A rapidly distilled sample of ethyl isodehydracetate (27-F) changed when irwas slowly redis tilled (13 0-180 drops per minute, 94%

recovery).

Table 4 7 •. Effect of Redistillation on Physiqal Properties of Ethyl Isodehydracetate n Distillation B.P., G.. 0 /mm. .D

Isolation (CaCO ) 165-190/ 6 to 8 3 25 0 Rapid 136-143/1.1 1. 4913 20 0 . Slow 109-121/ O. 8 to O. 7 1. 5129

Infrared spectra of th.e two samples differed as follow~ •. Peaks which had appeared at 3500-3200 cm- 1, 1390 cm- 1 and 920 ctri-l but which were absent in the redistilled material can be assigned as H-bonded hydroxyl and ( possibly) in-plane and out-of-plane deformation of a terminal -1 -1 methylene. group. New peaks which appeared at 2950 cm , 1650 cm and 1540 cm -l may be assigned asymmetrical -CH stretch, lactone 3 carboxyl and conjugated carbon-carbon double bond stretch, respectively.

Ultraviolet spectra of a sample (4-F-6-D-l) treated the same as above and pure ethyl isodehydracetate which had been slowly redistilled, also

showed differences.

Table 48 •. Ultraviolet Spectra of Ethyl Isodehydracetate

.·EtOH )\, mµ

Mixture 293 293 247 --- 236

EIDA 293 293

247 ...124- Absolute Ethanol-..-Commercially available "100%" ethyl alct;>hpls have a trace

of water especially if they have been transferred from bottle to bottle. A

modified method fr.om a compilation by Fieser ( 11} was used to remove

small am<;>unts of water. Magnesium ethanolate was made by mixing 2. 5 grams

(0. 104 mole) of reagent magnesium turnings, 30 ml. Pure Ethyl Alcohol

(U.S. P. , U.S. Industrual Chemi.cals Co., 99. 9%} and O. 25 grams

(. 00 l .mole} of iodine catalyst in a 500-ml. round-bottomed flask. Carbon

tetrachloride was also used with some success, however. best results came

from Grignarq grade magnesium. The flask was fitted with a condenser

. and a P drying tube. The contents re;fluxed gently until a vigorous 2o 5 reaction took place. Frequently overn.ight storage was needed to complete

the reaction.

Four hundred milliliters (8. 6 moles} of 100% ethyl alcohol {USI} was

added by a dropping funnel and Claisen head arrangement. This arrange-

ment allowed simultaneous alcohol addition and dist.illation. Distillation

began after about 150 mls. were added. The succes.s of the operation

depended greatly on the exclusion of water. A vacuum take-off elbow fitted

with a P o dryip.g tube was used in conducting the fraction to a liter flask. 2 5 This fiask was previously washed with anhydrous alcohol to remove traces

of water. We obtained 392 grams, 493 ml., of absolute alcohol refractive

index 1. 3596D19° and boiling point 74"!'75 0 /ca. 650 mm.

Diethyl 13-Methylglutacon~te--Twenty three grams ( I mole) of freshly

trimmed sodium was rapidly added in small pieces to 470 grams ( 10. 2

moles) of absolute ethanol. Sodium was stored, trimmed and weighed under

dry Petrolatum. This clear white oil was l;>lotted from the sodium just •125- before addition.

Sodhtm ethoxide could be made with the amounts used by Bland and

Thorpe, 270 g (5. 88 moles) o~ ethanol, if sodium additions were very rapid and if a cooling bath was ke:pt in reserve f?r an_ occasional need to control the reaction. Our increased amount of alcohol gave. adequate reaction rates at 13 ...20°. The excess s.olvent, 200 grams, was removed by distilling at reduced pressure such that the pot temperature stay,ed below 20°.

If the alcohol was carefully purified sodium eth.oxicle crystallized from the reaction .mixture: Commercially available USI ethanol did not give this crystallizing .effect, After the excess solvent was removed_, 196 gram·s.

( 1 mole) of ethyl isodehydracetate was slowly added over a p~ltod ;of 15 to.

30 minutes. After two hours at room temperature (25-30°), the mixture was added to an equal amount of water. The result was chilled with cracked ice and extracte~ four times with 2: 1 e.ther•Skellysolve A mixture. The extract washed.with ice~cold water until neutral and dried over anhydrous

sodium sulfate gave a crude solution of ethyl !3... methylglutaconate.

Yields and boiling point ranges are given in Table 48. During dis .. tillation it was possible to detect plateaus of each isomer. A plateau at ca. 75° /1 mm. cor:re~ponded to the trans-form and another at ca." 80° / l mm. totne---.cts. ·(-2~;3?i. Usually ethyl~- 13-methylglutaconate was obtained in greater. quantity than the trans ...ester. .. l-2'6-:,.... Table49 . Yields and Physical Properties of Diethyl 13-methy lglutaconate

Ref. n E 13:SC Yi~lq, % B. P., 0 c. /mrn. D Expt. No.

0 16-F 2 135-167/1. 1 ------26-F 12 80. 5-85/1. 1 28-F 25 0 95•137/22 1. 4461 ____..,.,,.,,,,, 23 83-93/1. 5 7-LE 6 ca. 25 130-139/16-17 ...... ~.,,... 4-LE 6 25-30 94-:-96/2,97•100/2 -----¢·-- 28 97 .. 99/3 (dimethyl ester) 21 ______.,.._ 26 135/150(20) 6-LE 6

29 18 80•100/1 to 240 5-9 3} 1. 4497 29 a:, .. 102/ 1 to 2 6-0 18 31 134-158/20 ------.. 44-F 52 80-J00/3, 75-80/1 ------~- 25 25° 72 75-98/1. 0 (75-81/1. 0) 1. 4490 ---..------(81 ...~8/l.~ 1. 451325° 29-F ______.., 75 167 /68 3 200 81 135-155/1 to 1. 5 1. 4502 3-F

Although s~dium alkoxide ( l mole) concentrations and preparation

temperatures, except one attempt at reflux (0% yield), varied little

(3. 7 to 4. 6 m. and 10 to 38°) atj.dition time varied eight-fold

(0. 25 to 2. 0 hrs.)., Table 50. .121-

Table -50 • :Qiethyl 13-Methylglutaconate Syn the sis Variable,i1

E ~MG Ref. NaOR, m. Addition Temp. , oc. Addition Tune, ;Hrs. Expt. No.

3. 7 reflux gradual 16-F

3. 45 . running H 0 2. 17 26-F 2 3. 7 25

4. 58 10 .. 23 0.75 7--LE 6

-4.4 32-38 0.33 4-LE 6

3. S 25-32 o. 33 p-LE 6

3. 7 running H ca. 0. 33 18 2o s-o 3. 7 running H 0 ca. 0. 33 18 2 6-o 3, 7 19-22 ca. 1. 0 44-F

3. 56 cooling 0.25 24

3. 7 18-20 ca. O. 25 29-F

3. 7 running H 0 gradual 3 2 3,. 7 running HzO gradual 3-F

Two grade$ of sodium metal and two kinds of alcohol were used.

Addition order and qxygen contact varied. Table 51. -128- Table 51 • Reagent Variation During the Synthesil1 of Diethyl 13-Methylglutaconate

J. T. B'aker Addition Ej3MG Ref. Na Lot No. NaOR 0r.der EIDA, g. Na,g: ~pt. No.

61448 NaOEt Ester in 561 66 16 .. F

20002(AR) NaOEt Base in 676 79 26-F

61448 NaOEt Ester in 196 23 28-F

~0002 NaO~t B~se in 185 (Oz) 21. 7 7•LE 6

20002 NaOEt Ester in 238 30 4-LE 6

20002 NaOEt(Oz) Ester in 198 25 6-LE 6

20002 NaOEt Est~r in 196 23 5-0 18

20002 NaOEt Ester in 196 23 6 .. o 18

20002 NaOMe(NJ Ester in 196(N 2) Z3 44-.F

...... NaOEt(Oi Base in 283(0 ) 25 2 33 20002 NaOEt Ester in 196 23 29-F --.---- NaOEt Base in 196 23 3 61448 NaOEt Ester in 561 66 3 ...F

Since the sodium lot showed a possible connection to the yield,

probable impurities were examined. The analysis of J. T. Baker Lot No.

20002 metallic sodium revealed low levels Qf other metals such as iron.

A check for possible metal catalysis was obtained from ethyl isode~ydrq.ce-

tate ( 3-0, 3. 92 g. " O. 02 mole, n 250 1. 5126), ethyl alcohol (U. S. I. 1'00%,

5. 40 g,), sodium methoxide (M. C. and B .. Lot No. 334350, ca. 1. 1 g. ,

0.02 mole) and powered Fe, Cu and Zn (ca. 0.1 g. each, Fe tech. grade,

. Zn grade unknown, Cu B.-and A, Lot No. Nl48). These reagents were

combined in four erbmmeyer flasks (25 ml.). Afte-r two hours and a small temperature- rbe (from 22 to 26° in all cases) and added wate.r

( 10-12 ml.fa c'1"µ.de mixture of esters precipitated. The precipitate was wasp.ed three times with ti and then examined,. Table 52. 2o

Table 52 • Effect of Various Metals on the Synthesis of Diethyl j3-Methylglutaconate 25° Metal Ppt. Wt. , g. n Color FeC.13 Test

·I -----, Fe 3 1. 4654 red brown

Cu 2 1. 4583:· pale red brown

Zn 2 1. 4542 yellow brown

Blank 2 1. 4548 yellow brown

The aqueous phase was acidified ( 6N HCl) with the following result: · Fe 1 1. 4868 deep red ------Cu 2 1.4822 bright green ------Zn 2 1. 4797 yellow ------Blank 2 1. 4836 yellow deep red

Because none of the above correlated to the yield of ethyl j3 -methylglutaconate the synthesis of ethyl isodehydracetate was' surveyed. A

comparison of ethyl · j3-methylglutaconate yields and some ethyl isodehydracetate synthesis variables revealed a possible connection with the amount of time during the storage period at room tempe:ratuJ:"e, Table

53. -130• Table 53 ~ E:thyl Isfde:t,Lydraceta~e Reaction Mixtul;'e Treatment and Ethyl j3- M'ethylgtuta cpna te Yields

Storage at Total-EIDA HCl Generation Rm; Temp. Syn. Time, Time ;During Till I'solation, E j3MG Ref. EIDA Ref. Yield% Days. 2nd Wk., Hrs. Days Expt. No. Expt. No. 0 -~- --- 1 16-F 7-F 2 14 8. 5 0 26-F 18-F

12 20 14 11 28-F 27 .. F

23 18 7 3 7-LE 6 1-LE 6 ca. 25 18 7 3 4-LE 6 1-LE 6

26 18 7 3 6-LE 6 1-LE 6

I 29 19 7 28 5-0 18 3 ....p 18

29 19 7 28 (>... o 18 3-0 18

31 20 14 11 44-F 27-F

51 14 10 7( 1st wk. 25 25 at 0. 5(>C) 72 ca. 14 4+4- 6 + 1 z<,... F 4-F 75 14 0 7 3 3

81 17 2 4(9from ' main HCi) 3-F 2-F

Further storage effects were found by' sealing a sample of ethyl ho-

dehydra~etate (7-0--E--A) in ~y:rex and exposing a similar sample five - ; 0 .,

months to the air and then comparing cleavage of each. This erl~nnieyer

fla'sk experiment was similar to those in the metal catalyst check given

earlier. EIDA AT, °C sealed 14

exposed 20 -131- . An effect on t~e i-ise in temperature was also caused by storage of sodium

methoxide~ethan-91 solutions at r~9m temperature.

Table 54 . The Guerbet Reaction and the Yield of Diethyl 13... Methylglutaconate

NaOMe Storage, f-lrs. .6.T

0 6

24 7

48 20

Diethyl a -Cyano-1, 1., 1-ethanetriacetate (Michael Addition;}~.Th:~ -m'~thod

here was adapted from the work of Kohler and Reid (21) with dimethyl-

glutaconate. A dried three-necked 500 .. ml. round-bottomed flask was

fitted with a dropping funnel, mechanical stirrer, a straight condenser and

a P o drying tube connected to the condenser. Sodium ethyl cyanoacetate 2 5 was prepared by adding 3. 4 grams (0. 148 mole) of sodium metal through

the condenser to 16 grams (0. 144 mole) of ethyl cyanoacetate dissolved in

25 grams (0. 54 mole) of anhydrous ethanol. The drying tube was then

replaced, 35. 4 grams (O. 177 mole) of diethyl f3-methylglutaconate rapidly

added and the mixture heated for five hours. Just before boiling, a bright

red color developed which remained throughout the reaction. Th~ reaction

mixture was then chilled over ice, poured into 74 l'X}l. of 1. 0 N. ( 1'2. 3 ml; , ' cone. HCt in 61. 7 ml. ice water) hydrochloric acid also over ice, extracted

with four portions of ether, washed with a small amount of concentrated

.. s.odium bicarbonate solution, dried over anhydrous sodium sulfate and

distilled under reduced prei;sure. We obtained 47-55o/olyield,s,, boiling 80 point 179-186° /5 mm. and n 23 • 1. 4540. · A condensation product prepared from undried alcoh~l ,had a boilil1.g i 0 : pGint-of lSl /22 mm. on the-plateau. Subsequent ~edistiHations gave decarboxylation and the boiling points in Tabl~ 55 •

Table 55 . Decarboxylation of Diethyl a•Carboxy ·-1, l, 1-ethane- tr,ia.cetic: ·Ester Nit.rile, Michael Addition· p:rodti.ct

0 ' Re distillation Boiling Ppint R.an;e ,' C. /mm..

1 181/22

2 155-160 / 1. 8-1,'5, m. P• 34-37°

3 116-120/1.0

The second distillation product was diethyl 1, 1, 1-ethanetriacetic ester

0 . . . nitrtle, lit. Ill• p~37 (1, 35) ..,. Ari infrared trace was.:.ta;keni. ;Fig, ,lO,.'.,.The product from .the third dbtillati9n did not c:tystalUze. Acid hydrolysis of

0 all three products yielded l, 1, 1-ethanetriacetic' acid, m~ p. 11a • However, the third product gave a lowered yield and a melting point of l&S-170°.

'fbe dlstillatJon step could be safely omitted with some increase of yield. in .the synthesis of 1, 1, l•ethanetriacetic acid.

1, 1., t~Ethanetriacetic Acid--Hydr.olysls of the J>Urified Michael adq.ition l product was carried out three ways. In all c~ues the cyano ester w-., hydrolyzed in rielda of 80-90fq;, Experiments with Thorpe and Wood•s procedure (35} led u•to ,believe tha.t more water coul~ be profitably used during hydrolysis. The following reagent, 30-40% sulfuric acid, waa tried. Almost one and a half volumes of acid to ~yano.,.,.ester were mixe.d and ver,y 1ently boiled until solution. t-,k place. Alcohol esc~ and the reaction went r':apidly to completion if the flask was left exposed· to-the atmosphere and water replaced as needed.

After solution the mixture was refluxed for two hours. The triacetic acid readily separated on cooling. This solution <;:-ouldbe easily clarified by Norit , treatment and concentrated by evaporation.

An equal amount of hydrochloric acid (concentrated reagent grade) was added to a 1: 1 crude triacid and boiling water solution. At 70° began and crystallization/continued to 65° and pure white crystals, m~ p. 172. 4 ..

175. 2° were filtered from the mother liquor. Air drying gave the melting

0 point range 173. 0-175. i . Prior to the final recrystallization this sample was extracted with anhydrous ether to check for inorganic salts. None appeared.

The hydrolysis procedure of Thorpe and Wood (35) specified a mixt,ure of equal volumes of cyano ester and concentrated sulfuric acid, standing one hour, adding an equal volume of water and boiling for two hours. When the sulfuric acid was added, much heat developed and gas evolved. After water was added and the mixture heated for two hours., it was found difficult to induce crystallization. Three to four days of cooling, scratching, stirring, and seeding were required to get crystals. The crystallization rate proceeded very slowly. Three products were isolated from th.is mixture, the triacid, an internal monoanhydride, and a double anhydride. The acid could be grown in colorless branching needles, bi- pyrimidal ·shapes, or cube.s depending on temperature, purity, and rate of crystal growth. The acid anhydride crystals grew in long soft white 6 needles radiating from one se'ed nucleus,m.p. 97-99° (lit. m.p. 97 ) (35). l'

The double anhydride was a white chalky powder, m. p. 185° (lit. m- p. 180°)

(35). Both anhyd.rides could be slowly converted to the triacid with -134- boiling water. ~ineral acid catalyzed the reaction.

The triadd was colored and could be purified tp whiteness through

several Norite ti,"eatments. Three to four recrystallizations from " concentrated B:Cl, gave the m • .p. 172-174. 0

Kohler and ~eid 1s c-onstant boiling hydro~hlo:dc acid procedure (21)

was performed with 14 grams (0. 045 mole) of cyano ester suspended in

60 ml. (22. 2 gram1:J, O. 61 mol:e of E;Cl} concentrated hydrochloric acid.

Hydrochloric a.ci.9-was replaced and the mixture remained on th~ steam

bath for abdut forty hours. Two ~roducts resulted. Approximately twc;,-

thirds of the crystallized solid "imido 11 acid, m. p. 151-153° (lit. m. p. 6 155-156 ) (21) separated on cooling. An infrared curve was taken,

Fig. 11. On standing, a second crop, impure 1, 1, 1-ethanetriacetic

acid, m.p. 161-165°, resulted. Qur two products, being colored, were

difficult to purify further. Moreover, boiling water was found to partially

convert ,the imido acid to triacetic acid.

Recrystallization Experiments with 1, 1, 1-Ethanetria.cetic Acid--- A sample

· of l t 1, 1-ethanetriacetic acid was prepared by direct hyqroly!i!iS of the

Michael condensation product without purification of the product. according

to the directions of In~old (19).

This by pass of the extraction step eliminated ether contact with the

triacid. ~bout twenty grams of tria.cld was recrystallized from hydro-

chloric add. The first recrystallization product melte<;i at 164--169° and

the second at 166-167°. One milliliter of U.S. P. ethyl ether was added to

the third recrystallization system and gave the triacid sample, m..p. 171 0 •

A non-ether sample oftriacid prep 4 red as above, .m.p. 155-158°; was -

0 slightly deliquescent. Samples from the ether-HCl system, m. p. 172-4 , .135 .. could l;>e ~ri-ed readily.

Tit:ration of the two forms in benzen-e-methanol solutfon (12) with soehun n:ietho~ide gave transient endpoints. The non .. ether sample began this behavior at 2 equivalents of base. This transient endpoint lasted from sever~! sec<;mds to a few minutef!. The ether-sample •howed this behavior at.:Z../75 eqw.~lerits. The change at this endpoint latJted a few seconds. Both samples gave a final endpoint at 3. l equivalent$ •. · The sodium methoxide solution (O. 173 N. in 4: 1 benzene-methanol solutionl was standardized with benzoic acid (U.S. P. ·,xl,I Mallinckrodt,) and thymol blue indicator. The endpoiI).ts were taken at a cleali blue color~ All titration samples were uniformly niixe'1, at a standardized speed with a Magmix stirrer. ·Infrared curves of the non•ether sample of 1, 1, l •ethanetriacetic acid, Fig. 12., showed less intensity in the carboxyl region, 5. 8-S. 9p., than the ether sample, Fig .. 13. The other regions of the two curves were essentially the same. A peak at ca. 9""confirlllllleall the presence of ether.

1, 1, l•Ethanetriacetyl Bromide-- Phosphorous pentabromide formed readily from 10. 75 ml. (33. 5 g., 0. 21 mole) of bromine (Analytical Reagent,

Mallinckl'edt) added dropwise with initial swirling and final mechanical crush- ing to 20 ;ml~ (56. 9 g., O. 21 mole) of chilled pho111phorous. tribromid.e (White

Label, Eastman; Matheso,11, Coleman and Bell) and 1, 1, 1-ethq.netriacetic

0 a.cid (ll),o.p. 172-174. s , from hot 20% HCl, 14 .. 2 g.,,o.07 mole). If this mixture developed an orange cast, the addition was stopped and further cooling allowed (finely crushed ice bath). This cooling was continued until the lemon-yellow color of phosphorous pentabromide reappeared. .After the bromine addition was completed, the flasls (100-ml. RB f 14/35) and flask contents were transferred to a 20° ~th and a small straight co,p.denser -136- 14/35) and dryi:p.~ tube {GaC1 14/35) added. Hydrogen bromide was (f 2 g

evolved and solid ph.osphoryl bromide and 1, 1, 1-ethanetriacetyl bromide

--~:rmed. Tb.is reaction subsided to a low level after two days and remained

constant thereafter. A white mist of hydrogen bromide, observed by

_blowing at the outlet, was used as a x:eaction indicator. Hydrolysis yielded

the identity- of phosphoryl bromide, m. p. 56° (lit. m. p. 56°).

Bromide and phosphate ion tests )Vere positive. Silver bromide and

phosphomolybdate precipitates appeared as the appropriate reagents were

added.

The above mixture was kept under OaClz at 20°. It changed little over

6 monthS .1 time. The mixture after 6.months was fractionated with a Soxhlet

extractor and infrared spectra were taken of the various fractions. The

identity of the products were confirmed and the. monoanhydride of 1, 1, l ...

etha.net:Haco.iic acid ,was fQund pre sent •

. Ta'bt.e 5 .6. Extraction of 1, 1, 1-Ethanetriactyl Bromide Synthesis Products -1 Solvent Tim.e,days Important Peaks, cm. (Jl) Compound

Skellysolve A-ligroine 3 s 1280 (7. S)a POBr 3 0 JI Ugroine-methylene --- ; 4 s1800(5. SS)b,s1700(5. 85)b C-C(C-C-Br) 3 chloride m980( 10. 2, s855( 11. 7)

methylene chloride 4 s.w. 1820(5. 52), sl725(5. 8) monoanhydr ide s 1700(5. 85)

com.parison spectra sl 725(5. 8) C-C(C-COzH) 3

a. only peak b. moisture contact removed the 1st two peaks.

-1 Phosphoryl chloride has an only peak at 1_280 cm. • This peak identified

phosphoryl bromicl.e by analogy. Hydrolysis, due to moisture in the air -137- of the second and largest fraction gave a speetrum identi:cal with that of

1, 1, 1-ethanetriacetic: acid. Peaks of a carboxyl g:roup linked by an a.~bromo group /were absent. Also the four peaks before hydrolysie (the largest fraction) compared favorably with a typical acid bromide. Finally, the last and smaller fraction exhibited the expected carboxyl frequencies for both ds- , - anhydride and the carboxyl group of the internal monoanhydride of 1, 1, 1- ethanetriacetic acid, m~ p. 97-99° (lit. m. p. 97°),35 ).

Ethyl a, a.', a. 11 ,-Trib:romo-l, 1, 1-ethanetriacetate--Time variation,(unstated by Thorpe ·(2)i careful temperature control (20°) and close adherence to reactant amounts gave only acid bromide._ Possiple preparation relics were tested as promoters of a.-bromination.

A procedure very similar to the synthesis of 1, 1, 1-ethanetriac,etyl: bromide above allowed testing for reaction promotion. Bromine (0. 1-65'ml. , ~3 . O. 515 g., 7. 35 x 10 molesl slowly added to phosphorous tribromide (0. 350 -3 ml. , O. 999 g.) 7. 35 x 10 moles) and 1, 1, 1-ethanetriacetic acid (m. p.

173-175. 8~ from 20% aq. HCl, 0-. 50 g.,. 2. 45 x 10- 3 mo.les) gave a typical mixture of phosphorous pentabromide and triacid. Various materials were then added in trace amounts. As each system slowly reacted over a month's tune solid POBr 3 appeared and the halogen color disapp-eared. Further a¢1.dition:s of bromine gave various results. A promoter from the preparation of 1, 1, 1-etha.netriacetic acid was finally obs(;lrved. A number of items which occur along the course of the p.repar~tion of 1, 1, 1-ethanetriacetic add were tried and are listed below. The mixtures were esterified and the product checked for a.-bromination. -138- Table 5-7 • Trace Effects on a-Bromination of 1, 1, 1-Ethanetriacetyl ,.Bromide-

Probable -Snythee•i~,ReUc -Result

1 no net change NH:4~1 (NH ) no net change 4 2so 4

H 0 no net change 2 c;:onc. HCl no net change

mix liquified 1 no lactones

benzoyl peroxide trace of dilactone. and triacid

EtOH brief bromination

Et 0 vigorous action, liquified 2. mixture, lactones

dio:,tane no net change

a-Bromination with ether traces was confirmed in the experiments described below. A reactor preassembled from a 50 mi. erl~ntneyer flask, rubb~r stopper froxn,a blood receptor kit (Army Surplus), a small condenser and a drying tube (P on glass beads moistened withH P0 ) provided a 2o5 3 4 dry environment in a 20° £lowing water bath. Bromine (0. 165 ml., O. 515 g.,

7. 35 x 10· 3 mole) was slowly added to phosphorous tribromide (0. 350 ml., 3 O. 999 g., 7 .. 35 x 10- mole) and 1, 1, 1-ethanetriacetic acid (m.p. 171-2 from e,thyl ether, O. 50 g. , 2. 45 x 10 -3 mole). This gave a suitable mixture of phosphorous pentabromide and triacid. After the ma'ss had liqu-ified and -3 HBr evolution ceaseq., more bromine (0. 0275 ml. , O. 0857 g., 1. 27 x 10 mole) gave additional brisk action. Excess bromine was added and the reaction -139- completed by heating gradually to 84°. A crude benzene solution of tribro- moester resulted as the above reaction mixture was poured into 3 volumes of chilled (-80°) ethanol, washed with water, dissolved in an equal volume of benzene and placed over drierite. This solution precipitated the trilactone of 1, 1, 1-ethanetriacetic acid, m. p. 205-207° (lit. m·. p. 207°)(2) if the benzene solution was warmed with an equal volume of pyridine.

An infrared curve was taken, Fig. 14.

The second experiment conducted as above involved the same molar relationships of the reactants--bromine (0. 41 ml.), phosphorous tribromide

(0. 85 ml.) and 1, 1, 1-ethanetriacetic acid (m. p. 172-3° from aqueous dioxane and HCl, 1. 2 79 g. } . Two more equivalents of bromine ( 0. 069 ml.} gradually reacted and the final equivalent (0. 035 ml.} absorbed on warming at about 35°, only when a drop of ethyl ether was added. Synthesis and treatment of tI:e triester as in the experiment above gave a lactonic mixture, principally trilactone m.p. 205-207°,(lit. m.p. 207°) and a slight amount of dilactone m.p. 189°,(Ht. m.p. 186°) (2).

Infrared Spectra _ .. Perkin Elmer made the instrument, the Perkin Elmer

13, which provided access to the spectra represented in Figs. 10-14. The curve traces were calibrated by measuring the spectra of identical samples of 1, 1, 1-ethanetriacetic acid with the Perkin Elmer and with a Beckman instrument, the IR-5. The reproducibility of both instruments was better than 0.1' P· Samples were prepared by standard techniques. Both

Nujol mulls and KBr dispersions were ground by hand. -140-

; ' ,'_ _;,1,------1--- ~tcc-t-71'--t-=•ic=1=-r~ -\.,-,-,----,- -~ .-_')';:, J_p / =. - Ice -- -- _- ----

- 3,,_- .-- -- \ . -If - ~., =t-=+-t--+--H\:-t-· _- :. I\ _ -,~~~ _ \I ++'~C-J--+-+-+--1-t--+--+--i--+--t--+-t---,t+-+-+_-_ =+-_--,-!----l_ -t--+--+--1-•-t_ H_,+-+-_+-_~-~""_;_--t;~-_~-+--.+-!----lr- ..-+-..+--+-jt-t--c_--J_ =__~r-_ +-+-t--+-tt----J--1--+-t--l 1 ++--+---+-+-+-c-.t-.=1ccc+-+c=-F---+-- _ -+-+---IH+.--+e~i....-=-~-•+·-+-l-+-+--tt/\-11+-c++-blH-.-"-l'c=-t-=+--t-++--li ~--t--El-"--f=-t--+-t--11-+-+-t---+'---I I ·'' \ -- /, I \J' I 1 IJ1 V I/ I - _\ ,, - ' I I \ -tt-+--->---+- u:-. J +--+--+--,+----11-t--+I.....+=V ----:_=-·-•l --+-t--+-t--+-+--+~-~ -- "I'\.• -LJ - 'I ,01 •[,.Q:'c- iO[ '.o_ 50 ~i _Jl_ .14.

C-CN I Fig.IQ C-C-C-COzEt ,in CCl4 I C-C02Et

~----J__

- -I _- - - I - -r- H--t-+=+-+--l--ll--+--+-+--t-+-+-+~1=_,,~8-+~=-'1=!-fc\J-\--+...+++++-+-+--f--+---+-+--+-+--+--+--"+-H--+--+-+--f-- 11 --+--- -- j;fj -- / ! ~+i t--f- tt--+-+=t--t-1t---+-+-+-+-+-+-+--t-=r--.-tt-.-+++--t--+t-l--'-tt-t-+lr I•r"-\/'1t----t---+--t-+-.-+------+ -+-+-+-t--1--+---t---11---i--t--1--+-t------.. I~ - f:-- V 1- -t-t-- -- ' .Im -----++t-- ,_ _:- II. ' 1,------l----,--,---i---,-,-----1- '\ I , I/ I\ \ \. IA " - \J I I .

- . ~ J __-+--,----+-r--+-1- -: - -'" 11,r- - A i I 11 i, i i i ~ .0 _• o I ·- :_ .Q -~ _ _ ,_.Q 7.0 i .!Q I - 'Z il3. I i/4. I .;Po Fig.II c-c "tmido"Add, c-6-c~~ in Nujol I 'o C-COzH

-f I , 1-+:_~~-f- __: -I + !

- ~- --f------,------.------I I I I __L_ - ! i ' i i l 1 1 1-- 1 - r · --,,-t-----r-T ~--j -t--t-i -+--+---+-+--+A--+-+-+-t-h-ft\-l-+--+-+-+--11--+-- -;b~i---,--j-~t-..--t---t---t- ---+-+---+ ~--1--1+---+--+~--➔--,-+--+--t-f---!- +-+ _--f- _IL _rr r---_-+'\1-11-_,,_111t--1\c-t---t-1--+-+----l-'+,/-- ~--1"',, : +--(

-F.l,-.-,_+--H-+-+-+-+--+--+\1-+,-..1::-~-+--+--,,-+_/-li'-__-ir-V,/--l--f-----e-- +-r-····· I i '-_-_- [' rf +-~:-·-:~ 1 \ I . I +,~

I I i I - •--- I

-I - 3.4) - -- 4.£ ;s. 6.c 1 .o I fl! 11,

Fig.12 C-C(C-COzHl 3, in KBr -141-

--•-+--- -- :-H--4---1--t--+P,---+--+---,------ttt-4--+----t----+ L - _J_+-i-- j_' / i\ c:/_ . - ~ -, I I I , 1 1 1 <-+--+--+--+/ l--ll---t'-\._t--"'---'1_1----\."--r-t---- -t---- I -- - }- - I 1·-\H-H---t--cc=-c--c+c-ci-+--t-v-f- +----..1\ I ' +--•!-+-i-- I . ' -+_,_l+--ll--l·-t-----ft----+-\,,_f+-1-+ .__\t--1_-t,,1----+-:--e- --1,1-1---+-+---+--'n-t------+-+ -tr i

,__'_.__,,+I-+--+---+----+--t---t--+-t--+---1---+--t--+--t---t--+-c-+-i' --+--+-----t-+--t--t--+-+- __-t----t--t--+i-+-·-+--+--c- I - ' -- --r--i ------~--+-:- ! 1---l-_TL_t---->----t-+--t---+--+-+-t--+-+--r-+--+---+--+--t----+--+---1--+-+--t-+- _-•-e--t---t-~-t----L~ L _JI, - , -- l -t---- t-··- -- .: 1.,-1- 1 . =:-:;- , 1 r I I I I I i I I I 5. 7 I It, I~ I

Fig.13 C-C(C-C02Hl 3, from ether, in KBr

L , . i =-..: +- I -+-t---tt---t-+-+--+----+--+---+--+-t---t--+-+--+--+----+-+--- - r------r-- t------t--+--+--~-+-cc--t---1

+----J--+-+-+-+--+--+--+-+--f--+---+-+-+---+-=+=+=+----J! ._--- ·-- : __ ---1------r~ -- -i------

/ I/ l '"' \ IC _. __ \\, [:::"~.__: -- •-~ ~- --[\ ~- ----l----1--C--1------1--1--f!/-/--1~--J-V\--"l-.-+--+--1--+-----+--_-+--__~'_r ----+----t-+--r--+--+---+--+-+-t--+---t--t---+--1[ __lti--tt-\ I 'J_ f~ ' L_I\ lb _. \ " == -_.~ "' 1 LLI ---- 1-- 1"- J v ,_r--r, Jr' ~ \ · 1/ i , I - -== '-I---' I\ / I'- / I >-+-..~.'d-+--_+cc--_-rl--r +-- ~ --- -•--+----t---l--+--•-+--t---t--+-t----+---1---t--t---t----+--t---t---+-t- ...... '-+---t-__,,,.-----t--+--+---+---t--V--,____,----,,,r-t- ,-+-~1c--1-,

,,110 I I l lO I , .0 co_ _ _LI?_ I_ =! -

Fig.14 "Trilactone':in KBr -145-

Bibliography

1. R. M. Beesley and J. F. Thorpe, ~- Chem. Soc. 29, 346(1913).

- - 2. R. M. Beesley, J. F. Thorpe and C. K. Ingold,_:!_. Chem. ~ 117, 610, 618(1920).

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6. L.-i.Eaves, private communication.

7. M. G. Ettlinger and F. Kennedy, Chem. and Ind. 1957, 891.

8. E. H. Farmer, 1...:,Chem. Soc. ·123, 3337 (1923).

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10 .. L. N. Ferguson, 1...:,Chem. Ed. 23, 550 (1946).

11. L. F. Fieser, "Experiments in Organic Chemistry, 11 3rd Ed., D. C. Heath and Co., Boston, 1955, p. 286.

12. J. S. Fritz, "Acid-Base Titrations in Nonaqueous Solvents 11, The G. Frederick Smith Chemical Co., Columbus, Ohio, 1952, p. 28.

13. M. Gomberg,~ 33, 3150 (1900).

14. M. Gomberg,..:!_: ~ Chem. Soc. 22, 757 (1900).

15. M. B. Goren, Doc. Diss., Harvard Univ., 1949, p. 6, 51.

16. F. R. Goss, C, K. Ingold and J. F. Thorpe,..i!._. Chem. Soc. 123, 348 (1923).

17. E. S. Gould, "Mechanism an.d Structure in Organic Chemistry", Holt, Rinehart and Winston, New York, 1959, Chapter 12.

18. D. Guillot, private comm~nication, Brigham Young University, 1962.

18a. J. A. Gurney, Master's Thesis, Brigham Young University, 1958, P• 19.

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20. C. K. Ingold, 11Structure and Mechani·sm in Organic Chemistry", r_ o 11 -145-

Bibliography

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3 0. R~ Sch re ck, 2· Am. Chem. Soc. ~ 1881 (1949).

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37. E. F, Wesp and W.R. Brode, -J--. Am. Chem. Soc. 56, 1037(1934).

38. K. B. Wiberg and R. P. Ciula, J. Am. Chem. Soc. 81, 5261(1959). -- . ---- 39. R.:1-M~ Wiley and N, R. Smith, J. ~ Chem. Soc.~ 353 (1951). [Contribution from the Eyring Science Center of Brigham Young Universityt Provo, Utah]

THE SULFONATION OF CHLOROBENZEfE AND THE SELECTIVITY llELATION 1• ··

. . . . . - ' . , . . . ' ...... -~· ... {l) Aromatic Substitution. I. Sulfonation of the .Halobenzenes. I. (2) Based on a Doctoral Dissertation submitted by John A. Gurney to the Graduate School of Brig9-am Young University.

By K. LeRoi Nelson and John A. Gurney

Aromatic sulfonation and some substitution reactions of chlorobenzene show deviations in the selectivity relation. A determination of chlorobenzene sulfonation provided the following rate ratio relative to benzene and partial rate factors: 1. o; ot O. 0640, mf 1. 7· and Pf 4. 2, air work, Olah' s nitration, Ferguson's bromination, Stock's chlorination and our sulfonation partial rate data define a new relation that can be expressed by adding an entropy term (A) to the selectivity relation.

, Introduction

Simple linear relationships exist between the relative rates of many

aromatic substitution reactions. 3 ' :

(3) (a);H.C. Brown and K. LeRoiNelson, J. Am. Chem. Soc., 75, 6292 (1953); (b) L. M. Stock and fi. C. Brm¥n, ibid.,~• 1242 (1962).

The·rates of substitution at the various positions relative to benzene : •. ' i. ': ~ found definition as the partial rate factors- ...•ortho (of)' meta (mf)

and para factors (pf). The para partial rate factor has been adopted

as the measure of reagent reactivity and the ratio of the para and

· meta factors as the measure of the selectivity of these two positions

toward the reagent. The reagent activity was found to be proportional

to the selectivity. 3 -xv ...

(Ii

,Application of equation 2, a NernEJt free energy-equilibrium relation to the rate constant, similar to that

/:i,.·yf: = RT ln k (2) of Hammett has led to an assignment of two parameters. One of these parameters is related to the reagent in use (P) and the other 1to a ring substituent 1s ability (o-+) to withdraw or supply electrons to the reaction site

(the Hammett•Brown equation )4•

(4) C. W. McGary, Jr., Y. Okamoto and H. C. Brown, ~, 77, 3040 (1955).

lpg Pf= + + ( 3) u- p - u-m

Many of the available data such as nitration, bromination and mecuration gave l¼near plots and fit in equation 3; others deviated by relatively small amounts 5•

(5) I..,. M. Stock and H. C. Brown,~., 81, 3323(1959).

While the same is apparently true of meta substitution in the halbbenzenes, para substitution varied much more. The variation of the substituent constant at the para position (U-p)+ of the halobenzenes indicated deviation of the halobenzenes from a simple fit in the Brown-Hammett equation (Eq. 3),

: 1 • -xvi- 6 Fig. 1.

{6) (a) H. C. Brown and Y. Okamoto, ibid., 80, 4979 (1958·); (b) y. Okamoto and H. G. Brown, ------J. Org. Chem-., -22, 485(1957).

Plotting of the partial rate values available for the sulfonation of toluene also showed a significant lack of agreement with other reactions 3at5 o f to 1 uene, Fig. 2•

Because the data for sulfonation of toluene and for substitution of the

halobenz,enes, apparently both fail to fit a simple linear correlation,

determination of the partial rate factors of halo benzene sulfonation is

needed and should serve as a test of (ree energy relationships in aromatic

substitution.

The :results of an investigation of chlorobenzene sulfonation are reported

in this paper.

Results

Until recent wor:f.c., sulfonation of the halobenzenes was thought to 1 provide 100% para substitution. The ortho and meta isomers had escaped

(7) · A. F. Holleman, Chem. ~ •.,..!_, 187(1924).

detection, Table l.

Table 1 AVAILABLE ISOMER DISTRIBUTION DATA QF ttALOBENZENE SULFQNATION Subs. %Ortho %Meta %Para Cla 3. 8 ± 2 14. 6 ! 2 81. 6

Brl;> 13 37 50

r"J 0.8 o. 6 98. 6 -xvii-

0.6

0.4 0

0 0 0.2 0 OQ) 0 p-C\ 0 00 0 0 0 0.0 0

'2> -0.2 0 0 +6 Oo p-Me

0 -0.4 0

-0.6 0 0 0 0 p-OMe Q, -0.8 0 0 0 0 0 -1.0

-7.0 -6.0 -5.0 -4.0 -3.0 -2.0 -1.0 p Fig. I Variation in cr-+ of Para Substitutionin Chlorobenzene,Toluene and Anisole as a Functionof p. -xviii-

4.0------,

3.0

ci c,, 2.0 .3

1.0

0,0_...,_____ ,....______..,______,..__

0.0 1.0 2.0 3.0

Log p1lm 1 Fig.2 Comparisonof the Para and Meta PartialRate Factors for Substitution of Tolueneand Benzene. a.. A. A. Spryskov and O. I. "achurin, Zhur. Obschei I

c. Ref. 26a

Factors other than the ratio of ortho, meta .and para isQmers may well

affect the sa,mple counts. Since p-chlorobenzene sulfonic acid monohydrate

formed readily during recrystallization~ hygroscopic salts were possible

(8) V. Q. Lultashevich, Doklady Akad. Nauk S.S. S. R. , J2, 995 ( 1954) [ C. A. , ~, 21 7 g ( 19 5 6 )J. . ·

and would lower count values. The extensive displacement of at-butyl

group from .E,-di-!_-butylbenzene (88. 4% g•(,!_-butyl} benzenesulfonic acid)

with chlorosulfonic acid at 20-25° 9 presented the possibility of chloro

(9) D. I. Legge, I: Am. Chem. ~, 69, 2086(1947).

group displacement with sulfur trioxide. Such a chloro group displacement

became likely with the observation of iodo displacement. 10

(10) J. Knight, Master's Thesis, Brigham Young University, 1957, pp. 28, 29.

partial rate The/values for chlorobenzene were determined by an isotopic dilution method.

After reaction with sulfur trioxide .. s35 , aliquots of the sulfonation mixture

were introdude4 into large samples of individual isomers and were then

recrystallized to a constant count. The ratio of the counts revealed the

isomer distribution and the rates relative to toluene. -xx-

Isomer Distripution---The i•otopic dilutlon techll:ique of determining isom~r

and competitive rate '.ratios required fairly pure individual isome:rs. The

Sand~eyer reaction 11 provided a means of obtaining reasonably pure

( 11) H. Meerwein, G. Dittmar, R. Gollmer, K. Hafner, F. Mensch ana. 0. Steinfort, ~• , _12, 841 ( 1957)

sodium~-; ~- and g•chlorobenzenesulfonates. 12 . 35 Equal molal\ amounts · of chlorobenzene and sulfur trioxide-S · were

(12) K. D. Wadsworth and c. N. Hinshelwood, J. Chem. Soc., 4680944). Excess is known to form an adduct with chlorobenzenesulfonic acid. so 3

combined in ca. 170 ml. of refluxing sulfur dioxide. The sulfur dil):Xide was

removed and the mixture was neutralized with aqueous sodium ca;rbonate.

Aliquots of the isomeric mixture were added to equal amounts of the

pure isomers and recrystallized with a two-crop system. The first crop

grown under slower crystallizing conditions generally provided the better

purity. The second crop grown more l'apidly gave a comparison of the

filtrate purity to that of the first crop. This method gave converging

values in addition to the constant count of ,uccessive recrystallizations.

The convergence of ·values was more prominant than the changee of

successive counts and allowed much shorter co:untingtimes during scanning

bf the various recrystallizations. Such a technique also lent confidence to the

values obtained.

The counting deviation was calculated with a propagation of random -xxi- 13 error equation and compa:red to the - counting deviation -values.

(13) A. F. Palmer, "The Theory of Measurements," McGraw-Hill, New York,. 1930.

Agreement occurred between the two sets of values and indicated an

adequate performance of the counting equipment.

Comparison of our isomer distribution data with those available

(Table 2) show~d a high percentage of meta isomer and may intj.icate some

isomerization of ortho and para isomers.

Ta:ble 2 AVAILABLE ISOMER DISTRIBUTION DAT A OF THE SULFONATION OF CHLORO:BEN ZENE

Reaction Conditions o/oOrtho %Meta %Para

o a _. ____ H So t 238 5 9. 3 40. 7 2 4 · ·o a H SO , 22.0 3 5. 8 64.2 2 4 ----- SO , liq. SO , -10° 1.0, 28. 8 70 • 3 2 so 3, CzH4Clz, .. 12ob 3. 8 ~ 2.' 14. 6 ~ 2. 81. 6

a. A. A. Sprysk ov and O. I. Kachurin, Zhur. Obshchei Khim, 28, 2?13 ( 1958).

b. I. Tana,eseu c:tnd M. Mac~rovici, Acad. rep. populare Romane, Bul. · stiint., Sect. stiint. ~ .!!_chim., .?_, 57ll953) [ C.~, ~, 14'61lc (1956)].

Competitive Sulfonation--The probable displacement of the chloro group

required the selection of a competitor molecule other than benzene. Toluene

was chosen. Sodium p-toluenes.ulfonate could be separated from sodium

benzenesulfonate by recrystallization 14• The values of the toluene-benzene

(14) J. Duvall, Diss. in Preparation, Brigham Young University, (1962), -xxii-

rate ratio and the isomer distribution of tpluene allowed calculation of the

chlorobenzene-benzene rate ratio.

A ratio of 50 parts chlorobenzene and 25 parts toluene to one of sulfur

trioxide-s 35 was selected to provide enough sodium p-chlorbbenzenesul-

fonate for purification and to allow complete consumption of sulfur trioxide-

s35. Pure sodium p•toluenesulfonate and .e-chlc:>robenzenesu1fonate were

added to aliquots of the neutralized sulfonic-s 35 acid mixture and determined

the isotopic dilution for the two par~ positions. These two mixtures were

then recrystallized using the two-crop system described earlier. The

converging pattern of sodium p-toluene sulfonate showed a delayed count

minimum in the second crops as compared to the first crops. The final

crops :rose in counting rate. The minimum counts, however, agreed as

to value. Rising counts apparently indicated a ~lk ~density less .·, t.p.~J:l.

the standard · usually produced during sample grinding. 15 Although

(15) J. S. Merritt, J. G. V. Taylor, W. F. MerrittandP. J. Campion Anal. Chem. 32, 310 ( 1960).

the values of the two crops of sodium p-chlorobenzenesulfonate did not

converge (low activity~ 163 cts/min. , prevented further recrystallization),

they did approach a constant value. The values o.f the two crops were

extrapolated to get the final value.

Corrections for l:>ackground ( 16. 1 ± LO cts. /min.) and for dilution of

the .sodium p ...chlorobenzenesulfonate ( 10. 14) gave count values of .

sodium p-chlorobenzenesulfonate 1, 176 :!:21 cts./min.

sodium p-toluenesulfonate 7, 864 ! 25 ct.s. /min~ -xxiii-

· . . 16 The derivation of Ingold ts equation for calculating rate constant ratio's

{16) . C. K. Ingold and F. R. Shaw, J. Chem. Soc., 2918 (1927).

was extended. If the kinetics were of the form

"' ~ = k (x)(z)n ( 4) dt X

n = 2 for sulfonation

x = niono-substituted benzene

z ::; sulfur trioxide

equation 5 followed regardle1;3s of the value of~•

log a/(a - x ) 00 ( 5) log c / ( c ... y ) 00

a · = aroma.tic x initial

c = aromatic y initial

X oo = a.rc;>roatiic x reacted at t = 00

Yoo = arom~tic y reacted at t = oo Many mono-substituted benzenes in the reaction with sulfur trioxide, includ-

mgchlorobenzene, are first order with respect to the mono-substituted

benzene. 17 We concluded that equation 5 held for sulfonation.

(11) (a) W. A. Cowdrey and D. S. Davies, ibid., 187 (1949); (b) E. Dresel and C. N. tlinshelwood, ibid. , 649 (1944); ·(c) E. E. Gilbert and E. P. Jones, Ind. Eng. Chem., ~ 501 (1961); (d) ;IL. E. Oi\pert, B. Vedhins, E. J. Car hon and S. L. Giolito, ibid.,' 45, 2065 ( 1953)'; (e) A.. M. Grigrovskii, N. N. Dykhanov ~nd Z. M. Kimen:--zhur. Priklad, Khim. , 28, 616 (1955) l~•A·, 50, 3279£(1956)]; (f) D. R. Vkary ~1'-d C. N. Hinshelwoc,d,_!. Chem. Soc.,. 1372(1939). -xxiv-

A derivation .check· similar to that used in extending Ingold •s equation reaffirmed the direct relationship of rate constant ratios at the various positions (0-- 1 -m- and - p-) to the percentage of the isomers. k /k ortho 0 X = %

km/kx = o/ometa

k /k % para p X =

An evaluation of the relationship between the para and meta rate ratio constants at infinite rea.gent activity reproduced the partial rate factors and the selectivity relation.

( 6)

(1)

The total l"ate ratio was calculated with equation 5 and converted to the ortho, meta and para factors of chlorobenzenesulfonation.

kPhMe/~hCl = 8.8

of = o. 064\

mf = 1.7

pf = 4.2

log Pf = 1.:63 ·

lo£ p/mf = o. 6 9

Neithe:r the a~ount of isomerization of chlorobenzenesulfonic acid nor that of ch1oro group displacement were determined. These possible corrections -xxv-

were negleeted, a-s rea&onable- estimates of each did not greatly affect the

partial rate fact.a:ir-a. A gr~-phic compal'hon (Fig. 3) of the selectivity

relation for sulfonatlon compared reason~bly well with Olah •s nitratio,n 18,

Ferguson•s bromination 19 and Stock's chlo:dnation 20 of chlorobenzene.

(18) G. A. Olah, S. J:. Kuhn and S. H. Flood, J. Am. Chem. Soc., 83, 45 71 ( 19 61) . .

(19) L. N. Ferguson 1 A. Y. Gc11-rner and J. L. Mack, ibid., 76, 1925 (1954).

(20) L. M. Stock and F. W. Baker, ibid., 84, 1611 (1962). I ' ,___,__ -

21 Other available data generally fit a line going through the origin.

(21) (a) M. L. Bird and C. K. Ingold, J. Chem. Soc., 918 (1938); (b) H. C. Brown and Y. Okamoto, J. Am. Chem. S~c. , 80, 4979 ( 1958); (c) F. B. Deans and C. Eaborn, J. Chem. Soc., 2299 (1959); (d) H. C. Brown and

G. Goldman, J. Am. Chem. Soc.---;-i4 1 1650 (1962.); (e) H. G. Kb1vila and .A,. G. Armou-;_:-, ibid., 79, 565-9(1957); (£) H. G. Kiuvila and:A. R. Hendrickson, ibfcf.': 1.r,-so'8(1952); (gl ref. 25; (h) J. 0... Ro'bert'S, J. K. S!ll:nforq,; ~~:.L~ J •."-Si~a7°H. Cerfo:rt,t,afn ahd R.~'Zagt,. 'J~. :A,rri./ Chem .'i Soc. 76, 45271(19,54).. . - . . - ... -- . --

&ome displacement reactions were also shown.

The line defined by a best fit· of the points of nitratien, chlorination

anq bro;mination did not rt.m through the origin bt;tt rather above and throu~h

the log Pf axis. This evidence could indicate a linear relation with a

difference of reactant randomness, activational ~ntropy ( AS'). ~tween

the halobenzene and benzene molecules. Such a difference in Ast of 14 chlo;robenzene sulfonation has been obs'erv~d.

Qlah has suggested the presence of two basic centers in the halof .

benzenes lS, 22 which can interac:t with the electrophilic reagent. The

(-22) L. J~ Andrews, Ch~m. Revs., 54, 750(1954). I •.-1

0.5

0 . OBenzylation

o Bromodeboronation

o.- CJI ..:l-0.5

Destannylation 0 BrominationO OegermanylationO OAcetylation (Ferguson)

-w BromodesilylatjonO

-1.5

0.0 0.5 /0 1.5 2.0 2.5 3.0 Logp/mt Fig. 3 Comparison of Some Substitution Reactions of Chlorobenzene. -xxvii-

basic center at the halo substituent could interact with an incoming reagent •

. Such a reversible interaction would give a loss of reactant randomness or a

net decrease in the entropy of activation relative to benzene. An intra-

molecular transfer of the reagent from the halo group to the para position

of the ring, the other basic center, would require less orientational

change. This would give a small difference of activational entropy ):>~tween

the meta and para positions.

In the selectivity relation, the entropy terms related to the para and

meta factors are about equal and of opposite sig.n and would essentially

subtract out on the right side and leave an entropy of activation term on

the left-hand side of equation 1. An additional entropy contribution has

been examined in biphenyl and shown to have a simple and non-linear 23 character. The additional entropy contribution in chlorobenz.ene sulfona-

(23) · L •. M •. Stock and H. C. Brown, J. Am. Chem. Soc., 84, 1242(1962).

tion may well be simple and linear. Chlorobenzene may represent the

second case in which ·an additional entropy factor (A) appears and can be

described with the selectivity relation, equation 7.

(7)

It is possible tha.t the factor A is a constant for chlorobenzene and a

variable for biphenyl. --xxviii 0

E~perimental Part

/ Materials- ...The Sandmeyer reaction l l provided a means of obtaining reasonably pure sodium 2,-, m- and ,e-chlorobenzene a.hd ,£-toluenesulfonates. Wet tests for chloride, sulfate and phenol with aqueo.us silver nitrate, barium acetate and ferric chloride provided criteria of purity during recrystallization. Final purity was checked with the preparation of S- benzylisothiouronium sulfonates;. z,4

(24) R. L. Shrin~r, R. C. Fuson and D. Y. Curtin, "The Systematic Identification of Organic Compounds," 4th ed., John Wiley and Sons, Inc., New York, N. Y., 1956, p. 269.

S- benzylis othiouronium The various r;1elting points of thi o-, m- and p-chlorobenzene-and p-toluenesulfonates were 159-160 o , 138-139 -o , --174-174. 5 0 and 182-182. 5 0 respectively. - 25

(25) Lit. values 160. 8, ...----, 174. 4 and 182. 2°, Y,. Muramoto, M. Morita and N._ Hirao, Science and Ind. (Japan), 28, 347 [C:.A., 49, 14582e,~ (l955)]r - - - - -

Sulfur trioxide (Sulfan-B, Allred Ch~ical and Dye Corp.) was ex• changed six weeks with 0. S g (ca. 3 me.) of barium sulfate-s35 • ·

(26) (a) T. G. Davies, Dissertation in preparation, :j3righam Young University, 1962; (b) J. L. Huston,.:!· ~ Chem.~,~• 3049 (1951).

Sulfur dioxide (Army Surplus) was dried over and distilled under cover from P ~ 2o 5 Sample l?repar_ation, ..... Dried samples ( 60 - 120 mg. , 48 hrs. at 120° /S min.) froni various recrystallizations were ground 40 seconds each in 1 ;, polystyrene vials and 3/8" ball pestles with a "Wig-L-Bug" amalgamator (Cresent . . · 27 Dental Mfg. Co. , Chicago, Ill.,).

(27) A technique used to prepare KBr windows for IR Spectra. D. O. Emerson, Am. Mineralogist, 44, 661 ( 1959).

Ground samples of an even thickness settled from ether (r:Jvkrck, anh., planchet 1/3 to 1/2 full), if they were weighed tQ 50 ~ 1 mg. with a Mettle1' balance, dispersed with a small rod having an end flattened at a right angle and swirled in. an elliptical counter .. clockwise motion~ I~ the elliptical motion were smoothly reversed to a clockwise m<>tion for -xxix~

one turn at the end of the swirling, unifor~ity of s:ample thickness . imp.roved. · Evap<>ration ~f the ether a.t room temperature an~ st.ora.ge in a vacuum de,siceator (anh.. Ca:Clz~ S mm.) completed the sample preparation.

Counting Equipment--'Iracerlab: (Boston 10, Mass.) made the followlng equipment which was used in the counting of s35:,a ~thiri-window geiger tube (TOG 14,ser. No. 411) and preamplifier (ser. No. 1126), an automatic sample changer (model SC-GD, No. 550), a printer (model SC SF No. ~0..3')and a Gompu/Matic II scaler (model SC-71 ser. No. 3~4}. The geiger tube' helium bubble rate, voltage and sensitivity were kept at 1. 0 / sec. ~. 1250 v... and O. 25J respectively.

Isotner Distribution- - .A rEtaction :.. mixture of o-, m- and p-benzenesulfonic- s35 acids resulted as 2. s, g.c{O~OZ5 mo1e, made' upto 10 ml. with liq. S0 2) was added dropwise over twenty minutes to 2g (0. 025 mole) sulfur trioxide- s35 in 160 ml. of liquid sulfur dioxide at reilux.

. When the reaction solution was evaporated to dryness, neutralized with aqueous sodium carbonate and re~ueed in bulk to about thirty milliliters, no sulfone could be extracted with. ether. Ten-millilite11 ,aliquots of this solution added to equal 25. 00 g.. portions each of sodium o- t m- and p- . ~ chlo.robenzenesul!onate determined the isotopic dilution of each-- isomer~-

Two crystal crops (25 and 0 0 ) were taken during each successive recrystallization of sodium o-, m• ~nd p-chlorobenzenesulfonate before the mother-liquor was dlsca~de;[° The first crop grown under slower crystaUization conditions (95 to 25°, on an asbestos pad) provided the better. purity. The secop.d crop grown more rapidly (25 to o0 ,. in an ice bath) gav• a comparison: of the filtrate purity to that of the firat crop. Frequent supe'r saturatiqn of the meta is9mer could be relieved by seeding . . ' and scratching. Crop sample• were taken from each recrystallization and th~n prepared for counting.

, Constant purity was taken at the point of agreement of counts between the' two crops. In each case the last three samples were recounted on _the s~m.e .day at 3Q,:OOO cts.

Table 3 IS.OMER DISTRIBUTION RECOUNT DAT A FOR THE SULFONATION OF CHLOROBENZENE.

Isomer 1st C3"C)_,P, mins. 2nd Crop,·:tnins. I Or.tho 412 •. 30 407. 67 408 .• 01 423.73

Meta 22.09 21~'77 22.08 21.94 21. 9JJ 22. 05 Table continued-- -xxx-

Isomer 1st -Crop, mins. 2nd Crop, mins.

Para 8.99 9. 16 8.82 9.26

9. 11 9.21

' ' Competitive Sulfonation--Toluene served in the following experiment to avoid benzenesulfonate enrichment. After so.lfonation had occurred, a small amount of chloride ion was found in the mixtu-re. 35 2 Sulfur trioxicle-s (0. 892 g., l. 11 x 10- mole) in ZOQ mLof liquid sulfur dioxide was added over. twenty minutes time to 50. 0 ml (0. 492 mole) of chlorobenzene (City Chem. Corp.; b. p. 131-132°, under Na) and 25. 0 ml (0. 235 mole) of toluene (Baker reagent, over Na). together in the same 275 ml. of liquid sulfur dioxide.

All additions and transfers were kept at reflux temperature with a dry ice-acetop.e cold-finger condenser and under the cover of calcium chloride drying tube.

The crude arylsulfonic-s 35 acids deposited on evapo~ating the mixture overnight. The crude acid residue in 110 ml. of water neutralized easily with sfl.all portions of sodium carbonate. Extractipn of the sulfonate-s 3 solution with fou:r 10-ml. portions of methylene chloride (no sulfone found) provided a solution of labeled sodium o-, m- and p- toluene-and chlorobenzenesulfonates. Fifty-milliliter aiiquots of this soluUon w~ e added to 10. 00 g. each of sodium p-toluenesulfonate . __ , 2 (5. 15 x 10 2 mole) and of sodium p-chlorobenzenesulfonate (4. 62 x 10 mole) .. to set the isotopic dilution of each-para isomer. After two crops of crystals were taken from each recrystallization (25° and 0°), they were prepared for counting.

Constant purity was taken at the point of greatest count time. Extended recounts were begun on the same day at 100,000 cts.

Table 4 COMPETI'rIVE SULFONATION RECOUNT DATA OF TOLUENE AND CHLOROBENZENE

Recrys. Mins •. Recrys Mins.

T-7 12.57 c ...27- 523.02 12.45 530. 95 12. 47 534. 49".

T-8 12. 63 C-29 556,. 09 12. 66 559.65 12.77 Table continued-- -xxxi ..

Recrys. Mins. Recrys. Mins.

T-12 12. 69 12.64 12.74

Calculation of the total rate ratio from the raw counts above and the isomer distribution data came through an isotopic dilution equation 28 and

(28) Based on the accuracy of single dilµtion calculation. H. Weiler, Intern.. .. J. Appl. Radiation and Isotopes, g_, 4'1 (1961)

Ingold 1s equation.: ..,xxxii-

[Contribution from the Eyring Science Center of Brigham Young University, Provo, Utah]

BROMINE ADDITIO;(\T TO CYCLOHEXENE IN DICHLOROMETHANEl- 3

(1) Low Temperature Kinetics in Aprotic Solvents. I. Bromine addition to cyclohexene. L. (2) Based on a Doctoral Dissertation submitted by John A. Gurney to the Graduate School of Brigham Young University. (3) This work was supported by the National Science Foundation, NSF 410-07-110-28 and NSF 410-07-130-28.

by K. LeRoi Nelson and John A. Gurney

We determined the rate of bromine-cyclohexene addition in dichloromethane at o0 to provide a basis for a systematic variation of solvents at low temperature. An unusual· zero-order reaction was encountered. The reaction was light catalyzed and related to hydrogen bromide concentration. The reaction was independent of bromine, cyclohexene, hydroperoxide and oxygen concentration. The reaction order detended on a steady-state concentration of the simple bromonium ion (Br ). We also observed a novel photo effect with mixtures of oxygen, nitrogen and air.

Introduction

The three reactive intermediates of chlorine and hydrogen chloride addition and olefin basicity bear a strong resemblance to one another,

A limited comparison of addition rates and olefin basicity has shown not only the same response of chloro substituents but a linear relationship 4 t9 olefin basicity, Fig. 5.

(4) (a) L. K- Domash, DQc. Diss., Purdue University, 1952; (b)M. E.

Havill, Doc. Diss., Purdue University 1 1952; (c) B. E. Swedlund and P. W. Robertson, J. Chem. Soc., 630(1947); (d)J. R. Shelton and L. H. Lee, l_: Org. Chem., 25, 428 {1960). -xxxiii-

3.0 0

Cl G(-46°C) 'c=c 2.0 Cl

C: 0 -.;::

:s"1:1 -~ <( ..ll&: ..,_ Cl 0 0 Q) ...J ~ /.0 OCl 2 OHCl,-78.5°C

0.0

Since the relative rates of chlorine and bromine addition under similar conditions are the same, 5 bromine addition data should be similarly linked to olefin basicity.

(5) P. B. D. de la Mare and P. W. Robertson, J. Chem, Soc, 2838 (1950).

The rates of reactions having_, a charged intermediate and neutral reactants are strongly affected by changes in the polarity of reaction

6 solvents. The bromonium intermediate requires a charge and the

(6) E. D. Hughes and G. K. Ingold, ibid. 244(1935), reactants, bromine and olefin, are uncharged. Increases in solvent polarity may be provided by changing or mixing solvents and by adding various salts, thereby increasing the rate of bromine addition.

We have determined the rate of bromine-cyclohexene addition in dichloromethane at 0° G. This was done to provide a basis for a systematic variation of solvents at low temperatures. The third-order term in acetic acid-carbon tetrachloride mixtures decreased with decreasing 7 temperature in bromine addition to cyclohexene. Finally, a check of the

(7) I. M. Mathai; Proc. Indian Acad. Sci.,. SIA, 164 (1960). relationship between hydrogen chloride and bromine addition would shed lig~t on their close linear relationship with olefin basicity, Fig. 5. -xxxv-

Experimental Part

Purification of Materials - Dichloromethane (Eastman, b. p. 39-40° / 760 mm., d. 1. 322/ 20 6 ) was distilled from calcium hydride (City Chem. Corp., New York, no. J357) which gave a short fore-fraction at 34° / 647 mm, and a general fraction at 36.5°/649 mm., 41.3°/760 mm. (lit. 41°) 8 . The take-off rate through a 50-plate vacuum-jacketed

(8) L. H. Horsley, "Advances in Cheil').istry" no. 6, American Chemical Society, 1952, p. 268;-.

column was: regulated ,forxthis c!,istillataon at 1: 25 with a column head having a valve magnetically operated from a distillation timer and relay (Precision Distillation Apparatus Co., Santa Monica~ California, E-7).

Passage of dichloromethane through fresh silica gel (W.R. Grace Co., mesh size 28-200, grade 12), deoxygenation fQr two hours over calcium hydride with pure nitrogen (Whitmore Oxygen Co., 11 p. p. m. of o 2 and 60 p.p.m. of total impurities) and storage over calcium hydride packets made with filter paper completed the preparation.

All obtainable regions of a dichloromethane cooling curve 9 were horizontal. The value of 15. 730 ohms was converted to a temperature

(9) K. L. Nelson, Anal. Chem., 29; 512 (1957).

0 value of -95. 04° C .. (lit .... 95 .14°/ with the aid of the Callender equation.

(10) • R. R. Dreisbach, "Physical Properties of Chemical Compounds ff, Vol. 3, Advances in Chemistry, Series No. 29, American Chemical Society,. Washington, D. C. 1961, p. 12.

Leeds and Northrup provided a table of Callender equation parameters and calibration values fo,; the platinum resistance thermontete::f (Leeds and Northrup, model no. 8163) and Meuller Bridge (Leeds and Northrup, Speedo- max G} which we re used to get the cooling_, curve. -xxxvi-

Sudborough 1 s acid wash and recrystallization method of purifying btotnine 11 has received a kinetic evaluation 12 and formed the basis of

(11) J. S. Sudborough and J. Thomas, J. Chem. Soc., 97, 715 (1910). (12) s. v. Anantakrishnan, J. Anna.malai Univ., l"I:-r70(1942) [c.A·~. 44, 5760e (1950). - - -- our purification. A pound (450 g.) of bromine (reagent grade, Baker and Adams, Allied Chemical, S197) was vigorously shaken in a separatory funnel , with three successive portions of 10% sodium hydroxide solution (analytical reagent, Mallinckrodt) 13 and concentrated sulfuric acid

(13) (a) H. C. Brown and L. M. Stock,~ Am. Chem. Soc., 'I.2J1424 (1957)J (b) A. Scott, Proc. Chem. Soc., 29, 124(1913); o-~.1 Chem. Soc. 103, 847 (1913). ------1 --

(reagent grade, Dupont, sp. gr. 1. 842), respectively. The bromine separated cleanly from the acid when the mixture was allowed to stand for three hours. The sample was distilled from 10 g ~ of anhydrous copper emlfate (analytical reagent, Mallinckrodt) and the fore-fraction rejected. The remainder was treated one more time with acid. Six to seven recrystallizations in a methanol-ice bath held in a Dewar flask gave at first large rhombahedral crystals and finally well ...defined needles. A. pair of glass-stoppered 300;._ml. Erlenmeyer flasks (greaseles s, 24/ 40 ~ , dried at 120° /15 mm.) were used during the recrystallizations. The final heart-cut was sublimed twice at ca. 7 mm. Only the final mid- fraction was kept.

Cyclohexene (99. 83 +mole %, Phillips) was refluxed 30 minutes over sodium and distilled 14 at 77° / 648 min. into a glass-stoppered bottle and

(14) H. I. Waterman and A. A. van Weston, Rec.~- chim., 48, 637 (1929). stored under pure nitrogen.

15 A ferrox test, performed with acidified ferrous thiocyanate, showed -xxxvii-

{15) J. L. 0 1 Brien, Chem. Eng. News,33, 2008 (1955). no hydroperoxide in the cyclohexene after storage for ten days. The ferrox reagent was prepared by dissolving ferrous sulfate and potassium thj:ocyanate in dilute hydrochloric or sulfuric acid and decolorizing the pink solution with a miniflum of zinc dust. A test with anhydrous aluminum chloride and chloroform 1 indicated with an orange color a trace of benzene

(16) D. P. Stevenson, C. D. Wagner, O. Beeck and J. W. Otvos, _.:!_:Am. Chem. Soc., 74, 3269(1952). or homo log of benzene.

A cooling curve of cyclohexene prepared as above was taken with the same equipment m;ed with dichloromethane. The cyclohexene contained 1 mole% of impurity and an extrapolaffd m.p. of 14. 806 ohms or -103. 53° C. {lit. m.p. -103.500 + 0.015°C.). Infrared peaks due to impurity

(17) A. J. Streiff, J. C. Zimmerman, L. F. Soule, M. T. Butt, V. A. Sedlak, c. B. Willingham and F. D. Rossini, J. ResearchNat'l. Bur. Standards,41, 323 (1948) (paper no. 1929). - - -- were found at 5.9, 9.4 and 10.5p and were assigned to cyclohexenone.

A less conventional procedure of purifying cyclohexene was based on a cuprous bromide adduct method. 18 The process was carried out in a

(18) L. C. Morris, U.S. 2, 386, 256, Oct. 9, 1945 [.£:~40, 585 5 (1946)]. one-liter Erlenmeyer flask stoppered with a polyethylene covered cork and cooled in an ice bath in a large Dewar flask. One hundred and fifty mls. (14. 8 moles) of cyclohexene (99+mole % , Phillips) was mixed with a water solution containing 112. 3 g. (2.1 moles) ammonium chloride (reagent grade, Baker and Adams), cuprous bromide (prepared from 60 g., 0. 455 moles, of copper sulfate, analytical reagent, Mallinckrodt, potassium bromide and sodium bisulfite) or cuprous chloride (analytical reagent, Mallinckrodt) -xxxviii- and 7.5 g. of sodium bisulfite (U.S.P., Industrial Distributors, Inc.). Enough liquid detergent rTergitbl,, ca. 1. 5 ml.) was added to give a permanent emulsion. The mixture was vigorously agitated and stored in an ice bath for 12 hours. Less time or insufficient mixing lowered the yield of about 30-40%. Greater time periods gave increased amounts of 3-methyley,clopentene," (3. 7 p) 19 by an acid catalized rearrangement 2 0

(19) P. Lambert and J. Lecomte, Ann. phys. 10, 503 (1938)[C.A. 33, 41277 (1939)J. --,-,------(20) (a) N. I. Shuikin, Bull. acad. sci. U.R.S,S., Classe sci. chim. 1944, 40 [C .A. 39, 4319°(1945)]; (b) W. D. Zellinskii and Y .A. Arbuzov, -Compt. rend.--- acad. sci. U.R.S.S.,~, 794(1939) [C.A. 34, 3696 5 (1940)]. and bromination of the double bond (positive Beilstein and KI/ acetone tests). The mixture proved to be light sensitive.

The adduct was filtered at o0 and rapidly washed three times with ice water. After the washed solid was quickly transferred to a standard and preassembled distillation set•up (250 ml. 24/ 40 JR. B. flask, 24/ 40 and 10/ 30 J three-way distilling head, etc.), water was added and cyclohexene steam distilled at ca. 67°/ 650 mm. A half-degree cut was taken.

The wet p.ydrocarbon was salted from the water phase with sodium sulfate, separated, partly dried over anhydrous sodium sulfate and com- pletely dried over calcium hydride. This product contained mainly methylcyclopentene impurities. The olefin (still over CaHz) was chilled in a dry,-ice-ethanol bath as an ethanol slush was prepared. The slush was ·made by first chilling with dry ice to ca. -80°. This not only gave initial cooling but enough CO2 to lower the melting-freezing temperature of the slush below the supersaturation point of the olefin. The super ... natant liquid (1-2 ml.) was decanted, the solid melted and the process repeated three to four times. he refractive index of the retained fraction 2 was 1.446525° (lit 1.444025°). 1 The mole fra~tion of impurities was

(21) A. J. Streiff, J.C. Zimmerman, L. F-. Soule, M. T. Butt, V. A: Sedlak, C. B. WillinghamandF. D. Rossini, J. Research Nat'!. Bur. Standards 4;t..-- 323 {1948) (paper no. 1929).

estimated at ca. 0.1 mole %. The extrapolated m. p. was -103. 80° {lit. -103.50 + 0.015° ).

Infrared peaks turned up again at 5. 9, 9,4 and 10. 5 as well as peaks at 12, 12. 8, 13.4, and 13. 7 Jl• . The peaks at 12, 13.4 and 13. 7 p. were assigned to cyclohexene hydroperoxide. The peak at 12. 8 p. was -xxxix- tentatively as signed to cyclohexenol. The infrared peaks due to impurity were detected by comparison to the spectra of fresh cycclohexene prepared from cyclohexano122, m.p, 24-25° (lit. 25.15°), 23 b.p. 155. 5-

(22) B. B. Corson and V.R~ Ipatieff, Org. Syn. (Col. Vol.)~ 152 (1943); L. F. Fieser, "Experiments in Organic Chamistry", 3rd ed.,

D. C. Hea_ih and Co;, 1955 1 p. 61. (23) J. Timmermans and Mme. Hennaut-Roland, J. chim. phys. 34, 693 (1937) [C,A. 32, 32176 (1938)]. -

155. 7°/646 mm. (lit. 161.1°). If contact of the cyclohexene and 85% phosphoric acid were kept to a minimum, little 3-methylcyclopentene appeared.

Rate Study - Use of various light sources confirmed the sensitivity of 9romine-cyclohexene addition to light. A capsule with two compartments separated by a thin glass diaphragm or break.;.seal allowed rapid combination of thee reactants in the dark. It was possible to record the sound of the breaking seal and quenching of the reaction with a magnetic tape recorder (Wollensak, model T-1500, foot control) (Wollensak TF..:.404)) and Mylar magnetic tape (1600 ft., 1 mil., Scotch 141 Tartan series). Time intervals we re reproduced with '. less than 0.1% deviation.

Pressure-filling pipets were designed and calibrated to fill the reac ... tion capsule with dichloromethane solutions of bromine and cyclohexene. Since individual volumetric flasks varied in heighth, the pipets were mated to specific 50 ml. g. s. volumetric fla.sks during construction and both given a common label.

Light promoted a bromine substitution of dichloromethane containing traces of water. Forty five minutes were required for complete reaction of O. 05 .M. B!z solution. Samples drie_d with either activated alumina (12 hTs. at 1850) or calcium hydride took several· hours to react by substitution. A safety light was made from a 10 watt bulb behind a Wratten 0 filter which was covered with a piece of violet spotlight. gelatin and the pipets and flasks were painted with several coats of black Testor' s Butyrate Dope (insoluble in dichloromethane). The safety light and paint,.. ing allowed measurement of bromine solution volumes without detectable substitution.

Evacuation of the lower compartment of the reaction capsule gave a pressure flush of the solution into the lower chamber. This gave rapid mixing. A syringe needle sealed with Apiezon picene wax to a length of pressure tubing and a Duoseal pump were used for evacuation. Bromine solutions were made by adding bromine (chilled to 0°) with a 1. 0-mL -lx- tuberculin syringe to a tared and N 2 flushed volumetric flask. The amount of bromine was weighed and the flask filled to the mark with dichloromethane. The weighed amount of bromine agreed with titrated values of an aliquot of the dichloromethane solution if it were protected from light. Concentrations deviated+ 1. 0 o/odue to solvent evaporation during transfers.

Hydrogen bromide was introduced by exposing the solution and was determined by difference between the titrated and weighed values. Bromine was converted to iodine with a 40% potassium iodide solution for titration to a starch endpoint with thiosulfate solution. 24 The stability of the

(24) I. M. Koltoff and E. B. Sandell, "Textbook of Quantitative Inorganic Analysis", 3rd ed., New York, The MacMillan Co., 1925, p. 594. potassium iodide solution improved if it was made up from distilled water which had been saturated for a minute with pure N2 through a medium dispersion tube. The stability of 0.10 l:i· thiosulfate solution also improved if 10 mg. of mercuric iodide was added to a liter of solution.

The cyclohexene solution was made up in a manner similar to the bromine solution. Direct weighing determined the concentration of the olefin solution. Cyclohexene hydroperoxide was introduced on exposure of cyclohexene to the air.

Results .. Each point, determined independently, represents an individual experiment. With samples of cyclohexene distilled from sodium, the total reaction time remained independent of bromine, cyclohexene, hydroperoxide concentrations and pumping time but depended on hydrogen bromide content of the system, Table 1. -lxi-

Table 1. Inhibition of Bromine Addition to Cyclo- rexene by Hydrogen Bromide. Cyclohexene Distilled from S:odium

Total Pumping Reaction Time Time,secs. Brzxlo- 2 M HBrxl0- 3 M >c;=C

< 1. 8 1.62 0.5 2.45 1 X 10- 7 10 7 < 2 2. 16 1.0 2.45 6 X 10"" 4

3 2.04 2.2 4.79 3 X 10- 5 2-3

6 4-5 1.62 6.0 2.45 5 X 10- 10

Table 2. Bromine Addition to Cyclohe~ene Distilled from Sodium

Br2 1. 62 x 10- 2 M. >C--G< 2.45 x 10- 2 M. HBr 6 x 10-. 3 M- R0 H 5 x 10- 6 M- 2 10 mins. pumping time

Reaction Time, secs.

0.0 3. 19

2.0 1.90

2.5 1.83

3.5 1.64

Rate data taken from Table 2, cyclohexene distilled from sodium, were plotted with the second order expression, and gave the rate constant,

~' 1 k2 = 9. 6 mole•l f se~": .

With samples of cyclohexene prepared from a cuprous chloride

adduct, the total reaction time was dependent on hydrogen bromide

content of the system and independent of bromine, .cyclohexene, hydroperoxide and pumping time. Th_is system also proved to be independent -lxii-- of calcium hydride and glass surface are a.

Table 3. Inhibition of Bromine Addition to Cyclo- hexene by Hydrogen Bromide, Cyclohexene from a Cuprous Chloride Adduct

Total Pumping Reaction Time Time, secs. Br xio- 2~ HBr x 10-3M >C=C< x 10- 2~ R0 H x 10-ZM mins. 2 2

5. 6.,: 1.89 less* 2.10 1 6

5.7 1.27 more* 2,10 1 6

14 1.7 3 4. 58 8 10

18 8.9 11 4. 58 1 10

*Both less than 3 x 10-3 M.

Rate data plotted from Tables 3 and -4 revealed a zero order with a

slope related to hydrogen bromide concentration and independent of bro• ., mine, cyclohexene, hydroperoxide concentrations and pumping time,

Figure 6.

Table 4. Bromine Addition to Cyclohexene Purified Through a Copper(I) Chloride Adduct. Zero-Order

Reaction Time, secs. HBr, M

0.0 1.98 less*

3.2 0.87

4.9 0.85

0.0 I. 17 more)!c

3.7 0.27

4.3 0.14 Table continued ..• I •.-1 ,,-1 •.-1 ~ I

1.5

-t" ~~ c¼s'I' .....~ "' '< -~a:l lO 15 !:: ~ iil ~ % %1..5 1..5

0.5 HydrogenBromide Content A

5.0 100 15.0 Time,seconds Fig. 6 Inhibitionof Bromine Addition to Cyclohexeneby Hydrogen Bromide from Bromine Substitutionof Dichloromethane. -lxiv- Table 4, continued.

Reaction Time, secs. , mls.

o.o 1.72 3 X 10• 3

7.5 0.80

9.5 0.56

o.o 0.89

6.25 0.58

9,5 0.42

10.3 0.37

*Both less than 3 x 10- 3 M,

Discussion

While oxygen affected some addition reactions this effect is either

25 absent or has gone unobserved with most olefins. Oxygen or hydrogen

(25) (a) W. H. Bauer and F. Daniels, J. ~ Chem. Soc., 56, 2014 (1934); (b) Y. Urushibara and M. Takebayashi, Bull. Chem. Soc., Japan, £, 356 (1937) [C.A., 31, 77278 (1937)]; (c) J. Willard and F. Daniels,.2.:_ -Am. Chem. -- Soc., - 57, 2240(1935). bromide 26 retam_ded the reaction of bromine and cinnamic acid. Oxygen

(26) o. Shimamura, Bull. Chem. Soc., Japan,!.L_ 274 (1942) [C.A.,41, 4471i {1947)]. catalysis was absent with most a, '3-,unsaturated acids 27 , however oxygen

(2 7) F. F. Rust and W. E. Vaughn, 1.:, Org. Chem. ,--2.!_4 72 (1940). ~lxv- reacted with bromine and cyclohexene, styrene, a-phenylstyrene, allyl bromide and allyl chloride to give a-bromo•peroxides. 28 Temperature

(28) W. Bockernueller and L. Pfeuffer, Ann., 537, 178 (1939). and decreasing solvent polarity, HOAc

system by back diffusion through the pump. However none oi our rate measurements changed with changes in oxygen or hydrope1mxide content.

The reaction between bromine and cyclohexene in dichloromethane did show reaction promotion by light, Table 5.

Table 5. Promotion of Bromine Addition to Gyclohexene by Light

2 2 Br 2 L 7 x 10- M >C=C< 4. 58 x 10- M 3 HBr 3 x 10-2 M- RO 2H 8 x 10- M -

Light Source Total Reaction Time, seconds

Oxygen Torch 2

Tungsten light bulb, 5 00 W 9. 5 + 2

Fluorescent tube, 15 W 1 o. 3 + 2

Hood pilot light, 6 W 12. 8 + 2

None 14. 0 + o. 5 29 The similar effect of light on various unsaturated acids, esters , nitriles 30

(29) (a) A. Berthoud .and M. Mosset, J. chim. phys., 33, 272 (1936) [G.A.,2.£, 5130 3 (1936)]; (b) A. Berthoud and D. Perret,. Helv. Chem. Acta, 17, 1548(1934); (c)J. A. A. Ketelaar, P. F. vanVelden, G. H. J. Borers and H. R. Gersmann, J. Phys. and Colloid Chem., 55, 987 (1951) [c.A •• ~, 37£(1952)]; (d)I. s. Plotnikov, ~ ~- sci. -lxvi-

Petrograd, 1916, 1083 [C.A., 11, 48 6 (1917)]; (e) I. S. Plotnikov, z. wiss, Ph~ 19, 1 (1919) [C.A.,14, 2131 (1920)]; (f) J.S. Sud- borough and J. Thomas, J. Chern.Soc., 97, 715(1910); (g) J.S. Sudborough and J. Thomas, Proc. ~-Soc., 22, 318 (1906) [C.A. ,h_17307 (1907)]; (h) N.A. Yajnik and H. L. Uppal,..l_. Indian Chem.,Soc., 6, 729(1929). (30) (afl:-s6Plotnikov, Bun. aca~. sci. Pet~ograd, 1916, 1083 [C.A.,11, 48 (1917)]; (b) r.s. Plotn1kov, z. w1ss. Phot., 19, 1 (1919) [C.A.,M, 2131(1920)]. - - -

and chloroethylene s 31 was confirmed by light promotion of bromine

(31) (a) LS. Plotnikov, Bull. acad. sci. Petrograd, 1916, 1083 [C.A., 6 ------11, 48 (1917)]; (b) J. A. A. Ketelaar, P. F. van Velden, G. H. J. Broers and H. R. Gersmann, J. Phys. and Colloid Chem., 55, 987 (1951) [C.A.,46, 37f (1952)].

addition to cyclohexene.

The effect of the reaction medium on bromine-olefin addition

followed the pattern of a polar intermediate. The substitue.nt response

at the double bond was greatest with second-order addition·in pure acetic 32 acid, Fig. 7.

-4 (32) (a) 1 x 10 M Br 2 /HOAc, P. W. Robertson, W. E. Dasent, R. M. Milburn and W. H. Oliver, J. Chem. Soc. 1628 (1950); (b)lxl0-2r.A Brz/ HOAc, P. B, D .. de la Mare, Quart. Rev., 3, 145 (1949); (c) CC1 4 - - P2O5, H. S. Davis, .:!..:_Am. Chem. Soc., 50, 2770 (1928); (d)MeOH, . W. Walisch and J. E. DuBois.Ber., 92, 1028 (1959); (e) HOAc-HBr, P. B. D. de la Mare, Quart. Rev., 3, 145 (1949); (£) CH 2c1 2 , C. K. Ingold and E. H. Ingold, J. Chem. Soc., 2354(1931); (g) S. V. Anan- takrishnan and C. K. Ingold, ibid.,984, 1396 (1935); (h) S. V. Anan- takrishnan and R. Venkatara~ ~c. Indian Acad. Sci., 12A, 290 (1940); (i) S. V. Anantakrishnan, ibid., 25A, 184 (1948); (j) I~ Mathai, ~• 51A, 164(1960); (k)J. R. SheltonandL. H. Lee,2._. Org. Chem., 25, 428(1960). -lxvii-

4 Ix 10.. M Br2 /HOAc /6.0 kz

14.0 lo 0

~ C 0 ; :a,:, > :.= 0 &

:c :c N 0 0 ~ 0 :c s= :c (,,) (,,) (,,) Q. (,,) (,,) (,,) V I ·u" I (,,)' (,,)' (,,) (,,)' (,,) (,,) (,,)' (,,) 0 (,,) (,,) u,o (,,) (,,)" " (,,)" (,,)" (,,)" (,,) " " (,,) " Q (,,)" " I I I I I ·-.!?" 1 'U u'Y ~'U 0 s= I\ (,,) s= (,,) s= (,,) (,,) Q. Q. 0.. Ou

Relative Rate of Atomic Oxygen Addition, Log(kre1>0 Fig. 7 Effect of the Reaction Medium on Bromine-Olefin Addition. The relative rotes of crotonic acid were set equal to one. -lxviii-

Cyclohexene in comparison with other olefins may be similar to cis-2-butene and faster than ethylene. Comparison through other addition reactions showed this generally to be true. Graphic comparison of several addition reactions 33 revealed extensive linear relationships,

(33) (a) 1 x 10- 4 M Br2/HOAc, W. Robertson, W. E. Dasent, R. M. Milburn and W. H. Oliver, J. Chem. Soc., 1628 (1950); (b) phthaloy,1 peroxide, F. D. Greene and W.W. Rees, J. Am. Chem~ Soc., 80, 3432 (1958); (c) epoxidation, D. Swern, ibid., 68, 1692 (1947); ~ dichlorocarbene, A. F. Trotman-Dickenson, Ann. Reps., 55, 53 (1958); (e} W. van E. Doering and W. A. Henderson, Jr., J. Am. Chem. Soc., 80, 5274 (1958).; (f) dibromocarbene, P. S. Skell and A. Y. Garner, ibid.,

78, 5430 (1956); (g), W. van E. Doering and W. A. Henderson, Jr., ibid. 1 80, 5274 (1958); (h) bromine addition in dichloromethane, C. K. Ingold and E. H. Ingold, J. Chem. Soc., 2354, (1931); (i) S. V. Anantakrishnan and C. K. Ingold, ibid., 984, 1396 (1935); (j) S. V. Anatakrishnan and R. Venkatar.aman,Proc. Indian Acad. Sci., 12A, 290 (1940); (k) S. V. Anan- takrishnan, ibid~, 25A, 184 (1948); (1) I. M. Mathai, ibid., 51A, 164 (1960); (m) J. R. Shelton and L. H. Lee, J. Org. Chem., 25, 428 (1960); (n) atomic oxygen, R. J. Gvetanovic., Can._[:_ Chem.,~. 1678 (1960).

Fig. 8. Excepting the higher reactivity of atomic oxygen, bromine addition

spanned the full range of substituent response. More determinations of various addition reactions with the less reactive olefins would add much to this addition selectivity relationship. This would also provide an important check on the validity of such a selectivity relationship. Addition 34 reactions were also linearly related to ionization potential, olefin basi-

city35 and possibly heats of hydrogenation 36 and spectroscopic excitation

(34) (a) J. Collin and F. P. Lossing, J. Am. Chem. Soc., 81, 2064 (1959); (b) R. E. Honig, J. Chem. Phys., 16:-105 (1948). -. - - (35) R. West, J .-Am. Chem. Soc. 71. 1614 (1959). (36) P. E. M. Allen, H. W. Melville7nd G. J. Robb, Proc. Roy. Soc. (London), A218, 211 (1953). -~I ~ I

lx10-4 M Br_2/HOAc J 7.0 lo 0

6.0

5.0

c0 ~ ~· "0 4.0 c::( 0 f --Ill .:,,: /~~ G) O> 0 a::- .3 :s.o aCI) .:? . . . O /=CCl 2 0 G) 0::: / _/o/ 2.0 ,.,?V•CO,, ~ 00/~ - ----Br2/CH 2Cl2

:c d' 't ~ 0

2.0 !(YO 0 0 .2 <.> ❖ ~,Q .!! • o ~'u o'i i,o

-1.0 Rek,tive Rote of Atomic Oxygen Addition, Log(kre1>0

Fig.8 Comparison of Second-Order Bromine Addition with Other Olefin Addition Reactions. The relative rates of ethylene were set eaual to one. -L.,. energies. 37 The addition reactions did not correlate with silver

(37) S. Sato and R. J. Cvetanovic, J. Am. Chem. Soc., 81, 3223 (1959). complex stability. 38 The silver complex formation was apparently

{38) {a) S. Winstein and H. J. Lucas, ibid., 60, 836 {1938); {b) J. G. Traynham and M. F. Sehnert, ibid., 78, 4024(1946). subject to steric influences. Other simple and non-linear relationships exist between olefin reactivity and olefin spectra. 39

{39) S. V. Antakrishnan, Proc. Indian Acad. Sci., 27A, 184 {1948) [C.A., 44, 4762f (1950)].

4 Th ese h ave receive. d some t h eore t· 1ca 1 d" 1scuss1on. . o

(40) (a) R. R. Myers, Ann, N. Y. Acad. Sci., 72, Art. 10, 339 (1958); {b)J. Duchesne, J. Chem •. Phys., 18, 1120(1950).

Thus, our results fit with a large body of information. The appli-- cation of an addition selectivity relation is suggestive of fresh avenues of approach. (COMMUNICATION TO THE EDITOR)

Sir:

During a study of bromine addition which was carried out in total darkness, we observed a novel photo effect. The total darkness allowed complete dilation of the eyes and the observation of an emission of pale blue light when various mixtures of oxygen, nitrogen and air were jarred.

The intensity of this effect increased with increasing oxygen content, with a lower temperature and with the presence of dichloromethane solutions of cyclohexene o:r. bromine. An intensity maximum occurred at ca. 10 mm.

The number of times the effect was repeated related directly to the pressure. The samples could be recharged even with a safety light.

A high level laboratory effect, the Lewis-Rayleigh, was observed with nitrogen in. an electric discharge tube. The Lewis-Rayleigh effect is a golden-yellow afterglow due to recombination of nitrogen atoms . 1

(1) K. R. Jennings and J. W. Linnett, Quart. Revs. (London), 12, 116(1958).

However it is different from our effect. Apparently we are the first to see in the laboratory the oxygen effect as described above.

Although we have not determine.d the wave length of the light emitted, our effect may be related to natural phenomena of the atmosphere such as

St. Elmo's fire, afterglow of the night sky and the northern and southern auroras. Some of the reactions of the atmosphere have been studied with 2 rockets and simulated in the laboratory. .. 1ii-

(2) P. Harteck and R.R. Reeves, Angw~ Chem. (Eng.Ed), l (1), ~5 (1962).

St. Elmo's fi:t-e, named by mariners of the Middle Ages who saw.1 it.in the ship 1 s rigging, is observed today ln and about aircraft and apparently in tornadoes. Static electricity is generally, associated with St. Elmo's fire which is usually a b:dght blue or green color.

Night afterglow is observed in many places and is a low level effect. 3

(3) J. P. Heppener and L. H. Meredith, J., Geophys. Research, 63, 51 (1958) (c . .A,.,_g, 16030a (1958)].

4 Blue lines were observed in the spectra of the night afterglow.

(4) D. E. Blackwell, M. F. InghamandH. N. Rundle,Ann. geophys., 16, 152 (1960) [C. A., 54, 23779i (1960)].

The spectacular northern and southern lights often contain blue either mixed with green or as a pure color. Blue color has been related to the nitrogen molecule and has appea~ed particularly in th~. '.high ,atmosphe'.£e (600 5 miles). The light of the aurora is caused by collision of protons and

electrons with oxygen and nitrogen molecules.

(5) J. W. Chamber1ain, Sky and Tel., 17, 268, 339 (1958). -liii-

DEPARTM~NTOFCHEMIBTRY K. LEROI NELSON

BRIGHAM YOUNG UNIVERSITY JOHN A. 'GURNEY

PROVO, UTAH -liv-

(A'.Communication to the Editor)

Sir:

The synthesis of the Thorpe I s caged triacid, 4-methyltricyclo-

[l. 1. 0. o2- 4]butane-l, 2, 3-tricarboxylicl acid has never been repeated

(1) R. M. Beesley, J. F. Thorpe and C. K. Ingold, J. Chem.~-, 117, 610 (1920). or verified. We foµnd it possible to recreate a key step in the synthesis

sequence leading to the caged compound above.

The creation of Thorpe's c.lassic synthesis of the caged triacid originally required eight years and five students. 2 Generally each step

(2) (a) Blande and J. F. Thorpe; J. Chem. Soc., 101, 1565 (1912); (b) J. F. Thorpe and A. Wood, ibid., 103, 1583 (1913 ); (c) R. M. Beei;;ley and J. F. Thorpe, Pro~he~Soc., 29, 346 (1913); (d) J. F. Thorpe, J. Chem. So~15, 681 (1918); (e) J. F. Thorpe and L. A. Jordon, ibid., 107, 387 (1917); (f) R. M Beesley, J. F. Thorpe and C. K. Ingold, J. Chem. Soc., 117, 610 (1920). · -- __,,_

in the sequence was pursued and reported as a unit, The synthesis up

to 1, 1, 1-ethanetriacetic acid has been repeated 3 and has been confiriped ( '\

(3) C. K. Ingold, J. Cher.p. Soc., 121, 1148 (1922);(~))E.P.1Kolderand:' ,G. '.H.·-Reed~ J. 'AtR-:-Cn.em.:=so~~i;~4v,(~80~ {-1925J; ·(c,)·H, O.;.Lairsen, :·o~·C{~-:I:>:£~~~'~.\1Marvar.ciUniv.' 195(). -

1 by an inde'pendent synthesis. 4 Mono- 5 , di. and n,i~;..bromination Q' ·:of

(4) E. H. Farmer and J. R.oss, J. Chern. ,Soc.;,:127, 2358 (1925). (5) E. H. Farmer, J. Chem. Soc., 123, 3337 (1923). -lv ..

- - - (6) R. M. Beesley, J. F. Thorpe, Proc. Chem. Soc., 29, 346 (1913)

1, 1, 1-ethanetriacetic acid have been reported. However a more 3,C recent a-bromination attempt gave a product different from those

(7) H. O. Larsen, Doc. Diss., Harvard Univ., 1950;. reported. This product proved to be useless for ring closure.

Thorpe reported two ring closures of the a-dibromo ester of

1, 1, 1-ethanetriacetic acid when it was treated with hot concentrated potassium hydroxide. This gave three isomeric methylbicyclobutane triacids.

Further a-bromination of the first two products produced bromo esters but the third passed directly to the caged triacid which contained no bromine and was the same as the tris-dehydrobrominated product of ethyl a., a', a 11, -tribromo-1, 1, 1-ethanetriacetic acid. More recently an alternate explanation was devised for the three bicyclo compounds. 8

(8) M. B. Goren, Doc. Diss., Harvard Univ., 1949, p. 6, 51.

Three isomeric isoprenetricarboxylic acids were p:,;oposed and synthesized. Anhydride formation guided the selection of isomers. -lvi-

However the behavior of these triacids toward bromine and permanganate was much different than Thorpe's compounds and it was concluded that this explanation was not likely.

Exc~pting the clafm for synthesis of etp.yl bicyclo[l. L O]h4.tane-l -- carboxylate 9 •-the bicyclobutane triacids of Thorpe are the only known

(:9): K. B.. Wiberg and R. P. Ciula, J. Am. Chem. Soc.,~, 5261(1959).

compounds containing bicyclobutane. And Thorpe's tricyclo triacid is the only known example of tricyclo butane.

rhe key step in Thorpe's synthesis involved 1, 1, 1-ethanetriacetic acid. 1, 1, 1-Ethanetriacetic acid was readily converted to 1, 1, 1-ethanetriacetyl bromide with phosphorous pentabromide. We were able to isolate this acid bromide from the reaction mixture by sohxlet extraction with a mixture of ligroine and methylene chloride. Phosphoryl bromide and a small amount of the monoanhydr-ide of 1, 1, 1-ethanetTiacetic acid were also isolated and identified.

A number of compounds occurred along the course of the synthesis, synthesis relics of 1, 1, 1-ethanetriacetic acid/ig~e tried as reaction promoters. -lvii-

Table 1 . Promotion of a.•Bromination of l, 1, 1-Ethanetriacetyl Bromide

Synthesis Relics Result

no change

done. HCl no change

cone. H 2so 4 liquified mixture, no lactones benzoyl peroxide a trace of dilactone

EtOH brief bromination

vigorous action, liquified mixture, lactone s

dioxane no change

If ethyl ether was either in the triacid i;;ample or added to the reaction mixture, the triacetyl bromide could be a.-brominated by adding bromine to the mixture. If ethyl ether was absent, the triacetylbromide could not be a-brominated even during six months time. We can now say that ethyl ether present by reason of recrystallization of 1, 1, 1-ethanetriacetic acid is required for a-bromination.

Ether was also found in simple beaker experiments to double the

rate of reaction with moisture in the air or with acetic acid. This co- promotion of a-bromination, the Hell-Volhard-Zelin..ski reaction, may be related to the formation of an oxonium compound from ether and bromine lO and the catalysis of certain Friedel-Crafts reactions by -lviii-

{10:} A. McKenzie, J. Chem. Sac., 101, 1196 (1912}.

11 aluminum bromide monomer complexes (2A1Br - Et 0}. We believe 3 2

(1 l;) D. G. Walker, Chem. Eng. ~s, 39(38),: 48:(1:961).

the successful bromination of 1, 1, 1-ethanetriacetic acid represents

an important br.eaktl,i.rough in recreating Thorpe's synthesis. Completion

of the sequence will al16w a modern dete:r'mination of structure and acceptance or rejection of the caged acid.

DEPARTMENT OF CHEMISTRY K. LEROI NELSON

BRIGHAM YOUNG UNIVERSITY JOHN A. GURNEY

PROVO, UTAH SULFONATION OF GHtbROBENZENE AND

THE SELECTIVITY RELATION

BROMINE ADDITION TO CYCLOHEXENE

IN DICHLOROMETHANE

THORPE I S ,SYNTrJESIS :PF THE CAGED ACID~ 2-4 / 4-M~THYLTRIGjYGLO[l. l_. O_.0, . ] BUTANE-:-

An Abstract of a Dissertation

Submitted to the

Department of Chemistry

Brigham Young University.

Provo, Utah

In Partial Fulfillment

of tro.e'Requireiments, for: the Degr~e

Doctor of Philosophy

in Organic Chemistry

.:rohn A,. Gurney

August, 19 62 ABSTRACT

Stock'. 1 s chlorination:";defink,a- new 1 relation that can be e~press~~-by add- fog· an'.entropy te·rm {A)'to the seleotivity relation~

We determined the rate of bromine-cyclohexene addition in dichloro- me_thane at o0 to provide a basis for a systematic variation of solvents at low temperature. An unusual zero•order reaction was encountered.

The reaction was light catalyzed and related to hydrogen bromide concentration. The reaction was independent of bromine, cyclohexene, hydroperoxide and oxygen concentration. The reaction order depended on a steady-state conceritra(ion-:of bromobium ion·fBr+). We also: ohs_ell'ved a novel photo ef~ec:t; with: mixtures of .oxygen, nitrogen and air.

2 4 The synthesis of Thorpe's caged triacid, 4-methyltricyclo[l. 1. O. 0. - ] butane-!, 2, 3-tricarboxylic acid has never been repeated or verified. A key intermediate, 1, 1, 1-ethanetriacetic,was readily converted to l, 1, 1- ethanetriacetyl bromide . This last compound could only be a- brominated in the presence of a trace of ether. This successful a.-bromination represents an important breakthrough toward getting Thorpe' s caged acid.

-1- ABSTRACT APPROVED:

-2-