A Kinetic Investigation of the Thermal and Acid-Catalyzed Decompositions

Home , Diphenylketene, Insertion reaction, Wolff rearrangement

This dissertation has been 65— 13,248 microfilmed exactly as received

J O R D A N , David Milton, 1937- A KINETIC INVESTIGATION OF T H E THERMAL AND ACID-CATALYZED DECOMPOSITIONS OF ci-DIAZOACETOPHENONES.

The Ohio State University, Ph.D., 1965 Chemistry, organic

University Microfilms, Inc., Ann Arbor, Michigan A KINETIC INVESTIGATION OF THE THERMAL

AND AC ID-CATALYZED DECOMPOSITIONS

OF a-DIAZOACETOPHENONES

DISSERTATION

Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University

David Milton Jordan > B.A

The Ohio State University 1965

Approved by

Department of Chemistry ACKNOWLEDGMENT

I wish to express my appreciation to Professor Harold Shechter for his suggestion of the research problem* for many helpful dis cussions in the course of the investigation* and for his assistance in preparation of this dissertation.

I am grateful for financial support provided by the National

Science Foundation and the Phillips Petroleum Company.

ii VITA

August 19, 1937 Born - Ashtabula, Ohio

1955 Graduated from Mount Pleasant High School, Wilmington, Delaware

1959 B.A., The College of Wooster, Wooster, Ohio

1959-1961 National Science Foundation Cooperative Fellow, Department of Chemistry, The Ohio State Uni versity, Columbus, Ohio

1961-1963 National Science Foundation Graduate Fellow, Department of Chemistry, The Ohio State Uni versity, Columbus, Ohio

1963-1964 Phillips Petroleum Company Fellow, Department of Chemistry, The Ohio State University, Columbus, Ohio

1964-1965 Research Fellow, Department of Chemistry, The Ohio State University, Columbus, Ohio

MAJOR FIELD OF STUDY: Organic Chemistry

iii CONTENTS Page

ACKNOWLEDGMENT...... ii VITA ...... ill TABLES...... vi FIGURES ...... vii

INTRODUCTION...... 1

HISTORICAL...... 2

The Wolff Rearrangement ...... 2

Thermal Decomposition of a-Diazoacetophenone .... 6

Photolytic Decomposition of Diazoketones ...... 13

Copper-Catalyzed Decomposition of Diazoketones . . . 16

Reactions of Diazoketones with Bases ...... 19

Ac id-Catalyzed Decomposition of a-Diazoacetophenones ...... 19

Participation in Decompositions of ortho- Substituted a-Diazoacetophenones in Acetic A c i d ...... 24

General Acid-Catalysis of a-Diazoacetophenone .... 26

DISCUSSION AND RESULTS ...... 28

Discussion of the Kinetics of Decomposition of Substituted a-Diazeacetophenones in Acetic Acid...... 65

EXPERIMENTAL...... 84

General Procedures and Techniques ...... 84

Melting and boiling p o i n t s ...... 84 Elemental analyses...... gjj, Spectra determinations ...... 84 Vapor phase chromatography ...... 84

Material for Kinetic R u n s ...... 86

Syntheses of substituted benzoyl chlorides . . . 86 Synthesis of a-diazoacetophenones ...... 86

iv CONTENTS (Contd.) Page

Materials Used for Kinetic Measurements...... 88

Cetane (hexadecane) ...... 88 Tetraglyme ...... 90 Quinoline ...... 90 n-Decanol ...... 90 Tenox B H A ...... 90 Tenox B H T ...... 90 Tri-n-butylamine...... 90 Cyclooctane...... 90 DABCO (1 >&-diazobicyclooctane...... 91 Tri-n-propylamine...... 91 Di-n-bu ty la m i n e ...... 91 Di-n-propylamine...... 91 1-Chloronaphthalene ...... 91 Acetic A c i d ...... 91 T o l u e n e ...... 92

Procedure for Kinetic R u n s ...... 92

Constant temperature bath ...... 92 Thermal decomposition procedure ...... 92 Reactions catalyzed by acetic a c i d ...... 97

Development of Solvent System for Thermal Decomposition...... 99

Product Studies...... 112

Products of Thermal Decomposition of a-Diazo acetophenone in Tripropylamine...... 112

Products of Thermal Decomposition of a-Diazo acetophenone in Dipropylamine • 116

Products of Decomposition of a-Diazoaceto- phenone in Cyclohexene ...... 118

Product of Thermolysis of a-Diazoaceto- phenone in Cyclooctane and N»N- dimethylcyclohexylamine . 122

Product of Thermal Decomposition of a-Diazo acetophenone in Cyclooctane Containing l*^-Diazobicyclo[2.2.2]octane (DABCO) ...... 123

v TABLES Table Page

1* Average First Order Rate Constants (lO^sec*"1) for Thermal Decomposition of Substituted a-Diazoacetophenones ...... 35

2. The Thermal Decomposition of Substituted a-Dia zoac etophenones in Tripropylamine......

3. Relative Rates of Thermal Decomposition of Substituted a-Diazoacetophenones and Benzazides...... 41

4. Products of Thermal Decomposition of a-Diazo acetophenone in Tripropylamine at 156° ...... 5?

5 . Acetic Acid-Catalyzed Decomposition of Substituted a-Dia zoacetophenones...... 67

6. Relative Rates of Acetic Acid-Catalyzed Decompo sition of Substituted a-Diazoacetophenones .... 69

7* Preparation of Substituted Benzoyl Chlorides Z-CgH^COCl...... 87

8* Preparation of Substituted a-Diazoacetophenones . . . 89

9« The Decomposition of a-Diazoacetophenone in Decanol-Quinoline-Tenox BHA (Yates and C l a r k ) ...... 104

10. Decomposition of a-Diazoacetophenone in Cetane- Tributylamine at I3 0 .50 ...... 108

11. Thermal Decompositions of a-Diazoacetophenones in Tripropylamine ...... 125

vi FIGURES Figure Page

1. An isokinetic relationship of activation parameters for thermal decomposition of substituted a-diazoacetophenones ...... ^7

2. Hammett relationship for thermal decompositions of meta- and para-substituted a-diazo acetophenones ...... 50

3. Hammett relationship for acetic acid-catalyzed decomposition of meta- and para-substituted a-diazoacetophenones ...... 71

4. Hammett relationship for acetic acid-catalyzed decomposition of meta- and para-substituted a-diazoacetophenones ...... 72

5. Correlation of rates of thermal and acetic acid- catalyzed decompositions of substituted diazoacetophenones ...... 82

6. Modified reaction f l a s k ...... 93

7* Reaction vessel for acetic acid-catalyzed decomposition of diazoacetophenones ...... 98

8. Thermal decomposition of a-diazoacetophenone in c e t a n e ...... 101

9. Thermal decomposition of a-diazoacetophenone in cetane at 1 1 9 ° ...... 102

10. Thermal decomposition of a-diazoacetophenone at 1 3 0 . 5 ° ...... 13*4-

11. Thermal decomposition of ortho-bromodiazoacetophenone at 130.5° ...... 135

12. Thermal decomposition of ortho-chlorodiazoO acetophenone at 130.50 ...... 13&

13. Thermal decomposition of ortho-iododiazoacetophenone at 110.9° ...... 137

vii FIGURES (Contd.) Figure Page

14 • Thermal decomposition of ortho-methyldiazoacetophenone at 130.50 ...... 138

15• Thermal decomposition of ortho-methoxydiazoacetophenone at 110.9° ...... 139

16. Thermal decomposition of meta-methoxydiazoacetophenone at I3O.50 ...... 1^0

17. Thermal decomposition of meta-nitrodiazoacetophenone at 1 3 0 .9 ° ...... 1^-1

18. Thermal Decomposition of para-methoxydiazoacetophenone at 130 *3° 142

19* Thermal decomposition of para-nitrodiazoacetophenone at 130 . 5 ° ...... 143

20-29. Arrhenius plots ...... 144-133

viii INTRODUCTION

The primary object of this research was determination of the effects of structure on the kinetics of thermal decomposition of substituted a-diazoacetophenones (Wolff rearrangements).

COCHN. Z

Z represents electron-donating and withdrawing substituents in ortho- > meta-, and para-positions, The purposes of this investigation were to attempt Hammett and related correlations and to obtain information concerning the electrical requirements and reaction mechanisms of these systems. The study of steric acceleration and proximity effects in decomposition of ortho-substituted a-diazoacetophenones was em phasized.

It was also of interest to compare the kinetics of the acetic acid-catalyzed decomposition of ortho-substituted a-diazoacetophenones

•with the results of kinetic studies previously conducted on the acetic acid-catalyzed decomposition of meta- and para-substituted a-diazoacetophenones (1),

(1) (a) J. F. Lane and R. L. Feller* J. Am. Chem. Soc.* 22* ^230 (1951); (b) Y. Tsuno* T. Ibata, and Y. Yukawa, Bull. Chem. Soc. Japan* j2, 960 (1959); (c) Y. Yukawa and Y. Tsuno, ibid., ^2, 965 (1959).

1 HISTORICAL

The Wolff Rearrangement

In 1902 L. Wolff reported the conversion* by reaction with boiling water, of ethyl a-diazoacetoacetate (I) to the half ester of methyl malonic acid (II) and of 2-diazo-l-phenylbutane-l»3-dione (III) to benzyl methyl ketone (IV) (2). He later reported (3) that the rearrange-

0 N2 ch3c -c -c o2ch2c 3h ch3c h (co2h )co2c2 hch3

I II

0 IfeO II H II C^C-C-CCH^ C6H5CH2COCH3

III IV

(2) L. Wolff, Ann., 2 ^1 * *29 (1902).

(3) L. Wolff, ibid., 23 (1912). ment could be applied to many simple diazoketones under a variety of conditions. For example, a-diazoacetophenone in water at 5O-6 O0 in the presence of silver oxide and sodium thiosulfate gives phenylacetic acid; in ethanolic ammonia at ^0-50° with silver ion present, phenylacetamide is the product; in aniline at I850 , N-phenyl-2-phenylacetamide

is obtained. In boiling water with catalyst absent, a-diazoacetophenone is converted to the ketol C^H^C0CH20H. 3

The rearrangement was little studied until a ready synthesis of diazoketones from diazomethane and acid chlorides was developed (4).

(4) (a) F. Arndt, B. Eistert, and W. Partale, Ber., 60, 1364 (1927); (b) F. Arndt, B. Eistert, and J. Amende, ibid., 6l» 1949 (1928); (c) W. Bradley and R. Robinson, J. Chem. Soc., 1310 (1928).

It is now the basic step in the Arndt-Eistert homologation procedure

(5). Arndt and Eistert reported that finely divided silver, copper,

(5) F. Arndt and B. Eistert, Ber., 68, 200 (1935). and platinum would effect the rearrangement. Yates (6) has since

(6) P. Yates, J. Am. Chem. Soc., £4, 5376 (1952). reported that in cases where a-diazoacetophenone was decomposed in alcohols with copper-bronze present, reaction does not lead to re arranged products.

Later attempts at effecting the Wolff rearrangement using silver oxide and metallic catalysts revealed the method to be erratic, and

Wilds and Meader found it poor in their attempts to rearrange a-diazoketones derived from diazoalkanes other than diazomethane (7). Newman

(7) (a) A. L. Wilds and A. L. Meader, Jr., J. Org. Chem., 13, 763 (1948); (b) H. Kagi, Helv. Chim. Acta, 24, 141 E (1941); (c) M. S. Newman and P. F. Beal, III, J. Am. Chem. Soc., 2 1* 5163 (1950); (d) P. Pfeiffer and E. Enders, Ber., 84, 247 (1951). and Beal obtained reproducible results for rearrangement of 1* a-diazoacetophenone when a solution of silver benzoate in triethylamine was used as catalyst. They speculated that the rearrangement followed a free-radical path. Pfeiffer and Enders treated an alco holic solution of ortho-methoxydiazoacetophenone with silver oxide.

Coumaranone was the main product. Small amounts of the expected product of Wolff rearrangement could also be isolated. Yates and

Fugger (8 ) hava reported a homogeneous procedure for the conversion

(8 ) P. Yates and J. Fugger* Chemistry and Industry, 1511 (1957)* of a-diazoacetophenone to methyl phenylacetate by addition of the diazoketone to a solution of cuprous iodide in acetonitrile and methanol.

Wolff (2) suggested the following generalized reaction mechanism for the rearrangement:

aC0C(R*)N2 RCOCR -» R(R» )C=CO SL R(R* )CHCOB where HB is water, alcohol, ammonia or an amine (primary or secondary).

Several facts support this mechanism. Diphenylketene is obtained by heating azibenzil in benzene (9 ); other ketoketenes of type

(9) B. Schroeter, Ber., ff2, 2336 (1909).

R(R*)C=C=0, where neither R nor R* is H, are obtained by heating diazo ketones in aprotic solvents (10). No aldoketenes (R'=H) or aldoketene

(10) W. E. Hanford and J. C. Sauer in R. Adams, ed.» "Organic Reactions," Vol. Ill, John Wiley and Sons, Inc., New York, 1 9 ^ » P» 108. 5 dimers have been isolated from decomposition of diazoketones.

Huggett, Arnold and Taylor (11) decomposed labeled o-diazoaceto-

(11) C. Huggett, R. T. Arnold* and T. A. Taylor* J. Am. Chem. Soc., 64, 3043 (1942).

phenone (2 .51$ in carbonyl carbon) by the Arndt-Eistert method.

The fact that 2.53$ d 3 was found in the carbonyl carbon of the result

ant phenylacetic acid was considered proof of a rearrangement mechanism.

That the migrating group migrates with its electron pair has been veri

fied by studies of the rearrangement of optically active diazoketones

(12). Lane and Wallis converted (+)-2-methyl-2-phenylhexanoic acid

(12) (a) J. F. Lane and E. S. Wallis, J. Am. Chem. Soc., 1674 (19^1); (b) K. B. Wiberg and T'. W. Hutton, ibid., 78, 1640 (1956).

(V) to the homologous heptanoic acid and reconverted it to the original

acid (V) via a Barbier-Wieland degradation. Nearly complete retention

of the configuration was observed. Wiberg and Hutton subjected sec-

butyl diazomethyl ketone (VI) to the Wolff rearrangement under a variety

CH^CHgCH(CH^)C0CHN2

c h 3

V VI

of experimental conditions. They found 97 t 3$ retention of configura

tion for the migrating group. Thermal decomposition of a-diazoacetophenone

In 1916* Schroeter (13) reported that decomposition of a-diazo-

(13) G. Schroeter, Ber., 2697 (1916). acetophenone in xylene at I3O-I6O0 gave an unidentified high melting powder [(ca. 12%),presumably *4-,5-dihydroxy-2,*+»5»7-tetraphenyl-2,6- octadienedioic acid di-V-lactone (VII),

VII m.p. 289° (!*+)]» a solid (<5%) which upon recrystallization f rom ethyl

(1*0 (a) P. Yates and T. J. Clark, Tetrahedron Letters, 13, 435 (1961); (b) T. J. Clark, Ph.D. dissertation, Harvard (i960). acetate melted at 217° [(presumably trans-1 ,2,3-tribenzoylcyclopropane, m.p. 215-217° (15)]and the remainder, an undistillable oil. Grundmann

(15) (a) C. Grundmann, Ann., 536, 29 (1938); (b) J. F. Neumer, Ph.D. dissertation, University of Chicago (1957). found minor amounts of trans-1 ,2 ,3-tribenzoylcyclopropane as the only identifiable product when a-diazoacetophenone was decomposed in refluxing isoamyl ether.

Wilds and Meader (7a) observed that para-substituted diazoaceto phenones undergo Wolff rearrangement in benzyl alcohol at 170-180° tn the absence of metallic catalysts. Somewhat improved yields

(70-80$) of the benzyl ester of phenylacetic acid are obtained if a tertiary amine such a s y -collidine or isoquinoline is present.

The rearrangement also proceeds well in hot aniline. These solvents provided results superior to those obtained using a silver oxide catalyst.

It has been reported (16) that decomposition of a-diazoaceto-

(16) W. R. Bamford and T. S. Stevens, J. Chem. Soc.» 4675 (1952)* phenone in hot benzyldimethylamine leads to the formation of a small quantity of ^-benzyl-w-dimethylaminoacetophenone. It is believed that this is produced by the reactions:

f&C0CHN2 — 0COCH + N2

...... 0 © . H tfCOCH + j&CH2N(CH3)2 - )6C0C-N(CH3)2CH2j2f - 0CO^N(CH3)2

H c h 20

A mechanistic study of the thermal decomposition of a-diazoaceto phenone has been conducted by Yates and Clark (14). They were led into choosing n-decyl alcohol as a reaction solvent by the report of

Wilds and Meader (7a) that high yields of rearranged product could be obtained by the homogeneous decomposition of the diazoketone in hot benzyl alcohol. They found that decomposition in decanol at 140° followed no simple kinetic order, was non-reproducible and exhibited autocatalysis due (presumably) to acid formed during reaction. When the reaction was run in the presence of quinoline and Tenox BHA, a free radical inhibitor, the rate of disappearance of diazoketone 8

(measured by following the disappearance of the infrared absorption of the diazomoiety) was reported to be first order in diazoketone.

Further experiment demonstrated the reaction to be zero order in decanol* quinoline and Tenox BHA. The product of Wolff rearrange ment decyl phenylacetate, was formed in essentially quantitative yield.

This kinetic order is consistent with two mechanisms:

(1) 0COCHN2Z.N.2.»- 0COCH — 0C»sC=O

(2) 0CGCHN2 ---- ► 0CH=C=O 0CH2CO2R

Mechanism 2 requires that the migration of the phenyl group be simul taneous with the'loss of nitrogen. The rates of decomposition of a-diazoacetophenone, para-methoxydiazoacetophenone and para-nitrodiazoacetophenone were studied. If correlation of the rates by the

Hammett equation (17) yielded a large negative rho value (/>)» the

(17) L. P. Hammett, "Physical Organic Chemistry," McGraw-Hill Book Co., Inc., New York (1940), p. 184. concerted mechanism 2 would have been indicated. If p were small, or if the rates were not correlated, no unambiguous conclusion could have been reached.

The rates of decomposition of the para-substituted a-diazoacetophenones were correlated by the

A negative value of /> is consistent with the development of an electron-deficient transition state. The small value of p may be taken as evidence that the migration of the aryl group is not concerted with the loss of nitrogen in the decomposition* and that therefore carbenes are intermediates.

Their opposite interpretation was that although participation occurs * the effects of substituents in the ring (para-position) are dual and in opposition. An electron-withdrawing substituent may retard participation* but resonance by an electron-donating one such as para-methoxy would decrease the relative contributions of canonical structures A and B to the resonance hybrid with a resultant increase

O H ©

A BC in the double bond character of the C-N bond and decrease in decomposi tion rate (18).

(18) T. J. Clark, op. cit.* p. 8 3 .

When decomposed in dodecane* a-diazoacetophenone gave a number of products. The major isolated product was the di-r-lactone VII.

This dilactone may be derived from Z,U—diphenyl-^-hydroxy-3-butenoic acid y -lactone (VIII)* formed from reaction of a-diazoacetophenone with phenylketene. Tautomerism of VIII, followed by a radical induced coupling process yields the dilactone VII. Two other products identi fied require addition of dodecyl radicals to these lactones• Formation 10

VIII of 1,2-dibenzoylethane, trans-1,2»3-tribenzoylcjdk>propane and aceto-

phenone, all found in the product mixture# could be rationalized by

invoking a benzoylmethylene intermediate.

Attempts by Yates and Clark to trap a carbenic species by the decomposition of a-diazoacetophenone in trans-stilbene were unsuc

cessful. The authors concluded that the question of whether there is an intermediate divalent carbon species in thermal decomposition of diazoketones remained unresolved.

In thermal d ecomposition of a-diazoacetophenone in benzonitrile o at 150 , Huisgen and co-workers (19) have apparently captured a 1,3-

(19) R. Huisgen, H. Konig, G. Binsch, and H. J. Sturm, Angew. Chem.# 22* 368 (1961). dipole resonance form of singlet benzoylmethylene:

-N? •• ffi® c6h ^c o c h n 2 ► [c6h 5-c -ch c6h5-c=c h ]

c6h 5-c =n ^

T-' The product, 2,5-diphenyloxazol, was obtained in 0.4$ yield in the

absence of catalysts. With various copper catalysts, the yield was

about 16$. The lactone VIII and dilactone VII were obtained in yields

of 32$ and 19$. These results would seem to indicate that mechanism 1 11 is the path for Wolff rearrangement, and that the intermediate carbene is probably a very short-lived species* rearranging rapidly to phenyl - ketene unless its energy is lowered by complexing with copper in some manner.

It has been reported (20) that electron-attracting para-substitu-

(20) W. Kirmse, "Carbene Chemistry,” Academic Press, New York, (1964) p. 138. ents facilitate the 1,3-dipolar addition of benzoylcarbenes. Qxazoles are obtained in 35 and 46$ yields, respectively by the thermal decomposition of para-chloro- and para-nitrodiazoacetophenone in benzonitrile.

Other instances of 1,3-dipolar carbene additions to multiple bonds have been reviewed (21).

(21) R. Huisgen, Angew. Chem., 21* 634 (1963)*

Thermal decomposition of naphthalene-2,1-diazo oxide (IX) (22) in

(22) P. Yates and E. W. Robb, J. Am. Chem. Soc., 21* 5760 (1957).

boiling xylene gave 2-indenylidenenaphtho(l»2)-l,3-dioxole (X) in 36$ yield. The following mechanism was proposed:

2 '2

m 12

A highly resonance stabilized carbenic intermediate could account

for the relatively slow rate of rearrangement to phenylketene and the consequential high yield of trapping product than found tiy Huisgen and co-workers. It is also possible that the product results from reac tion of the diazo oxide with ketene formed by Wolff rearrangement (23)•

(23) J. Hine, "Divalent Carbon»" Ronald Press Co., New York, 1964, p. 144.

Diarylketenes have been prepared (24) by thermal decomposition of diazoketones of the following type:

(24) E. F. Jenny, H. Droescher, and A. Melzer, Angew. Chem., intemat. Edit., J, 650 (1964).

C=C=0

(a): X = Y = OCH^j (b) X = Y = N02 ; (c) X = OCH3 ; Y = N02 ;

(d) X = Y = H.

The kinetics of the thermal Wolff rearrangements were determined in ethylene chloride. The decompositions were first order in diazoketone.

The relative rates are as follows: (a), 2000; (b), 2; (c)» 1;

(d), 5 0 . The activation parameters for these reactions form an 13 isokinetic straight line. The authors favor an intermediate ketocarbene in the rearrangement mechanism because diazoketone (c)» which is substituted in a manner to favor concerted rearrangement* decomposes at a rate comparable to that of diazoketone (b). It thus appears that the Y-substitueni has by far the greater effect on the reaction rate and that migration of the X-substituted phenyl does not occur in the rate-determining step.

Photolvtic Decomposition of Diazoketones

When diazocamphor is decomposed by photolysis in the presence of water, the product of Wolff rearrangement is obtained (25). Diphenyl-

(25) L. Homer and E. Spietschka, Ber., 88, 93^ (1955)* ketene is the product of the photolytic decomposition of azibenzil

(26). Franzen eliminated the possibility of a diphenylacetylene

(26) V. Franzen, Ann., 614, 31 (1958). oxide intermediate in the rearrangement by showing that azibenzil labeled in the carbonyl group with yields diphenylketene labeled

only in the carbonyl group. Kirmse and Homer (27), in a study of

(27) W. Kirmse and L. Horner, Ann., 625, 3^ (1958).

the quantum yields for the photolyses of substituted a-diazoaceto

phenones in methyl alcohol, found that the products of reaction were 14 those expected from Wolff rearrangements. Ziffer and oharpless (28)

(28) H. Ziffer and N. E. Sharpless, J. Org. Chem., 2£» 194*+ (1962).

have correlated the data of Kirmse and Horner for substituent effects on the quantum yields with the Hammett constants of the substituents.

They rationalize the rho value of -0.26 as meaningful if the reactive species is a triplet carbene.

A study has been reported of the mechanisms of photochemical and copper-catalyzed decomposition of a-diazoacetophenone in olefins (29).

(29) 0. Cowan* M. H. Couch* K. R. Kopecky* and G. 3. Ham mond, ibid.* 2£, 1922 (1964).

Sensitized and direct photochemical decomposition both appear to produce triplet benzoylmethylene* which adds to cis- and trans-2- butenes nonstereospecifically. The benzoylmethylene is relatively unreactive and exhibits radical properties as indicated by the large amounts of bicyclohexenyl and acetophenone produced in the direct and sensitized photolysis of a-diazoacetophenone in cyclohexene. In the direct irradiation of the diazoketone in cyclohexene, a 10-12$b yield of 7-norcaryl phenyl ketone and a yield of over 70/b of acetophenone is found. The photolyses give only traces of the dilactone VII, found

in thermal (14) and in solid state photochemical (30) decomposition

(30) K. B. Wiberg and T. W. Hutton* J. Am. Chem. 3oc.» 76» 5367 (1954). 15

of a-diazoacetophenone. When copper ion is present during photolyses,

the yield of 7-norcaryl phenyl ketone is as high as 62%.

Other instances have been reported where photochemical decomposi

tions do not give the product of Wolff rearrangement. Attempted forma

tion of di-tertiary-butyl ketene by photolysis (or by thermal decomposition) of 4-diazo-2,2,5»5-tetramethyl-3-hexanone gave less than

3$ of the expected ketene (31)* The major product was 2,2,4,5-tetra-

(31) M. S. Newman and A. Arkell, J. Org. Chem., 24, 385 (1959)*

methyl-4-hexene-3-one. Presumably this is formed by the migration

of a methyl group to a carbenic site when steric effects prevent the

migration of a tertiary-butyl group: N2 „ CH3 0 || 0 M I (CH)C-G-C-C(CH) - (CH)C-G-G-C(CH) - (GH)C-C-G=C(CH) 3'3 373 3 3 3'3 3*3 y2

Franzen (32) has studied the decomposition of diazoketones of

(32) V. Franzen, Ann., 602, 199 (1957).

type RCOCN2CH2R* (where R ^ H) by photolysis. The major products

are a,P-unsaturated ketones derived from 1,2 hydrogen shifts in the

possible intermediate methylenes; the expected Wolff rearrangement

products are minor. When silver oxide is used as catalyst, no Wolff

rearrangement products are found, and when the photochemical decomposi

tions are carried out at elevated temperatures the yield of Wolff re

arrangement product increases, while that of the unsaturated ketone

decreases. 1 6

Copper-Catalyzed Decompositions of Diazoketones

Decompositions of diazoketones in the presence of copper give products of carbene insertion into carbon-hydrogen bonds. Heating of diazocamphor with copper powder at 140° yields dehydrocamphor (33)i

(33) • Bredt and W. Holz, J. prakt. Chem., 2 1* 133 (1917).

Carbon-hydrogen insertion as well as carbon-carbon insertion has been observed in the copper-catalyzed decomposition of o-t-butyldiazo- acetophenone (3*0 in various solvents. In benzene* decomposition gave

(3*0 P. T. Lansbury and J. G. Colson, Chem. & Ind. (London) 821 (1962).

4,4-dimethyl-l-tetralone (XI), the product of intramolecular carbon- hydrogen insertion, in 1 2% yield. It was not formed in more polar

CH, CH

0 0

XI XII 17 solvents. The product of carbon-carbon insertion* 2,3,3-trimethyl- indan-l-one (XII) was formed in 1# yield in dimethyl sulfoxide and was not found in decompositions in benzene. Lansbury and Colson suggested that the transition state for the carbon-carbon insertion reaction is more polar than the transition state for carbon-hydrogen insertion.

The copper-bronze catalyzed decomposition of 3-diazo-l>5>5-trimethyl-bicyclo[2.2.l3heptan-2-one (XIII) in refluxing benzene provides a 53# yield of the tricyclic ketone (XIV), the product of carbon- carbon insertion (35)*

XIII XIV

(35) Yates and S. Danishefsky, J. Am. Chem. Soc.» 84, 879 (1962).

Whereas Hammond, et al. (29) added the elements of benzoylmethylene to olefins by a photochemical process, others have apparently added substituted methylenes to olefins by decomposing diazoketones thermally in the presence of copper catalysts.

Diazoacetone on thermal decomposition in cyclohexene in the presence of cupric sulfate yields 7-norcaryl methyl ketone (36).

(36) J. Novak, J. Ratusky, V. Sneberk, and F. Sorm, Collection Czech. Chem. Commun., 22, 1836 (1957)* 18

Thermal decomposition of l-diazo-7-octene-2-one (XV) in refluxing 0

CH2=CH(CH2)ifC0CHN2

XV XVI cyclohexane with copper bronze gives the product of internal addition* bicyclo[4.1.0]-2-heptanone (XVI) (37)* Copper-catalyzed decomposition

(37) Cx. Stork and J. Ficini, J. Am. Chem. 3oc., 8 3 , 4678 (1961).

o of a-diazoacetophenone in 1,1-diphenylethylene at 140 provides 2,2- diphenylcyclopropyl phenyl ketone in better than 30$ yield (38).

(38) B. Ream and M. S. Newman, private communication, Ohio State University.

Copper-bronze catalyzed decomposition of a-diazoacetophenone (6) in alcohols and amines (primary and secondary) does not give products of Wolff rearrangement, but rather those of insertions across 0-H and N-H bonds. It is very possible that the carbenic intermediates are not involved in copper-catalyzed decompositions of diazoketones but rather that the active reagents are organo-copper compounds.

In studies of cyclopropane formation by the copper-ion catalyzed addition of diazo-compounds to olefins, Faraum (39) observed that four

(39) Famum, unpublished results. coordination sites of the copper ion catalyst must be available. If 19 two of these sites in the catalyst are tied up in a diamine complex* for example* nitrogen evolution occurs, but cyclopropanes are not formed.

Reactions of Diazoketones with Bases

The reactions of diazo compounds with bases and nucleophiles have been reviewed (40)*

(40) R. Huisgen, Angew. Chem., 6£, 439 (1955)*

Yates and Shapiro have reported (41) that reaction of a-diazo-

(41) P. Yates and B. L. Shapiro, J. Am. Chem. Soc.» 81, 212 (1959). acetophenone with sodium hydroxide or sodium ethoxide in ethanol gives benzoic acid* acetophenone* 3-benzoyl-4-phenylpyrazole (XVII), 3- benzoyl-5-hydroxy-4-phenylpyrazole (XVIII), hydrogen cyanide, hydroxyl amine and ammonia. It was speculated that initial attack by the

0 CO0 0 CO0

Y ~ i Y Y N H0 K

XVII XVIII base occurred at the terminal nitrogen of the diazo group.

Acid-Catalyzed Decomposition of q-Diazoacetophenones

The first kinetic study of decomposition of o-diazoacetophenones was conducted by Lane and Feller (la). Five para-substituted 20

a-diazoacetophenones were decomposed in acetic acid at 40 and 60°.

The para-substituents were nitro-> bromo-, chloro-> methyl- and

hydrogen-. The rates of decomposition were (pseudo) first order

in all cases with respect to diazoketone* and products of reaction

were the appropriate para-substituted-phenacvl acetates. A plot of the

logarithms of the rate constants against the appropriate Hammett para

meter gave a straight line of negative slope (/> = -0.914 at 40°;

/ = -0.898 at 60°).

They proposed as a first step in the decomposition process a

reversible proton transfer between diazoketone and solvent:

C£,H5C0CHN2 + HQAc C6H^C0CH2N2® + QAc®

XIX

Several possibilities were considered for the fate of the ketodiazonium

ion XIX: 1) bimolecular reaction with the solvent* 2) loss of nitro

gen followed by reaction with the solvent of the carbonium ion so pro

duced* 3) bimolecular reaction with the acetate ion. The addition of

a relatively large amount of sodium acetate had only a slight effect on

the rate of the decomposition of para-nitrodiazoacetophenone at 60°.

For this reason* and because decomposition of this compound was acceler

ated when lithium chloride was present, leading to the formation of

para-nitrophenacyl chloride, while demonstrating kinetics consistent

with a bimolecular reaction* Lane and Feller favored the third possi

bility for the rate-determining step of the decompositions. They con

cluded that the negative value of p indicates that the primary effect of 21 substituents is on the ability of the diazoketone to accept a proton from the solvent.

For comparison with kinetic studies of the sulfuric acid- catalyzed rearrangement of substitued benzazides, Yukawa and co workers (lb) studied the kinetics of the acetic acid-catalyzed decom position of meta- and para-substituted-a-diazoacetophenones, a similar electrophilic reaction.

Their primary interest was to investigate the effect of electron- releasing para-substituents, such as para-methoxy, that had been omitted in the study of Lane and Feller. They reasoned that such substituents would accelerate1 the rate to a greater extent than would be expected from the normal Hammett sigma constants. Further* they desired information regarding the contribution of substituents in a reaction in which effects were transmitted through a carbonyl group to an electron deficient reaction center.

Plots of log k against the corresponding Hammett a- values gave a linear relationship only for meta-substituents and the para-nitro group. The values of log k for all other para-substituents lay above and curve upwards from the meta line (/» = -0.830); the deviations were greatest for the para-alkoxy substituents. This was not considered un usual in that limitations of the Hammett

(42) H. H. Jaffe, Chem. Revs., 191 (1953). such as alkoxy, alkyl, phenyl and halo groups. The upward curvature of the data for these compounds was attributed to the abilities of the 22 para-substituents to stabilize, by resonance, a positively charged transition state.

Yukawa and co-workers suggested that if the transition states of the acid-catalyzed decompositions of a-diazoacetophenones have positively charged reaction centers that may be delocalized through resonance interaction, the driving force for the reaction must be the unimolecular elimination of nitrogen from the ketodiazonium ion, followed by attack of acetate ion (or solvent) upon the carbonium ion so produced.

Z-C/-H,lC0CHo 0Ac

The carbonium ion produced by loss of nitrogen would be delocal ized by resonance with electron-releasing para-substituents. Tautomer- ism might also provide stabilization of the carbonium ion;

Use of

(43) Y. Okamoto and H. G. Brown, J. Org. Chem., 22, 485 (1957), J. Am. Chem. Boc., 80, 4979 (1958). 23

Deno (44), produced better correlation of log k than do Hammett sigma

(44) N. C. Deno and A. Schriesheim, J. Am. Chem. Soc.» 77, 3051 (1955). values, but are still not completely satisfactory in that they some what overcorrect the deviations produced by use of Hammett sigma values. Yukawa and Tsuno (45) subsequently defined a modified Hammett

(45) X. Yukawa and Y. Tsuno, Bull. Chem. Soc. Japan, 22,* 971 (1959). relationship for electrophilic reactions that takes into account resonance interactions by a para-substituent that depend greatly on the nature of the reaction.

The rates of decomposition of a-diazoacetophenones (lc) are significantly increased in aqueous acetic acid (255b water). Acid- catalyzed hydrolysis of four diazoketones [C^H^CH(0Ac)C0CHN2 (XX),

C6H5CH(OCOOCH3 )COCHN2 (XXI), C6H5CH2C0CHN2 (XXII) and para-nitrodiazoacetophenone] was followed kinetically at 25° in aqueous dioxane in the presence of perchloric acid (46). The reactions followed the

(46) (a) H. Dahn and H. Gold, Chem. & Ind. (London), 19^3» 37; (b) H. Dahn and H. Gold, Helv. Chim. Acta, 4£, 983 (1963); (c) H. Dahn, A. Donzel, A. Merbach, and H. Gold, ibid., 4§» 994 (19^3)5 (d) H. Dahn, H. Hauth, and H. Gold, ibid.T~£5> 1000 (19&3)* the Hammett acidity function HQ . By effecting the decomposition of diazoketone XXI in D20> kinetic isotope effects of kjj/k^ = 3*14 were detected. When diazoketone XXI was decomposed in D^0+ and the 24 reaction stopped after 19$ decomposition* complete hydrogen-deuterium exchange had taken place at the a-carbon of the recovered starting material. The authors interpreted these facts as supporting & mechanism in which loss of nitrogen from a ketodiazonium ion is the rate-determining step* followed by reaction of the carbonium ion with water to give R-CO-C^OH. The entropies of activation for diazoketone XXI and 2-diazo-l-indanone are only slightly negative* and thus favor unimolecular decomposition of ketodiazonium ion as opposed to a bimolecular process possessing more rigorous steric requirements.

Dahn and Gold found that when the strongly nucleophilic chloride ion was present* the product was the alpha chloroketone* RCOCHgCl, instead of the ketoalcohol. It was considered possible that this change of product may reflect a change to a bimolecular decomposition of the ketodiazonium ion in the presence of strong nucleophiles.

Participation in Decompositions of ortho- Substitutid a-Diazoacetophenones in Acetic Acid

Upon treatment with acetic acid* ortho-nitrodiazoacetophenone is converted to N-hydroxyisatin (XXIII) (4a).

XXIII 25

Various mechanisms proposed for this reaction (47) require as the

(4?) (a) E. C. Taylor and D. R. Eckroth, Tetrahedron, 20, 2059 (19&0; (b) J, A. Moore and D. H. Ahlstrom,. J. Org. Chem., 25254 (1961). first step nucleophilic attack by a nitro oxygen atom upon the protonated diazo carbon atom.

Marshall, Kuck, and Elderfield (48) have reported that when

(48) E. R. Marshall, J. A. Kuck, and R. C. Elderfield, J. Org. Chem., It 444 (1942). acetic acid is mixed with ortho-methoxydiazoacetophenone at room temperature, a "violent exothermic reaction" immediately takes place and coumaranone (XXIV) crystallizes from the reaction mixture as the only isolable product. Based on studies of the decomposition of ortho-methoxydiazoacetophenone in aqueous suspension by hydrochloric acid (49)^ the following mechanism for the acetic acid-catalyzed

(49) A. K. Bose and P. Yates, J. Am. Chem. Soc.» 24» 4703 (1952). decomposition might be written. A similar mechanism would account for the conversion of ortho-acetoxydiazoacetophenone by acetic acid to coumaranone (7d) (48). 26

CH c h ^ q c OCH H OAc 3 C H 0- N CHM ® ) c H i C II fi 0 0 o

XXIV

General Acid-Catalysis of g-Dia zoac e tophenone

Decomposition of a-diazoacetophenone has been effected by the conjugate acids of various heterocyclic amines (e.g. pyridine hydro chloride) to yield the corresponding phenacyl quaternary ammonium compounds (e.g. phenacyl pyridinium chloride) (50). In the presence

(50) L. C. King and F. M. Miller, J. Am. Chem. Soc.» 22* 4154 (1948). of the Lewis acid, boron trifluoride etherate, a-diazoacetophenone reacts with alcohols to give ketoethers (C^HtjCOCI^OR) (51) •

(51) M. 3. Newman and P. F. Beal, III, Ibid., £2» 5l6l (1950). When toluene is used as solvent* a-diazoacetophenone is converted by boron trifluoride etherate to 3>5-dipbenyl-2-furandiazonium tetra- fluoroborate (XXV) (52)•

(52) W. iteid and W. Bodenstedt, Ann., 6671 96 (1963)* DISCUSSION AND RESULTS

At the Inception of this study, no prior efforts to follow the kinetics of Wolff rearrangements had been reported. Kinetic para meters had, however, been determined for thermally induced Curtius rearrangement of substituted benzazides which are isoelectronic with the correspondingly substituted a-diazoacetophenones (53)- By analogy

(53) (a) Y. Yukawa and Y. Tsuno, J. Am. Chem. Soc.» 79, 5530 (1957); (b) Y. Yukawa and Y. Tsuno, ibid., 8fi, 6y*6 (1958). to the Curtius rearrangement, it was assumed that thermal decomposi tion of a-diazoacetophenones would follow first order kinetics.

Such a first order process could proceed by two possible mechanisms:

-N? 0 v (1) C6H5C0CHN2 ► C6H^C0fik -a* ^c=c=o

products dimers, etc•

C^H.COCHN,

Mechanism 1 requires a divalent carbon intermediate which may re arrange to phepylketene, react with the reaction medium or possibly undergo spin inversion to another carbene. It is possible that 29 neighboring group participation by the carbonyl oxygen atom may con tribute to the transition state for mechanism 1. Mechanism 2 does not permit formation of a carbene*. but rather a concerted process. If rearrangement is simultaneous with loss of nitrogen* participation of the phenyl group may occur in the rate-determining step. The nature of phenyl substituents might then exhibit marked effects on decompo sition rates if mechanism 2 is followed. Efforts to determine which of these mechanisms is operative have been discussed (l*t).

The rates of thermal decomposition of a-diazoacetophenones were determined by measuring the volume of nitrogen evolved as a function of time when dilute solutions of diazoketone were heated at tempera tures greater than 100°. Cetane* an aprotic hydrocarbon* was ini- tally employed as solvent. Several decompositions in cetane at temperatures of 110 to 119° without exclusion of air led to first order kinetics.

When a-diazoacetophenone was decomposed at 119° in cetane from which oxygen had been excluded* the results of nearly identical runs were non-reproducible. The deviations from first order kinetic be havior were attributed to autocatalysis* presumably brought about by the formation of acid during decomposition.

After discovery of the results of Tates and Clark (14)» the sol vent system:cetane-quinoline was employed in an effort to quench interfering acid-catalyzed processes. Induction periods characteristic of autocatalysis were still observed. Repeated attempts to duplicate the kinetic data of Yates and Clark using similar experimental condi tions were unsuccessful. Autocatalysis was found in more than half 30

of the experiments and results were non-reproducible. Communication with Professor Yates revealed that Clark had experienced similar difficulties in reproducing his kinetic data by a gasometric technique

and that the difficulties had not yet been resolved.

It was then discovered that if the thermal decomposition of diazoacetophenone (ca. 0.006 molar) is effected in cetane or cyclo—

octane containing sufficient concentrations (>0.3 molar) of tertiary alkyl amines in the absence of oxygen* the thermolyses are strictly

first order. The tertiary amines used were tributylamine» N»N- dimethylcyclohexylamine* l»h—diazobicyclo[2.2.2]octane and tripropyl amine. The same rates are found when diazoacetophenone is decomposed

in tripropylamine alone. Two decompositions of diazoacetophenone in di-n-butylamine alone did not proceed in a first order manner. A later experiment in di-n-propylamine indicated secondary amines are satisfactory solvents for thermolysis.

Vapor phase chromatographic analyses of the concentrated reac

tion solutions from thermolyses in hydrocarbon-tertiary amine systems

indicated the formation of numerous products. In order to simplify

eventual product studies* all kinetic measurements were made using

tripropylamine alone as solvent. Tripropylamine is the simplest sym

metrical tertiary amine of boiling point sufficiently high to be

employed in a gasometric measuring system. Small quantities (7-10 ml.)

of 1-chloronaphthalene were used as cosolvent to dissolve and inject

samples of diazoketones that were insoluble in tripropylamine at room

temperature•

The experimental results and difficulties encountered in the 31 evolutionary development which led to the selection of tripropylamine as solvent are described in greater detail in the experimental section*

Early in the studies using tripropylamine as solvent* it was ob served that in the initial stages of some decompositions gas evolution was rapid* accounting for as much as 50$ of the total gas srolved during reaction. However* by the time one-half of a half-life period had elapsed* and usually sooner* rapid gas evolution ceased and further evolution of nitrogen invariably obeyed a first order rate law. This initial fast evolution of nitrogen was not observed in the first use of any particular lot of freshly distilled amine. Use of a second portion of this lot caused initial rapid evolution of nitrogen, ac counting for 10 -30$ of the gas evolved; a third portion from this flask of solvent caused the extent of fast gas evolution to be equal to* or greater than that found in the previous run.

It became apparent that the increasing extent of the process which lead to rapid gas evolution was caused by increasing contamination of the tripropylamine with oyygen as its container was repeatedly opened to the atmosphere for removal of reaction solvent. Because the solvent was distilled under nigrogen* freshly distilled amine had not yet been contaminated* and its use did not result in initial rapid gas evolution.

In one kinetic run in which oxygen and then nitrogen had been passed through the solvent prior to reaction, over 70$ of the nitrogen evolved was due to this initial fast reaction.

The sample of amine with which initial rapid reaction occurred had been used as solvent for previous kinetic runs and had been re purified by the normal procedure. Original use of this lot of amine* 32 though exposed to oxygen* had not led to such initial fast gas evolu tions. The explanation for this phenomenon must be that trace amounts of some product of the a-diazoacetophenone decompositions are not re moved by the purification procedure. Oxidation of this material by absorbed oxygen produces an acid or other substances which allows rapid decomposition of the diazoacetophenones. This substance is consumed in the reaction with diazoketone. After its consumption* the thermal de composition of diazoketone proceeds in a normal first order manner.

Accelerated decomposition is totally eliminated by excluding oxygen from the distilled amihe and transferring solvent under nitrogen.

The kinetic measurements were made using these precautions.

That the measured rates in tripropylamine are that of thermal decomposition of a-diazoacetophenones and not of base-catalyzed decom position is based on several observations. Yates and Clark found that thermolysis of diazoacetophenone in decanol-quinoline-Tenox BHA is zero order in amine and each of the other solvent constituents (lh).

In the present work it was observed that thermal decomposition of a-diazoacetophenone in cetane at 119 ° is a first order process with a half-life of 236 minutes. In tripropylamine alone at 120.7°* the half- life for thermolysis is 320 minutes. These differences may be attributed to variations in solvation effects. Because the decomposition occurs more slowly in tripropylamine than in cetane (where catalysis is im probable)* it is unlikely that base-catalysis has any significant effect upon the rate of decomposition of

(5^) Reactions of o-diazoacetophenone with trialkylamines have* however* been found. B* Darre and M. S. Newman (private communication* The Ohio State University) have found that addition of triethylamine to a CH3OD solution of a-diazoacetophenone leads to rapid deuterium- hydrogen exchange at the a-carbon atom. In the absence of amine no deuterium-hydrogen exchange occurred in CH3OD alone during a 10 minute period* Within minutes after addition of the amine (concentration equal to that of diazoketone)* the intensity of the NMR signal for the hydrogen atom decreased by more than 60$. These workers propose re moval of the alpha hydrogen by triethylamine as a first step of the exchange mechanism: O 0

This intermediate may have stability in that it is isoelectronic with azide ion: © © © © © N = N = N

This anion may then accept a dsuterium atom from CHoOD. Alternative mechanisms for exchange may be imagined. The hemiketal (i) may result from base-catalyzed addition of CHoOD to the carbonyl group. The following scheme illustrates two possible routes leading to deuterium-hydrogen exchange. Et3N/CH3OD OD , ? © © I © © 0 - C — C — N = N: 0 C - C - N H H OCH,

0 OD 0 @ DOCH, OD n OCHa qd D ^ I T © 3 Et,N i I © 0 —C -C-NHN: ja-^0-C-C-N=N: I H I A -Hi© © OCH

-C H 3OH -DOCH-

0-C1 © N = N: N = N : N = N:

Kinetic parameters for the thermal decomposition In tripropylamine of a number of substituted-diazoacetophenones are summarized in Table !•

Table 2 contains a complete listing of experimental results in this solvent. Representative data of kinetic measurements for each compound are presented in table and graphical form in the Appendix* Table 11 and Figures 10 to 19.

The enthalpies of activation* Ailt* were determined through use of the following equation (55)s

* AS = Ea - RT

(55) A. A. Frost and R. G. Pearson* "Kinetics and Mechanism*" John Wiley & Sons* Inc.,. New York, (1961)*, pp. 97-100. TABLE 1 4 _T Average First Order Rate Constants (10 k»sec ) for Thermal Decomposition of Substituted a-Diazoacetophenones (Half-life values (min.) in parentheses) Temperature Substituent 100.97° 110.88° 120.68° 125.76° 130.48° 135.88° 140.95° 146.97° AH* tiS*

None — — O.36I — 0.974 1.98 3-36 — 35.5*2 .# 10.5*7.2 (320) (118) (58.2) (3^.3) ortho-Br 1.24 3.68 10.4 32.4*1.0 7.5*2.5 (92.9) (31.*0 (11.1 ) ortho-Cl 0.963 2.88 9.09 34.2*2.6 11.6*6.7 (120) (*K>.1 ) (12.7) ortho-I 0.550 1.98 4.83 31.5*4.1 5 .8*9.9 (210) (58.2) (23.9) ortho-CH^ 1.74 4.26 6.64 12.2 29.4+2.5 0 .05*6.2 (66 .2 ) (27.1) (17.4) (9.5) ortho-OCHo 1.18 3.10 8.43 28.3*2.8 -1 .2+6 .9 (97.7) (37.3) (13.7) meta-OCH^ 1.38 4.00 7.13 33.0*2.1 4.8*5.2 (83.6) (28.9) (16.2) meta-N'Qo O.676 1.14 2.03 3.64 33.9*1.4 5*9*3*5 (171) (101) (57.0) (31.7)

oara-OCHo 1.32 4.12 8.75 37.6*2.3 16.0*5.7 (87.4) (28.0) (13.2)

para-NOo 0.713 2.18 3.902 34.2*2.2 6.5*5.^ (162) (53.0) (29.6) 36

TABLE 2

The Thermal Decomposition of Substituted a-Diazo- acetophenones in Tripropylamine

Substituent Temperatures0 Half-life (nin.) I0^k» sec. ^

None 120.7 336 0.344 If II 301 0.384 If It 324 0.356 ti 130.5 127 0.910 it If 12 5 0.924 ti It 121 0.955 n II 118 0.979 ti ft 103 1.122 ii II 117 0.987 N •1 96 1.203 ii ft 136 0.849 ft 135.9 63.0 I .834 ii It 5^.0 2.139 it It 57.5 2.009 it 141.0 33.2 3.480 it if 36.4 3.174 n it 33.25 3.474 ortho-chloro 110.9 134 0.862 If ii 122 0.947 n if 104 1.111 t» 120.7 43.7 2.643 it ft 37.3 3.097 ii II 39.2 2.947 it 130.5 12.5 9.24 it It 12.9 8.96 ii II 12.7 9.10 ortho-bromo 110.9 93.0 1.242 It II 92.6 1.248 If tl 93.2 1.240 II 120.7 31.15 3.708 It II 31.2 3.702 If »l 31.7 3.644

If 130.5 10.6 10.90 ft If 11.7 9.87 If II 11.0 10.50 37 TABLE 2 (Contd.)

Substituent Temperature*0 Half-life (min} loSc* sec ortho-iodo 101.0 223 0.518 II n 185 0.624 H H 223 0.518 II 110.9 54.3 2.127 It it 69.0 1.674 It it 55*7 2.074 II it 54.0 2.139 II 120.7 21.2 5.449 It 27.1 4.263 II it 23.5 4.916 ortho-methyl 110.9 62.7 1.842 It n 68.3 1.691 It N 67.6 1.709 II 120.7 29.7 3.890 It it 25.5 ^.530 II it 26.8 4.306 It 125.8 17.4 6.639 It 130.5 10.1 11.44 It it 9.0 12.84 ft 11 9.3 12.46 ortho-methoxy 101.0 97.7 1.182 ll It 99.3 I.I63 II II 96.0 1.203 It 110.9 36.2 3.191 M II 37.1 3.113 If It 38.7 2.985 tl 120.7 11.9 9.71 H It 15.5 7.45 meta-methoxy 130.5 85.7 1.348 If II 82.7 1.397 II It 82.5 1.400

II 141.0 27.1 4.263 II n 30.7 3.763

II 147.0 15.6 7.405 It n 16.7 6.917 38

TABLE 2 (Contd.)

Substituent Temperature*0 Half-life (min) 10^k» sec.-^ meta-nitro 130.5 177 0.653 N II 160 0.722 II H 176 O .656

135.9 101.3 1.140

" 141.0 56.3 2.052 II It 57.7 2.002 II II 57.0 2.027

" 147.0 32.2 3.588 31.2 3.702 para-methoxy 130.5 87.7 1.317 II II 87.0 1.328

" 141.0 27.7 4.170 II If 28.3 4.082

" 147.0 13.1 8.818 II N 13.4 8.621 para-nitro 130.5 167 0.692 II II 158 0.731

" 141.0 55-5 2.081 II tl 30.6 2.283

" 14?.0 29.3 3.943 11 n 30.0 3.851 3 9 The Arrhenius activation energies, Ea * were calculated from the slopes of the straight lines obtained in the plots of log k against reciprocal temperature. The slopes of these regression lines were determined by- least squares treatment (5 6 ) of the log k and reciprocal temperature

(5 6 ) 0. L. Davies, "Statistical Methods in Research and Production," Oliver and Boyd, London (1957)» P» 19^. data. These Arrhenius activation energy plots are contained in

Figures 20 to 29 of the Appendix. The uncertainty of the AH* values, with 95# confidence limits, was determined by a statistical treatment

(57) which provided the standard error of the Arrhenius slope.

(57) 0. L. Davies, ibid., p. 200.

Entropies of activation, £S^> were calculated through use of the following thermodynamic relationships (5 5 )•

^ AH* - AF* AS* ----^----

AF* = - RT In K*

The uncertainties of the enthalpies of activation magnify the uncer tainties calculated for the entropies of activation.

Thermal decomposition of ortho-nitrodjazoacetophenone was conducted in tripropylamine at 130°. The reactions did not obey first order kinetics and more than the theoretical volume of gas was evolved. o However, two kinetic runs at 130 in cyclooctane had first order half-lives of 25*2 and 25 • 3 minutes. Approximately 150$ of the theoretical volume of gas was collected. It is presumed that the excess gas was due to intromolecular reaction of a carbenic center with the ortho-nitro group* leading by some rapid process to unidenti fied gaseous product(s). Carbenic insertions into nitro groups have been reported (58); photolysis of 2 *6-dimethyl-para-benzoquinone

(58) J. K. Stille* P. Cassidy* and L. Plummer, J. Am. Chem. Soc., 8£, 1318 (1963). diazide in nitrobenzene gives nitrosobenzene and the corresponding quinone. This second process may account for as much as 50$ of the fate of the carbenic center. It must be a relatively rapid process, with the result that loss of nitrogen is rate-determining and follows first order kinetics.

Relative rates of thermal decomposition of substituted a-diazo acetophenones at 120.7 and 130.5° are given in Table 3« Included in this table are calculated relative rates at 35° for comparison with the relative rates of first order thermal decompositions of ortho substituted benzazides (Curtius rearrangements) at 35°»

Examination of the relative rates of decomposition of meta- and para-substituted diazoacetophenones indicates that the rates are only little affected by the polar nature of the substituent. The marked rate increases produced by ortho-substituents must therefore be at tributed largely to steric acceleration of decomposition. It can also be seen that the magnitudes of the relative rates correlate in general with the sizes of the ortho-substituents. The data for 41

TABLE 3

Relative Rates of Thermal Decomposition of Substituted a-Diazoacetophenones and Benzazides

Relative Rates a-Diazoacetophenonesa Benza zides Substituent 120.7 130.5° 35c 35°

None 1 1 1 1 ortho-chloro 8.91 8.56 14 147 ortho-bromo 11.0 10.0 33 203 ortho-iodo 15.4 13.6 63 ortho-methyl 13-5 11.2 119 100 ortho-methoxy 24.8 19.8 318 100 ortho-nitro — 4.6° meta-me thoxy 1.4 2 1.34 meta-nitro 0 .7 3 0.64 para-methoxy 1.17 I.25 para-nitro 0.71 0.68

a Rates calculated using least squares regression lines. Data from work of Yukawa and Tsuno> Ref. 53b. c Two kinetic runs made in cyclooctane. ortho-nltrodiazoacetophenone> though subject to question* indicate that even a strongly electron-withdrawing ortho-substituent produces a con siderable rate increase. These results are very similar to those found for the Curtius rearrangements of ortho-* meta-*, and para-benzazides

(53).

Further evidence that steric factors prevail over polar factors may be found. In acidic hydrolyses of ortho-substitued benzoates* ortho-methyl and ortho-bromo groups have the same steric effects (59).

(59) R* W. Taft* Jr.* in Newman* "Steric Effects in Organic Chemistry*" J. Wiley & Sons, Inc., New York (1956)* Chap. 13.

If this result is applicable to the thermal decomposition of a-diazoacetophenones* the steric effects of the ortho-methyl and bromo groups may be assumed to be similar. Any significant differences in rates between ortho-methyldiazoacetophenone and ortho-bromodiazoacetophenone might therefore be attributed to polar effects. Although the electrical effects of methyl and bromo substituents upon reaction

rates are generally opposite and considerable* only a 12# difference

is observed in thermal decomposition of ortho-substituted diazoaceto-

phenone. The primary effect of the ortho-substituents seems* there

fore to be steric.

Yukawa and Tsuno (53b) have suggested that the acceleration ex

hibited by ortho-substituted benzazides undergoing Curtius rearrange ments is due primarily to steric restriction of resonance of aiyl with

azidocarbonyl groups in the ground state. In the transition state proposed for the Curtius rearrangement, XXVI, steric interaction 0 ©

n =N:

with ortho-substituents is reduced.

In meta- and para-substituted diazoacetophenones, the -COCHN2 group can be coplanar with the aryl nucleus and resonance between

it and the aryl nucleus is enhanced. Resonance as in XXVIII leads

( X © /'N = N: © © C = etc. Z 3X3ZE

to increased double bond character of carbon-nitrogen in the ground

state. The energy required for carbon-nitrogen bond breaking is thus

increased and results in stabilization of the molecule to thermolysis,

With ortho-substituents, there is steric interaction and resonance of

the benzene ring with the -COCHNg group is reduced by the restriction

to coplanarity. The following structures illustrate the possibility of steric interaction with ortho-substituents: 44

As a result) ortho-substituted diazoacetophenones, compared to the meta- and para-isomers» are less resonance stabilized in the ground

state and their carbon-nitrogen bonds have less double bond character*

Transition states for the carbenic and concerted rearrangement mechanisms may be represented as XXIX and XXX respectivelys

In the transition state of the carbenic mechanism, XXIV, carbon- nitrogen bond elongation occurs. The conformation of the transition

state XXX for concerted rearrangement is such that the carbonyl group and carbon atom from which nitrogen is being expelled define a plane perpendicular to the plane of the aromatic ring.

The extent of resonance in transition states of type XXIX for

carbenic decomposition processes is diminished due to partial loss

of the contribution of the diazo group. Because delocalization is

less extensive in the transition state, ground state considerations

are of greater importance in determining potential energy differences

between the two states. Therefore, steric inhibition of resonance

in the ground state may lead to a decreased activation energy for

ortho-substituted diazoacetophenones relative to the meta- and para-

isomers•

Accompanying carbon-nitrogen bond elongation in the carbenic

transition state, there may be reduction in steric compression. *5

Such a relief of steric interaction could be responsible for the

ortho-acceleration effect.

A third possible interaction mechanism leading to rate accelera tion may be effected by ortho-substituents bearing non-bonded

electrons. Direct participation of these electrons with the o-carbon

atom might play a role in either the ground state or in the transition

state* or in both. The effect of an ortho-methoxy substituent* for example* in the transition state might be partial stabilization of a developing positive charge at the a-carbon atom. This would facilitate expulsion of N2 and thus have a rate accelerating effect.

In the transition state represented for concerted rearrangement*

(XXX)* conjugation between the -COCHN2 group and the aiyl nucleus is minimal because of the perpendicularity of the planes defined by these groups. However, resonance may occur in each plane and electrical

effects may be transmitted from one plane to another through the partially formed and partially broken sigma-bonds. Although steric

retardation of resonance is not important in the transition state,

its effect on ground state potential energies may, as in the carbenic decomposition mechanism* be responsible for steric acceleration.

Steric effects of ortho-substituents are minimal in transition

states of type XXX for concerted rearrangement processes in contrast

to the more severe steric interactions in the ground state. Relief

of steric interaction between the substituent and the -COCHN^ group will be an important factor if the Wolff rearrangement is a concerted

process. In this mechanism, as in the alternative carbenic 46 mechanism* direct participation of non-bonded electrons of the ortho

substituent may also provide a rate-accelerating effect.

It is of interest to examine the isokinetic relationship (60)

(60) (a) J. E. Leffler, J. Qrg. Chem., 20, 1202 (1955); (b) J. E. Leffler and E. Grunwald, "Rates and Equilibria of Organic Reactions,." John Wiley & Sons, Inc., New York, 19&3» Chap. 9 •

between the enthalpies and entropies of activation for thermolyses of a-diazoacetophenones. Although the uncertainties in the values of these activation parameters dictate caution in drawing conclusions from any resulting relationship, plots of the most probable values of dHt and for the thermal decomposition of substituted a-diazo acetophenones have been made. These are contained in Figure 1. It appears that the data are best correlated by two parallel isokinetic lines, one for meta- and para-substituents, and another for ortho- substituents . The slopes of these lines, 425°K, are equal to the

isokinetic temperature. The uncertainty of this value, however, may

be considerable, due to the probable error of the activation parameters.

Kinetic measurements were made in the temperature range 384-420°K.

Pairs of parallel isokinetic lines are not uncommon. They might

result from the effects of steric strain on the conformational composi

tion of the ground state or the transition state. A certain critical

amount of steric hindrance could cause a new conformation to be the

favored one, yet the discrete change in conformation need not effect the continuous mechanism (60b). It has been further suggested by

Leffler that the fact that the isokinetic lines are parallel shows •H- kcol

30 mole 34 28 29 33 36 38 37 35 ees o Teml eopsto o Sbtttd — Substituted of Decomposition Thermal Diazoacetophenones. for meters iue . n skntc eainhp f ciain Para- Activation of Relationship Isokinetic An I. Figure 0 - - OCH 0 O-CH 2 m ~ N 02 o m -OCH p-NO 6 deg. mole I - o fi- Br fi- 8 10 /3 =■ 425° K /3 =■ 425° -H 12 o - Cl 416414 £-OCH, 7 * 48 that the Interaction mechanism which produces the variable displacements along the lines is not affected by the change in steric interaction which produces the dispersion.

Yukawa and Tsuno found that the isokinetic plots of the activation parameters for Curtius rearrangements of substituted benzazides were correlated by two nearly parallel lines (53b )* The line for the ortho- substituted benzazides was displaced from the meta- and para-correlation line to lower energies. It was reasoned that the difference of about

3 kcal. between the lines would be equal to the additional resonance energy possible for the ground states of meta- and para-substituted benzazides. The isokinetic temperature for the meta- and para-substituents was 375°K» Kinetic measurements were made in the temperature range 298-353°K*

If the rates of thermal decomposition of o-diazoacetophenones had been measured at the isokinetic temperature, the variation in rates would have been small but not necessarily zero. This does not appear to be the case. That the linear correlations are not merely fortuitous may be seen in the fact that the order of points on the isokinetic line for ortho-substituents is not random, but can be rationalized on the basis of steric bulk and inductive effects of the substituents.

Attempts were made to establish Hammett relationships for the rates of decomposition of substituted-diazoacetophenones. The use of available ortho-substituent constants (6l) did not correlate the

(6l) A. W. Baker and A. T. Shulgin, J. Am. Chem. Soc., 81, 1523 Cl959). *9

rates of decomposition of ortho-substituted diazoacetophenones. The

rate constants resulting from meta- and para-substitution are best correlated by Hamnett O constants* rather than by 0* constants. The

Hamnett plots are contained in Figure 2. The reaction constants,p »

at 120.7° (/»* -0.24) and at 130.5° (/>* -0.28) were calculated by the method of least squares* following the procedure of Jaffe (42). The

slope of the regression line of log k^/kg on o is equal to/>» Correla

tion coefficients* r* were calculated by a standard method described by Jaffe. If the points representing the data for meta-methoacydiazo- acetophenone are not considered* the correlations are much improved.

The results of such omissions are that at 120.7°*^ » -0.20; r = 0.99 and at = -0.26; r - .99* lates and Clark determined that at

130° * p - -0.24. The apparent anomalous behavior of the meta-me thoxy

substituent might be due to resonance of the following type: ©

COCHN

c h 3°

Inductive relay of the charge placed in the ortho-ring position will

lead to an increase in reaction rate* resulting in displacement from

the Hammett correlation line (62).

(62) J. £. Leffler and E. Grunwald* o£. cit.* p. 214.

As reaction temperature is lowered* the rate of decomposition

of para-me thoxydiazoacetophenone relative to that of diazoacetophenone

decreases. It has been calculated that at 99°» the rates are equal. 50

m-OCH 40.10

p - OCH

0 -H

-0.10 Temperature : 120.7 - N Oo p = -0 .2 4 c o p — NO2 r = 0.81

4 0.10

-0.10 Temperature: 130.5

- 0 . 2 8

0.90 - 0.20

-0.5 0 + 0.5 0" Figure 2. Hammett Relationship for Thermal Decomposition of meta- and para-Substituted oc — Diazoacetophenones. At lower temperatures this substituent would have a decelerating ef fect. This may be due to the fact that an electron-releasing para- methoxy group can participate in resonance as indicated:

As discussed previously, such resonance leads to an increase in the double bond character of the carbon-nitrogen with resultant stabiliza tion of the molecule to loss of nitrogen as shown by the high energy of activation for this diazoacetophenone.

It was found in study of the Curtius rearrangement that the rates of decomposition of meta-substituted benzazides are correlated by the

Hammett equation with f> - -0.29 at 65°. However, all para-substituents, and para-methoxy in particular, retarded the reaction, presumably because of resonance analogous to that just described.

In spite of possible abnormal interactions by methoxy substituents, it may safely be asserted that the reaction constant p for the thermal decomposition of meta- and para-substituted diazoacetophenones is a small negative number and that the rate data are fairly well correlated by the Hammett O constants. If it is true, as it has been indicated, that the rate determinations have been carried out at temperatures sufficiently far from the isokinetic temperature, the small negative value of p may be considered evidence against a decomposition mechanism involving backside phenyl participation simultaneous with loss of nitrogen. Ejy default, the alternative decomposition mechanism in volving the intermediary of a carbenic species, is implied. Evidence 52 for participation toy the carbonyl group has not been found* The fact that isokinetic lines exist and are parallel indicates that all of the diazoacetophenones studied decompose in such a manner. Proof that a carbenic decomposition is operative may be obtained by examination of the products of the thermal decomposition of a-diazoacetophenone in various solvents.

The products of decomposition of a-diazoacetophenone in cyclooctane-tripropylamine-mesitylene were concentrated by vacuum distil lation of the solvent. The distillate» upon acidification and addition of 2 ,4-dinitrophenylhydrazine * gave acetophenone 2 ,4-dinitrophenylhydrazone* Vapor phase chromatography of the residue indicated the presence of more than twelve volatile products. The residue also con tained trace amounts of dilactone VII. Several of the products were collected as they were eluted from the chromatographic column. N»N-

Dipropyl-2-phenylacetamide comprised ca. 20% of the volatile fraction and was identified by its infrared and NMR spectra. 'Hie yield based on a-diazoacetophenone was undetermined, but was certainly much lower than 20%t because there was extensive formation of involatile tars.

Another high-boiling product occurring in approximately the same extent as acetophenone was benzalUcetophenone; the benzalacetophenone was identified as its 2,4-dinitrophenylhydrazone. No other products could be identified.

The hot reaction mixtures resulting from decomposition of sub stituted diazoacetophenones in tripropylamine were yellow and clear.

The solutions from kinetic experiments with a-diazoacetophenone were concentrated for product study by: 1) distillation of tripropyl amine at reduced pressure or 2) chromatography of the residue on basic alumina followed by elution with ethyl alcohol. Vapor phase chromato

graphic analyses of both concentrates indicated the presence of over

16 volatile products. Acetophenone comprised ca. 5$ of the volatile

fraction. An attempt was made to collect several other products of

lower yield and boiling slightly higher than acetophenone. This was

difficult because of overlap of the numerous peaks. Small quantities

of some of the products were obtained, lhese all had infrared carbonyl

absorptions at 6.0-6.1 p; there were no other distinctive absorption

bands to facilitate characterization.

Four high-boiling products comprised 65# of the V.P.C. volatile

material. The lowest boiling of the products (3*5# of the volatile

materials) was a colorless solid when eluted from a SE 30 column.

Its retention time and infrared spectrum were identical to those of

authentic N-propyl-2-phenylacetamiide. The next major peak to be eluted

(13$ of products) was a liquid. Its retention time» infrared and NMR

spectra were identical to those of authentic N»N-dipropyl-2-phenyl-

acetamide (b.p. 139°/2.4 mm.). N»N-Dipropyl-2-phenylacetamide is

possibly formed by addition of tripropylamine to phenylketene to give

XXXI and subsequent decomposition (Equations 1 and 2) s

c Pr J -.PK --► tfCH,-C + CH -ch=ch 2 h ^ y NPr2 (I) ^ ch2 / \ In a later product study* propylene was detected. Structures similar

to XXXI have been proposed as the intermediates responsible for the

catalytic effect of tertiary amines in certain ketene reactions (63)*

(63 ) L. A. Miller and J. R. Johnson* J. Org. Chern.* 1* 135 (1936).

At high dilution* as in the present case* intramolecular rearrangement may prevail. The possibility that phenylketene reacts with dipropyl amine present as a trace impurity in the tripropylamine is responsible

for N,N-dipropyl-2-phenylacetamide is unlikely. The third (31$) and

fourth (18$) major products were of higher boiling point and were not

cleanly separated by the chromatographic column. Analysis of the

concentrated product from another series of kinetic runs indicated that

in this instance the higher boiling of these two products was formed

in greater amount. Careful collection of the V.P.C. eluent provided

small amounts of these liquids for infrared and NMR spectral study.

The infrared spectra of both products were identical in most respects

to that of N»N-dipropyl-2-phenylacetamide which had carbonyl absorp

tion at 6.11 |x. The NMR spectra of these materials had complex ali

phatic proton absorption in addition to that for aromatics. Considera

tion of the high boiling points and spectral data for these compounds

leads to the assignment of amide structures XXXII and possibly XXXIII. Amide XXXII might be derived from Intermediate XXXI via rearrangement of the Stevens type: H i2r“ C _ C \ © ^ Pr n /> n — 2-*- m n N ^ \ Pr c h 3- c h 2- c h 2

These initial investigations of decomposition of a-diazoacetophenone indicated that the products result from Wolff rearrangement or from the carbenic intermediate* A more detailed study of the products of thermolysis of a-diazoacetophenone was subsequently made.

To facilitate isolation of products, a relatively concentrated solu tion of diazoacetophenone (0.136 molar) was decomposed in refluxing tripropylamine (156°). Chromatographic analysis of the gas evolved revealed three components occurring in the approximate ratio 40:1:3 and accounting for less than 5$ of the total volume. The first eluted was major and had a retention time for that of carbon dioxide.

The second and third peaks had retention times identical to those for propane and propylene respectively.

After removal of an aliquot for quantitative V.P.C. evaluation, the reaction solution was concentrated by vacuum distillation. Vapor phase chromatography indicated that the major volatile product was N »N-dipropyl-2-phenylacetamide; the amide was identified by its re tention time and spectral properties. Ten lower boiling products were detected, two of them in amounts sufficient for collection. The lower boiling of these was acetophenone, identified as its 2,4-dinitrophenylhydrazone. The other has tentatively been identified as 1-phenyl-

2-pentanone. Experiments on which this assignment is based will be described.

Chromatography at a higher column temperature revealed the presence of eleven products of boiling point higher than the amide.

The second of these was collected and identified as benzalacetophenone; benzalacetophenone was identified as its 2,4-dinitrophenylhydrazone.

A small peak (representing less than 0.5$ yield) had a retention time identical to that of 1,2-dibenzoylethane. A still higher boiling product (eluted as a white solid and occurring in about 5$ yield) was not characterized. From the reaction flask used for the decomposi tion and from the residue of vacuum distillation was isolated dilactone

VII (6 .3$ yield).

Yields of volatile products were determined by addition of 1- chloronaphthalene as an internal standard to an aliquot of the reac tion solution and subsequent quantitative V.P.C. analysis.

The products isolated from the thermal decomposition of a-diazo acetophenone in tripropylamine at 156° and their yields are listed in Table h. These products account for ^8$ of the a-diazoacetophenone.

All of the other unidentified volatile products, except the one men tioned, occurred in less than 1$ yield. Theccnbined yield of all of these uncharacterized products is 10-15$* 57

TABLE 4

Products of Thermal Decomposition of a-Diazoacetophenone in Tripropylamine at 1 5 6 °

Compound $ Yield

Acetophenone 3.6

"1-Phenyl-2-pentanone" 6 .1

N ,N-Dipropyl-2-phenylace tamide 30.0

Benzalacetophenone 2

4 ,5-Dihydroxy-2,4,5 ,?-tetraphenyl-2,6 - octadienedioic acid di-Jf-lactone 6.3

The involatile products account for the remaining 40$. Base- catalyzed condensations of ketones 1 and of acetophenone in particular! may be responsible for some of the higher molecular weight material.

If such condensations occur, the reported yield of acetophenone does not indicate the true extent of its formation. It has been established that aldoketene dimers yield higher polymers on moderate heating (64).

(64) W. E. Hanford and J. C. Sauer, "Organic Reactions," Vol. Ill, John Wiley & Sons, Inc., New York, 19**6» p. 128.

Polymerized phenylketene is very likely the major high molecular weight constituent. The fact that such a multitude of products is formed has no effect upon the results of the kinetic treatment of thermolysis rates of a-diazoacetophenone. 58

A mechanism for formation of acetophenone possibly involves a benzoylmethylene intermediate as indicated:

spin inversion

0 11 -I- Y

It is proposed that thermal decomposition of a-diazoacetophenone leads initially to the singlet ketocarbene. This may undergo re arrangement to phenylketene or, via spin inversion, to triplet ketocarbene. Argument that phenylketene is formed by rearrangement of singlet rather than triplet ketocarbene is based on the fact that in any rearrangement of the triplet species, a re-pairing of the unpaired electrons is required. Intermediacy of a triplet ketocarbene for formation of acetophenone is not mandatory, however, in that no evidence exists that singlet carbene cannot effect hydro gen abstraction (65 ).

(6 5 ) W. Kirmse, 0£. cit., p. 255*

That triplet benzoylmethylene reacts as a biradical is illustrated by the previous work (29) concerning photochemical decomposition of a-diazoacetophenone in cyclohexene. The high yields of the product of hydrogen abstraction, acetophenone, and bicyclohexenyl, the product 59 of coupling of the radicals formed by hydrogen transfer, suggest that

triplet ketomethylene is very capable of hydrogen abstraction. Con versely, the fact that only traces of dilactone VII are formed indicates

that at least under photochemical conditions, triplet ketocarbene does not undergo appreciable rearrangement to phenylketene. Reaction of phenylketene with either a-diazoacetophenone or benzoylmethylene is

required for formation of intermediate £-lactone VIII which is readily,

converted to dilactone VII. The small amounts of phenylketene required for formation of observed dilactone VII might have been produced by

rearrangement of a photolytically produced singlet benzoylmethylene prior to spin inversion.

Mechanisms for formation of N,N-dipropyl-2-phenylacetamide and dilactone VII have been previously proposed. Benzalacetophenone

could arise in the manner indicated:

C = C — 0 CV / j -CO H \ / H cx C - c g 0 x c-J6 0 CO/ II H C 0 II 0 It has been suggested (66) that the following mechanisms may also

(66) T. J. Clark, op. cit., p. 68.

account for formation of benzalacetophenone. 0 It was of interest to examine the nature and number of products from decomposition of a-diazoacetophenone in dipropylamine (b.p. 110°)» a solvent that will react readily with phenylketene.

a-Diazoacetophenone> sufficient to allow isolable amounts of product* was decomposed in dipropylamine at 107*5° under conditions identical to those used for kinetic measurements in tripropylamine*

Nitrogen was evolved quantitatively. The decomposition proceeded in a first order manner with a half-life of 1990 minutes. Calculation based on the regression line of the Arrhenius plot for decomposition of a-diazoacetophenone in tripropylamine provides a predicted value of 1720 minutes at 107*5°* The difference in values might be due to solvent effects or to a slight error in the predicted value resulting from the uncertainty of the Arrhenius regression line*

The reaction solution was concentrated and the identities and yields of products were determined in the same manner as that in which tripropylamine was solvent. Vapor phase chromatographic analysis revealed that three products accounted for 92# of the a-diazoaceto phenone. Five minor peaks were detected. Acetophenone (15# yield) was the first of the major products to be eluted; it was identified as its 2 ,^-dinitrophenylhydrazone.

The major product was N»N-dipropyl-2-phenylacetamide (71# yield)* Its identity was confirmed by comparison of its retention time and infrared spectra with those of authentic material.

The third major product (ca. 6jt> yield) had a retention time less than that of the amide» but identical to that of a crude sample of a-(N»N-dipropylamino)-acetophenone; the infrared spectra were identi cal in most respects. Analogous products have been obtained in copper- catalyzed decompositions of a-diazoacetophenone in secondary amines (6).

The fact that acetophenone is formed in significant yield has important mechanistic implications. This yield of acetophenone indicates that thermal decomposition of a-diazoacetophenone does not lead solely to rearrangement by a concerted process. Either aceto phenone and phenylketene (the precursor of N,JN-dipropyl-2-phenylacetamide) have a common precursor* or two separate mechanisms for the thermal decomposition of a-diazoacetophenone operate simultaneously.

If it may be inferred from the linearity of the Arrhenius plot for thermolysis that only one decomposition mechanism is operative* the mechanism of decomposition must require a benzoylmethylene inter mediate .

Elevated temperatures favor the Wolff rearrangement (32*67).

(6 7 ) W. Kirmse* og* cit.* p. 19 •

Wilds and Meader (7a) effected the Wolff rearrangement of a-diazoacetophenone in high yield by conducting the decomposition in benzyl alcohol at 170-180°. This result may imply that while the percentage of rearrangement product increases with rising temperature* the rela tive amount of unrearranged products decreases. This may account for 62

the difference in acetophenone yields of 15$ at 10?.5° in dipropyl

amine and 3*6$ at 156° in tripropylamine. However* although the

extent of base-catalyzed condensation of acetophenone by dipropylamine

at 107*5° appears negligible* the amount of condensation at 156° in

tripropylamine is unknown.

These phenomena may be rationalized if the following is accepted

as the mechanism of Wolff rearrangement:

-N ° © £ V C £H k COCHIN, c= c = o 6 D 4 C 6 H 5 - C C © K H Singlet K_ HB I t Produ cts

C H c — C — C - H 6 5 • C 6 H 5 C V CXB Tri pie t

Produ c*ts

If the energy of activation for rearrangement of singlet carbene to

phenylketene is greater than the energy of activation for spin inver

sion of singlet to triplet carbene, the ratio of rates k^/kj will

increase with rising temperature. The rate of increase of this ratio will depend upon the magnitude of the difference in activation energies.

Possible evidence for a carbenic intermediate in thermolysis of

a-diazoacetophenone might be obtained by conducting the thermal decomposition in cyclohexene. Isolation of 7-norcaryl phenyl ketone

XXXIV, the product of carbene addition to cyclohexene (29) would be

X-XST-GL indicative of a divalent intermediate. Decompositions were effected in cyclohexene at 125° and 135°• The products and yields were determined by V.P.C. techniques described previously, with 1-chloronaphthalene added after reaction as an internal standard.

At 125°» 7-norcaryl phenyl ketone is the major volatile product detected by V.P.C. (26# yield). At 135°» it is formed in about 13# yield. The infrared, NMR and ultraviolet spectra of the adduct and the melting point and ultraviolet spectra of its 2 ,4-dinitrophenylhydrazone match those of the authentic materials and the corresponding literature values (29)* The 7-norcaryl phenyl ketone can be prepared in 60# yield upon addition of catalytic amounts of cupric sulfate to a cyclohexene solution of a-diazoacetophenone at 25-30°.

The major product of thermolysis at both temperatures is dilactone

VII. Large amounts of this white solid were deposited on the tube wall at completion of reaction, and more forms slowly upon admission of oxygen in the opened tubes. In addition to 7-norcaryl phenyl ketone, other products are formed in lower yields. At the higher temperature, 64 acetophenone is produced in 4$ yield. A peak immediately preceding that of 7-norcaryl phenyl ketone is found in 2$ yield and has an NMR spectra compatible with that expected for o-(l-cyclohexenyl) aceto phenone. Other products occurring in comparable or lesser yields were not isolated for identification.

A previous example of trapping benzoylmethylene generated by thermolysis of a-diazoacetophenone has been reported (68). Thermal

(68) H. Strzelecka and M. Simalty-Siematycki» Compt* rend., 252, 3821 (1961). decomposition of a-diazoacetophenone at an unspecified temperature in the presence of acenaphthalene provides XXXV in 10$ yield.

It was also reported that thermolysis in the presence of cis-1,2- dibenzoylethylene gave tribenzoylcyclopropane in 27$ yield. However» trans-1,2-dibenzoylethylene did not act as a carbenophile. The possible role of pyrazolines as intermediates in the formation of tribenzoylcyclopropane or ketone XXXV was not investigated.

In that the thermal decompositions of substituted a-diazoacetophenone appear to follow the same mechanism as that established for unsubstituted a-diazoacetophenone, the products of decomposition of these substituted a-diazoacetophenones were not studied in detail. 65

However* a V.P.C* analysis of the residue obtained on concentrating

the reaction solutions from kinetic experiments with ortho-methyldiazo-

acetophenone indicated the formation of a large number of products.

The greater than theoretical yield of gaseous products from thermolysis

of ortho-nitrodiazoacetophenone suggests that the divalent carbon atoms

of the reaction intermediates may react with ortho-substituents. Such

subsequent reactions of the divalent intermediates do not* however*

effect the mechanism of thermal decomposition for o-diazoacetophenones*

The cumulative evidence of both kinetic and product studies of

the thermal decomposition of a-diazoacetophenone indicates that a

carbenic species is the primary product of decomposition. This

carbene may suffer a variety of fates* Wolff rearrangement predominating.

Discussion of the Kinetics of Decomposition of Substituted a-Diazoacetophenones in Acetic Acid

Upon completion of the study of the effects of ortho-substitution upon the rates of thermolysis of a-diazoacetophenones* it was of inter

est to determine the influences of these same substituents upon the

rates of acetic acid-catalyzed decomposition of the diazoacetophenones

to phenacyl acetates.

'CHN,+ HOAc

This investigation would permit direct comparison of the effects of ortho-substituents on the kinetics of two reactions of a-diazoacetophenones. Further* the rates of acetic acid-catalyzed decomposition 66

of ortho-substituted diazoacetophenones may be compared with the

previous kinetic data for meta- and para-substituted diazoaceto

phenones (1) •

The rates of substituted diazoacetophenones in acetic acid were

determined from the volume of nitrogen evolved as a function of time

after injection of the diazoketone into acetic acid. Decomposition

of ortho-methyIdia zoacetophenone at 40° proceeded in a first order

manner with a half-life of 230 minutes. Subsequent studies were con- ✓ ° ducted at 60.05 i two satisfactory kinetic experiments with each diazoacetophenone were effected at this temperature. All decomposi

tions obeyed first order kinetics.

Upon injection of a toluene solution of ortho-methoxydiazoaceto-

phenone into acetic acid at 6o.05°» vigorous evolution of nitrogen

ensued. This result is consistent with the previously discussed ob

servation (^8) that this diazoketone reacts violently with acetic acid

to give coumaranone due to participation of the methoxy group with the

protonated diazo carbon atom.

0 ii cx ^ 0 CH N H O Ac ► \)H2 + C H 3- C

o X o c h 3

Measurable rates of decomposition of ortho-methoxydiazoacetophenone were obtained at 17.05°» slightly above the freezing point of acetic

acid. Two runs were made at this temperature.

Table 5 contains the rate constants and the half-lives at 60.05°

and 17*05° as determined in this study. Included in Table 5 are the Table 5 Acetic Acid-Catalyzed Decomposition of Substituted a-Diazoacetophenones

This Study Lane & Feller Yukawa & Tsuno Average Average, Average, Average, Substituent lO^k, sec"1 half-life (min.) 60.0° half-life, 6 0 .3° half-life, 40.0° half-life, 40.0° (ave. value in paren.) (min.) (min.) (min.)

-H 2.86 40.3» 40.5 (40.4) 36.0 235 252 ortho-Br 1.24 95.7, 91.3 (93-5) ortho-Cl 0.902 132, 124 (128) ortho-I 1.95 55.8,, 62.5 (59.2) ortho-CH. 3.06 38.0 , 37.5 (37.8) ortho-OCiL 24.5a 5.2, 4.25 ( 4.7)a ortho-NOo 3.39 37.8, 30»3 O . o ) meta-OCH^ 2.87 42.3, 38.3 O 0 .3) meta-NOo 0.814 138, 147 (142) 928 para-QCH^ 8.34 13.0, 14.7 (13.8) 89 para-NQo 0.608 187, 194 (190) 172.5 1095 1152 meta-Br 523 meta-CH-j 220 para-Br 58 .5 354 361 para-Cl 57.5 349 349 para-CH^ 22.8 141 159

1 At 17.05°

O' ->0 68 half-lives calculated from the data of previous decompositions of meta- and para-diazoacetophenones (1) catalyzed by acetic acid.

The relative rates of acetic acid-catalyzed decomposition of substituted a-diazoacetophenones are contained in Table 6. The rate constants of Lane and Feller (la) for a-diazoacetophenone were extrapolated graphically to provide a calculated half-life at 17.05°.

This value is compared with that for ortho-roethoxydiazoacetophenone at this temperature. Estimated half-lives for meta-bromo and meta- methyldiazoacetophenone at 6 0 .05° were calculated from the rate data of Yukawa and Tsuno (lb)» assuming that AH^ for decomposition of meta-substituted diazoacetophenones is equal to that for para- isomers -» 1 8 . 0 - 1 8 . 8 kcal./mole (la).

The products of decomposition of mata- and para-substituted a-diazoacetophenones are phenacyl acetates (Z-G^H^COCH^OAc) (1).

When a change in decomposition mechanism is brought about by partici pation of ortho-substituents such as methoxy- and nitro-» the products are coumaranone (48) and N-hydroxyisatin (47) > respectively.

The electrical effects of meta- and para-methoxy substituents lead to accelerated rates of decomposition for the corresponding a-diazoacetophenones relative to the decomposition rate for unsub stituted a-diazoacetophenone in acetic acid. Nitro-substituents* in either the meta- or pare-position, produce retardations in decomposi tion rates.

Three different sets of sigma constants were used to correlate the decomposition rates of meta- and para-substituted and unsubstituted

correlation 69

Table 6

Relative Rates of Acetic Acid-Catalyzed Decomposition of Substituted a-Diazoacetophenones

Average half-life (min.) Relative rate Substituent 60° 17.05° 60° 17.05'

-H 40.4 2940a 1.00 1.00 ortho-Br 93.5 0.43 ortho-Cl 128 0.32 ortho-I 59.2 0.68 ortho-CH^ 37.8 1.07 ortho-OCH-j — 4.7 625 ortho-NO„ 34.0 1.19 meta-Br 87b 0.46b meta-CH^ 37b 1.09b meta-OCH^ 40.3 1.00 meta-NOo 142 0.28 para-Br 58.5° 0 .61°' para-Cl 57.5° 0 .62° para-CH^ 22.8° 1.58° para-QCH^ 13.8 2.93 para-NO? 190 0.21

— Calculated from data of Lane and Feller (la). — Estimated value. £ Data of Lane and Feller (la). 70 coefficients (r) were calculated by a least squares treatment (42).

The results of these Hammett correlations are plotted in Figures 3 and 4.

Plots of log fcjr/kg against the corresponding normal Hammett o values provide the parameters: - -0.995? r = 0.987* Use of the

constants of Brown and Okamoto (43) affords better correlation of the rate data: f> = -0.728; r = 0.992. The data are best correlated

(figure 4) by using the available <**"constants of Yukawa and Tsuno (lb) for the para-methoxy- and para-nitro substituents and employing the

O’+ constants of Brown and Okamoto (43) for meta-substituents. This correlation provides a reaction constant of /a = -0.849; r = 0.999*

The rate constants for decomposition of ortho-substituted diazoacetophenones could not be correlated by available substituent constants.

Inspection of the data of Table 6 indicates that the relative rates of decomposition of ortho-halo- and ortho-methyl-substituted a-diazoacetophenones are less than those of decomposition of the corres ponding para-isomers. These ortho-substituted diazoacetophenones react at rates comparable to those for the corresponding meta-isomers.

Accelerated decomposition rates are observed when nitro and methoxy substituents are located in the ortho-position.

The half-lives for decomposition of a-diazoacetophenone and para- nitrodiazoacetophenone at 60° are approximately 10# greater than the values determined for these compounds by Lane and Feller (la). The half-lives determined by the experiments of Yukawa and Tsuno for the diazoacetophenones studied by Lane and Feller (see Table 5) are equal to* or as much as 12# greater than the corresponding rate values of 71

+0.6 p -O C R

+ 0.2

m — O C H -H

- 0.2 p = - 0 . 9 9 5

r = 0 . 9 8 7 rn - N 0 2 - 0.6 x p-NO;

N cr ( Ha m m e t t ) o>

+ 0.6

+ 0.2

- 0.2 - 0 . 7 2 8

0. 99 2

- 0.6

1.0 - 0.6 - 0.2 0 + 0.2 + 0.6 + 1.0 cr+ (Brown and Okamoto)

Figure 3. Hammett Relationship for Acetic Acid— Catalyzed Decomposition of meta - and para - Substituted oc -Diazoacetophenone. + 0.6

X + 0.2

m -0 C H -H o» o - 0 . 2 p = - 0 . 8 4 9

r = 0 . 9 9 9 m - N O

- 0.6 p- NO

- 1.0 - 0.6 - 0.2 0 + 0.2 + 0.6 + 1.0 cr+ (Yukawa and Tsuno)

Figure 4. Hammett Relationship for Acetic

Acid — Catalyzed Decomposition of meta- and para — Substituted c* — Diazoacetophenone. 73

Lane and Feller. These small deviations may be attributed to variations in experimental technique and reaction temperature or to slight dif ferences in the acetic acid used as solvent. Water will accelerate the decomposition rate; the decomposition of diazoacetophenone in 75$ aqueous acetic acid at 25 .2° is approximately twice that at 40° in glacial acetic acid (lc).

Valid rate comparisons of data of the present study with previ ously reported results appear possible when the differences are significantly more than 10$. Rate differences of less than 10$ are assumed to be insignificant. Inspection of the half-lives in

Table 5 reveals that with the exception of ortho-methoxy- and ortho- nitro-groups, substituents in the ortho-position of diazoacetophenone generally retard the decomposition rate relative to diazoacetophenone.

Further* the rate of decomposition of ortho-methyldiazoacetophenone at 60° (^1/2 = 37»8 is less than that of para-methyldiazoacetophenone = ^2.8 min.). At 40°» the decomposition of ortho- methyldiazoacetophenone = ^^0 min.) occurs at approximately the same rate as the meta-isomer = min.) but significantly slower than the para-lsomer ( t = 141-159 min.).

The decomposition rate of ortho-chlorodiazoacetophenone at 60°

(ti/2 = 128 min.) is less than that of the para-isomer (t^y2= 57*5 min.). The ortho- and para-bromodiazoacetophenones have half-lives of 93*5 and 58*5 minutes, respectively. Extrapolation of the half- life of 523 minutes for meta-bromodiazoacetophenone at 40° to 60°

(assuming to be approximately 1 8 .0 -18.8 kcal./mole) provides an approximate half-life value of 87 minutes. The meta- and ortho-isomers thus have similar rates of decomposition*

An acceptable mechanism for the acetic acid-catalyzed decompo sition of a-diazoacetophenone must explain a number of experimental observations. Correlation of the kinetic data for meta- and para- substituted diazoacetophenones by o + substituent constants requires a decomposition mechanism in which the transition state contains a positively charged center as delocalizable by the aryl nucleus. If a-diazoacetophenone is substituted by methyl and halo substituents in the ortho-position the rates of decomposition are comparable to those for the corresponding meta-isomers» but significantly less than the rates of the corresponding para-substituted diazoacetophenone*

Further* the fact must be explained that at 25°» decomposition of a- diazoacetophenone in 75$ acetic acid-25^ water occurs at a rate about ten times that in glacial acetic acid at 25° (rate in glacial acetic acid as estimated from AH*) (lc). The rate of decomposition of a- diazoacetophenone in aqueous dioxane in the presence of perchloric acid follows the Hammett acidity function Hq (46). It has been established by experiments in D^O + that protonation of diazoketones is reversible

(46). The following* similar in principle to the mechanism proposed by

Yukawa* Ibata, and Tsuno (see p.22) may represent the mechanism of acetic acid-catalyzed decomposition of a-diazoacetophenones; XXXVT

0 II HOAc c \ CH2- 0 Ac 4- H© xyyv n :

Alternatively, the a + correlation might be a result of direct phenyl

participation:

0 H C (2 ) \ — N2 c h 2 - n = n

o XXXVIII

HOAc CH2 — OAc © max + H The transition state (XXXVI) of mechanism 1 involves neighboring group participation of the carbonyl group. Similar participation of

the carbonyl group has been proposed for silver ion assisted solvolyses

of chloro ketones in 80$ ethanol (6 9 ) •

(6 9 ) D. J. Pasto and M. P. Serve* J. Am. Chem. 3oc.» 82* 1515 (1965).

(CH2)n ( C H 2)n

C6 H 4Z J4 ..Cl'' " ° « . W / / Ag Ag X L X LI

Where n = 3» the log kg/kjj was correlated by Hammett a constants, but

not by a + constants. The solvolyses were therefore assumed to proceed

through transition state XLI, where no delocalization to the aryl ring

occurs, rather than XL in which resonance with the aryl nucleus is

possible.

Developing positive charge in transition state XXXVI of mechanism

1 for acid-catalyzed decomposition of a-diazoacetophenone may be

delocalized via H interaction. Coplanarity of the carbonyl group with the plane of the aryl nucleus facilitates resonance stabilization of the transition state.

It may be reasoned that a substituent in the meta-position pro duces a lower rate of decomposition than the same substituent in the para-ppsition because of inability of the meta-substituent to stabilizei or delocalize through resonance interaction, an electron deficient reaction center in the transition state.

In transition state XXXVIII of mechanism 2, the COCH2 group is not coplanar with the aryl nucleus; the extent of delocalization of the developing positive charge would not be large unless there were marked participation of the aryl nucleus. In that this mechanism pre dicts marked steric acceleration by ortho-substituents, which is not observed, it may be excluded from further consideration.

The acceleration in decomposition of a-diazoacetophenone brought about by changing the solvent from glacial to aqueous acetic acid indicates that solvent effects are important in the transition state of the reaction. If the ground state for the acid-catalyzed decompo sition represented by the equilibrium:

is relatively non-polar (equilibrium to left), the ability of the solvent medium to solvate a charged transition state (and hence lower the potential energy of the transition state) may be expected to have a large effect upon the rate of decomposition. The accelerated rates of decomposition in aqueous acetic acid relative to those in glacial acetic acid may be explained by the fact that water will donate un shared electron pairs for solvation more readily than will acetic acid and that watert because of its smaller size* is less apt to be sterically restricted from a positive reaction site.

A mechanism for decomposition of substituted a-diazoacetophenones in acetic acid must account for the facts that ortho-halo- and ortho- methyldiazoacetophenones decompose less rapidly than do their corres ponding para-lsomers. The transition states for decomposition of para-methyldiazoacetophenone and ortho-methyldiazoacetophenone might be illustrated as follows: Considering only the stabilization provided by extended and cross-conjugated orbital overlap, the ortho-transition state would be of lower energy than the para-transition state. The electron- donor inductive effect of ortho-methyl is greater than that for the para-methyl group. This also would provide stabilization of the ortho-transition state relative to that for the para-. If the ground state potential energy of the ortho-isomer is greater or even equal to that of the para-isomer» ortho-methyldiazoacetophenone will be expected to decompose at a faster rate than does para-methyldiazoacetophenone•

Perhaps the most likely reason for retardation of the rate of decomposition of ortho-methyldiazoacetophenone relative to that of para-methyldiazoacetophenone in glacial acetic acid may be that the bulk of the ortho-methyl group restricts coplanarity of the transi tion state for reaction of ortho-methyldiazoacetophenone. With coplanarity prevented* delocalization in the transition state is minimized and the potential energy of the transition state is higher; the increase in activation energy leads to rate retardation for ortho- substituents relative to the corresponding para-isomers.

Other factors may retard the rate of decomposition of ortho- methyldiazoacetophenone relative to pa ra-methyldia zoac etophenone in glacial acetic acid. In the ground state, steric blocking by ortho-substituents may reduce the ability of the solvent medium to protonate the a-carbon atom. The equilibrium conversion to ketodiazonium ion will thus be lowered*

In the transition state for acetic acid-catalyzed decomposition 80

of ortho-methyldiazoacetophenone» solvation of the developing posi

tive charge may be restricted by the ortho-substituent. The potential

energy of the transition state may therefore be increased relative to

a more completely solvated transition state and the activation energy

is higher.

It was observed in this study that with increasing size of the ortho-halo substituent» the rates of decomposition increase. This is counter to the argument that restriction of coplanarity in the transition state causes rate retardation. For such acceleration it is possible that the non-bonded electrons of the halo-substituents participate in the transition state in the development of the elec tron deficient centers

This effect may operate simultaneously with neighboring group participation of carbonyl. With increasing size of the halo-substituent, there is greater proximity of its non-bonded electrons to the reaction site and hence the rates of decomposition increase in the order kCl kBr ^ kI* More dramatic ortho-participation effects are observed for ortho-methoxydiazoacetophenone and ortho-nitrodiazoacetophenone«

The accelerated rate of decomposition of ortho-nitrodiazoacetophenone

relative to the rates of the meta- and para-isomers is consistent 81 with the thesis (4?) that nucleophilic attack by the oxygen atom of the ortho-nitro-group upon the protonated diazo carbon atom is re sponsible for the formation of N-hydroxyisatin (XXIII).

0 ii C, HOAc CHISt CH2-N = N: —- II 0

c=o

Such participation may be responsible for the rate acceleration.

Similar participation by non-bonded electrons of the methoxy-oxygen atom is apparently responsible for the markedly accelerated rates of decomposition in acetic acid of ortho-methoxydjazoacetophenone.

CHp-N=N: HOAc

•CH3OAc, © H

A correlation of the rate ratios k^/k^ for thermal and acetic

acid-catalyzed decomposition of diazoacetophenones is contained in

Figure 5» That a rough correlation exists for meta-» and para-

and some ortho-substituents indicates that these substituents in M / k H Thermal Decomposition 0.5 ctc cd-Ctlzd eopstos of Decompositions Acid - Catalyzed Acetic Figure usiue Diazoacetophenones. Substituted _ O N - p log .Creain f ae o Teml and Thermal of Rates of 5. Correlation z/kH k / kz 5 . 0 - • — m NO o -Cl o- o- Br ctc a t lyzed a C - d i c A Acetic l - o 0 H - H C O - m o-NO, O N - o • H C - o H C O - p

82 general exert similar influences in both decomposition processes.

The divergence of the data for ortho-nitro*. and ortho-methoxydiazoacetophenone may indicate participation of these groups in the rate-determining step for acetic acid-catalyzed decomposition of these diazoacetophenones.

In that steric effects of the "normal" ortho-substituents ac celerate thermal decomposition and retard the rate of decomposition of diazoacetophenones in acetic acid* the correlation for these sub stituents may be fortuitous. As the ortho-halo substituents increase in size* the increased steric bulk should result in greater rate re tardation of acid-catalyzed decomposition; with the increasing size of the halo-atom (greater proximity of the non-bonded electrons to the reaction site) participation of non-bonded electrons might be enhanced. These effects are in opposition. The net result may be that the opposing effects largely cancel one another; therefore changes in ortho-substituent would have minimal effects on acid- catalyzed rates of decomposition. Such minimization of substituent effect would facilitate a correlation of rates of acid-catalyzed de composition with those of thermal decomposition.

Correlation of the rates of acetic acid-catalyzed decomposition of meta- and para-substituted diazoacetophenones by o + constants is in agreement with a mechanism in which delocalization of positive charge occurs in the transition state. Such delocalization can be accomplished through participation of the neighboring carbonyl group.

In acetic acid-catalyzed decompositions of ortho-substituted diazoaceto phenones, other participation mechanisms may operate concurrently. EXPERIMENTAL

General Procedures and Techniques

Melting and boiling points. Melting points were determined on a

Fisher melting point block or in oil or water baths. Unless otherwise noted, all melting points are uncorrected. All boiling points are un

corrected.

Elemental analyses. Elemental analyses were performed by Micro-

Analysis, Inc., Marshallton, Delaware, and by Galbraith Laboratories,

Inc., Knoxville, Tennessee.

Spectra determinations. Infrared spectra were obtained with Perkin-

Elmer, Infracord, Perkin-Elmer, Model 137» and Perkin-Elmer, Model 237 recording infrared spectrophotometers. The spectra of solid compounds were determined from pressed potassium bromide wafers. Spectra of

liquids were obtained from a film of the liquid between sodium chloride

blanks.

Ultraviolet spectra were obtained with a Perkin-Elmer, Model 202

recording spectrophotometer.

Nuclear magnetic resonance spectra were determined with a Varian

Associates nuclear magnetic resonance spectrometer, Model A-6o.

Vapor phase chromatography (gas-liquid chromatography). Vapor phase chromatography (V.P.C.) was often the method used for product

identification, separation, and purification and for composition

m analyses of reaction mixtures. The gas chromatograph employed was an

Aerograph* Model A-90-P* equipped with a hot-wire detector, connected to a one millivolt full-scale deflection Bristol Bynamaster recorder.

Helium was used as the carrier gas.

Columns in the gas chromatograph were prepared by packing copper tubing (outside diameter of l/4 or 3/8 inch) with either fire brick or Chromosorb W (42-60 mesh), coated with substrate, 20-3056 hy weight.

Columns of 1/4 inch outside diameter were used for product identi fication and composition analysis. Product compositions were deter mined from peak areas; corrections were not made for differences in the thermal conductivity of the compounds.

For preparative vapor phase chromatography, columns of 3/8 inch outside diameter were generally employed, although columns of 1/4 inch outside diameter were occasionally required for better peak separation.

The injected sample was varied in size up to a maximum of about 250 microliters depending upon the peak separation provided by the column.

The material represented by a peak was collected manually by attaching a coiled receiver to the detector exit as the peak was being recorded.

The receiver was made of Pyrex tubing (5 mm. outside diameter, length

30 cm.) wound into a coil and terminating at a bulb of 1-2 ml. capa city. This coil was wound around a straight piece of tubing (6 mm. outside diameter, length 10 cm.) that was connected to the bulb and served as a vent for the carrier gas and as a port for removal of collected material. As high as 9256 recovery of injected material could be attained through use of this type of receiver. Material for Kinetic Runs

Syntheses of substituted benzoyl chlorides. A weighed amount of

the appropriate benzoic acid was refluxed for 3 hours with at least a

3-molar excess of thionyl chloride. Occasionally several drops of

pyridine were added as catalyst. The thionyl chloride was removed

by distillation at atmospheric pressure. Anhydrous benzene (30 ml.) was then added to the residue and distilled off to aid in removal of

the last traces of thionyl chloride. The acid chloride was then distilled at reduced pressure. Experimental data relating to the preparation of the individual acid chlorides are contained in Table 7*

Synthesis of a-diazoacetophenones. The procedure of preparation

of a-diazoacetophenones from benzoyl chlorides and diazomethane was

similar to that of Newman and Beal (70). As a general procedure* a

(70) M. S. Newman and P. F. Beal, III, J. Am. Chem. Soc.» 71> 1506 (1949).

solution of benzoyl chloride (0.17 mole) in anhydrous ether (50 ml.)

was added dropwise in 20 to 40 minutes to an e+her solution (350 ml.)

of diazomethane (0.25 mole) and distilled triethylamine (18 g., 0.18

mole) cooled to 0-5°• Ether solutions of diazomethane were prepared

as described by Arndt (71). The ether solutions of diazomethane,

(71) F. Arndt, Org. Syntheses, Coll. Vol. 2, 165 (1943).

prepared from N-nitrosomethylurea, were dried for 2 to 3 hours before

use. Immediate vigorous evolution of nitrogen occurred upon addition

of the benzoyl chloride. The mixtures were stirred for 4 to 12 hours 8?

Table 7

Preparation of Substituted Benzoyl Chlorides z -c 6h^c o c i

Substituent Boiling point at P (m.m.) £ Yield o-Br 117.5-120.5 12.7 95 o-Cl 105-107 13.7 ca. 100 o-I 135.2-136.0 12.5 85 - pink solid, m.p. ca.29°

0-CH3 93.5-95.0 12 ca. 70 o-OCH-j 145.5-147.5 26 ca. 100 o-N02 “ 1 5 3 14.5 33

m-OCH-j 124 12 69 m-N02 154-155 15 95 - pale yellow solid

JD-OCH3 148.5 24 95

£-N02 151-153 15 95 - pale yellow solid

— Distillation of this benzoyl chloride has been reported to produce violent detonations - W. A. Bonner and C. D. Hurd* J. Am* Chem. Soc.» 6 8 , 344 (1946)* S. Hayao* Chem. and Eng. News* 42, No. 13» 39 (1964). 88 with no further cooling. The reaction mixture was filtered* the pre cipitate was washed several times with cold anhydrous ether (50 ml. portions)* and the filtrate collected was concentrated at reduced pressure (water aspirator). The crude product after evaporation of solvent was recrystallized as indicated in Table 8 until its melting point did not change (72»73)» All a-diazoacetophenones were stored

(72) All nitro compounds were not appreciably soluble in ether. The triethylamine hydrochloride was washed from the crude product using several portions (100 ml.) of water.

(73) Recrystallization of low-melting ortho-methyl-a-diazoacetophenone and ortho-methoxy-a-diazoacetophenone required use of a large excess of petroleum ether to prevent oiling-out of product. These compounds were recrystallized 3 to ^ times without observing melting point changes. at -15° in brown bottles washed in alcoholic potassium hydroxide. A sample of para-methoxydiazoacetophenone stored 3 years in this manner was unchanged. Table 8 contains information pertinent to the pro perties and preparation of the diazoacetophenones used.

Materials Used for Kinetic Measurements

Cetane (hexadecane). Humphrey-Wilkinson* Inc. ASTM Normal Cetane was washed with fuming sulfuric acid* concentrated sulfuric acid* sodium carbonate solution, and water. It was dried over potassium hydroxide and distilled (b.p. 159»8-l6o.4°/l5 mm.) under vacuum from calcium hydride. Analysis by V.P.C. revealed the cetane to be greater than 99•5% pure. Table 8

Preparation of Substituted a-Diazoacetophenones

Melting point (°Cj Analysis Substituent Solvent Found Reported Calculated Found none b o-Br Pet. ether (30-60°) 46.8-47.5 49-50 Vt o-Br 42.0 42-43° C,42.69; H,2.24; N,12.44 C,42.52; H,2.51; N»12.45(D) n o-Cl 48.7-49.6 50-51d C,53.28; H,2.79; H»15.50 0,53.34; H,2.86; N,15.30(D) it o-I 60.2-60.9 — c» 35.31; H,1.85; H,10.29 0,35.45; H,1.8l; N,10.49(D) it o-CH^ 21.0*22.2 — 0,67.49; H»5.03; N.17.49 0,67.31; H,5.00; N,17.73(D) N o-OCH^ 25.0-26.2 19-20d C,6l.36; H,4.58; N.15.90 C,60.48; H,4.35; N, 15.94(D) 60.69 4.29 o-N02 Absolute methanol 104.5-105.0 105-106e m-OCH^ Benzene-pet* ether 35.2-35.9 — 0 ,6 1 .36; H,4.58; N.15.90 0 ,61.20; H,4.64; N,16.07(D) m-N02 Absolute methanol 148.5-149.5 146-I47d

J2-0CH3 Benzene-pet# ether 90.2-90.7 90-91f

£-N02 Absolute methanol 120.0-120.6 117-H8g

t For recrystallization, £ L. Wolff, Ref. 2. - W. D. Horraann and E. Fahr, Ann., 663, 1 (1963)* — W. Kirase and L. Homer, Ref. 27. 2. F. Amdt et_al., Ref. 4a. _ A. Burner and S. Avakian, J. Org. Chem., jj>, 606 (1940). £ Karrer and J. Sehukri, Helv. chim. acta, 28, 820 (1945)• 90

Tetraglyme (tetraethyleneglycol dimethyl ether). Ansul Ether-181 was stored over sodium wire and distilled (b.p. 138.7-139.5°/9»3 mm.) twice from calcium hydride.

Quinoline. Eastman quinoline (white label) was dried* distilled from potassium hydroxide (b.p. 105*2°/11 mm.), and stored under nitrogen. Analysis by V.P.C. showed no impurity.

n-Decanol. Matheson, Coleman and Bell n-decyl alcohol was dis tilled (b.p. 127.5-129.8°/21.5 mm.) from calcium hydride. Analysis by V.P.C. indicated the presence of trace amounts of high boiling impurities.

Tenox BHA. Tennessee Eastman Corp. Tenox BHA (Butylated Hydroxy- anisole) was recrystallized twice from Skelly B, yielding white needles, m.p. 5 8 .0-58 *8°.

Tenox BHT. Tennessee Eastman Corp. Tenox BHT (Butylated Hydroxy - toluene) was vacuum sublimed (8 mm.) to provide white crystals, m.p.

6 9 .0-6 9 .8°.

Tri-n-butylamine. Katheson, Coleman and Bell tributylamine was dried over calcium hydride, distilled (b.p. 8l.5°/7.5 mm.) from calcium hydride and stored under nitrogen. V.P.C. analysis demonstrated the amine to be of purity greater than 99*5$•

Cyclooctane. Columbian Carbon Co., Inc. cyclooctane was washed in a manner identical to that of cetane. Before distillation, dry nitrogen was bubbled through the cyclooctane, and it was then dis tilled (b.p. 1^9«0-14’9.6°) under nitrogen from calcium hydride at atmospheric pressure. 91

DABCO (1,4-dlazoblcyclooctane). Houdry DABCO was sublimed under

vacuum to give white crystals, m.p. I56-I570 .

Tri-n-propylamine. Pennsalt tripropylamine was purified by

1) distillation at atmospheric pressure using a one-foot glass bead

column, 2) passage through a column of Woelm basic alumina (material was no longer collected when the visible colored bands neared the

bottom of the column), 3) passage for several hours of dry nitrogen

through the tripropylamine in the distillation pot, and 4) distilla

tion from calcium hydride under nitrogen. The first one-tenth of the material distilled was re-submitted to the purification cycle. The

remaining distillate boiled constantly at 155*6°. Air was rigorously

excluded from contact with the collected tripropylamine. Transfer

of solvent was conducted under nitrogen.

Di-n-butylamine. Matheson% Coleman and Bell dibutylamine was dried over potassium hydroxide and distilled (b.p. 158.0°) from

potassium hydroxide.

Di-n-propylamine. Pennsalt dipropylamine was dried over potas

sium hydroxide and distilled under nitrogen (b.p. 108.8-109»^°) after

thorough flushing of the amine with dry nitrogen.

1-Chloronaphthalene. 1-Chloronaphthalene was distilled. The

first one-third was discarded, and material distilling at 114.8-117.8°/

9 .5 was collected and stored under nitrogen.

Acetic acid. Baker acetic acid (analytical reagent, 99*9$ assay)

was refluxed 10 hours over chromic oxide and distilled from chromic

oxide under nitrogen in a 3-^oot glass helix column. The first one-

third of the distillate was discarded, and the remaining material 92 was collected at 115»0-115»2°. The purified acetic acid was stored

and transferred under dry nitrogen.

Toluene. Baker toluene (analytical reagent) was distilled under

nitrogen. The first one-quarter of distillate was discarded* and

the last quarter was left in the pot. The middle fraction was stored

and transferred in a dry nitrogen atmosphere.

Procedure for Kinetic Runs

Constant temperature bath. A thermostated bath filled with

Carbowax 400 (polyethylene glycol - Union Carbide Chemicals Co.) was used with Tenox BHA added as inhibitor. Temperatures were main

tained within ±0.05° through use of a Jumo thermoregulator and a

suitable relay. Temperatures were measured with Anschutz thermometers which were calibrated against National Bureau of Standards certified

thermometers. To maintain temperatures at 60° and below* a Sargeant

Heater and Circulator were employed.

Thermal decomposition procedure. Kinetic measurements using

tripropylamine as solvent were carried out by the procedure to be

described. When other solvents were used, the same general procedure

applied* and in these cases the co-solvent was used as the solvent

to inject the sample.

All reactions were carried out in a modified 500 ml. round bottom

flask (Figure 6 ). A condenser of 10 cm. length (22 mm. inside dia

meter) replaced the neck of the flask; immediately above the condenser

was a side ana (gas exit) of 8 mm. tubing as a connection to a gas

buret; directly above the side arm was a flanged lip (inside diameter 93

Stirring shaft

.cx Ring clamp

Gas exit

Capillary Condenser gas inlet tube

" 50 0 ml. Round bottom flask

Figure 6 Modified Reaction Flask 9**

22 mm.) with built-in ring to hold the Vibro-mixer (7*0 stirring

(7*0 Vibro-mixer, Patented Dr. Ing. H. Muller, A. G. fur Chemie- Apparatebau. Mannedorf - Zurich - Switzerland. shaft. A gas inlet side arm of capillary tubing (2 mm. inside diameter,

7 mm. outside diameter), parallel to the condenser, was ring-sealed into the flask. The end of the capillary tube extended to the 250 ml. level of the flask. From the ring seal this side arm extended up ward 16 cm. Near the top a stopcock was sealed perpendicular to the side arm; its purpose was to control the flow of nitrogen into the flask.

Before use, the flasks were washed with Haemo-Sol, an alkaline detergent, dried, and flushed thoroughly with high-purity dry nitrogen.

Tripropylamine (350 ml.) was then transferred to the reaction flask under a dry nitrogen atmosphere. The Vibro-mixer stirring shaft

(1 mm. inside diameter, 7 outside diameter Pyrex capillary tubing; total length 50 cm.) was then put in place. The first 8 cm. (from the bottom) of the stirrer shaft was a tightly-wound coil (9 turns) of outside diameter 21 mm. A rubber hermetic seal held the shaft from hitting the bottom of the flask and provided a leak-free system while the shaft was vibrated by the stirring motor. This type of stirrer provided mild circulation of the reaction mixture, but vigorous surface agitation, as is desirable for establishing rapid equilibrium of nitrogen between the liquid and gas phases.

After the rubber serum vial cap and the connection to the gas buret were wired tight and the system was tested for leaks under 95 pressure* the flask was placed in a constant temperature bath, and the system was allowed to come to thermal equilibrium. The water- cooled condenser neck prevented reflux of solvent into the capillary- tubing connection to the gas buret. The base of the condenser was

surrounded by aluminum foil for thermal insulation and to exclude light.

In order to avoid water condensation* the container containing the diazoacetophenone was brought to room temperature before ca.

0.002 moles was weighed into a 30 ml. weighing bottle. To the weighing bottle was added 15-25 ml. of tripropylamine to dissolve the diazoacetophenone (75) • The solution was injected into the hot

(75) For all nitro compounds and for both meta- and para-methoxydiazoacetophenone* 7-10 ml. of 1-chloronaphthalene was used as initial solvent. Slight warming was required to dissolve the nitro compounds. amine using a 20 ml. hypodermic syringe fitted with a 10 inch 18 gauge needle. The time when all of the solution had been injected was con

sidered t . The resultant hot reaction solution was ca. 0.006 molar o — in the diazoacetophenone.

The volume of nitrogen evolved was measured as a function of time,

using a gas buret system previously described (76). The gas buret was

(76) R. C. Peterson* J. H. Markgraf* and S. D. Ross, J. Am. Chem. Soc., 8 3 , 3819 (1961).

modified to permit compensation for changes in the external atmospheric

pressure* thus maintaining a constant pressure in the system during a

kinetic run. For this purpose, the gas buret (100 ml. capacity) was equipped with a parallel side arm of 6 mm. I.D. tubing connected both above the zero mark and at the base. Parallel to this side tube was an identical tube* open to the atmosphere. As the atmospheric pressure changed during a run* the mercury levels in the side tubes were adjusted to make the pressure in the system equal to its initial pressure. Ejy calibration of the volume of the side tube* it was found necessary to multiply the buret reading (B) by a factor of 1.147 to obtain the number of milliliters of nitrogen evolved. Corrections for changes in ambient temperature were made for the volume of gas in the buret plus the volume of the system extending to the gas exit of the reaction vessel.

The reactions were allowed to proceed for seven to ten half-lives to obtain an experimental infinity value for the buret reading (B).

The buret readings were not converted to milliliters (since a direct linear relationship exists), but were used (after temperature correction was made) directly for calculation of half-lives and rate- constants. Plots were made of Vco- (or B qq-B^) versus minutes on two-cycle semi-log paper. The visual straight line provided half- life and rate constant values. Occasionally when the reaction had been shown to be first order, the analytical method of Guggenheim (77)

(77) E. A. Guggenheim* Phil. Mag., 2, 538 (1926). was employed* and the reaction was not followed to completion. Agree ment between the two methods was good. As a rule* three kinetic runs were made at each of three different temperatures. Reactions catalyzed by acetic acid* A modified flat-bottomed

150-ml. extraction flask was used as reaction vessel (Figure 7).

To the flask was joined a straight 7 cm. side arm of 8 mm. Pyrex tubing.

This served as the inlet for charging the flask with solvent and for sample injection. Opposite the inlet tube was another straight side arm of length 10 cm. and outside diameter 14 mm. Sealed to its end was a 28/15 ball-joint socket. During a run this socket was tightly clamped to its counterpart, which was built into a small water-cooled condenser of length 12.5 cm. and inside diameter 6 mm. The condenser prevented solvent vapors from entering the gas buret, to which it was connected by means of ‘tygon tubing and capillary glass tubing.

Into the wide mouth of this flask was tightly fitted a number seven Neoprene stopper holding a complete Vibro-mixer stirring as sembly. The glass stirring plate was of J1 mm. diameter, only slightly less than that of the neck of the flask. When in use, this stirring arrangement forced liquid toward the bottom and created sur face agitation while providing a leak-free system.

Kinetic runs were conducted in the following manner. The flask and stopper holding the stirring assembly were joined and connected to the buret by clamping the ball joint (sealed with stopcock grease).

Through a three-way stopcock the system was flushed with dry nitrogen for 5-10 minutes. The inlet tube was capped and the system was checked for leaks under pressure. Acetic acid (75 ml.) was pipetted in under nitrogen. The flask was clamped into position in the constant tempera ture bath and allowed to attain thermal equilibrium. Approximately

0*002 moles of the diazoacetophenone were weighed in the manner Figure 7. Reaction Vessel forAcetic Acid--Catalyzed Decomposi- tion of Diazoacetophenones. \o 00 99 described previously. Dry distilled toluene (5»0 ml.) was added to dissolve the material. The nitro-substituted diazoacetophenones were only slightly soluble in toluene. To dissolve these compounds, either acetic acid or a toluene-acetic acid mixture was used. In the former case, 5.0 ml. of toluene was injected into the hot acetic acid prior to sample injection; the solvent composition was consistent with that for the runs with other substituted diazoacetophenone, i.e* 75 acetic acid and 5 nil. toluene.

Injection of the sample solution into the acetic acid, measure- , ment of gas volume evolved, and determination of kinetic parameters were carried out in a manner identical to that described for the thermal decomposition in tripropylamine. All diazoketones, with the exception of ortho-methoxydiazoacetophenone> were decomposed two times at 60.35lo.05°* In an attempt to decompose the ortho-methoxydiazoacetophenone at 60°, a vigorous reaction resulted which could not be followed kinetically. Two kinetic experiments for this com pound were conducted in acetic acid at 17.0510.05°.

Development of Solvent System for Thermal Decomposition

Initial attempts to follow the rate of decomposition of para- methoxydiazoacetophenone at 80° in bromobenzene indicated that a considerably higher temperature would be required to effect measurable decomposition. Subsequent rate determinations were made using cetane

(hexadecane) as solvent. The hydrocarbon was selected because of its availability in high purity, its low vapor pressure at the temperatures used and because it was hoped that the products of Wolff rearrangement 100 such as ketenes or ketene dimers might be isolable from such an aprotic solvent. Tetraglyme (tetraethylene glycol dimethyl ether) was selected as a cosolvent for injecting the diazoketone into hot cetane in the equilibrated gasometric system. The methods used for measurement of nitrogen evolved as a function of time have been discussed.

Thermal decomposition of para-methoxydiazoacetophenone at 111° in cetane (tetraglyme as cosolvent) proceeded in a first order manner with a half-life of ca. 330 minutes. Another experiment at the same temperature using only tetraglyme as solvent had a half-life of 335 minutes. Subsequent decompositions of o-diazoacetophenone in cetane at 110° and 119° obeyed first order kinetics with half-lives of 430 and 236 minutes respectively (Figure 8 ). The latter experiment had a short induction period. In these runs oxygen had not been excluded from the solvent ty purging with dry nitrogen for extended periods.

When a-diazoacetophenone was decomposed at 119° in cetane from which oxygen had been removed*, the results of very similar experiments were non-reproducible. Of nine runs* all had induction periods of varying length. In some cases the plot of log (V^ -V^) versus time never did resemble a straight line. In those experiments in which an apparent first order decomposition eventually became established* the half-lives varied from 122 to 240 minutes. For the decomposition in which the half-life was 240 minutes* tetraglyme was absent. Typical plots of log (A^ -V^) versus time for these experiments appear in

Figure 9»

It was believed that these deviations from first order kinetics 101

o— at 110.2° (t| = 430 min.)

-a t 119.1° (+i = 236min.)

o»

0.5

0 500 1000 1500 1700 Minutes — ► Figure 8. Thermal Decomposition of Diazoacetophenone in Cetane. log ( V 0.0 2.0 1.0 iue . hra Dcmoiin f ^-Diazoacetophenone of Decomposition Thermal 9. Figure n eae t 119° at Cetane in 200 0 800 600 0 0 4 iue — Minutes o o — 1000 — 236 min. 236 — 7 min.175 3 min.I 23 1200

102 103 were due to autocatalysis, resulting possibly from acid formed during the decomposition. Reaction of possible trace amounts of water in the solvent with phenylketene formed by Wolff rearrangement was considered a possible source of the acid catalyst. Rigorous exclusion of water, however, during purification of the solvents did not eliminate the apparent autocatalysis. In all of these reactions, formation of the white crystalline lactone dimer VII was observed.

At this stage of the investigation, the previously discussed results of Yates and Clark (14) were discovered.

It was of interest to determine if a tertiary amine, such as quinoline, would be effective in preventing autocatalysis. Thermoly- ses of diazoacetophenone in cetane at 119° with quinoline as cosolvent

(5 ml., 0.12 molal) had induction periods; the half-lives of two ex periments were approximately 270 and 290 minutes respectively. Attempts to make kinetic measurements using cetane with dodecanol and quinoline present gave poor results.

Effort was then made to duplicate by a gasometric measurement procedure the conditions and results of Yates and Clark, who had fol lowed the rate of disappearance of diazoketone by measuring the decreasing intensity of the infrared absorption of the diazo band.

They had found the analytical procedure of measuring evolved nitrogen to be unpromising because the solubility of the diazoketone in decanol is small, the rate of solution is slow, and vigorous agitation of the reaction vessel in the constant temperature bath was inconvenient.

From the present work it is believed that the technique of injecting 104

a diazoketone with a cosolvent into hot solvent agitated by a Vibro-

mixer surmounts these previous objections to the use of a gasometric

measurement technique.

Yates and Clark found that thermal decomposition of a-diazoaceto-

phenone in decanol in the presence of air exhibited autocatalysis.

Two products of these decompositions were decyl phenylacetate and

decoxyacetophenone. In the early stages of decomposition* decyl

phenylacetate was the more rapidly formed. As the decomposition pro

ceeded* the rate of formation of decoxyacetophenone became greater

than that of the ester. Since decoxyacetophenone is the expected

product of acid-catalyzed decomposition of a-diazoacetophenone in decanol the autocatalysis was presumed to result from formation of

acid during the experiment. Oxidation of decoxyacetophenone was sur

mised to be the source of the acid catalyst.

Yates and Clark found that decomposition of a-diazoacetophenone

(ca. 0.016 molar) in decanol in the presence of quinoline (0.11 molar)

and Tenox BHA (0.0033 molar), with or without exclusion of air followed

first order kinetics. The results are summarized in Table 9«

TABLE 9 The Decomposition of a-Diazoacetophenone in Decanol- Quinoline-Tenox BHA (Yates and Clark)

TempAverage lO^k, secAverage half-life (min.)

129.5 1.00 115

139.2 2.75 41.8

148.6 7.17 9.65 offfc = 34.2 kcal 105

The possibility that decanol was oxidized to acid was excluded by following the rate of decomposition in decanol that had been heated with air present for several hours prior to reaction. Upon addition of Tenox BHA and diazoketone to this decanol* first order kinetics were demonstrated.

Yates and Clark also found that the course of thermal decomposi tion of a-diazoacetophenone in dodecane in the presence of decanol

(0.03 to 0.37 molal) and tertiary amine (quinoline* 0.16 molal; tributylamine* 0.08 molal) was dependent on the presence of air. Decompo sition (at 140°) to give decyl phenylacetate was the only detectable reaction when a-diazoacetophenone was heated in dodecane containing quinoline and decanol without exclusion of air. .vith no air present, thermal decomposition in this solvent system led to much more rapid disappearance of diazoketone. Very little decyl phenylacetate was produced and the infrared spectrum of the product mixture was complex, indicating a number of products. These could not be identified. The presence of Tenox BHA did not inhibit the formation of these products.

It was further determined that the rate of decomposition of a— o diazoacetophenone at 100 is not accelerated ty benzoyl peroxide nor is its decomposition accelerated at 120° by tert-butyl perbenzoate.

On the other hand* when tributylamine is used in place of quino line in the presence of air, the reaction proceeds at a faster rate and leads to formation of unusual products that can be considered to arise from reaction of oxygen with a-diazoacetophenone. These are: a-benzoxyphenylacetic acid (12$)* N»N-dibutyl-2-phenylacetamide (12$), benzoic acid (5$) and decyl phenylacetate (333&)• In the absence of 1 0 6 air in this solvent system* decyl phenylacetate is the only detectable product and the reaction proceeds in a first order manner.

Attempts were made* using a gasometric technique* to duplicate the kinetic results of Yates and Clark. The concentration of a-diazo acetophenone (0.006 molar) was less than that used by Yates and Clark, but the concentrations of quinoline and Tenox BHA were the same. Oxy gen was excluded by distilling the solvents under nitrogen and purging the reactor and solvent, prior to reaction, with dry nitrogen of high purity. A plot of log versus time for the first run at 119° showed no autocatalysis and a first order half-life of 308 minutes.

A second run appeared to be autocatalytic; a straight portion of the curve for data of this run provided a half-life value of 220 minutes.

In attempts to follow the rate of decomposition at 129.7°* auto catalysis was found in more than half of the experiments. Half-life values ranged from 82 to 129 minutes (ave. 96 min.). Results were not improved by increasing the concentration of quinoline and omitting the antioxidant. In one reaction where a very small amount of water was injected into the reaction mixture, nitrogen evolution became extremely rapid after a short induction period. Water could not, however, have been responsible for the previous instances of auto catalysis .

The products of decomposition of diazoacetophenone (four runs) in decanol at 129.7° were analyzed after removal of most of the decanol by vacuum distillation. Decyl phenylacetate was the major product* predominating over decoxyacetophenone by ratios of from 2:1 to 1 2 :1 .

Small amounts of other unidentified products were detected. 107

Communication with Professor Yates concerning these difficulties

in obtaining satisfactory kinetic data revealed that Clark had at

tempted to reproduce the previous infrared spectrophotometric kinetic data using a gasometric technique but as yet had not been able to do

so.

The decanol-quinoline-Tenox BHA system was abandoned and a study was made of decomposition of a-diazoacetophenone in the solvent system

cetane-tributylamine at 130° under nitrogen. Water was rigorously

excluded from the solvents. Oxygen was not rigorously excluded in distillation of the solvents or in subsequent transfer steps. Dry nitrogen was bubbled through the solvent in the reaction flask for several hours prior to each kinetic run. Various amounts of the tertiary amine were used. The amine was also employed as a cosolvent to dissolve and inject the diazoketone into hot cetane (350 ml.).

Results of typical kinetic experiments in this solvent system are summarized in Table 10. All decompositions obeyed first order kinetics and evolution of nitrogen was essentially quantitative.

The reaction solutions at completion of decomposition were clear

and yellow. On cooling> solutions 0.12 molar in amine precipitated small quantities of lactone dimer VII. Less dimer was observed in

those solutions 0.23 molar in amine and none was detected when amine concentrations were 0.33 molar.

Identical conditions (0.33 molar in tributylamine) were employed

to effect thermal decompositions of ortho-nitro- and o rtho-methyIdia zoacetophenones. In decomposition of ortho-nitrodiazoacetophenone > a small amount of quinoline was used to aid dissolution of the diazoketone. 1 0 8

TABLE 10

Decomposition of a-Diazoacetophenone in Cetane- Tributylamine at 130.5°

Diazoketone conc. Bu?N conc. half-life (molar) (molar) (minutes)

O.OOlf 0.12 (10 ml.) 97

N 0.12 t« 9^

It 0.23 (20 ml.) 13 5

It 0.23 tt 119

tt 0.33 (30 ml.) 122

It n 0.33 138 «• 0.33 n 132

Decomposition proceeded in a first order manner with a half-life of

17.3 minutes. Three decompositions of ortho-methyldiazoacetophenone obeyed first order kinetics with half-lives of 9*8, 10.9» and 9»9 minutes respectively. Quantitative evolution of nitrogen was observed.

Continued use of cetane was undesirable because of its various carbon-hydrogen bonds. Possible carbenic or radical intermediates from decomposition of diazoketones could react with 8 different types of C-H bonds and form a multitude of products. To possibly simplify product studies, the symmetrical hydrocarbon cyclooctane was chosen to replace cetane. In addition to the advantage that its C-H bonds are indistinguishable, cyclooctane was available in high purity and had a sufficiently high boiling point (151°) yet one low enough to enable its removal by distillation from the higher boiling products 109 of the reaction. A tertiary amine of similar boiling point was re quired to replace the high-boiling tributylamine. By virtue of its availability, N»N-dimethylcyclohexylamine (b.p. 164°) was selected.

Three decompositions of a-diazoacetophenone (0.013 to 0.017 molar) were effected in cyclooctane containing N ,N-dimethylcyclohexylamine (0.7 to 1.0 molar) at 130.5° in a dry nitrogen atmosphere

(exclusion of oxygen not rigorous). These first order decompositions had half-lives of 131» 139 and 127 minutes. The solutions, at com pletion of reaction, were clear and of a deep yellow color. Vapor phase chromatographic analysis of the dark liquid after removal of sol vent revealed at least 10 volatile products. Two of these comprised about 90$ of the volatile portion of the reaction products. Small amounts were collected as these compounds were eluted from the column.

The first of these (representing 4-0 per cent of the volatile material) could not be isolated in purity sufficient for characterization.

The second major peak (ca. 50 per cent of volatile material) had a boiling point estimated to be above 300°. Elemental analysis, spectral measurements and a molecular weight(^termination suggest XLII as the structure of this substance.

\ N

CH„ mi

For the purpose of simplifying product studies, N ,N-dimethylcyclohexylamine was replaced by 1,4 diazabicyclo [2.2.2] octane (DABCO).

6 110

This tertiary amine is of such symmetry that all carbon atoms have identical environments* thus leading to a minimum number of products.

Because DABCO is a solid (m.p. 158°; b.p. 17^°)» kinetic runs were conducted by injecting a solution of a-diazoacetophenone in mesitylene

(3 ml.) into cyclooctane containing dissolved DABCO (O.l^f and 0.28 molar). Rigorous precautions were taken to exclude water from the materials, but oxygen was excluded only by passage of dry nitrogen through the solvent for several hours prior to reaction. Two decom positions of a-diazoacetophenone (ca. 0.12 molar in this solvent at

130*5° proceeded as first order processes with half-lives of 92 and

106 minutes. Neither concentration of DABCO was sufficient to prevent the formation of lactone dimer VII which precipitated out of the clear deep yellow reaction solutions upon cooling. Notably less lactone dimer was formed, however, at the higher concentration of DABCO.

Because of the experimental difficulty of purifying large quan tities of DABCO (which is hydroscopic, forming mono- and hexahydrates) and because the two runs made in its presence seemed to occur at slightly faster rates than previously observed, its use was discon tinued. If the function of tertiaiy amine is to neutralize acid formed in the reaction, the fact that DABCO is a weaker base than is a trialkyl amine (78) also legislated against its continued use.

(78) A. Farkas, G. A. Mills, W. E. Emer, and J. B. Maerker, Ind. Eng. Chem., 1299 (1959).

After removal of most of the solvent by distillation at reduced pressure, the product residue of these runs in the presence of DABCO Ill was examined by V.P.C. One peak comprised about 70$ of the V.P.C. volatile material. Several other peaks were obvious. A small amount of this material was collected as the peak was eluted from the column.

It formed a 2 A-dinitrophenylhydrazone which could not be identified.

The experimental attempts to identify it will be described.

Tripropylamine was substituted for DABCO. This tertiary amine is the simplest alkyl amine of suitable boiling point (156°) available in commercial quantities. Decomposition of a-diazoacetophenone in cyclooctane at 130.5° with tripropylamine present (concentrations greater than 0.^5 molar) obeyed first order kinetics. Small amounts of mesitylene (3-7 ml.) were used to inject the diazoketone into the hot solvent. Oxygen was excluded only by passage of nitrogen through the solvent prior to reaction.

The solvent system was simplified further by omitting cyclooctane and mesitylene. Nine decompositions of a-diazoacetophenone and three of ortho-methyldiazoacetophenone in tripropylamine alone proceeded in first order fashion. The kinetic reactions were run henceforth in about 370 ml* of amine* 20 ml. of which were used to dissolve and in ject the diazoketones. In kinetic runs with meta- and para-substituted diazoacetophenones small amounts of 1-chloronaphthalene are used as injection solvent because it is impossible to dissolve the nitro- substituted diazoacetophenones in tripropylamine at room temperature•

Before commencing with extensive kinetic measurements* it was of interest to examine di-n-butylamine (b.p. 159°) as a reaction solvent.

This secondary amine offers the advantage that it reacts rapidly with any phenylketene formed* and thus reduces the number of products and 112 possible complications. Two decompositions of a-diazoacetophenone were effected in the solvent at 130.5° under the conditions previously described for runs with tripropylamine. The plot of logCV^ - V^) versus time for the first of these experiments roughly described a straight line with a slight upward concave curvature. The half-life was about 90 minutes. The reaction solution was clear and colorless.

The second run under seemingly identical conditions* occurred much more rapidly. Use of this solvent was discontinued.

Product Studies

Products of Thermal Decomposition of g-Diazoacetophenone in Tripropylamine

A saturated solution (128 ml.) of a-diazoacetophenone (4.561 g.j

0.031 mole) in tripropylamine was added in small portions (ca. 20 ml.) to refluxing tripropylamine (100 ml.) in 4 hours. The tripropylamine had been distilled and stored Tinder nitrogen. The reaction vessel had been thoroughly purged with pure* dry nitrogen prior to addition of reagents. While the reaction mixture was still hot* a sample of the gas immediately above the surface was analyzed on a Dowtherm A column at room temperature. In addition to nitrogen, there were three peaks accounting together for less than 5 per cent of the total gas volume.

The major of these had a retention time identical to that of carbon dioxide. Having a total areasbout one-tenth that of the major peak, were two peaks in a 1:3 ratio. The second of these had the retention time of authentic propylene; the first, a shoulder of the propylene peak, had the retention time of propane. 113

A small amount of the reaction solution (5 ml.) was saved for quantitative V.P.C. analysis of the products. The remaining solution

(after filtering out small quantities of lactone dimer VII) was con centrated by distillation of the tripropylamine at atmospheric pressure. This concentrate was vacuum-distilled to collect products distilling at l60°/l.0 mm. Vapor phase chromatographic analysis

(SE 30 column) of this distillate revealed eleven products up to and including a peak having the retention time of authentic N,N-dipropyl-

2-phenylacetamide. The identity of this amide* the major volatile product, was confirmed by comparison of its infrared spectrum with that of authentic material (b.p. 139.0°/2.4 mm.). The spectra were identical in all respects: carbonyl absorption at 6 . U p.. Two other products, the first and third eluted, were present in amounts suffi cient to warrant their collection by preparative V.P.C. methods.

The lowest-boiling product had a retention time identical to that of authentic acetophenone. As the product was eluted from the column, the eluent gas was passed through 2,4-dinitrophenylhydrazine reagent

(2 ml.) that had been diluted with 95$ ethanol (2 ml.). Immediate formation of a solid was observed. This solid, after reciystalliza- tion from ethyl acetate, gave red needles whose mixed melting point with authentic acetophenone 2,4-dinitrophenylhydrazone was not de pressed (m.p. 248-249°). The infrared spectra of the 2 ,4-dinitrophenylhydrazone and acetophenone 2,4-dinitrophenylhydrazone were identical.

The boiling point of the third product eluted from the column was estimated to be about 240°. It was collected as a pleasant smelling, colorless liquid. Carbonyl absorption at 5»84 p was noted in the 114 infrared spectrum. The NMR spectra had singlets at 2.82 t and 6.45 T> a triplet centered at 7*72 T and a complex absorption pattern centered at about 9*0 t . The integrated relative intensities of these peaks were 5*1*8:2.5*8. The presence of small amounts of impurities was indicated. Upon addition of 2 ,4-dinitrophenylhydrazine reagent to an ethanolic solution of this compound, a slow growth of crystals de veloped. Filtration and washing with cold ethyl alcohol gave bright yellow needles, m.p. 126.8-128.4°. On recrystallization from boiling

95 per cent ethyl alcohol, decomposition or isomerization of the 2,4- dinitrophenylhydrazone occurred, as evidenced by a darkening of the solid and a change in the melting point to 123-143°• These properties are consistent with those of l-phenyl-2-pentanone (XLIII) a liquid of

0 II J2f — CH 2 — C — CH 2 C H 2 CH 3

■ XXJTL boiling point 244° (79)* The melting point of the 2,4-dinitrophenyl-

(79) I- Heilbron, "Dictionary of Organic Compounds," Vol. 4, Oxford University Press (1953)> P« 244. hydrazone of this ketone is reported to be 129.5-130»5° (80). As

(80) E. T. Gilsdorf and F. F. Nord, J. Am. Chem. Soc.» 74, 1837 (1952). authentic l-phenyl-2-pentanone was unavailable for purposes of direct comparison, this structural assignment is only tentative. 115

The red tarry residue remaining after distillation of products volatile at l6o°/l mm., was chromatographed on an SE 30 dolumn at /• o 263 • Eleven peaks were observed having retention times greater than that for N»N-dipropyl-2-phenylacetamide. The second of these had a retention time identical to that of authentic benzalacetophenone.

The material responsible for this peak was collected by passing the gas chromatograph eluent through 95$ ethyl alcohol. Addition of

2.4-dinitrophenylhydrazine reagent to this ethanol solution gave an orange solid, which after washing with ethanol had a melting point of

236-242°. A mixture of this solid and authentic benzalacetophenone o 2.4-dinitrophenylhydrazone at 238.5-243.5 • The infrared spectra of the 2,4-dinitrophenylhydrazone and that of benzalacetophenone 2,4- dinitrophenylhydrazone were identical in all respects.

The fourth peak (representing less than 0.5$ yield) had the retention time of authentic 1 ,2-dibenzoylethane. As it could not be separated cleanly from the preceding peak, no further characteri zation was effected. The seventh peak, representing about a 5$ yield was eluted from the column as a yellow liquid. It solidified on cooling to a solid which was not further identified. No other vola tile product was formed in more than 1$ yield.

From the reaction solution, the walls of the reaction vessel and the tarry residue of vacuum distillation were isolated 0.23 gram

(6.3$ yield) of dilactone VII, m.p. 287-288°.

Yields of volatile productB were determined by addition of an internal standard to the reaction solution. To a 3<>00 nil. aliquot of reaction solution, 1-chloronaphthalene (15*^ mg*j 0.0316 molar) 1 1 6

was added. The concentrations of products in this solution were too

dilute to be detected by V.P.C. analysis. The solution was concen

trated by distillation of most (80-90$) of the tripropylamine at

atmospheric pressure. The concentrate was chromatographed on SE 30

(20$ on 42/60 firebrick) at 182° and 2650 . The peaks of interest

in the resulting chromatograms were cut from the paper and weighed;

the weights were compared with that of the peak for 1-chloronaph-

thalene to obtain the concentration (and hence the yield) of the product in question. The calculated yields are listed in Table 4.

Products of Thermal Decomposition of o-Diazoacetophenone in Dipropylamine

The kinetics of thermal decomposition of a-diazoacetophenone at 107.5° were followed by injecting a-diazoacetophenone (l.?4 g.;

0.0119 mole) in dipropylamine (33 ml.) into dipropylamine (250 ml.) at the reaction temperature. The kinetic apparatus was that described for thermolyses in tripropylamine. Before reaction, the flask and solvent were thoroughly purged with high-purity dry nitrogen.

The evolution of nitrogen was followed to ca. 97$ of completion

(7 days). Guggenheim analysis (77) of the kinetic data demonstrated that the reaction was first order with a half-life of 1986 minutes.

At 107.5°» the predicted half-life was 1720 minutes. This value was calculated from the regression line of Arrhenius plot (Figure 20) for thermal decomposition in tripropylamine.

The gas above the surface of the hot reaction solution was chromatographed on a Dowtherm A Column. No gas other than nitrogen 117 was detected. A small amount of the solution was saved for quanti

tative V.P.C. analysis. The remainder was concentrated by distilla

tion of the dipropylamine » first at atmospheric, then at reduced pressure. Chromatographic analysis on an SE 30 column at ca. 200°

indicated the presence of three major and five very minor products.

The three major products accounted for 92# of the diazoacetophenone.

The largest peak (71# yield) had the retention time of authentic

N,N-dipropyl-2-phenylacetamide. Infrared spectra of this product

(collected as eluted from the column) and the authentic amide were

identical in all respects.

The lowest-boiling major product (15# yield) had the retention

time of authentic acetophenone. The eluent gas containing this product was bubbled through ethanol (3 ml., 95#)• Upon addition of 2,4-dinitrophenylhydrazine reagent an orange solid was formed. When a mixture of

this solid with authentic acetophenone 2,4-dinitrophenylhydrazone was melted, no depression of melting point occurred. The infrared spectra

of the two 2,4-dinitrophenylhydrazones were identical in all respects.

The third major peak (6#) separated preceded the amide peak and was presumed to be a-(N,N-dipropylamino)-acetophenone; analogous

products have been obtained from the copper-catalyzed decompositions

of o-diazoacetophenone in secondary amines (6).

A sample of o-(N,N-dipropylamino)-acetophenone was prepared by

additition of an ether solution of phenacyl chloride to an excess of

dipropylamine, followed by slight warming. The precipitated dipropyl

amine hydrochloride was filtered, and the ether and excess dipropylamine removed under reduced pressure. V.P.C. analysis of the residue indi cated one major product and the presence of high-boiling impurities

(purity ca. 70%). The retention time of the major peak was identical to that for the product of diazoacetophenone thermolysis. The infra red spectra of the two materials were identical in most respects (the product of thermolysis had all of the absorptions of the crude amino- ketone and some additional bands possibly due to impurities). Both materials had strong alkyl C-H absorption and carbonyl absorption and carbonyl absorption at 5*98 P-. Addition of a solution of picric acid in ethyl alcohol to a sample of o-(N*N-dipropylamine)-acetophenone resulted in the formation of a derivative: m.p. 108-110° (recrystal lized from ethyl alcohol; washed with ether). The infrared spectrum of this derivative had carbonyl absorption at 5 .95 M-i absorption at

6 .2-6.3 H and characteristic nitro and quaternary nitrogen absorption.

Addition of picric acid solution to the product of diazoacetophenone thermolysis did not provide a derivative; on standing» the mixture became dark red in color. No further efforts were made to characterize the product.

The yields of product were determined in the manner described for that in tripropylamine; as an internal standard* 1-chloronaphthalene

(25.8 mg.) was added to a 2.00 ml. aliquot of reaction solution.

Products of Decomposition of a-Diazo- aoetophenone in Cyclohexene

a-Diazoacetophenone (0.508 g.; 0.0035 mole) was dissolved in cyclo hexene (25.O ml.* distilled at 81.8-82.0° from calcium hydride under nitrogen - exclusion of oxygen not rigorous). Portions (I.25 to 2.0 ml.) 119 of this solution were put into 16 Pyrex tubes (6 and 7 mm* outside diameter; length 25 cm.) sealed at one end. Into each of 8 of these tubes was placed 3 mg• of anhydrous cupric sulfate; within minutes, gas evolved. The tubes containing cupric sulfate were not sealed, but allowed to stand in the dark until no further reaction was evident. The tubes without cupric sulfate were capped, cooled in an isopropanol-Dry Ice bath, sealed under nitrogen and placed in a bomb containing ca. 30 ml. of cyclohexene to counterbalance the vapor pressure increase inside the sealed tubes during heating. After being o heated at — 125 for 20 hours, the tubes were cooled and the seals broken. Suspended in the solutions was lactone dimer VII. The amount of dimer increased on standing. This is presumably due to the entry of oxygen which may induce dimerization of lactone monomer by a free radical mechanism.

A sample of the reaction solution was chromatographed on an SE 30 o column at 230 . The yields of the products detected were determined by adding 1-chloronaphthalene as an internal standard to an aliquot of the solution reaction. Six volatile products were detected; the three higher boiling ones were major and are designated in order of increasing retention time as A, B, and C; the percent yields were 4.0> 2 5 ,9 , and

3 .6 , respectively. The reaction mixtures derived from cupric sulfate catalysis were also chromatographed on SE 30. Five products were detected, three of them in measurable quantity. These were A, B, and D (no C was detected). Yields of A, B, and D were ?.5» 59»5» and

5 .0$, respectively.

To obtain sufficient quantity of product B for its characterization, decomposition was conducted on larger scale. To a solution of a-diazo-

acetophenone (0.99 g.» 0.0068 mole) in cyclohexene (40 ml.) was added

cupric sulfate (100 mg.). The reaction flask was connected to a gas

buret. No reaction occurred; the mixture was stored overnight with

no apparent change. In the morning, due to a stimulus provided pos

sibly by light or the heat of the magnetic stirrer, evolution of nitrogen

began suddenly. Nearly quantitative gas evolution was observed in

15-20 minutes. Cyclohexene was removed by distillation. The residue was distilled (bath temperature of 180° at 2 mm.). A white solid which melted at room temperature collected in the cold side arm. Chro matographic analysis of the distillate indicated the major component to have the retention time of compound B. The material was collected when

eluted from the column as a colorless liquid that solidified when cooled o below 25-30 . Infrared spectrum; 5*96 n. Ultraviolet spectrum:

^max^ = 245 roP-* The NMR spectrum (CCl^) exhibited aromatic proton absorption at 2.0 t and 2.55 T (integrated ratio 2 :3 )» and broad ab

sorptions for alkyl protons at 7.65 T» 8.20 t , and 8.72 t . The ratio of aromatic to alkyl protons was 5 *H» the absorption at 7.65 t repre

sented one proton. Overlap of the broad signals at 8.20 t and 8.72 t

prevented precise integration for these peaks; the relative ratio was

approximately 6:4.

Compound B formed a 2,4-dinitrophenylhydrazone. After chromatog

raphy on a talc column (elution with benzene) and recrystallization o from ethyl acetate-ethyl alcohol, the m.p. was 200-205 » Ultraviolet

spectrum of the 2,4-dinitrophenylhydraaane: = 385 mix.

The properties of this product agree with those reported for 121

7-norcaryl phenyl ketone (29*81)* = 244 mu; NMR absorption for

(81) M. Mousseron* Compt. rend.» 243* 1880 (1956). benzoyl and absorption at 7*75 T* 8.45 T> and 8.90 t• The properties

reported for the 2,4-dinitrophenylhydraaone are: m.p. 200.5-202.5°

(29)» 195-196° (81); xCHCl^ 383 max Chromatography of this distillate on a diethylene glycol suc cinate DEGS) column at 200° indicated that peak A consisted of two products; the lower boiling one was minor. Small amounts of the major component were collected. The NMR spectrum (CCl^) had* in addition

to signals for the benzoyl group* absorption at 4.4 t and 7.25 T and broad absorption at 7*9-9*4 t. The relative intensities are in the

ratio 5 *1*2:8. Small amounts of impurity were evident from the

spectrum. Such absorption suggests that compound A might be a-(l-

cyclohexenyl)-acetophenone: H QH,

ch2 ch2

The compound was not further characterized.

For further examination of the major product of thermolysis in

cyclohexene* cyclohexene (30.0 ml.) containing diazoacetophenone

(0.768 g.; 0.0525 mole) was sealed in a Pyrex tube and heated at

—135° for 12 hours. The reaction solution contained large amounts

of lactone dimer VII. Several milliliters of the solution were 122 saved for quantitative analysis; the remainder was concentrated by distillation of the cyclohexene» and the residue chromatographed on an SE 30 column. The first product to be eluted (*$ yield) had the retention time of authentic acetophenone; it was collected by passing the eluent gas through ethyl alcohol. Addition of 2,4—dinitrophenylhydrazine reagent to this solution gave a solid which had an

IR spectrum identical to that for authentic acetophenone 2 ,*4-dinitrophenylhydrazone. A mixed melting point with acetophenone 2 »*+-dinitrophenylhydrazone was not depressed.

The major volatile product had the retention time of 7-norcaryl phenyl ketone (13$ yield). The two peaks immediately preceding it were formed in ca. 0.5 and 2.0 percent yield. The major product was collected. Its IR and NMR spectra were identical to those of 7- norcaryl phenyl ketone. The minor products* C and D» were not col lected for characterization.

Product of Thermolysis of q-Diazoaceto- phenone in Cyclooctane and N*N- Dimethylcyclohexylamlne

The solution resulting from three thermal decompositions of o-diazoacetophenone (ca. 0.015 molar) in cyclooctane containing

N,N-dimethylcyclohexylamine (0.7 to 1.0 molar) at 130.5° were con centrated by vacuum distillation. Preparative V.P.C. on an SE 30 column at 250° permitted isolation of a high-boiling colorless liquid which represented ca. 50^ of the volatile material. The infrared spectra showed strong alkyl C-H absorption and carbonyl absorption at 6.1*4- pi. The NMR spectra had aromatic and alkyl proton absorption.

These appeared (in order of increasing t value) in the approximate 123 ratio 5:2.2:2.3*8.6. The material had a molecular weight of 229

(osmometry of CC1^ solution). This compound has been tentatively identified as N-cyclohexyl-N-methyl-2-phenylacetamide (XXXVI),

M.W. = 231.3.

Anal. Calculated for C ^ R ^ N O * C, 77.9; H, 9.15; N, 6.05

Found: C, 74.7; H, 9.24; N, 5*92

Product of Thermal Decomposition of q-Dia zoa c e tpphenone in Cyclooctane Containing 1,4-Piazoblcyclo t2.2.2l octane (DABCQ)

The reaction mixtures resulting from kinetic experiments in cyclooctane containing DABCO (0.14-0.28 molar) were concentrated by vacuum distillation. Vapor phase chromatography (SE 30 column at 23O0) of the residue indicated that one product composed ca. 70$ of the volatile material. This peak was collected as a liquid as it was eluted from the column. It darkened slightly on standing; addition of 2,4-dinitrophenylhydrazine reagent gave a yellow precipi tate. After two recrystallizations from 95$ ethanol* the 2,4-dinitrophenylhydrazone (yellow needles) melted at 95*8-96.4°.

Anal. (2,4-dinitrophehylhydrazone): C» 6 3 .7 ; H» 4.6l; N, i3 .ll

The NMR of the 2,4-dinitrophenylhydrazone (15$ in benzene) had two alkyl proton absorptions of nearly identical intensity at 6.42 t and 6.72 t. Aromatic proton absorption was masked by benzene. The

NMR spectrum in acetone solution had absorption at 1.0-2.0 t (due presumably to the 2,4-dinitrophenylhydrazone moiety), phenyl proton absorption at 2.65 t and 2.69 T (doublet) and absorption at 6.14 t

(singlet). The intensities of these peaks were in the ratio 4:10:4. 124

An essentially identical spectrum was obtained in dimethyl sulfoxide

solution* In methylene chloride* phenyl proton absorption occurred

at 2.67 t (one peak predominant; a small shoulder peak at slightly

higher t value); two alkyl proton absorptions of unequal intensity

occurred at 6.16 t and 6*19 T - the peak of lower t value pre

dominated. The infrared spectra of the 2,4-dinitrophenylhydrazone

had absorption at 6.23 I* in addition to that expected for nitro-

groups; carbonyl absorption was not observed. This 2,4-dinitrophenyl hydrazone could not be further characterized. 125

Table 11

Thermal Decompositions of a-Diazoacetophenones in Tripropylamine a-Diazoacetophenone: 0.260 g. Tripropylamine? 370 ml. (20 ml. for injection) Temperature: 130*5°

Minutes P (m.m.) AP Buret reading (ml./l.l47) -V^

1 741.8 0.3 2 0.8 3 1.7 5 3.6 10 6.45

15 7.1 20 8.3 28.4 25 9.25 27.45 30 9.65 27.05 40 10.5 26.2

50 12.05 24.65 60 13.3 23.4 70 14.75 21.95 80 15.9 20.8 90 17.25 19.45

110 19.3 17.4 120 741.3 0.5 20.75 15.95 140 22.5 14.2 160 24.4 12.3 210 26.3 10.4

300 741.5 0.3 30.55 6.15 330 31.1 5*6 360 31.85 4.85 390 32.75 3.95 488 34.75 1.95 00 742.5 1.1 36.7 ortho-Bromodlazoacetophenone: 0.505 g. Tripropylamine: 3&9 ml. (19 ml. for injection) Temperature: 130.5°

5 9.2 38.8 10 19.35 28.65 15 744.0 27.65 20.35 16 29.1 18.9 17 30.45 17.45 1 2 6

Table 11 (Contd.)

Minutes P (m.ra.) AP Buret reading (ml./l.!47 Voq -V-^

18 31.65 16.35 19 32.65 15.35 20 33.7 14.3 21 3^.7 13.3 22 35.55 12.45

23 36.3 11.7 24 37.2 10.8 25 37.85 10.05 26 38.5 9.5 2? 39.1 8.9

28 39.7 8.3 29 40.2 7.8 30 40.8 7.2 31 41.3 6.7 32 41.6 6.4

33 42.0 6.0 3^ 42.35 5.6 5 35 42.65 5.35 36 43.0 5.0 37 43.35 4.65

38 43.7 4.3 39 43.95 4.0 5 40 44.05 3.95 42 44.55 3.45 44 44.95 3.05

46 45.45 2.55 48 45.75 2.25 50 46.05 1.95 55 46.5 1.5 6 o 47.0 1.0

65 47.35 70 47.5 — 00 744.0 0 48.0 0 127

Table 11 (Contd.) ortho-Chlorodiazoacetophenone: 0.423 g. Tripropylamine: 376 ml. (28 ml. for injection) Temperature: 130.5

Minutes P (num.) AP Buret reading (ml./l.147) Vco-Vt

2 1.9 4 6.1 6 10.2 8 14.35 39.6 10 18.1 35.85

12 21.8 32.15 14 25.1 28.85 16 28.1 25.85 18 746.2 30.85 23.1 20 33.4 20.55

22 35.55 18.4 24 37.5 16.45 26 39.2 14.75 28 40.8 13.15 30 42.1 11.85

32 43.4 10.55 34 44.4 9.55 36 45.4 8.55 38 46.35 7.6 40 47.2 6.75

42 47.9 6.05 44 48.5 5.45 46 49.05 4.9 48 49.6 4.35 50 50.0 3.95

55 51.0 2.95 60 51.7 2.25 65 52.2 1.75 70 52.75 1.2 118-ao 746.6 0.5 53.95 0 ortho-Iododiazoacetophenone: 0.431 g. Tripropylamine: 281 ml. (31 ml. for injection) Tempera ture t 110.9°

2 0.15 4 3.0 6 5.2 8 6.8 10 8.1 128

Table 11 (Contd.)

Minutes P (m.m.) Buret reading (Ml./l.147) Voo-Vt

15 10.8 28.6 20 12.65 26.75 25 14.55 24.85 30 16.5 22.9 35 745.5 18.2 21.2

40 19.55 19.85 45 20.95 18.45 50 22.2 17.2 55 - 23.45 15.95 60 24.35 15.05

80 27.9 11.5 90 29.15 10.25 100 30.0 9.4 120 32.35 7.05 130 33.1 6.3

140 33.^5 5.95 150 34.45 4.95 co 745.9 0.4 39.2 0 ortho-Methyidiazoacetophenone: 0.306 g. Tripropylamine: 312 ml. (12 ml. for injection) Temperature: 130.5°

2 743.7 1.6 39.2 3 3.8 37.0 4 6.25 3^.55 5 8.9 31.9 6 11.1 29.7

7 12.9 27.9 8 15.3 25.5 9 17.25 23.55 10 19.1 21.7 11 20.9 19.9

12 22.45 18.35 13 23.8 17.0 14 25.25 15.55 15 2 6 .4 14.4 16 27.5 13.3 129

Table 11 (Contd.)

Minutes P (m.m.) AP Buret reading (ml./l.l47)

17 28.5 12.3 18 29.4 11.4 19 30.3 10.5 20 31.05 9-75 21 32.0 8.8

22 32.6 8.2 23 33.2 7.6 24 33.6 7.2 25 34.2 6.6 26 34.6 6.2

27 35.1 5.7 28 35.45 5.35 29 35.8 5.0 30 36.2 4.6 31 36.55 4.25

33 37.05 3.75 35 37.6 3.2 40 743.7 - 38.6 5 2.15 45 39.35 1.45 55 40.0 0.8 ortho-Methoxydiazoacetophenone: O .365 g. Tripropylamine: 364 ml. (14 ml. for injection) Temperature: 110.9°

4 3.2 6 7.25 9 12.35 12 16.4 15 18.9

20 744.1 2 1 .5$ 20.1 25 23.65 18.0 30 25.8 15.85 35 27.6 14.05 40 28.7 12.95

45 29.8 11.85 55 31.75 9.9 60 32.6 9.05 65 33.5 8.15 72 34.55 7.1 130

Table 11 (Contd.*)

Minutes P (m.m.) a P Buret reading (ml./l.147) Voo-Vt

80 35.65 6.0 90 36.4 5.25 100 37.4 4.25 110 38.2 3.^5 120 38.8 2.85 130 39.4 2.25 744.2 0.1 41.65 0 meta-Methoxydiazoacetophenone: 0.327 g. Tripropylamine: 350 ml. 1-CJiloronaphthalene: 7*0 ml. for injection Temperature: 130.5°

1 -3.0 6 753.5 -1.25 39.0 10 0.35 37.4 15 1.6 36.15 20 2.8 34.95

30 5.4 32.35 40 7.8 29.95 50 10.3 27.45 60 12.4 25.35 70 14.4 23.35

80 16.25 21.5 90 17.9 19.85 100 19.5 18.25 110 21.05 16.7 120 22.3 15.45

130 23.5 14.25 140 24.6 13.15 180 752.3 1*2 28.25 9.5 190 28.9 8.85 200 29.7 8.05

210 30.35 7.5 220 30.85 7.0 240 31.9 5.95 260 32.7 5.15 280 33.^5 300 3^.1 3.75 735-® 752.0 1.5 37.6 0 131

Table 11 (Contd#) meta-Nitrodiazoacetophenonet 0.365 g. Tripropylamine: 350 ml. 1-Chloronaphthalene: 10 ml. for injection Tempera ture: 130.5°

Minutes P (m.m.) 4P Buret reading (ml./l.147) V® -*■

1 749.8 0.05 5 0.5 10 00.65 36.75 20 1.55 35.85 30 2.5 34.9

40 3.6 33.8 50 5.8 31.6 60 8.1 29.3 70 9.3 28.1 80 10.65 26.75

90 I I .65 25.75

100 12.65 24.75 110 13.5 23.9 120 14.45 22.95 140 16.35 21.05 150 17.2 20.2

170 18.8 18.6 245 750.0 0.2 24.05 13.35 270 25.3 12.1 325 28.0 5 9.35 435 750.7 0.9 31.8 5.6

485 751.0 1.2 32.95 4.45 520 751.3 1.5 33.4 4.0 CO 751.4 1.6 37.4 0 para-Methoxydiazoacetophenone: 0.291 g. Tripropylamine: 275 m l • 1-Chloronaphthalene: 10 ml. for injection Temperaturer 130*5°

2 0.4 5 0.4 34.4 10 0.65 33.1 15 1.7 33.1 20 3.0 31.8 132

Table 11 (Contd.)

Minutes P (m.m.) Buret reading (ml./l.l4?) Voo“vt

25 5*05 29.75 30 6.2 28.6 40 747.0 7.95 26.85 50 9.9 24.9 66o 11.9 22.9

70 13.45 21.35 80 15.35 19.45 90 16.8 18.0 100 18.0 16.8 110 19.45 15.35

120 20.8 14.0 130 21.75 13.05 140 22.7 12.1 210 2 7.7 7.1 220 28.5 6.3

230 29.0 5.8 240 29.45 5.35 310 31.2 3.6 450 33.4 1.4 qo 739.0 8.0 34.8 0 para-Nitrodiazoacetophenone: 0.331 g* Tripropylamine: 350 ml• 1-Chloronaphthalenej 9 ml. for injection Temperature: 130.5°

0 746.9 -1.4 2 -3.0 8 -1.3 10 -0.65 15 0.35 34.1

20 1.15 33.3 30 2.65 31.8 40 3-9 30.55 50 4.85 29.1 60 6.05 28.4

70 7.1 27.35 80 745.8 1.1 8.0 5 2 6 .4 100 745.6 1.3 9.8 24.65 110 10.75 23.7 160 745.1 1.8 15.75 18.7 133

Table 11 (Contd.)

P (m.m.) a P Buret reading (ml./l. 147) V ^ - V ^

170 745.1 1.8 16.4 18.05 180 H 17.15 17.3 200 It 18.7 15.75 220 749.9 2.0 19.9 14.55 240 20.95 13.5

260 22.1 12.35 290 23.45 11.0 310 7^5.5 1.4 24.4 10.05 340 745.6 1.3 23.65 8.80 360 26.3 8.15

390 27.15 7.3 410 27.8 6.65 630 745.8 1.1 31.2 3.25 695 32.2 2.25 710 32.3 2.15 00 743.1 3.8 34.45 0 134

2.0

118 min.

o.oL 100 200 300 400 500 600 Minutes — ► Figure 10, Thermal Decomposition of < *-Diazoacetophenone at 130.5°. 2.0

10.6 min.

0.0 2 0 40 60 Minutes —► Figure II. Thermal Decomposition of ortho - Bromodiozooceto- phenone at 130.5°. 136

2.0

12.5 min.

o»

0.0 10 20 30 40 50 60 70 Minutes —► Figure 12. Thermal Decomposition ortho - Chip rod iozooceto - phenone at 130.5°. 137

2.0

54.3 min.

1.0

8 o>

0.0 0 50 100 150 Minutes —► Figure 13- Thermal Decomposition of ortho -Iododiozooceto- phenone ot 110.9°. 138

2.0

9.0 m i n.

o»

0.0 10 2 0 30 40 50 60 Minutes — ► Figure 14. Thermal Decomposition of ortho - Methyldiozoaceto- phenone at 130.5° . 139

2.0

36.2 min.

0.0 2 0 40 60 80 100 120 Minutes — Figure 15. Thermal Decomposition of ort ho - Methoxydiozooceto- phenone at 110.9°. 140

2.0

= 85.7 m i n.

1.0

0.0 100 200 300 Mi nutes — Figure 16. Thermal Decomposition of met a - Methoxydiozooceto- phenone at 130.5°. 141

2.0

160 min.

CT>

0.0 100 2 0 0 3 0 0 4 0 0 500 600 Minutes — ► Figure 17, Thermal Decomposition of met a -Nitrodiazooceto - phenone at 130.5° . 0.0 log (V..-V,) 2.0 phenone at Figure 18 . T h e r mDe a l c o m p o s i t iof o npo r o - M e t h o x y d i o z o o c e t o - 130. 5 ° . 0 0 1 i u e ^ Minutes 0 0 2 87.7 min. 87.7 0 0 3 142 1*0

2.0

167 min.

0.0 I 0 0 300 500 700 Minutes — — Figure 19. Thermal Decomposition of poro - Nitrodiazoaceto — phenone at 130. 5 °. 0.3 + 2 . 0 - log ( I04 k) 5 . 0 - 4 . 0 - 0.2 . 0 + 3 . 0 - 0.5 + 0.1 + + + 0.4 iue 0 Areis plot. Arrhenius 20. Figure 2.45 0 4 . 2 I03 / T / I03 o E o )= 19.668- 8 6 6 . 9 1 = k) 4 0 I ( log 2.50 ( 7 . 9 3 3 ± 0.618)- 0.618)- ± 3 3 9 . 7 ( ± 28^ ^ 2.8 ± 3 . 6 3 2.55 mole N H C 2.60 y I03 144 4 4- log 0.6 _ 0.3 0.8 0.4 0.5 0.7 0.9 0.2 1.0 i u e 2 . Arrhenius plot.Figure 21. 2.40 .525 2.55 2.50 2.45 I03 x I T / o 3. ± 1.0 ± 33.2 = Eo o 04) 19.015- = 4k) log I0 ( 726 226)-^ - ) 6 2 .2 0 17.266i 2.60 Br 2.65 mole kcol CHN

IO* 145 4 4 + log JC 0.4 + + 0.3 0.5 + + + 0.8 + 0.9 + - + 0.7 0.6 + 0.1 + 1.0 + - 0.2 0.2 0.1 iue 2Areis plot. 22.Arrhenius Figure 2.50 I I03 / T * o I4k 1 .920- 19 k)log (I04 = E a - 35.0 ± 2.6 — 2.6 ± 35.0 - a E (7.658 + 0.571)- -Ip- 0.571)- + (7.658 2.652.602.45 2.55 mole I02 6 4 1 log ( I 0 4 k) 0.4 + + 0.3 + 0.5 + 3 . 0 - + + 0.7 - - 0.1+ 0.2 0.6 0.2 0.1 iue . rhnu plot. 2 Arrhenius 3.Figure .5 .5 2.70 2.65 0 6 . 2 2.55 0 5 . 2 o (I4k = 18.648- 8 4 6 . 8 1 ( = log k) I04 E o = 3 2 . 3 ± 3 . 2 3 = o E / T 3 0 I ± 0.860) 0 6 8 . 0 ± 4 6 0 . 7 ( V C C = N V kcol kcol mole 4 4 log 40.6 -* 40.4 40.5 4 4 0.9 40.8 40.2 40.3 4 0.7 40. 41.0 4 1.14 Figure plot. Arrhenius 24. .02.45 2.40 .02.55 2.50 I/Tx I03 o 02 2.5^ 5 . 2 ± 30.2 = Eo log ( I04 k) = 17.394 - 17.394 = k) I04 log( 652 052 y 0.542) ± (6.592 02 2.5 ± 30.2 02.65 2 60 CH mole CH N = 03 |0 148 JC 4 + log + + 0.4 + + 0.7 + + 0.3 + + 0.5 + + 0. + 0.9 0.8 0.2 0.6 iu e 5 Areis plot.Figure Arrhenius 25. 2.50 2.55 2.60 1/T I03x log ( I04 k) = 17.073 - 17.073 = k) (I04 log 2.65 o 91 28 ^ 2.8 29.1 ± * Eo 632± 607)y- )-y 7 0 .6 0 ± 362 (6 2.70 OCH mole 2.75 N H C 10- 149 log ( I 0 4 k) + 0.4 3 . 0 + + + + 0.5 + 0.7 + 0.9 + + - + + 0.2 0.8 0.1 0.6 0.1 1.0 iue2.Areis plot. Figure 26. Arrhenius 0 4 . 2 5 4 . 2 1 0 3 / / T 3 0 1 -33.8+ 2.1 + 8 . 3 3 - o E 5 5 . 2 0 5 . 2 0 - 5 3 4 . 8 1 * ) k I04 ( g o l ~ ) 9 6 4 . 0 ± 4 8 3 . 7 ( H C O e l o m

log (I04 k) + -0.3 + 0.3 + + 0.4 +0.5 - - -0.4 -0.5 - + +0.6 0.6 0.2 0.2 0.1 0.1 iue 7 rhnu plot Arrhenius Figure 27 .02.45 2.40 I03/ T .02.55 2.50 EO o I4k 18.663- - 3 6 6 . 8 1 k) = log (I04 1.4 ^ ± 7 . 4 3 - (7.592 (7.592 NO ± 0.295)* C C = 2.60 log (I04 k) + + + + 0.4 + + 0.9 + + + + 0.3 +0.5 + + 0.7 - + 0.6 0.2 0.8 0 0 1.0 . . i gr 2.Areis plot Fi 28.gure Arrhenius 2.40 .52.50 2.45 H C 38.4 = o E log 03 / T I0 3 O (0 )« - 1 9 8 . 0 2 k) (104 « ( 8 . 3 8 8 1 0.504)- 1 8 8 3 . 8 ( ± C = 2.3 2.55 ^ mole log ( I0 4 k) 0.3 -0 .3 0 + -0.4 + + + - + 0.5 + + 0.4 + - 0.2 0.2 0.6 0.1 0.1 Figure 2.40 29. Arrhenius 2.45 o 3. ± 22 — 2.2 ± 35.0 - Eo o 1’ k - 18.813 — - k) log(10’ 654± 0. ) 7 7 .4 0 ± 4 5 .6 7 ( 0,N plot. 2.50 2.55 mole