A Thesis Entitled STUDIES on the ALKYLATION REACTIONS OF

Home , Sodium methoxide

A Thesis entitled

STUDIES ON THE ALKYLATION REACTIONS OF

SOME P-(METHANESULPHONYLOXY)-SULFHIDES AND

RELATED COMPOUNDS

Submitted by

AFARIN BEHZADI

in partial fulfilment of the requirements for the

Diploma of the Imperial College

of Science and Technology

1973 it

ABSTRACT

In the Introduction, the formation of episulphonium ions, and the factors which affect the formation and ring opening of this type of intermediate, are discussed; the chemistry of allylic halides and their alkylation reactions are also reviewed.

The first part of the original work described in this thesis concerns preparations of various 1-methanesulphonyloxy-l-ary1-2-

(arylthio)ethanes and 1-methanesulphonyloxy-2-aryl-2-(arylthio)ethanes and the study of their alkylation reactions with various nucleophiles.

The results proved that an episulphonium intermediate Was involved in many of these reactions, and the formation and ring opening of this intermediate was affected by the nature of the nucleophiles and the substituents on carbon and sulphur atoms. Electron-withdrawing substituents inhibited the formation of the episulphonium ion, whilst electron-donating substituents favoured the formation of this intermediate. Thus the reactions of those methanesulphonates in which the aryl group was phenyl and 27-methoxyphenyl proceeded entirely through an episulphonium ion to give the secondary products with almost all nucleophiles, whilst this intermediate was not involved in most of the reactions in which the aryl groups included 2-nitrophenyl or 2,4- dinitrophenylthio substituents. Elimination reactions were favoured in most of the reactions of these nitro-compounds.

The second part of this work involved preparation of 1-(phenylthio)-3-chloroprop-1-ene, 1-(11.-nitrophenylthio)-3-chloroprop-1-ene and 1-(2-nitrophenylthio)-3-methanesulphonyloxyprop-1-ene. The alkylation reactions of these allylic compounds (which were also vinyl sulphides) with various nucleophiles were investigated. The allylically iii

rearranged products were obtained in the reactions with most of the nucleophiles and the results showed that electron-withdrawing substituents on the X -carbon of such an allylic halide (or methanesulphonate) favoured the formation of the rearranged products.

Nuclear magnetic resonance spectroscopy was particularly useful in identification of the products, and differentiation between the isomers. iv

ACKNOWLEDGEMENT

I would like to express my gratitude to Professor L.N.

Owen for his advice and encouragement throughout the course of this work.

I would also like to thank Mr Ron Carter and Mr Tom Adey,

Mrs A. Boston and the staff of the Microanalytical Laboratory for the technical assistance that they provided.

Finally I thank the British Council for providing financial help to cover my fees for the last two years.

Armstrong Laboratory,

Imperial College, A. Behzadi

London S.W.7. April 1973 V

CONTENTS

Page

Introduction 1 Part 1: Episulphonium intermediates 1 Part 2: Allylic chemistry 16

Discussion 29 Part 1: Synthesis of 1-aryl-2-(arylthio)ethanol, 2-ary1-2- (arylthio)ethanol and their derivatives 31 Reactions of the methanesulphonates of:

1-phenyl-2-(phenylthio)ethanollIcand 2-pheny1-2- (phenylthio)ethano10 41

2-(2-methoxypheny1)-2-(phenylthio)ethanol 45 1-(p7nitropheny1)-2-(phenylthio)ethanol and 2- (27nitropheny1)-2-(phenylthio)ethanol 46 1-phenyl-2-(2,4-dinitrophenylthio)ethanol and 2-

pheny1-2-(2,4-dinitrophenylthio)ethanol 52

General discussion 55 Part 2: Synthesis of 3-(phenylthio)allyl alcohol, 3- (E7nitrophenylthio)ally1 alcohol and their derivatives 63

Reactions of:

1-(phenylthio)-5-chloroprop-l-ene 68

1427nitrophenylthio)-5-methanesulphonyloxyprop-1- ene 71 1-(117nitrophenylthio)-5-chloroprop-1-ene 74

General discussion 74

The n.m.r. tables 78

*Chloride, not methanesulphonate vi

Page Experimental

Part 1: 1-Phenyl-2-(phenylthio)ethanol, 2-pheny1-2- (phenylthio)ethanol and their derivatives 110

1-(27Methoxypheny1)-2-(phenylthio)ethanol, 2- (27methoxypheny1)-2-(phenylthio)ethanol and their derivatives 121

1-(27nitropheny1)-2-(phenylthio)ethanol, nitropheny1)-2-(phenylthio)ethanol and their derivatives 127

1-phenyl-2-(2,4-dinitrophenylthio)ethanol, 2-phenyl 2-(2,4-dinitrophenylthio)ethanol and their deriva-

tives 136

Part 2: 3-(Phenylthio)allyl alcohol and its derivatives 145

3-(11:-Nitrophenylthio)ally1 alcohol and its derivatives 153

References 159 1

INTRODUCTION

The new investigations to be described in this thesis involve many reactions proceeding through episulphonium intermediates and also some related studies on allylic systems. Consequently it is relevant to consider earlier work in both of these fields.

1. Episulphonium intermediates

The formation of the intermediate episulphonium ion (1) has been suggested in many alkylation reactions of P-halosulphides and related compounds as an alternative'to the formation of a normal carbonium ion (2). Thus the rapid hydrolysis of the chloride (3), in contrast to (4), under the same conditions, was interpreted by the formation of the episulphonium ion (5) which increases the rate of expulsion of 2 the halide . The oxygen, being more electronegative and less willing to share its lone pair of electrons, does not participate in cycliza- tion, and hydrolysis of (4) occurs by a normal displacement reaction.

The ability of sulphur to participate as a neighbouring group in the formation of episulphonium ions has been demonstrated by many workers. Havlik and Kharasch3 have shown that acetolysis of the chlorides (6) and (7) gives an identical product, which is explained by the intermediate formation of (8). Chlorination of the alcohols

(9) and (10) resulted in a single product (11)4. Attempted preparation of the dithiolan (12) from n-butylthioacetaldehyde dimethyl acetal (13) resulted in the formation of 2-butylthio-1,4-dithian

(14). The ring expansion was supposed to go through the episulphonium ion (15)5. The formation of 2-chloromethyl-l,4-dithian (17) from

3,6-dithia-l-cycloheptanol (16) also proceeds through an episulphonium 6 ion . Baig and Owen7 have postulated a common episulphonium intermediate 2

RT I S+

/ \ + R2" C CR2111 R'--cp;'-cRp'

(1) (2)

Et-S.,..., ra, CH2 > Et- CH2

CH2

(3) (5)

Et -0-CH2 -CI-12 -C1 rapid V (4) Et-S-CH2 -CI-12 OH

z N., Cl I r Ar-S-CH2 -CH-CH3 A S+ (6) CH3 -CH CH2 Ar-S-CH-CH2 -Cl Cl CH3 (8) / (7) Ar-S-CH2 -CH-CH 3 I OAc 3

■ -.. Et E t -S - CH2 - CHOH -CH3 ± S (9) Cl - CH2 CH- CH3 Et -S - CH-CH2 OH I CH3

(10) E t -S - CH2 - CH Cl cH3

OM e S CH2 / n-Cs H9 -S -CH2 -CH HS CH, -CH, SH n- C4 H9 -S-CH2 -CH \ 1 I OMe H± s CH2 (13) (12)

+ n- Cif H9 S

(15)

..„.„..- S ....„.,...... „,. S-C4 H9

r s) > ..---- OH s

(16)

s.,N,

Ns., s ...... _cH2 ci

(17)

r2 OMs "1/12 + Ph-S-CH PhS CH CH2 OMs Ph-S-CH2 -11-10Ms

CH2 OMs CH2 OMs

(18) Me0H (19)

Ph-S-CH-CH2 OMe + Ph-S-CH2 -CHOMe I CH2 OMe CH2 OMe

(OMs = OS02 Me) 5 in the methanolysis of the methanesulphonates (18) and (19);.both of the methaesulphonates gave the same ratio of the isomeric methyl ethers. The addition of alkanesulphenyl chlorides to olefins frequently gives a mixture of the products, through the intermediacy of episulphonium ions. Thus acrylic acid derivatives gave products (20) and

(21)8'9 whilst the reaction of propylene with P-chloroethanesulphenyl 4 chloride gives the dichloride (22) .

The carbohydrate field provides many examples of the intervention of episulphonium ions. The 6-benzylthio-sugar (23) was converted to the chloro sugar (25) by treatment with thionyl chloride and the stereochemistry of the product (25) was assigned on the assumption of the formation of the episulphonium intermediate (24).

The intermediacy of an episulphonium ion has been suggested in 11,12,13. e many ring expansion reactions of penicillin sulphoxides Th formation of (27) and (28) from a penicillin sulphoxide methyl ester can arise from the intermediate episulphonium ion (26) and subsequent 11 attack of the acetate ion at the primary or tertiary centre .

The orientation of ring opening of an episulphonium ion is affected by various factors, such as solvent, the substituents on each member of the ring, and the nature of the nucleophiles.

The products obtained from addition of sulphenyl chlorides (29) 14,15. to phenyl acetylene are reported to be solvent-dependent In ethyl acetate anti-Marcovnikoff orientation products (AM-product) predominated, whereas in acetic acid Marcovnikoff products (M-product) were favoured, and in chloroform and acetonitrile both of the products were formed in similar amounts. It was suggested that the change from M-product to AM-product was due to a greater separation of the chloride ion from the cation in the transition state, which is easier 6

CH2 =CH-0O2 Me + RSC1--, CH2 CH-0O2 Me Cl-

S 1 ,. R C1-CH2 - CH-0O2 Me + RS-CH2 -CH-0O2 Me I SR Cl ( 2 o ) ( 21 ) ... + S+-CH2 -CH2 Cl Cl-CH2 -CH2 -SC1+CH3 -CH=CH2 Cl CH-CH3

)1, CH3 -CH-CH2 SCH2 CH2 Cl Cl

(22)

CH2 Cl -SR CH2, R H-C-SR HO-C-H H-C

...... „..- 0 -...,,,,.. D- \Cr (0 0—CMe2

( 23 ) (24) (25)

R: cH2 q H5 7

0 II R ,...... „--- S , sc,...,,,,,

Ace 0 s .., CO2 Me

SOAc s4--'------./ \---- - >

Nco, me 02 Me (26)

..../„....."S CH2 OAc Me OAc N..,..,,,r___<- ss"---- CO2 Me CO2 Me (27) (28)

,,,.....„- S .„,..N., 1--

DI .---Me CO2 Me ( R = PhOCH2 CONH) 8

when the cation is more stable and when the anion is better solvated.

The results may therefore be explained in terms of tight and loose

ion pairs. Thus the episulphonium intermediate (30) dissociates into

ions which then interact to give the products. If the separation

between the ions is very small, the formation of AM-product is favoured,

but under the influence of a good solvent for the anion, the two ions ,

are able to separate sufficiently and have more freedom to reach the

most favourable orientation and result in M-product. (The effect of

the solvent was not related to the dielectric constant but to the acidic

property of the solvent which is related to a specific solvation for 14 the anions) .

The importance of steric effects on the orientation of ring opening

of an episulphonium ion has been shown by addition of methyl sulphenyl

chloride to alkyl-substituted terminal olefins1647. The products

contained predominantly the AM-adducts. With increasing size of the

substituent on the double bond, higher selectivity for the AM-products

-was observed.

To study electronic effects on product orientation, the reactions 17 of vinyl chloride and styrene with sulphenyl chlorides were investigated .

Phenyl substituents on the olefin resulted in the M-products which

could be explained by stabilization of the transition state (31) due

to ii-bond overlap of the R. orbital of the electron-deficient a-carbon

with the phenyl ring's rr cloud. The predominantly AM-product resulting

from the reaction of vinyl chloride with methanesulphenyl chloride

showed the destabilization of an electron-deficient a-carbon by the

electron withdrawal group, along with possible steric hindrance to

attack by the incoming chloride.

The nature of the R group on the sulphur has an equally important

ArSC1 + Ph-C -1-aCH Ph-C Cl- (29)

Ph Ar (30) > ArS-C=CHC1 + ArS-CH=C(C1)Ph AM-product M-product

(Ar=p7toly1,..E7nitrophenyl, o-nitrophenyl)

R+Z

(31)

/+\

RSC1 + CH2 = CMe2 > CH2 CMe2

(32)

CL -CH2 -CMe2 + RS -CH2 -CMe2 SR Cl AM-product M -product 0 tl (R=Me, MeCS)

TR Cl RSC1 + CH2 = CMe2 C1-CH2 -CMe2 + RS-CH2 -CMe2 + RS-CH2 -C=CH2 .70 (R=(Me0)2 P ) CH3 (33) 10

influence on the product orientation. This has been shown by the addi- 17 tion of different sulphenyl chlorides to isobutylene . The results

suggested that the electron-withdrawing effect of R, for example in

acetylthiosulphenyl chloride, tends to destabilize the positive charge

on the sulphur atom in the episulphonium ion (32), thus contributing

to the development of an electron-deficient centre on the substituted

carbon atom which results mainly in the M-product. In the case of

0,0-dimethylphosphoryl chloride, the electronegative phosphoryl group

is directly bonded to the sulphur atom which impairs the sulphur's

bridging ability and thus allows formation of thedefinic product (33)

along with the adduct-products (mainly M-product). With an electron-

donating group R (eg, Me), AM-product predominates.

The alkylation reactions of the methanesulphonates (34-37) have 18,19,20,21 been studied by Baig and Owen7 and Khan and Owen. The

substituent on the phenyl ring had an important effect on the forma-

tion of the episulphonium ion. The 2.-methoxy group, being the best

- electron-donor, assists this formation; thus the alkylation reactions

of the 27methoxyphenylmethanesulphonates proceed through the episul-

phonium ions (38,39) with all types of nucleophiles. In contrast,

the 2,4-dinitro substituent, being the strongest electron-withdrawal

group, impairs the sulphur's bridging ability and as a result only

reactions with weak nucleophiles (eg, solvolysis reactions) proceed

through the intermediates (38) and (39).

The episulphonium ion (38) was involved in the solvolysis reac-

tions,of the bismethanesulphonates (34) and (35) to give thermodynamically

or kinetically controlled products. With potassium acetate in acetic

anhydride mixtures of isomeric diacetates were formed in which the 11

CH2 OMs

Ar-S-CH Ar-S-CH2 -CHOMs

CH2 OMs CH2 OMs

(34) (35)

Ar -S -CH -CH20Ms Ar -S -CH2 -CHOMs Me Me

(36) (37)

CH2

+/I Ar--S CH Me CH2

(38) (39)

OMs: OSO2 Me Ar: Phenyl, 2-methoxyphenyl, 2-methylthiophenyl, :-chlorophenyl, 2,4 -dinitrophenyl 12

proportion of 1,3-isomers decreased with increasing electron-withdrawal

character of the aryl group. This was attributed to both steric and

polar effects on the direction of ring opening of the episulphonium

ion. The reactions with tetramethylammonium acetate in acetone gave

mixtures of isomeric acetates and unsaturated acetates (4o) and (41).

These unsaturated acetates were obtained in higher yield with increas-

ing electron-withdrawal effect of the aryl group. No elimination

product was obtained in the reactions of p-methoxy derivatives. The

reactions of the 1,3-bismethanesulphonates with sodium methoxide

resulted in unsaturated methyl ethers (42). Of the 1,2-bismethane-

sulphonates, the 2,4-dinitro-compound gave the unsaturated methyl

ether analogous to the acetate (41), but the.others (except for the

p-methoxy-compound which yielded only a mixture of isomeric dimethyl

ethers) gave the allylically rearranged methyl ethers (44). The

formation of these unsaturated methyl ethers was attributed to the intermediacy of the allylic methanesulphonates (43). Episulphonium ions were not involved in any of the elimination reactions, because

different unsaturated products were obtained from isomeric methanesulphonates. The reactions of the bismethanesulphonates with sodium thiophenate proceeded mainly by direct SN2 displacement (i.e., not through an episulphonium ion) whilst with sodium azide both episulphonium and

S 2 type displacement were involved. N In comparison with bismethanesulphonates, the monomethanesuiphonates were more reactive, as would be expected on the basis that the electronic effect of replacing one of the methanesulphonyloxy-groups by a hydrogen atom is to favour electron-release by sulphur and facilitate the formation of the episulphonium ion (39). - Thus the attempted preparations of

CH2 OMs CH2 ArS-CH NOAc ArS- , OMs C OAc

(34) (4o)

ArS-CH2 -CHOMs Me4 NOAc ArS-CH.CH-CH2 OAc

CH2 OMs

(35) (41)

(Ar: phenyl, E-methylthiophenyl, 2-chlorophenyl, 2,4-dinitrophenyl)

CH2 OMs CH2

ArS-CH Me0Na y ArS-C-CH2 OMe CH2 OMs

(34) (42)

(Ar: phenyl, p-methylthiophenyl, k-chlorophenyl, 2,4-dinitrophenyl)

1I+

ArS -CH2 Me0Na CHOMs > ArS-CH=CH-CH20Ms CH2 OMs

(35) (43)

[ ArS-CHwar2:CH2 ----H›- Ar-S-CH-CH=CH2 OMe (44)

(Ar = phenyl, E-methylthiophenyl, 1.-chloropheny1)-

Me4 NOAc ArS-CH-CH2 OMs ArS-C=CH2 Me Me (36) (45a)

Me4NOAc ArS -CH2 -CHOMs > ArS-CH=CH Me Me

(37) (45b)

(Ar = 2,4-dinitrophenyl) 15

the primary methanesulphonates (36, Ar = E-methoxyphenyl, 2.-methyl-

thiophenyl, p-chlorophenyl) from the corresponding alcohols resulted

in the isomeric secondary methanesulphonates (37), whereas in the 1,3-

bismethanesulphonates series only the p7methoxyphenyl-compound under-

went isomerisation to the 1,2-dimethanesulphonate.

The solvolysis reactions of the monomethanesulphonates (36) and

(37) in acetic acid and methanol proceeded through the episulphonium

ion (39) to give thermodynamically controlled secondary products

(kinetically controlled in the case of the 2,4-dinitro-compounds).

Episulphonium intermediate was also involved in the reactions of all

the monomethanesulphonates with lithium bromide and sodium azide and

in the reaction of the 2.-methoxy-compound with sodium phenyl sulphide.

The 1:, --methylthio and the .p7chloro-compounds reacted with sodium phenyl

sulphide by an SN2 mechanism. The reactions of the methanesulphonates

(37, except for the 2,4-dinitro-compounds) with potassium acetate,

tetramethylammonium acetate and sodium methoxide proceeded through

an episulphonium ion to give mixtures of isomeric products. The

2,4-dinitro methanesulphonates (36) and (37) reacted with sodium

methoxide and tetramethylammonium acetate to give mainly elimination

products (45a) and (45b). As with bismethanesulphonates, the episul-

p4onium ion was not involved in the elimination reactions. 16

Part 2:

The chemistry of compounds with functional group in the allylic

position is a broad field with. a voluminous literature, and the reac-

tions of allylic compounds are important from both the practical and

theoretical points of view. The ethylenic bond of the allylic system

activates the functional group with the result that allylic compounds

undergo replacement reactions much more rapidly than analogous saturated

compounds. Allylic compounds are also of theoretical interest because

of the ease with which they undergo rearrangement reactions. Migrations

of electronegative substituents from one end of an allylic system to the other are well known, and rearrangement frequently accompanies replacement reactions in these systems.

Allylic substitution reactions in which one electronegative functional group is replaced by another may occur with or without ' rearrangement:

Y- RR' C=CR ""-CR" 1/1"-X RR'C=CR"-CR"Rm-Y + RR'C-CR""=CR"R"'

Many reactions of this type reported in the early literature, prior to 1920, were assumed to give only normal (unrearranged) products whereas rearranged products were actually formed.

Nucleophilic replacement reactions of allylic compounds can be 22 divided into four types . One mechanism, designated S 2, is a N bimolecular substitution of the halogen by a nucleophile resulting in unrearranged products.

Y + RX ----4 YR + X (1)

Another mechanism, designated as SNi, involves an intramolecular rearrangement. The third mechanism, called unimolecular nucleophilic substitution SN1, involves electrophilic attack of solvent or nucleophile on the substituent group to form an intermediate alkyl carbonium 17

ion or ion pair, which subsequently reacts rapidly with an electron

donor to yield the rearranged or unrearranged products:

,+ Y- RX----*A X ›RY (2)

Finally the nucleophilic reagent can attack the unsaturated carbon atom of the allylic system and give the rearranged (abnormal) products.

6 5+ Y: + (yt - - - c C - - - + X-

This process is called abnormal bimolecular substitution and is represented by the symbol SN2'. To classify a reaction as an SN2' type, three conditions should be noted: (i) The reaction must be of second-order.

(ii) An isolable amount of abnormal product must be formed. (iii) It must be demonstrated that the abnormal product does not arise either from prior rearrangement of the allylic halide (followed by a normal

SN2 displacement reaction) or subsequent rearrangement of an SN2 product.

Early attempts to establish the existence of the SN2' mechanism 23 were not successful. Hughes, in 1941, briefly mentioned unpublished work on the reaction of a- and Y-methylally1 chlorides with sodium ethoxide in.ethanol in which only normal substitution products were 24 obtained. Roberts, Young and Winstein , in 1942, published the results of an independent investigation of the same and other reactions, in which it was found that the bimolecular reactions of neither primary nor secondary chloride give isolable amounts of abnormal substitution products. In a study of the exchange reaction between a-methylallyl bromide and radioactive bromide ion in acetone, it was found that the rate of the SN2' reaction is less than one-hundredth of the rate of

SN2 substitution, and the conclusion reached was that abnormal bimolecular substitution is usually not a mechanism of allylic rearrangements.25

As a result of these unsuccessful attempts to detect abnormal bimolecular 18

26 substitution, Catchpole, Hughes and Ingold concluded that substitu-

tion by the SN2' process apparently cannot be realized and they attributed

this to shielding of the ?-carbon atom of the allylic system by the

IT-electrons of the double bond.

In 1944 it was reported22 that a-methylallyl chloride undergoes

a bimolecular reaction with diethylamine which forms only the abnormal 27 product, and in the following year Young et al. published the first

evidence for the occurrence of an SN2' reaction. They found that a-

methylallyl and a-ethylallyl chloride (46) react with sodium malonic

ester in ethanol to give 10 and 23 per cent, respectively, of the

product which would result from an abnormal bimolecular displacement

involving attack on the X-carbon atom. Kinetic studies showed that

the reactions were second-order.

Once the existence of the SN2' mechanism had been demonstrated, 28 further examples were soon discovered. Meisenheimer and Link found that a-ethylallyl chloride (47) on treatment with diethylamine or methylaniline yielded abnormal products (48) which were the same as those obtained from Y-ethylally1 chloride (49). 29 Young et al. reported that both a- and X-methylallyl chlorides react with diethylamine in benzene to give (50). Formation of (50) was not due to rearrangement of a-methylallyl chloride or to rearrangement of an initially formed normal product. Kinetic studies showed that the reaction was a bimolecular process. 27 It was suggested by Kepner, Winstein and Young that the formation of abnormal products in reactions of diethylamine with secondary allylic chlorides might proceed through the intermediate (51). Owing 30 to this possibility of hydrogen bonding, England and Hughes and 31 Ingold chose to classify these reactions not as examples of the

R-CH-CH=CH2 + NaCH(CO2 C2 115 )2

(46)

R-r-CH=CH2 + R-CH=CH-CH2 -CH( CO2 C2 H5 )2

CH( 002 C.2 H5 )

C2 H5 -CH-CH=CH2 Cl (47) R2 NH > 02 H5 -CH=CH-CH2 N+HR2 Cl

C2 H5 -CH=CH-CH2 Cl (48)

(49)

CH2 =CH-CHC1 + ( C2 H5 )2 NH -r!►(C2 H5 )2 N-CH2 -CH=CH cH3

(50)

(51)

C6 113 c12 coo HB:

(52) (53) 20

S 2' mechanism but as examples of the S i mechanism (substitution by N N intramolecular rearrangement of an intermediate compound).

Stork and White32 found that trans-6-alkyl-2-cyclohexenyl

2,6_dichlorobenzoate (52) undergo a bimolecular reaction with piperidine to give products (53).

The reaction of a-chlorocodide (54) with methoxide ion and similar displacements are examples of SN2' reactions forced to occur by steric hindrance to the normal products.33

Braude et a1.34 have studied the exchange and isomerization reactions of a-phenylallyl £-nitrobenzoate (55) in chlorobenzene solutions of radioactive 2.-nitrobenzoic acid. The acid-catalyzed rearrangement is bimolecular and may involve attack of the unionized acid at the i-carbon atom of the allylic system through a cyclic transition state involving a hydrogen bond to give the rearranged product (56). This would be an S 2' mechanism; however it is also N possible that a preliminary proton transfer occurs followed by intra- 22 molecular rearrangement (S i'). N In scheme I (page 22) Bordwell35 has summarized the pathways, other than SN2', by which abnormal products may be formed. He says although the SN2' mechanistic classification has been suggested for numerous abnormal substitution reactions, relatively few completely unambiguous examples have been described and in many cases no attempt has been made to exclude the SNi-SN2 pathway. In his previous papers

Bordwell reported that the reaction of 3-chloromethylbenzo Eb]thiophene

1,1-dioxide (57) with piperidine in benzene gave the product (58) which was also obtained from the reaction of the bromide (59) with piperidine.

The reaction on the bromide was thought to proceed through several steps: (i) Tautomerism to an allylic halide. (ii) An SN2' reaction 21

OM e >

( 54)

Ar—CH—CH=CH2 + RC* 00H

OCOR

( 55)

CH X...... , Ar — CH CII2

,- A r CH= CH— ?H2 RCO OCOR II - OC* OR 0 '. 7 * -. H

( 56)

Scheme I

Path a (SN2-SNV)

Y CH2 =CH-CHR ) CH2 =CH-CHR CH2 -CH=CHR - I SN2 S i X Y N

Path b (SN1) I

CH2 =CH-CHR slow CH2- 5. z.:CHCHR X fast

Path c (SNV-SN2) .-t- I_____"___‘ fast fast CH2 =CH-CHR , CH 2--GH --CHR X- CH2 -CH=CHR X [

Y CH2 -CH=CHR slow

Path d (rate-limiting attack of Y-: on an ion pair)

,____ fast Y CH2 =CH-CHR CHi-LICH=CHR X- 2 > > CH -CH=CHR slow [ Y

Path e (S Ni')

fast CH2 =CH-CHR < CH2 -CH' 'CHR slow CH2 -CH=CHR Y-H ...X Y....H -X

:Y-H 23

CH2 C1

S 02 (57) C5 Hi n NH Benzene

(58)

(59)

C5 H1 NH (59) (i) (ii)

CH2 NHC5 H10 Br- CH2 NC5 H10 + —H I \ (58) (iii) I / (iv) SO

CRR

-60 R=R'=H, X=01 63 - R=H, X=C1, Br, I 61 R.H p R'=Me, X=Br, Cl 64 - R=Me , X=Br 62 - Rt=R=Me, X=C1

65 - R=H, X=Br

66 - R=Me , X=Br 24-

with piperidine. (iii) Loss of a proton. (iv) Tautomerism to form

an enamine. 36 On the basis of these results and studies of analogous compounds

and their kinetic reactions37'38 Bordwell et al. concluded39 that the

seven halides (60-66) react with nucleophiles by an SN2' mechanism.

The halides (60-62) reacted with piperidine to give the abnormal product

(67) which rearranged to the final product (68) by ring opening followed

by ring closing in a different position. The unrearranged abnormal

products (67) were isolated when nucleophiles like N3 CN , PhS02

were used, as these nucleophiles do not have an electron pair capable

of initiating a reaction to form an intermediate like-(67a). Piperidine

was chosen as an ideal nucleophile for SN2' reactions as this mechanism

requires the nucleophile to attack an electron-rich carbon atom and

this is more favoured by a neutral, basic nucleophile like an amine and

less effective with charged nucleophiles such as alkoxide ion. However,

in a following paper35 Bordwell changed his mind and reported that the

formation of abnormal products in the reactions of the above mentioned halides was due to a carbanion intermediate (69) and he claimed that the SN2' mechanism is a myth. 40 de la Mare says that Bordwell's criticism that no attempt has been made to exclude the reaction path SNi' (sequence 1, below) is not valid.

(1) CH2 =CH-CPI P2 Cl fast > CH2 -CH-CR1 P2 Cl-

fast Y Cl-CH2 CH= CRi 1R2 slow >Y CH2 -CH=CR1 P2

The rate of the supposedly fast rearrangement of 3-chloro-3-methylbut- 41 1-ene, for example, was Shown to be slower than that of bimolecular 25

SN2 '

( 6o- 62 ) ( 67 )

,Me HNs. .."' C ^-,--,1* 1 C I: --1 r .../.:.' = ...._. C . ., NC 5 H1 0 ■•:....• .. 7 s" ' s NC5 H10 "H Me ( 67a) 2 h

( 68 )

CRP' X

+ Y : <

( 60-62 ) ( 69 ) •

+ X-

( 67)

Y = N3 , CR— , PhS02 — 26

substitution with rearrangement. Competition of this rearrangement

with solvolysis, when it occurs, produces a very characteristic kinetic 41 42 41 form, ' which was not observed in ethanol . So rearrangement does not compete even with solvolysis in this solvent, let alone with the much more rapid bimolecular replacement with rearrangement. The other path which Bordwell wishes to be considered is the sequence (2) in which

fast (2) CH2 =CH-CR, R2 Cl CH2 -CH-CRi R2 Cl fast

Y products slow the bond to be broken is considered to be broken completely before attack by the nucleophile, thus forming an ion-pair in rapid equilibrium with the starting material. If the original C-Cl bond has completely broken before attack by nucleophile, rearrangement of the starting material would be observed after partial reaction. This is known to 41 42 happen in the absence of powerful nucleophiles ' but does not occur in the cases of nucleophilic displacement with rearrangement. 43 Bordwell has also studied the nucleophilic displacement reactions of allylic compounds (70-72). System (70) was expected to be an ideal type for SN2' reactions on many counts: (i) SN2 attack at the a- position is inhibited sterically by the presence of the two methyl groups. (ii) the electron withdrawing ArS02 group inhibits SN1 or SN2 reactions. (iii) the ArSO2 group decreases the electron density at the C=C bond and thereby promotes attack at the i-position (SN2').

However, reactions of halides and methanesulphonate (70) with nucleophiles gave normal substitution (73) and elimination products (74). 27

ArSO2 y /H C C Ri 11"..-- PN / d.C -- X \R2

Ar = 2.-toly1

70 - R, = R2 = Me, X = Cl, Br, OMs 71 - R1 = H, R2 = Me, X = Cl, Br 72 - RI =R2 = H , X = Br, OMs

ArS02 -CH=CH-CMe2 X Nu

ArS02 -CH=CH-C=CH2 + ArS02 -CH=CH-CMe2 Nu

(71+) (73)

ArSO2 -CH=CH-CHR2 N3 3 ArS02 -CH2 -CH=CR2 N3

(75) (76) 28

The reactions of the compounds (71) and (72) with different types of nucleophiles gave the normal substitution (SN2) products. The compounds (71, X=Br) and (72, X=Br) when reacted with LiN3 in DMF gave the azides (76) which were the result of tautomerization of the initially formed azide (75). 29

DISCUSSION

In the preceding chapter the factors which affect the formation

. and the subsequent ring opening of an episulphonium ion were described. 21 The methanesulphonates (36) and (37) were shown by Khan and Owen to

undergo alkylation reactions mainly through the episulphonium ion (39).

Replacing the methyl group in these methanesulphonates by a phenyl

group is liable to affect the formation and the ring opening of the

episulphonium ion. Therefore a research programme was carried out

involving studies of the reactions of the methanesulphonates (77) and

(78) with various nucleophiles. The effect of variations in the sub-

stituent on the sulphur atom was investigated by studying the methane-

sulphonates (79) and (80).

The intermediacy of the allylic methanesulphonates (43) was 20 suggested by Khan and Owen in the reactions of the bismethanesul-

phonates (35) with sodium methoxide. These reactions resulted in the

allylically rearranged methyl ethers (44). As mentioned before,

electron:withdrawing substituents on '-carbon of an allylic system

are expected to favour the formation of the rearranged products (SN2').

Hence a study of the alkylation reactions of the allylic methanesul-

phonates (43, Ar = phenyl, E-nitrophenyl) is also included in this

programme of work.

First part of this chapter includes the study of the methanesul-

phonates (77-80) and in the second part the reactions of the allylic

methanesulphonates (43) have been described. 30

CH3 CH3 ArS -CH -CH20Ms ArS -CH2 -CHOMs

(36) (37)

Ar /S +\\\ CH3 -CH CH2

(39)

Ar Ar 1 PhS -CH -CH20Ms PhS -CH2 -CHOMs

(77) (78)

(Ar = phenyl, k-methoxyphenyl, 2.-nitrophenyl)

Ph Ph t 1 ArS-CH-CH2 OMs ArS-CH2 -CHOMs

(79) (8o)

(Ar = 2,4-dinitrophenyl)

ArS -CH2 ArS -CH ArS-CHOMe 1 II I CHOMs CH > CH 1 I II cH, OMs cH2 OMs c112

(35) (43) (44) 31

Part 1:

Synthesis of Authentic Compounds

1-Phenyl-2-(phenylthio)ethanol, 2-phenyl-2-(phenylthio)ethanol, and

their derivatives

The reaction of mercaptans with unsymmetrical epoxides has been 61,62 studied by several workers and it is suggested that these expoxides 63,64 cleave in basid media to give the secondary alcohols.

However, in the present work, the reaction of styrene oxide with sodium thiophenate followed by subsequent hydrolysis gave a mixture

of the primary and the secondary alcohols (81) and (82) in a ratio of ca. 1:1 which were separated by chromatography. The secondary alcohol

(82) is known and has been prepared by the reduction of phenyl phenacyl sulphide65 (identified by the analysis results). In order to confirm the constitution of the alcohols (81) and (82), the primary alcohol (81) was also prepared by conversion of methyl mandelate into its toluene-

11.-sulphonate followed by reaction with sodium thiophenate. The reduction of the resulting compound with LAH gave a 60% yield of the alcohol

(8L) and some thiophenol (partial fission of C-S bond).

Ph.CHOH.0O Me > Ph.CH(OTs).0O2Me 2 Ph.CH(SPh).00 Me > Ph.CH(SPh).CH 0H 2 2

The acetates (83) and (84) were prepared by treating the corresponding alcohols with acetic anhydride in pyridine44. The methyl ethers (85) and (86) were prepared by the reactions of the respective alcohols with dimethyl sulphate and powdered sodium hydroxide in tetrahydrofuran45. The crystalline primary methanesulphonate (87) was prepared by treating the alcohol (81) with methanesulphonyl 46 chloride using triethylamine as the base ; this compound was very unstable at temperatures above 00. The secondary methanesulphonate 32

(88) could not be obtained by this method as the reaction (at 0°)

resulted in formation of the secondary chloride (90). This chloride,

when heated, partially isomerized to the primary chloride (89), as

shown by the change in the n.m.r. spectrum. To prevent the subsequent

reaction of the secondary methanesulphonate with chloride ion, the

preparation was carried out using (i) sodium hydride as a base,

(ii) silver oxide as a base, (iii) methanesulphonic anhydride instead

of the methanesulphonyl chloride, but in all these cases the secondary

alcohol was recovered with a 15-20% yield of the ether (91) which

was identified by analysis and n.m.r. spectrum. The proposed mechanism

for the formation of this ether (91) is given on page 33 . It was

concluded that the secondary methanesulphonate (88) was very reactive

and hydrolyzed during working up of the reaction mixture. To confirm

the formation of this compound, the reaction of the secondary alcohol

(82) with methanesulphonyl chloride, using silver oxide as a base,

was carried out in deuteriochloroform. The reaction mixture was then

filtered, concentrated to 0.5 ml and the n.m.r. spectrum of this solu-

tion was recorded. This methanesulphonate was very unstable and

difficult to handle while the corresponding secondary chloride (90)

was comparatively stable and easier to prepare. As the behaviour of

the methanesuiphonates and the corresponding chlorides towards nucleo-

philes are not expected to be very different, the displacement reactions

in this series were carried out using the primary methanesulphonate

(87) amd the secondary chl oride (90).

PhS-CH-CH2 X PhS-CH2 -CHX I I Ar Ar

(Ar = phenyl)

A • X = X=

OH (81) OH (82)

OAc (83) OAc (84)

OMe (85) OMe (86)

OMs (87) OMs (88)

Cl (89) C1 (90)

COMB

PhS-CH2 -CHOH > PhS-CH2 -CH- Ph - Ph /0

PhS-CH2 -CH=Ph

PhS-CH2 -CH-Phs > `0 / PhS-CH2 -CH-Ph

(91) 34

1-(p-Methoxypheny1)-2-(phenylthio)ethanol, 2-(p-methoxypheny1)-2-

(phenylthio)ethanol and their derivatives

The alcohols(92) and (93) were prepared by the reaction of 2-methoxy-

styrene oxide with sodium thiophenate. Ring opening again occurred in

both directions, and the two resulting alcohols were separated by

chromatography. 217Methoxystyrene oxide was prepared essentially by

the method described by Franzen and Driezen,47 in which a mixture of

anisaldehyde and trimethylsulphonium iodide was treated with sodamide

in dimethyl sulphoxide. It was found that using a lower temperature

resulted in better yield and higher purity of the product. The secondary

alcohol (93) was also prepared by the reaction of anisole with chloroacetyl

chloride48, followed by reaction with thiophenol in pyridine49, and 50 reduction of the product with sodium borohydride .

Me0Ph + CH C1.00C1 27Me0C H .COCH Cl 2 6 4 2 1,7Me0C6H4.COCH2SPh ).2 .-Me0C6H4.CHOH.CH2SPh

The acetates (94) and (95) were prepared by treating the respective alcohols with acetic anhydride'in pyridine44. The methyl ethers (96) and (97) were obtained by the reactions of the corresponding alcohols with dimethyl sulphate and powdered sodium hydroxide in tetrahydrofuran45.

The crystalline primary methanesulphonate (98) was prepared by the reaction of methanesulphonyl chloride with the primary alcohol (92) using 46 triethylamine as the base . This compound was very unstable at temperatures above 0°. The reaction of the secondary alcohol (93) with methanesulphonyl chloride, under the same conditions gave an impure mixture of the isomeric chlorides (100) and (101) with a ratio of

1:3 respectively. The reaction was carried out using sodium hydride as a base, but the secondary alcohol was recovered. It was concluded that

PhS-CH-CH2 X PhS- CH2 - CH X Ar Ar (Ar = 2.-methoxyphenyl)

X OH (92) OH (93) OAc (94) OAc (95) OMe (96) OMe (97) OMs (98) OMs (99) Cl (100) Cl (101)

PhSCH-CH2 OMs PhS- CH2 -CHOMs Ar Ar "(102) (103) (Ar = 2 ,4-dinitrophenyl)

+ - Br Base PC) Ph3 P CHH 2

/0 + - Ph3 PCH2 + Ar— Ph3 Pt - - -12F - (1) 6-- - Ar

Ph3 PO Ar - CH = CH2

(Ar = 2,4-dinitrophenyl) 36

the secondary methanesulphonate (99) hydrolyzed during working up

of the reaction mixture and alkylation reactions in this series

were carried out only with the primary methanesulphonate (98).

1-(p-Nitropheny1)-2-(phenylthio)ethanol, 2-(p-nitrophenyl)-2-(phenyl-

thio)ethanol and their derivatives

It was originally intended to include the alkylation reactions of

the 2,4-dinitro substituted methanesulphonates (102) and (103). For

this purpose several methods were tried to prepare 2,4-dinitrostyrene

oxide. The reaction of this epoxide with sodium thiophenate should

give one or both of the alcohols (102) and (103).

An attempt was made to prepare this epoxide using trimethylsul-

phonium iodide. Sodamide was added to a stirred mixture of 2,4- 47 dinitrobenzaldehyde and trimethylsulphonium iodide in dimethylsulphoxide ,

resulting in complete decomposition of the aldehyde. To prevent decom-

position of the aldehyde by base, if that was the case, the aldehyde

was added to the mixture of base and excess trimethylsulphonium iodide51,

however, the same result was obtained. The attempted preparation of

2,4-dinitrostyrene using triphenyl methyl phosphonium bromide also

failed and the aldehyde was recovered. Having two nitro groups on the

phenyl ring of the aldehyde should promote the first step of the

• reaction (page 35) by increasing the positive charge on the carbon 52 atom , but apparently the second step was inhibited. Finally the

following route for preparing the epoxide was examined.

bromination nitration Ph.CH:CH Ph.CHBr.CH Br 2 2

nitration T.-NOC6114.CH(ONO2).CH2Br2 2,4--(NO ) C H .CH.CH Br 2 2 6 3 , 2 1 ONO 2 hydrolysis sodium hydroxide 2,4-(NO )C H.CHOH.CH Br 2 2 6 2 /0\ if \ 2,4-(NO ) C H .CH CH 2 2 6 3 2

A yield of 10-15% was obtained in the dinitration step (a Russian

paper has reported a 50% yield for this step using the corresponding

chloride53) resulting in an overall yield of 3-4% which made this

method practically useless. However, as 27nitrostyrene oxide could be

obtained in a good yield by this method, the dinitration step was

omitted and the alcohols (104) and (105) were prepared by the reaction

of sodium thiophenate with the 2-nitrostyrene oxide thus obtained. The

acetates (106) and (107) were prepared by treating the corresponding

alcohols with acetic anhydride in pyridine44. The secondary methyl

ether (109) was prepared by the reaction of the alcohol (105) with

dimethyl sulphate and powdered sodium hydroxide. The primary alcohol

(104) decomposed under the same conditions and no methyl ether was

obtained. This methyl ether (108) was prepared in a low yield by

treating the primary alcohol with an ethereal solution of diazomethane 54 in the presence of fluoroboric acid as catalyst. The crystalline

methanesulphonates (110) and (111) were prepared by the reactions of

the corresponding alcohols with methanesulphonyl chloride, using • triethylamine as the base46. These methanesulphonates partially isomerized at temperatures above 15-20°, so the alkylation reactions in this series were carried out mainly at 0°.

PhS-CH-CH2 X PhS-CH2 -CHX

Ar Ar

(Ar = .i-nitrophenyl)

X X

OH (104) OH (105)

OAC (106) OAc (107)

OMe (108) OMe (109)

OMs (110) OMs (111) 39

2-Phenyl-2-(2,4-dinitrophenylthio)ethanol, 1-pheny1-2-(2,4-dinitro- ._ phenylthio)ethanol and their derivatives

The reaction of 2,4-dinitrothiophenol (as sodium salt) with

styrene oxide resulted mainly in decomposition products. The fission

of the phenyl-sulphur bond in 2,4-dinitrophenyl sulphides by nucleo-

philic attack of base has been reported by Kharasch and Swidler.55

The secondary alcohol (113) is known and has been prepared by

the reaction of 2,4-dinitrophenylsulphenyl chloride with styrene and

hydrolysis of the resulting secondary chloride (120)56. To prepare

the primary alcohol (112), 2-bromo-2-phenylethanol was prepared by

treating styrene oxide with hydrogen bromide. The reaction of this bromo-alcohol with sodium 2,4-dinitrothiophenate gave the primary alcohol (112). In an attempt to improve the yield and to prevent side- reactions involving the hydroxyl group, the bromo-alcohol was converted into its tetrahydropyranyl ether57 (119) which then was treated with sodium 2,4-dinitrothiophenate followed by hydrolysis of the resulting ether (121); however, no improvement in the overall yield was noticed.

The acetates (114) and (115) were prepared by treating the corresponding alcohols with acetic anhydride in pyridine." Attempted preparations of the methyl ethers (116) and (117) using dimethyl sulphate and sodium hydroxide resulted in decomposition of the alcohols (fission of the phenyl-sulphur bond by base55). These methyl ethers were prepared in a low yield by treating the respective alcohols with ethereal solutions of diazomethane in the presence of fluoroboric acid as 54 catalyst. The crystalline methanesulphonates (118) and (119) were prepared by reaction of the corresponding alcohols with methanesulphonyl chloride, using triethylamine as the base46.

ArS -CH2 X ArS-CH2 -CHX

Ph Ph

(AT = 2,4-dinitrophenyl)

X = X = OH '(112) OH (113)

OAc (114) OAc (115) OMe (116) OMe (117)

OMs (118) OMs (119)

Cl (120)

(0) Ph -CHBr -CH2 OH Ph-CHBr -CH2 (119)

ArSNa hydrolysis Ph-CH cg2 o > (112) -'N. SAr (121) 41

The n.m.r. spectra of all these authentic compounds were recorded,

and the resonances are summarised in tables 1, 5, 8 and 12 on pages 80,

86, 89 and 95.

In the reactions of the methanesulphonates (or chloride) now to

be described, products were identified (unless otherwise specified),

and compositions estimated from their n.m.r. spectra given -on pages 80-100.

Reactions of 1-methanesulphonyloxy-2-phenyl-2-(phenylthio)ethane and

1-chloro-l-phenyl-2-(phenylthio)ethane

(i) With acetic acid

The solvolysis of the primary methanesulphonate in acetic acid in

the presence of acetic anhydride afforded exclusively the secondary acetate (84). The same product was obtained from the secondary chloride under similar conditions. A control reaction showed that the primary acetate (83) did not isomerize to (84) .under the conditions of the solvolysis reaction.

(ii) With potassium acetate

Both the primary methanesulphonate and the secondary chloride with potassium acetate in acetic anhydride gave only the secondary acetate (84). When the reaction of the primary methanesulphonate with potassium acetate was carried out in acetone a 5% yield of the unsaturated compound (122) was also obtained. The structure of this olefinic compound was shown by the n.m.r. spectrum (page 82) and by a further reaction described below. Its formation can be explained by the mechanism given on page 43.

(iii) With tetramethylammonium acetate .

Tetraethylammonium acetate, in its reactions with butenyl chloride, 42

has been reported to react by an S 2 mechanism to give the normal N products58 Tetramethylammonium acetate was prepared by neutralizing

tetramethylammonium hydroxide with acetic acid and working up as

described by Steigmann and Hammett59 for tetraethylammonium acetate.

The reaction of the primary methanesuiphonate with this reagent

in acetone gave a mixture of secondary acetate (84) and some (ca. 20%)

of the olefin (122). No olefin was obtained when the reaction

with the same reagent was carried out in acetic anhydride. The

reaction of the secondary chloride with tetramethylammonium acetate

in acetone for four days yielded the secondary acetate (84). A trace

(ca. 2%) of the olefin (122) was suspected in the nal.r. spectrum of

the crude product. This could be attributed to partial isomerization

of the secondary chloride to the primary chloride followed by the

elimination reaction (a small sample was worked up after 18 hours

and the n.m.r. spectrum showed a mixture of the secondary acetate and

both isomeric chlorides). The olefin (122) was unstable and gradually

(in 3-4 days) became oxidized to the ketone (123). A possible mechanism

for the oxidation of this type of olefinic compounds is suggested on

page 49 (for a closer study of the oxidation of this type of olefin,

see page 50 ). The structure of the olefin (122) was confirmed by

the reaction of a fresh sample of this compound (separated from the

acetate 82 by preparative t.l.c.) with acidic 2,4-dinitrophenylhydrazine

to give acetophenone 2,4-dinitrophenylhydrazone (125). As a vinyl

sulphide, it was expected that the olefin would hydrolyse to give 60 the ketone (124) .

(iv) With methanol

Solvolysis reactions of both the primary methanesuiphonate and

the secondary chloride in methanol gave the secondary methyl ether (86).

OAc - H PhS-C-CH2 GMs > PhS-C=CH2 Ph Ph

(122)

PhS-C=CH2 PhSCH2 -C.-0 Ph Ph

(122) (123)

H. +A H H t0H2 up + PhS-C=CH2 > Ph-S —C=CH2 —).PhSH + C=cH2 I iti 1 / Ph Ph Ph

2,14-DNP HO-C=CH2 0=C-CH3 Ph Ph

(124)

CH3 -I =N-NH-C6 H3 (NO2 )2

(125)

PhS-CH-CH2 X PhS-CH2 -CHX

Ph Ph

X = X =

scH2 c6 H5 (126) Br (127)

Br (128) N3 (129) 44

A control reaction showed that the primary methyl ether (85) did not isomerize to (86) under the conditions of the solvolysis reaction.

(v) With sodium methoxide in methanol

Both the primary methanesulphonate and the secondary chloride, when reacted with sodium methoxide in methanol, afforded the secondary methyl ether (86).

(vi) With sodium benzylmercaptide in methanol

The reaction of both the primary methanesulphonate and the secondary chloride with sodium benzylmercaptide in methanol gave a single sulphide. As will be described on page 78 the identification of azides and sulphides (compounds with only one of the isomers available) was-' accomplished by comparison of the difference between the chemical shifts of -CH2 and -CH of that compbund with of the primary ACH-CH2 authentic and A of the secondary authentic compounds of that CH2CH series. For example, in this series the difference between the chemical

foi. the primary authentic compounds (n.m.r. tables shifts (ACH2-CH) page 80) varies from 0.0 to 0.63 ppm while this range for the secondary authentic compounds is 0.95-2.5 ppm. The sulphide, obtained in the above reactions, has .z,;..x - CH = ca. 0.5 ppm, therefore, it was CH2 identified as the primary sulphide (126). .

(vii) With lithium bromide

The reaction of both the primary methanesulphonate and the secondary chloride gave the same bromide. This compound had A CH2-CH = ca. 1.3 ppm which fell in the range of the corresponding secondary compounds, and so it was identified as the secondary bromide (127).

This bromide partially isomerized on heating. The primary isomer (128)

(not isolated) had A'CH2-01-1 = ca. 0.65 ppm. 45

(viii) With sodium azide

Both. the primary methanesulphonate and the secondary chloride

with sodium azide -gave an identical azide. This compound had

. 1.34 ppm and was therefore identified as the secondary ACH2- CH azide (129).

Reactions of 1-methanesulphonyloxy-2-(p-methoxypheny1)-2-(phenylthio)

ethane

(i)-(iii) With acetic acid, potassium acetate and tetramethylammonium

acetate

Reactions of the primary methanesulphonate with acetic acid,

potassium acetate in acetic anhydride and with tetramethylammonium

acetate gave only the secondary acetate (95). A control reaction

showed that the primary acetate (94) did not isomerize to (95) under

the conditions of the solvolysis reaction.

(iv), (v) With methanol and with sodium methoxide

Reactions of the primary methanesulphonate with methanol and with

sodium methoxide in methanol afforded the §econdary methyl ether (97).

The control reaction showed that the primary methyl ether (96) did not

isomerize to (97) under the conditions of the solvolysis reaction.

(vi) With sodium azide

The azide obtained from the reaction of the primary methane-

sulphonate with sodium azide in DMF had . 1.33 ppm. The aCH2-CH difference between the chemical shifts of -CH and for the primary 2 -CH authentic compounds of this series is from 0.0 to 0.6 ppm (n.m.r. tables, page 86). This range for the secondary authentic compounds

is,1.0-2.5 ppm, therefore, the above azide was identified as the

secondary azide (130).

(vii) With lithium bromide

The reaction of the primary methanesulphonate with lithium bromide

in acetone resulted mainly in decomposition, but there was a product

which had -1.\, CH - CH = ca. 1.3 ppm and was probably the secondary 2 bromide (131). A trace (ca. 5%) of the primary bromide (132) was also

suspected in the n.m.r. spectrum of the crude product. These bromides

were unstable and could not be purified.

PhS -CH -CHN 2 3 Ar (130)

PhS-CH -CHBr PhS-CH-CHBr 2 1 2 Ar Ar

(131) (132)

(Ar = 11-methoxypheny1)

Reactions of 1-methanesulphonyloxy-1-(p-nitropheny1)-2-(phenylthio)

ethane and 1-methanesulphonyloxy-2-(p-nitropheny1)-2-(phenylthio)

ethane

(i) With acetic acid

The solvolysis of both the primary and the secondary methanesul-

phonates with acetic acid in the presence of acetic anhydride gave the

secondary acetate (107). The control reaction showed that the primary

acetate (106) did not isomerize to (107) under the conditions of the

solvolysis reaction. 47

(ii) With potassium acetate

The reaction of the secondary methanesulphonate with potassium

acetate in acetic anhydride gave the secondary acetate (107). The

primary methanesulphonate, under the same conditions, decomposed and

no product was obtained.

The reaction of primary methanesulphonate with potassium acetate

when carried out in acetone gave the olefin (133) with some of the ketone (134), the latter being formed by oxidation of the olefin

(133); a closer study on this oxidation will be described later.

The secondary methanesulphonate, under the same condition, yielded the secondary acetate (107) with a trace (5%) of the olefin (133).

Formation of this olefin in this reaction was attributed to a minor isomerization of the secondary methanesulphonate (111) to the primary form (110) followed by the elimination reaction.

(iii) With tetramethylammonium acetate

The primary methanesulphonate when reacted with tetramethylammonium acetate in acetic anhydride and in acetone afforded the olefin

(133) with some of the ketone (134). The secondary methanesulphonate with tetramethylammonium acetate in acetic anhydride gave the secondary acetate (107). This reaction when carried out in acetone afforded the secondary acetate (107) and a trace (5%) of the olefin (133), probably due to isomerization of the secondary methanesulphonate.

(iv) With methanol

' The solvolysis of both the primary and the secondary methanesulphonates in methanol gave the secondary methyl ether (109). The control reaction showed that the primary methyl ether (108) did not isomerize to (109) under the conditions of the solvolysis reaction. 1+8

(v) With sodium methoxide in methanol

The reaction of the primary methanesulphonate with sodium methoxide

in methanol afforded a mixture of the primary methyl ether (108), the

olefin (133) and the ketone (134) in the ratio of ca. 6:2:1, respec-

tively. The secondary methanesulphonate under the same conditions

gave the secondary methyl ether (109).

(vi) With sodium thiophenate in methanol

Both the primary and the secondary methanesulphonates when

reacted with sodium thiophenate in methanol gave the sulphide (135),

which is the only sulphide which can be formed from the displacement

reaction of either of the methanesulphonates. It was interesting to

note that of this compound (ca. 0.9 ppm) was between the ACH2-CH ranges of the authentic primary compounds (0.0-0.65) and the authentic

secondary compounds (1.1-2.5) of this series (n.m.r. tables, page 89 ).

(vii) With lithium bromide

The reactions of both the primary and the secondary methane-

sulphonates with lithium bromide in acetone gave an impure mixture of

the secondary bromide (136), - CH = ca. 1.3 ppm and the primary Z CH 2 bromide 0137), LS = ca. 0.7 ppm in the ratio of 3:1, respectively. CH2-CH These bromides were unstable and decomposed on attempted purification.

(viii) With sodium azide

The reaction of the secondary methanesulphonate with sodium

azide gave the secondary azide (138), 2.-CH -CH = 1.45 ppm. The 2 primary methanesulphonate under the same condition afforded a mixture

of the olefin (133) and some of the ketone (134).

OAc H // PhS-C-CH2 -0Ms ). PhS-C=CH2 1 I Ar Ar

(11o) (133)

PhS PhS PhS.

C.--=----- CH2 ______3„ ,/1C — 6H2 ---7->Ar C > I

Ar ' -0. Ar 0 0 Os 0, 0 PhS-CH2 - C-0- 0 PhS-CH2 -C=0 + -0-0H Ar Ar

(131+)

PhS-CH-CH2 °Ms Ar (110) PhSNa > PhS-CH2 -CH-SPh Ar PhS-CH2 -CHOMs Ar (135)

PhS-CH2 -CHBr PhS-CH-CH2 Br Ar Ar

(136) (137)

PhS-CH2 -CHN3 Ar (138)

(Ar = 2Tnitrophenyl) 50

Oxidation of the olefin (133) to the ketone (134)

In many cases the reactions of the primary methanesulphonate

(110) with nucleophiles gave the olefin (133) along with some of the ketone (134). This olefin when exposed to air for a few days became

completely oxidized to the ketone (134),There seems to be no analogy

for this reaction, which might occur by the mechanism given on page 49 .

The oxidation was very fast when the olefin was exposed to air on a large surface, for example on a preparative t.l.c.. To confirm that

oxygen in the air was used for this oxidation, the following experi-

ments were carried out:

The olefin was prepared by the reaction of the primary methane-

sulphonate with sodium azide at 0°. The freshly obtained olefin

(which already contained ca. 10% of the ketone) was dissolved in

deuteriochloroform and divided into three n.m.r. tubes: (A) sealed

and under nitrogen, (B) open, containing some 2,6-di-tert-buty1-2-

cresol (anti-'oxidant), and (C) open. The oxidation was followed by

recording the n.m.r. spectra of these samples every day. The graph

1, (page 51) shows that the oxidation reaction in sample (C) was

complete in about nine days (oxidation was not very fast as the

surface of contact to air was small). The sample (A) was nearly

unchanged after the first day, but then the oxidation slowly proceeded

(para-film was used for sealing the tube and possibly was not very

efficient). The oxidation reaction in sample (B) was very slow up

to four days, and then, as the anti-oxidant was used up, the oxidation

proceeded slightly faster. To the sample (A) after seven days (which

then contained ca. 30% of the ketone) benzoyl peroxide was added

(sample D). Following the oxidation of this sample by recording the 51

Ketone %

100

■ )0. 1 2 3 4 5 6 7 Days

Graph 1 52

n.m.r. spectrum (graph 1, page 51 ) showed that the addition of the peroxide had no effect and in fact oxidation in this case (tube was stoppered) was slower than in sample (C) which was exposed to air.

Reactions of 1-methanesulphonyloxy-l-phenyl-2-(2,4-dinitrophenylthio) ethane and,l-methanesulphonyloxy-2-phenyl-2-(2,4-dinitrophenylthio) ethane

(i) With acetic acid

The solvolysis of both of the methanesulphonates in acetic acid in the presence of acetic anhydride gave the secondary acetate (115).

A control reaction showed that the primary acetate (114) did not isomerize to (115) under the conditions of the solvolysis reaction.

(ii) With potassium acetate

The reaction of the secondary methanesulphonate with potassium acetate in acetic anhydride yielded only the secondary acetate (115).

The same reaction when carried out in acetone gave a mixture of the acetate (115) and the olefin (139) in the ratio of 2:1, respectively.

The primary methanesulphonate when reacted with potassium acetate in acetic anhydride gave only the olefin (140).

(iii) With tetramethylammonium acetate

The reaction of the secondary methanesulphonate with this reagent in acetone gave a mixture of the secondary acetate (115) and the olefin (139), ratio 1:3 respectively. The same reaction when carried out in acetic anhydride gave a mixture of the acetate and the olefin in a ratio of 3:1, respectively. The primary methanesulphonate with tetramethylammonium acetate in acetone gave only the olefin (140).

ArS-CH-CH2 OMs ). ArS-C=CH2 I Ph Ph (118) (140)

ArS-CH2 -CHOMs D ArS-CH=CHPh Ph (119) (139)

ArS -CH -CH2 SPh ArS -CH2 -CHBr I I .Ph Ph (141) (142)

ArS-CH-CH2 Br ArS -CH2 -CHN3

Ph ' Ph (143)

(Ar=2,4-dinitrophenyl) 54

(iv) With methanol

The solvolysis of both of the methanesulphonates in methanol

gave the secondary methyl ether (117). A control reaction showed that

the primary. methyl ether (116) did not isomerize to (117) under the

conditions of the solvolysis reaction.

(v) With sodium methoxide in methanol

The reaction of the secondary methanesulphonate with sodium

methoxide in methanol at 70° gave a mixture of 2,4-dinitroanisole

(ca. 80%) and some (10%) of the secondary methyl ether (117). This

reaction was carried out at room temperature to obtain a mixture of

the olefin (139), the secondary methyl ether (117) and 2,4-dinitro-

anisole in a ratio of 5:3:2,, respectively. The formation of 2,4-

dinitroanisole is due to nucleophilic attack by Me0 on the ring

and breaking the sulphur-phenyl bond. This type of fission has been

reported by Kharasch and Swidler55.

The primary methanesulphonate when reacted with sodium

methoxide at room temperature yielded mainly 2,4-dinitroanisole with

some (5%) of the olefin (140). When the reaction was carried out at o 0 , a high yield of the olefin (140) was obtained with some (ca. 5%)

2,4-dinitroanisole.

(vi) With sodium thiophenate in methanol

The reaction of the secondary methanesulphonate with sodium

thiophenate resulted mainly in 2,4-dinitrophenyl phenyl sulphide

(attack of nucleophile on sulphur-phenyl bond) and some (10%) of

the secondary methyl ether (117, solvolysis product). 55

The primary methanesulphonate under the same conditions gave

mainlyidinitrtchenyl phenyl sulphide and some (ca. 10%) of alkylation

product which had A cli = ca. 0.8 ppm. This compound was therefore 2 probably the primary sulphide (141), as the range for the CH -CH 2 primary compouhds of this series is 0.3-0.8 ppm and for the secondary

compounds is 1.1-2.4 ppm.

(vii) With lithium bromide

The secondary methanesulphonate when reacted with lithium bromide

gave the secondary bromide (142) which is a known compound.56

The primary methanesulphonate under the same conditions afforded

the primary bromide (143) with a trace (5%) of the olefin (140).

(viii) With sodium azide

The secondary methanesulphonate when reacted with sodium azide

at room temperature gave the secondary azide (144), LSCH -CH = 1.27 2 ppm. The primary methanesulphonate under the same conditions decomposed

and no product was obtained. The reaction was therefore repeated at 0°.

After three hours, as the mixture was becoming brown, it was worked

up. The product was.an impure mixture of the unreacted primary methane-

sulphonate and the olefin (140).

General discussion on the reactions of the methanesulphonates

Although the carbon atoms in the episulphonium ring are, strictly speaking, secondary and tertiary, these will be called the "primary" and the "secondary" positions, corresponding to the products formed

by attack of the nucleophiles at these positions.

The results of the reactions of different substituted methanesulphonates have been reported in the previous pages and are summarized 56

in simplified form in page 62 . As expected, an electron-donating

substituent in the aryl ring increased the reactivity of the methane-

sulphonates (77) and (78) by promoting the formation of the episul-

phonium ion (145); this effect was particularly noticeable in the high

reactivity of the secondary methanesulphonates (78, Ar = phenyl, 11.-

methoxyphenyl). The reactions of the primary methanesulphonates

(77, Ar = phenyl, 2.-methoxyphenyl) with different nucleophiles must

have involved the episulphonium ion (145). The ring opening of this

intermediate was favoured at the "secondary" position as the.stabili-

zation of charge at this position would be helped by the aromatic ring.

The only exception was the reaction of the methanesulphonate (77,

Ar = phenyl) with sodium benzylmercaptide which gave the primary

product. This can be explained by direct S 2 displacement (not invol- N ving episulphonium ion) or by sterically controlled opening of the

episulphonium ion; but since the secondary chloride (90) with sodium

benzylmercaptide also gave the primary product, the episulphonium ion

(145) is probably involved in both cases. The reactions of the secon-

dary chloride (90) with other nucleophiles resulted in the secondary ion products. It is possible that the episulphoniumj(145) was not involved

in these reactions as the carbonium ion (146) can be stabilized by

the aromatic ring. However as the reaction with the strong nucleophile

PhCH2S did proceed through this episulphonium intermediate it is reasonable to accept that the reactions with weaker nucleophiles also proceeded by the Same mechanism.

The £_nitro substituent on the aryl ring of the methanesulphonates

(77) and (78) (Ar = 11:.nitrophenyl) inhibited the formation of the

episulphoniumi, ion (145) to the extent that only solvolysis reactions 57

PhS -FI -CH2 -0Ms PhS -CH2 -CH -Ws

Ar Ar

(77) (78)

Ph + S PhS-CH2 -CH /+\ 1 Ar CH2 CH -Ar (146) (11+5)

(Ar . phenyl, 2.-methoxyphenyl, E-nitrophenyl)

PhS -CH2 -CHC1 Ph (9o) 58

proceeded through this intermediate. The reactions of the secondary

p-nitrophenyl methanesulphonate with potassium acetate, tetramethyl-

ammonium acetate, sodium methoxide and sodium azide gave the normal

products. The reactions of the primary 1.-nitrophenyl methanesulphonate

with these nucleophiles resulted mainly in elimination products due

to the high acidity of the (3 -proton in this compound. The reactions

of both of the k-nitro-methanesulphonates with lithium bromide gave an

impure mixture of the secondary and the primary bromides (ca. 3:1).

A sample of the reaction of the primary methanesulphonate with lithium

bromide was worked up after a short time and showed a mixture of the

secondary and the primary bromides (ca. 3:1) and both methanesulphonates

(1:1). This showed that due to isomerization of the methanesulphonates,

it is possible (though unlikely) that only direct displacement was

involved; that is, a mixture of the bromides with a ratio of 1:1 could

be first obtained followed by partial isomerization of the primary

bromide. (The isomerization of the halides was also observed in the

phenyl and 1,7methoxyphenyl series).

The strong electron-withdrawal effect of the 2,4-dinitrophenyl

group in the methanesulphonates (79) and (80) had an important effect on impairing the sulphur's bridging ability; thus only the solvolysis reactions of these methanesulphonates proceeded through the intermediate

(147) to give the secondary products. However, it is again possible that this episulphonium ion was not involved in the solvolysis reactions of the secondary methanesulphonate, due both to stabilization of the secondary carbonium ion (148) by the phenyl ring and also to weakening of the sulphur's bridging ability. Owing to the high acidity of the fi -proton in the methanesulphonates (79) and (80), the elimination 59

reactions were favoured in most of the reactions of these methanesul- 66 phonates . The elimination reactions were more common in the reactions of the primary methanesulphonate (79) as the P-proton is more acidic in this isomer than in the secondary methanesulphonate.

Episulphonium ions were not involved in any of the elimination reactions of the above methanesulphonates, as different unsaturated products were obtained from the isomeric methanesulphonates (79) and

(80). Elimination products were obtained in the reactions of the primary methanesulphonates (77, Ar = phenyl, p-nitrophenyl) whilst no elimination reaction occurred in the reaction of the secondary methanesulphonate (78, Ar = k-nitrophenyl) and the secondary chloride

(90); the difference is again due to the higher acidity of the (5-proton in the primary compounds.

In the reactions of the above methanesulphonates with potassium acetate and tetramethylammonium acetate, it was noticed that solvent, as well as the nucleophile, had an important effect on the formation of the unsaturated products. The highest yield of the olefins was obtained when tetramethylammonium acetate in acetone was used. A lower yield of the olefins was obtained with tetramethylammonium acetate in acetic anhydride and the reactions with potassium acetate in acetone gave no olefin. The effect of solvent on the formation of the unsaturated products can be explained in two ways: (i) if the formation of an ion-pair (from the reagent) is involved in the elimination reactions, as shown on page 60, it is possible that the formation of this ion- pair is more favoured in acetone than acetic anhydride, (ii) it is possible that the rate of the alkylation reactions was slower in acetone than in acetic anhydride, thus favouring the elimination reactions. The minor isomerization of the methanesulphonates (78) to

ArS - CH- CH2 0Ms ArS- CH2 -CHOMs

Ph Ph

(79) (80)

+ Ar ArS- CH2 -CH I S / +\ Ph

(148) CH2 CH-Ph

(147)

(Ar = 2,4-dinitrophenyl)

OAc ....Me4 N+ HH 11 ArS-C-CH2 OMsMs ArS-C=CH2 I Ar Ar

- Or OAc ....Me4 N+ H

11 OMs ArS-CH=CH-Ar • I I H Ar 61

(77) which was observed only when these reactions were carried out in acetone was attributed to a slow rate of the alkylation reaction

(in comparison with the rate of the alkylation reaction in acetic anhydride) which allows the much slower isomerization reaction of the methanesulphonates. (The effect of solvent was not related to dielectric constant as acetone and acetic anhydride have similar dielectric constants). Summary of the results of the reactions of the'methanesulphonates with nucleophiles

. _ KOAc KOAc Me4 NOAc Me4 NOAc Ar Ar' AcOH Me0H Me0Na in Ac2 0 in Mee C0 in Ac2 0 in Mee C0 in Me0H LiBr NaN3 PhCH2 SNa

Prim. Ph Ph S S S (E) S , S (E) S S S S P Sec.* S S - S S S S S P Prim. Ph .p.-Me0C6H4 S S - - . " S S S S S _ PhSNa Prim. S D E E E S P (E) S (P) E S=P Ph 2:-.NO C6 H4 Sec. S S S S S S S S (P) S S=P Prim. 2,4(NO2)2 S E - - E Ph S E (X) P (E) E D X (P) Sec. -C6 H3 S S (E) S S (E) E (S) S S(E)(X) S S X

P = Primary substitution products ArS.CHAr'.CH2.0Ms = Prim. S = Secondary substitution products ArS.CH2 .CHAr'.0Ms = Sec. E = Elimination products X = By products (e.g. 2,4-dinitroanisole) *: chloride D = Decomposition ( ) indicates minor products

rn 63

Part 2:

Synthesis of Authentic Compounds

3-(Phenylthio)allyl alcohol and its derivatives

The reaction of thiophenol with propargyl alcohol in the presence

of powdered potassium hydroxide has been reported to give a 60% yield

of trans-3-(phenylthio)allyl alcohol (151) (the product was identified 67 by i.r. spectrum and analysis results) . However, in the present

work, when the reaction was carried out using 3-4% powdered potassium

hydroxide, the product (90% yield) was a 3:2 mixture of the cis alcohol

(152) and 2-(phenylthio)allyl alcohol (149). Using 15-20% potassium

hydroxide resulted in a large amount of decomposition and the product

(50% yield) was a 2:1:1 mixture of the trans and cis alcohols (151),

(152), and the isomer (149). Using larger amounts of potassium hydroxide caused complete decomposition. Isomerization of the cis alcohol (152) to the trans alcohol (151) in the presence of base was confirmed by heating the cis isomer in ethylene glycol (containing sodium) to obtain a mixture of the cis and trans alcohols. This type of isomerization 68,69,70 has been reported in similar compounds. The alcohols (149) and (152) were separated by chromatography, the cis and trans isomers

(151) and (152) could not be separated, but their individual presence was evident from the n.m.r. and i.r. spectrum. The structure of the alcohol (149) was confirmed by preparing the corresponding acetate

(150); a crude sample of this acetate has been reported by Baig and

Owen7. The cis acetate (154) was prepared by reaction of the cis alcohol with acetic anhydride in pyridine44. The cis methyl ether (155) was obtained by treating the corresponding alcohol with dimethyl 64

45 sulphate and powdered sodium hydroxide in tetrahydrofuran. The

mixture of the cis and trans alcohols was acetylated and methylated by

the above methods to obtain a mixture of the cis and trans acetates

(154) and (153) and a mixture of the cis and trans methyl ethers (156)

and (155) respectively. The preparation of these mixtures of isomeric

acetates and isomeric methyl ethers as authentic samples was necessary

as in most of the alkylation reactions the trans isomers were obtained.

Attempted preparation of the methanesulphonate (158) using methanesul-

phonyl chloride and triethylamine as the base46 failed and the trans

chloride (157) was obtained (a trace of the ether 159 was also suspected

in the n.m.r. spectrum of the crude chloride). Using sodium hydride

as the base resulted in recovery of the alcohol (i.e. hydrolysis of

the methanesulphonate during work-up of the reaction mixture).

To prevent formation of the ether (159) in preparation of the

chloride (157), the alcohol was added to the mixture of the base and

methanesulphonyl chloride, but the reaction did not work and most of

the alcohol was recovered. In the usual procedure in which methane-

sulphonyl chloride is added to the mixture of triethylamine and the 71, 72 alcohol, the intermediacy of sulphene has been suggested.

+ CH SO C1 + Et N E----.1.Et NH Cl + CH SO 3 2 3 3 2 2

CH SO + ROH ------ROSO Me 2 2 2

ROSO2Me >RC1 OSO Me (in the case of formation of Cl 2 chloride)

Borowitz73 found that in the reactions of morpholine enamines with methanesulphonyl chloride, using triethylamine as the base, to give four-membered cyclic (3 -aminosulphones, the yield was very low when methanesulphonyl chloride and triethylamine were mixed before 65

CH2 =1-CH2 X SPh

X = OH (149) OAc (150)

PhS \/ H PhS ,CH2 X \ / C=-----C C=.-- C / \ / \ H CH2 X H _ H

X= X= OH (151) OH (152) OAc (153) OAc (154) OMe (155) OMe (156) Cl (157) PhS-CH=CH-CH2 0Ms (158)

PhS-CH=CH-CH2 OMsMs "C..., _ > (PhS-CH=CH-CH2 )2 0 PhS-CH=CH-CH2 0 % (159) 66

the addition of the morphonine (a good yield of the product was obtained when the methanesulphonyl chloride was added to the mixture of the morpholine and base). It was concluded that the initially formed sulphene was converted to another compound (possibly a polymeric form of the sulphene) which was no longer reactive.

However, the trans chloride (157) was obtained in good yield

(and free from the ether 159) by addition of the mixture of the alcohol and triethylamine to methanesulphonyl chloride (which is in agreement with Borowitz's results) and the alkylation reactions were carried out using this chloride.

3-(p-Nitrophenylthio)allyl alcohol and its derivatives

The reaction of propargyl alcohol with 2-nitrothiophenol in the presence of powdered potassium hydroxide (3%) gave a 1:3 mixture of

2-(27nitrophenylthio)ally1 alcohol (160) and cis-3-( 7nitrophenylthio) allyl alcohol (161), which were separated by chromatography. The acetate (162) was prepared by treating the alcohol (161) with acetic 44 anhydride in pyridine . The methyl ether (163) was obtained by the reaction of this alcohol with dimethyl sulphate and powdered sodium hydroxide45. The reaction of methanesulphonyl chloride using triethylamine as the base at room temperature gave a mixture of the cis and 0,46 trans chlorides (165). This reaction, when carried out at 0 gave the cis methanesulphonate (164) as a very unstable oil which decomposed in 1-2 minutes. However, this methanesulphonate was comparatively stable in solution and in order to record the n.m.r. spectrum, the preparation was carried out in deuteriochloroform and after working up of the reaction mixture the solution was concentrated to about 0.5 ml and the n.m.r. spectrum of this solution 67

CH2 =C-CH2 OH I SAr (16o)

PhS\ / /CH2X

C== C / \ H H

X = OH (161) OAc (162) OMe (163) OMs (164)

ArS-CH.CH-CH2C1 (mixture of cis and trans) (165)

(Ar = 2-nitrophenyl) 68

was recorded. The freshly prepared solutions of this methanesulphonate were used for the alkylation reactions. Two reactions (with methanol and with sodium methoxide) were also carried out using the chlorides

(165).

The n.m.r. spectra of all these authentic compounds are summarized in the tables 16 and 18, pages 101-102 and 105.

In the reactions of the methanesulphonate and chlorides now to be described, products were identified (unless otherwise specified), and compositions estimated from their n.m.r. spectra, given on pages 102-108.

Reactions of trans-3-chloro-1-(phenylthio)prop-1-ene

(i) With acetic acid

Solvolysis of the chloride in acetic acid in the presence of acetic anhydride resulted mainly in decomposition. A trace (5%) of the trans acetate (153) was suspected in the n.m.r. spectrum of the crude product.

(ii) With potassium acetate

The chloride reacted with potassium acetate in acetic anhydride to give an impure mixture of the trans acetate (153) and the allylically rearranged acetate (167) in the ratio of 1:2 respectively. The latter compound was unstable and could not be purified.

(iii) With tetramethylammonium acetate

The reaction of the chloride with tetramethylammonium acetate in acetone gave a mixture of the trans acetate (153) and the acetate

(167) in the ratio of 5:2 respectively. 69

(iv) With methanol

The solvolysis reaction of the trans chloride in methanol gave a

70% yield of the dimethyl ether (169). When this reaction was carried

out in the presence of calcium carbonate, the product was an impure

mixture of the dimethyl ether (about 30%) and traces of the methyl

ethers (155) and (168). The structure of the dimethyl ether (169)

was confirmed by the reaction with 2,4-dinitrophenylhydrazine (page

71 ) which gave a good yield of 3-(phenylthio)propionaldehyde 2,4-

dinitrophenylhydrazone (172). A possible mechanism for the formation

of the dimethyl ether (169) is given on page 70.

(v) With sodium methoxide in methanol

The reaction of the chloride with sodium methoxide in methanol

gave a 1:2 mixture of the trans methyl ether (155) and the allylically rearranged methyl ether (168).which were separated by chromatography.

(vi) With sodium azide

The reaction of the chloride with sodium azide in DMF gave the

trans azide (166).

(vii) With hydrogen chloride

The reaction of the chloride with hydrochloric acid (gas) in

dichloromethane gave a dichloride, probably (170) (addition of H01

to the olefinic bond). However, the structure (171) could also be

possible from the n.m.r. spectrum of the product (the mechanism of

formation of 171 would be similar to the formation of 169).

(viii) With lithium chloride

The reaction of the chloride with lithium chloride in acetone resulted in isomerization and a mixture of the cis and trans chlorides

(157) and (173) was obtained.

PhS . \\\ C — C/ PhS-CH-CH=CH2

\ x H / eH2x X = X = OAc (153) OAc (167) OMe (155) OMe (168) Cl (157) N3 (166)

Me0H PhS-CH=CH-CH2 Cl PhS-CH=CH-CH2 0Me + PhS-CH-CH=CH2 OMe

(157) (155) (168)

isomerization (168) (155) Me0H/HC1 H PhS-CH=CH—COMe Me0H/HC1 PhS-CH2 -CH=CHOMe H ( 155)

Me0H PhS-CH2 -CH2 -CH( OMe)2 (169)

PhS-CH-CH2 -CH2 Cl PhS-CH2 -CH2 -CHCl2 Cl (170) (171)

PhS-CH2 -CH2 -CH=N-NH-C6 H3 (NO2 )2

(172)

PhS CH2 Cl

(173) NH 71

The above mixture of chlorides when treated with sodium azide gave a mixture of cis and trans azides.

Reactions of some of the alkylation products with 2,4-dinitrophenylhydrazine

The methyl ethers (155) and (168), the dimethyl ether (169), the acetates (153) and (167) and the chloride (157) reacted with acidic

2,4-dinitrophenylhydrazine in ethanol to give only one isolable product, identified (by the n.m.r. spectrum and also m.p. corresponding to that in the literature74) as the compound (172). The highest yield (70%) of this derivative was obtained from the dimethyl ether, which would be exiected from the structure (169). A 50-55% yield of (172) was obtained from the above acetates, a 30-35% yield from the above methyl ethers and about 20-25% yield from the reaction of the chloride (157).

The formation of the compound (172) from the reactions of these methyl ethers, acetates and chloride could be attributed to the formatiOn of an intermediate analogous to the dimethyl ether (169) under the conditions of the reactions (acidic ethanol).

Reactions of cis-1-(p-nitrophenylthio)-3-methanesulphonyloxyprop-1-ene

(i) With acetic acid

Solvolysis of the cis methanesulphonate in acetic acid in the presence of acetic anhydride afforded the trans acetate (175) in good yield.

(ii) With potassium acetate

The cis methanesulphonate when reacted with potassium acetate 72

in acetic anhydride gave a 1:2 mixture of the trans acetate (175) and

the rearranged acetate (177).

(iii) With tetramethylammonium acetate

The reaction of the cis methanesulphonate with tetramethylammonium

acetate in acetone afforded a 3:1 mixture of the cis acetate (162)

and the rearranged acetate (177).

(iv) With methanol

The solvolysis of the cis methanesulphonate in methanol afforded

a mixture of the cis and trans methyl ethers (163) and (176) and the

rearranged methyl ether (178) in the ratio of 1:3 (normal:abnormal).

A control reaction showed that the cis and trans methyl ethers did

not rearrange to (178) under the conditions of the solvolysis reaction.

(v) With sodium methoxide in methanol

The reaction of the methanesulphonate with sodium methoxide in

methanol gave a mixture of the cis and trans methyl ethers (163),and

(176) and the rearranged methyl ether (178) in the ratio of 1:4

(normal:abnormal). The methyl ether (178) when exposed to air for

5-7 days was converted into a product for which the probable structure

(by the n.m.r. spectrum and analysis results) was (179, mixture of

cis and trans isomers). A sample of the trans isomer was separated

by repeated crystallization. The major fragments of the compound

(179) in the mass spectrum were: 71(100%) CH2=CH-CH=0Me, 91(60%) not

identified, 108(25%) COO, 155(30%) 1171\102.004.SH, 225(30%) M2+,

308(26%) (27NO2C6H4S)2. Formation of the fragments of mass 71 and 308

can be explained as the results of allylic rearrangements as shown on

page 73 . However, the molecular weight (by vapour pressure osmometer)

was 258 which did not agree with the above structure (the M.W. of the

Ars H ArS /CH2 X

C C C = C /// c1-12 x H

X = X =

OAc (175) OAc (162)

OMe (176) OMe (163)

N3 (174)

ArS-r-CH=CH2 ArS-CH.CH-CH2 C1

X (165, mixture ofcis and trans) x=

OAc (177)

OMe (178)

ArS-CH-CH=CH2 CH2 -CH-CH I I OMe OMe SAr /2 (178) (179)

allylic rearrangement CH2 -CH -CH=CH -CH - CH2 I [ I I OMe SAr ArS OMe (179)

allylic rearrangement CH2 -CH=CH—CH—CH—CH2 I I I OMe SAr SAr OMe

CH2 =CH—CHi-CH--CH—CH2 y CH2 =CH-CH + (SAr)2 I I I I II OMe SAr SAr OMe +OMe m/e = 71 m/e = 3a9

(AT = 2:-nitrophenyl) 74

compound 179 is 450) but no other structure could be reconciled with

the n.m.r. spectrum of this product (see page 157).

(vi) With sodium azide

The methanesulphonate when reacted with sodium azide in DMF gave

the cis azide (174).

Reactions of 1-(p-nitrophenylthio)-3-ch1oroprop-1-ene (mixture of

cis and trans isomers)

(i) With methanol

The solvolysis reaction of the chlorides (165) in methanol gave a

mixture of the cis and trans methyl ethers (163) and (176) and the

rearranged methyl ether (178) in the ratio of 1:1 (normal to abnormal

product).

(ii) With sodium methoxide in methanol

The reaction of the chloride with sodium methoxide in methanol afforded a mixture of the cis and trans methyl ethers (163) and (176) and the rearranged methyl ether (178) in the ratio of 1:2 (normal: abnormal).

General discussion on the reactions of the allylic methanesulphonate and chlorides

The results of the reactions of the allylic chlorides (157) and

(165) and the methanesulphonate (164) were reported in the previous pages. Rearranged products were obtained in the reactions with methanol, sodium methoxide, tetramethylammonium acetate and potassium acetate and higher yields of these abnormal products were obtained from the --nitro-compounds. 75

The reactions of the methanesulphonate (164) and the corresponding chloride (165) with methanol and with sodium methoxide in methanol showed that these reactions were leaving-group dependent, as the ratios of the normal and abnormal products obtained from the methanesulphonate were different from those obtained from the chloride.

These results suggested that the mechanisms of these reactions were not pure SN1, but possibly a mixture of an SN1 reaction (resulting in both normal and abnormal products) and SN2' reaction (abnormal products). A high yield of the abnormal products obtained in the reactions with sodium methoxide showed that the reactions proceeded mainly by an SN2' mechanism (especially in the 2.-nitro-compounds).

The higher yield of abnormal products obtained in the reactions with potassium acetate in acetic anhydride compared with the reactions with tetramethylammonium acetate in acetone can be attributed to the effect of solvent, as has been described before (page 59 ). The reactions with sodium azide presumably proceeded by an SN2 mechanism to give the normal products. 20 It was mentioned before that Khan and Owen have suggested that the reactions of the bismethanesulphonates (35) with sodium methoxide proceeded through the allylic methanesulphonates (43) to give the observed mixture of normal and rearranged products. These results are in agreement with the present results described above, but the reaction of the bismethanesulphonate (35, Ar=2,4-dinitrophenyl) with 20 sodium methoxide is reported to give only the normal elimination product, which would be formed by S 2 attack on (43) without rearrange- N ment. However, on the basis of the present work it would be expected that a high yield of abnormal product would result from the inter- 76

ArS-CH=CH-CH2 X

157 - Ar = phenyl, X = Cl

165 - Ar = E-nitrophenyl, X = Cl

164 - Ar = 27nitrophenyl, X = OMs

ArS -CH2:-CH -CH20Ms ArS-CH=CH-CH2 OMs I OMs

(35) (43)

(Ar = phenyl, 27methylthiophenyl, 2.-chlorophenyl)

0 +t/// Ar-S CH=CH-CR1 R2 X

(70) 77

mediate methanesulphonate (43, Ar = 2,4-dinitropheny1).

A consideration of these results leads to the conclusion that electron-withdrawing substituents on the '-carbon of an allylic halide (or methanesulphonate), as has been suggested by many workers, favour an S 2' mechanism by decreasing the electron-density at the N C=C bond thus promoting the attack of the nucleophile at this position.

However, in the case where there is a very strong electron-withdrawing group (eg: 2,4-dinitrophenylthio) on the X-carbon, the energy of the conjugation between this group and C=C could be so high that the nucleophile may not be able to break this conjugation and shift the olefinic bond. The compounds of type (70) which have been studied by 43 Bordwell et al. (introduction, page 27) could have the above disadvantage for an SN2' mechanism of reaction, in addition to the disadvantage of having two electronegative-charged oxygen in the neighbourhood of the X-carbon (surrounding the Y-carbon with negative charge) which does not favour the approach of the nucleophile to this carbon. 78

Interpretation of the n.m.r. spectra

Identification of the products of the reactions of the methanesulphonates and the chloride with acetic acid, potassium acetate, tetramethylammonium acetate, methanol and sodium methoxide was accomplished by comparing the products of these reactions with the authentic samples of the corresponding acetates and methyl ethers. The differentiation between isomeric bromides and isomeric chlorides was more difficult as the authentic samples were not available, therefore, the following criteria were used for the identification of the isomers in these cases.

The signal for CH2 in the secondary alcohols and their derivatives was at a higher field than the signal for CH2 in the primary isomers.

Also the signal for CH, in most of the cases, was at lower field for the secondary compounds than their primary isomers. The identification of the halides was based on these facts.

The reactions of the methanesulphonates and the chloride with sodium azide and benzyl or phenyl sulphides gave only one of the isomers, therefore, the above criteria were not applicable. To identify these compounds the parameter LI, was used, because CH2CH the differences between the chemical shifts of CH and CH in primary 2 compounds were always less than in the secondary compounds of the same series. Thus the azide and sulphide obtained in each series were identified by comparison of their -CH with the of the 4`CH LICH -CH 2 2 primary authentic compounds and `CH CH of the secondary authentic 2- compounds of that series. The above relationship was also applicable for the identification of the halides.

The L\ of some of the individual compounds, recorded in CH 79

the tables, is itself reported as a range because the chemical shift

for CH (a multiplet) is given as a range. These individual ranges 2 should not be confused with the above mentioned overall ranges for the

primary and for the secondary authentic compounds.

The differentiation between cis and trans isomers in the allylic

compounds was based on attributing the larger coupling constant

(ca. 15 Hz) between the olefinic protons CH=CH to the trans isomers

(also hadv 960 cm-1 in their i.r. spectra) and the'lower coupling max constant (ca.91 Hz) to the cis isomers.

Unless mentioned otherwise, the n.m.r. spectra given in the

following pages were recorded in deuteriochloroform on a Varian A-60

instrument using tetramethylsilane as internal reference, and the

chemical shifts are given in T values. The following abbreviations

have been used:

s for singlet

d for doublet

t for triplet

m for multiplet Table (1) - Authentic Compounds

Spec. Grupo Aromatic -CH) ppm No. Compounds -CH - CH2 X X L '(CH2 Ph.S.CH-CH2 OH 2.6-2.9 5.72 6.0-6.2 7.88 6 I m q m broad s OH 0.3-0.5 Ph 10H 1H 2H 1H Ph.S.CH-CH2 OAc 2.4-2.8 5.52 8.07 16 1 m s s OAc 0.0 Ph 10H 3H 3H Ph.S.CH-CH2 OMe 2.5-2.8 5.58 6.21 6.65 26A 1 m t d s OMe 0.63 Ph 10H 1H 2H 3H Ph.S.CH-CH2 OSO2 Me* 2.4-2.9 5.2-5.7 7.12 342 1 m m s os02 Me 0.0-0.5 Ph 10H 3H 3H Ph.S.CH2 -CHOH 2.5-2.8 5.30 6.7-7.0 7.15 5 I m q m broad s OH 1.4-1.7 Ph 10H 1H 2H 1 1H -CHOAc 2.5-2.8 4.10 6.5-6.8 8.00 24, Ph.S.CH2 1 m q m s OAc 2.4-2.7 Ph 10H 1H 2H 3H L.. * The spectrum of this compound was recorded at 100 MHz in acetone at 00

Table (1) continued

Spec. Group A No. Compounds Aromatic -CH -CH2 X X (CH2-CH) ppm Ph.S.CH2 -CHOMe 2.5-2.8 5.68 6.6-6.9 6.75 25 I m q m s OMe 0.7-1.2 Ph 10H 1H 2H 3H Ph.S.CH2 -CHOSO2 Me* 3.1-3.6 5.98 7.36 7.63 7.06 339 I m q q q s OS02 Me 1.38-1.65 Ph 10H 1H 1H 1H 3H Ph.S.CH2 -CHC1 2.4-2.9 5.07 6.3-6.6 57 Ph m q m - - 1.2-1.5 10H 1H 2H mixture of Ph.S.CH2 -CHC1 • I Ph 2.4-2.9 5.07 5.61 6.0-6.2 6.3-6.6 • 45 m m m _ _ Sec. 1.2-1.5 and q q Prim. o.4-o.6 Ph.S.CH-CH2 C1 10H 0.53H 0.47H 0.95H 1.05H Ph

* The spectrum of this compound was recorded at 100 MHz at 0°

00 Table (2) - Reactions of 1-methanesulphonyloxy-2-phenyl-2-(phenylthio)ethane

Spec. Reagent Products Aromatic -CH -CH X Group -CH) ppm No. Solvent 2 X ACH2 2.5-2.8 4.10 6.5-6.8 8.00 20 AcOH Sec. acetate m q m s OAc 2.4-2.7 10H 1H 2H 3H

2.5-2.8 4.10 6.5-6.8 8.00 AcOK Sec. acetate m in s OAc 102 in Ac20 q 2.4-2.7 10H 1H 2H 3H Sec. acetate 2.5-2.8 4.10 6.5-6.8 8.00 AcOK 101 and trace of m q m s OAc 2.4-2.7 ' in Me2C0 olefin 10H 1H 2H 3H (4.31 4.66) s s (=cH2 ) Sec. acetate 2.5-2.8 4.10 6.5-6.8 8.00 58, Mey NOAc and m q m s OAc 2.4-2.7 302 in Me2 C0 olefin 10H 0.7H 1.4H 2.1H (4.32 ' 4.69) . s s 0.3H 0.3H (=CH2 ) .

Table (2) continued , . Spec. Reagent Products Aromatic -CH . -CH X Group A -CH) ppm No. Solvent X (CH2

Exposure of mixture of the 2.0-3.0 (4.34 4.69) (5.75) 304 the olefin olefin and ketone m s s s - - to air 10H 0.5H 0.5H 1H (=CH2) (CH2 of ketone)

2.5-2.8 4.10 6.5-6.8 8.00 115 Me4 NOAc Sec. acetate m in Ae2 0 q m s OAc 2.4-2.7 10H 1H 2H 3H

2.5-2.8 5.68 6.6-6.9 6.75 23 Me0H Sec. methyl ether m q m s OMe 0.7-1.2 10H 1H 2H 2H 2.5-2.8 5.68 6.6-6.9 6.75 Me0Na Sec. methyl ether m 29 in Me0H q m s OMe 0.7-1.2 10H 1H 2H 2H

2.5-2.9 6.14 6.5-6.8 6.45 PhCH2SNa Prim. sulphide m 247 in Me0H q m s PhCH2 S 0.36-0.64 15H 1H I 2H 2H

2.5-2.8 5.40 6.74 N N3 48 inD .M.F. Sec. azide m t d - - 1.34 10H 1H 2H

Table (2) continued

Spec. Reagent Products Aromatic -CH -CH2 --- CH2-CH) ppm No. Solvent 2.5-2.8 4.99 6.2-6.4 54, LiBr Sec. bromide m q m 1.1-1.5 235 NCO 10H 1H 2H

Heating mixture of 2.5-2.8 4.99 5.57 6.1-6.4 Sec. 1.1-1.5 235B the.above ' sec. and prim. m q q m Prim. 0.5-0.8 compound bromides 10H 0.5H 0.5H 2H te

Table (3) - Reactions of 1-chloro-l-phenyl-2-(phenylthio)ethane

Reagent J Group LS H Spec. Products Aromatic -CH -CH X '(C a-CH) ppm No. Solvent 2 X 2.5-2.8 4.10 6.5-6.8 8.00 55 AcOH Sec. acetate m q m s OAc 2.4-2.7 10H 1H 2H 3H

2.5-2.8 4.10 6.5-6.8 8.00 Me4 NOAc 71 Sec. acetate m q m s OAc 2.4-2.7 in acetone 10H 1H 2H 3H ._., 2.5-2.8 5.68 6.6-6.9 6.75 64 Me0H Sec. methyl ether m q m s OMe 0.7-1.2 10H 1H 2H 3H

oo Table (3) continued

Spec. Reagent Group Products Aromatic -CH -CH X No. Solvent 2 X A CH2 -CH) ppm

2.5-2.8 5.68 ' Me0Na 6.6-6.9 6.75 Sec. methyl ether m 52 Me0H q m s OMe 0.7-1.2 10H 1H 2H 3H

PhCH2SNa 2.5-2.9 6.14 6.5-6.8 6.45 66, Prim. sulphide m Me0H q m s PhCH2 S 0.36-0.64 68 15H 1H 2H 2H

2.5-2.8 5.40 N aN 6.74 51 3 Sec. azide m DMF t d 1.34 10H 1H 2H

LiBr 2.5-2.8 4.99 6.2-6.4 56 Sec. bromide m Me2C0 q m 1.1-1.5 1OH 1H 2H

Table (4) - Control Reactions

Spec. Starting material Products Aromatic -CH -CH X Group (CH 2-CH) ppm No. with 2 X Ls

Prim. methyl ether 2.5-2.8 5.58 6.21 6.65 Prim. methyl ether m 33 with methanol t d s OMe 0.63 1OH IH 2H 3H

Prim. acetate 2.5-2.8 5.52 8.07 34 Prim. acetate m with acetic acid s s OAc 0.0 1OH 3H 3H

Table (5) - Authentic compounds (R = E-methoxyphenyl)

Spec. Compounds Aromatic -CH E-OCH Group No. -CH2 3 X X /-'--( CH2 -CH ) PPm Ph.S.CH-CH2 OH 2.5-2.8 3.14 5.69 5.98-6.3o 6.2o 7.9 73 ' [ m d q m s broad s OH 0.2-0.6 R 7H 2H 1H 2H 3H 1H Ph.S.CH-CH2 OAc 2.5-2.9 3.14 5.54 6.21 8.07 81 1 m d s s s ' OAc 0.0 R 7H 2H 3H 3H 3H Ph.S.CH-CH2 OMe 2.5-2.9 3.15 5.61 6.0-6.4 6.23 6.68 82 I m d t m s s OMe o.4-o.8 R 7H 2H 1H 2H 3H 3H 341 Ph.S.CH-CH2 OSO2 Me* 2.5-2.9 3.15 5.2-5.70 6.28 7.07 m d m s s OSO2 Me 0.0-0.5 R 7H 2H 3H 3H 3H -... Ph.S.CH2 -CHOH 2.5-2.9 3.14 5.30 6.7-7.0 6.22 7.3 74 I m d q m s broad s OH 1.4-1.7 R 7H 2H 1H 2H 3H 1H Ph.S.CH2 -CHOAc 2.5-2.9 3.13 4.13 6.5-6.8 6.22 8.01 86 I m d q m s s OAc 2.4-2.7 R 7H 2H 1H 2H , 3H 3H Ph.S.CH2 -CHOMe 2.5-2.9 3.12 5.74 6.6-6.9 6.20 6.78 87 1 m d q m s s OMe 0.9-1.2 R 7H 2H 1H 2H 3H 3H

* The spectrum of this compound was recorded at 100 MHz in t acetone at 00

Table (5) continued (R = 2:-methoxyphenyl)

Spec . No. Compounds Aromatic -CH -CH2 2-0CH3 A ( CH2 -CH) ppm • mixture of Sec. Prim. Prim. Sec. Ph .S .CH2 -CHC1 2.5-2.9 3.15 5.09 5.63 6.1-6.3 6.3-6.6 6.25 Prim. 0.5-0.7 93, 1 R m d q q m m s 95 and 7H 2H 0.6H 0.2H 0.41.1 1.2H 3H Sec. 1.2-1.5 R I Ph.S.CH-CH2 C1 . . with ca. 20% impurities

Table (6) - Reactions of 1-methanesulphonyloxy-2-(p-methoxypheny1)-2-(phenylthio)ethane r Spec. Reagent Group Products Aromatic -CH ( cH2 ppm No. Solvent - -CH2 2.-OCH3 X X -CH) 2.5-2.9 3.13 4.13 6.5-6.8 6.22 8.01 135 AcCH Sec. acetate m d q m s s OAc 2.4-2.7 7H 2H 1H 2H 3H 3H

AcOK 2.5-2.9 3.13 4.13 6.5-6.8 6.22 8.01 124 in Ac2 Sec. acetate m d q m s s OAc 2.4-2.7 0 7H 2H 1H 2H 3H 3H Me4 NOAc 2.5-2.9 3.13 4.13 6.5-6.8 6.22 8.01 136 in Me2 CO Sec. acetate m d q m s s OAc 2.4-2.7 7H 2H 1H 2H 3H 3H • 2.5-2.9 3.13 5.74 6.6-6.9 6.2o 6.78 134 Me0H Sec. methyl ether m d q m s s OMe 0.9-1.2 7H 2H 1H 2H 3H 3H

Table (6) continued (R = 2-methoxyphenyl)

Spec. Reagent Products Aromatic -CH -CH2 £-OCH3 Group A No. Solvent X X (CH 2-CH) ppm 3.13 Me0Na 2.5-2.9 5.74 6.6-6.9 6.20 6.78 123 in Me0H Sec. methyl ether m d q m s s OMe 0.9-1.2 7H 2H ' 1H 2H 3H 3H

2.5-2.9 3.10 5.44 6.77 6.20 NaNr3 129 in DMF Sec. azide m d t d Q - .- 1.33 7H 2H 1H 2H 3H . 2.5-2.9 3.17 4.97 6.2-6.4 6.22 110 LiBr Sec. bromide in Mee C0 with 50% impurities .., m d q m s - - 1.2-1.4 7H 2H 0.5H 1H 1.5H

Table (7) - Control Reactions

Spec. Starting material Product Aromatic -CH -0112 2.-OCH 3 Group No. X X

Prim. methyl ether 2.5-2.9 3.15 5.61 6.0-6.4 6.23 6.68 1260 with methanol Prim. methyl ether m d t m s s OMe 7H 2H 1H 2H 3H 3H

Prim. acetate 2.5-2.9 3.15 5.54 6.21 8.07 126B with acetic acid Prim. acetate m d s s s OAc 7H 2H 3H 3H 3H

Table (8) - Authentic Compounds (R = 2-nitrophenyl)

Spec. L''..\, No. Compounds Aromatic -CH -CH2 X Group X k CH2 -CH) ppm

Ph.S.CH-CH2 OH 1.87 2.57 2.74 5.60 6.04 7.59 149 I d d s q d s OH 0.44 R 2H 2H 5H 1H 2H 1H Ph.S.CH-CH20Ac 1.79 2.54 2.67 5.48 8.06 157 1 d d s s s OAc 0.0 . R 2H .2H 5H 3H 3H Ph.S.CH-CH2 0Me 1.81 2.53 2.67 5.51 6.16 6.67 161 1 d d s t d s OMe 0.65 R 2H 2H 5H 1H 2H 3H Ph.S.CH-CH20S02 Me 1.76 2.32-2.76 5.41 7.10 201 1 d m s s OSO2 Me 0.0 R 2H 7H 3H 3H Ph.S.CH2 -CHOH 1.84 2.49 2.6-2.8 5.18 6.5-7.2 6.87 148 1 d d m q m s OH 1.3-2.0 R 2H 2H 5H 1H 2H 1H Ph.S.CH2 -CHOAc 1.82 2.53 2.6-2.8 4.07 6.5-6.8 7.98 156 1 d d m t m s OAc 2.4-2.7 R 2H 2H 5H 1H 2H 3H Table (8) continued = p-nitrophenyl)

Spec. Compounds Aromatic -CH -CH2 X Group X A(CH2 -CH) ppm No. Ph.S.CH2 -CHOMe 1.77 2.48 2.69 5.58 6.6-6.9 6.71 158 1 d d s t m s OMe 1.0-1.3 R 2H 2H 5H 1H 2H 3H Ph.S.CH2 -CHOS02 Me 1.78 2.45 2.67 4.31 6.4-6.7 7.07 221 I d d s t m s osq2 Me 2.1-2.4 R 2H 2H 5H 1H 2H 3H

Table (9) - Reactions of 1-methanesulphonyloxy-1-(p-nitropheny1)-2-(phenylthio)ethane

Spec. Reagent Products Aromatic -CH X Group X 'L '( CH2 -CH) ppm No. Solvent -CH2 1.82 2.53 2.6-2.8 4.07 6.5-6.8 7.98 196 AcOH Sec. acetate d d m t m s OAc 2.4-2.7 2H 2H 5H 1H 2H 3H

226, AcOK 1.82 2.53 2.6-2.8 4.07 6.5-6.8 7.98 in Sec. acetate d d m t m s OAc 2.4-2.7 197 Ace o 2H 2H 5H 1H 2H 3H

Table (9) continued (R = 2-nitrophenyl) • • Spec. Reagent Z\ No. Solvent Products Aromatic -CH "CH2 X Group X (CH2 -CH) ppm

AcOK Sec. acetate and 1.82 2.53 2.6-2.8 4.07 (.0112 ) 6.5-6.8 7.98 258 in Me2 C0 trace of olefin d d m t 6.20, 6.4 m s OAc 2.4-2.7 2H 2H 5H 1H s s 2H 3H 1.82 2.53 2.6-2.8 4.07 (.0112 ) 6.5-6.8 7.98 255 Me4 NOAc Sec. acetate and in Me2 C0 trace of olefin d d m t 6.20, 6.44 m s OAc 2.4-2.7 2H 2H 5H 1H s s 2H 3H 1.82 2.53 2.6-2.8 4.07 .6.5-6.8 7.98 257 Me4NOAC in Ac20 Sec. acetate d d m t m s OAc 2.4-2.7 2H 2H 5H 1H 2H 3H

Sec. methyl 1.77 2.48 2.69 5.58 6.6-6.9 6.71 195 Me0H ether d d s t m s OMe 1.0-1.3 2H 2H 5H 1H 2H 3H

236, Me0Na Sec. methyl 1.77 2.48 2.69 5.58 ' 6.6-6.9 6.71 236B in Me0H ether d d s t m s OMe 1.0-1.3 2H 2H 5H 1H 2H 3H

218, PhSNa Ph.S.CH-CH2 .S.Ph 1.90 2.5-2.9 5.68 6.4-6.8 214B in Me0H 1 d m q m - - 0.7-1.1 R 2H 12H 1H 2H

Table (9) continued

Spec. Reagent Products Aromatic No. Solvent -CH . _-CH2 'A(CH2 -CH) ppm

Sec. Prim. Sec. and Prim. 1.84 2.4-2.8 4.99 5.47 6.1-6.4 220 LiBr Sec. and Prim. d m Prim: 0.6-0.9 in Me2 C0 bromides q q m 2H 7H 0.75H 0.25 2H Sec: 1.1-1.4

NaN3 1.78 2.4-2.8 5.28 6.73 215 in DMF Sec. azide d m t d 1.45 2H 7H 1H 2H

Table (10) - Reactions of 1-methanesulphonyloxy-2-(p-nitropheny1)-2-(phenylthio)ethane

Spec. Reagent Products Aromatic -CH -CH2 x Group Uti /,.....2l . No Solvent X -CH) ppm 1.82 2.53 2.6-2.8 4.07 6.5-6.8 7.98 208 AcOH Sec. acetate d d m t m s OAc 2.4-2.7 2H 2H 5H 1H 2H 3H

205, 1.77 2.48 2.69 5.58 6.6-6.9 6.71 206 Me0H Sec. methyl ether d d s t m s OMe 1.0-1.3 2H 2H 5H 1H . 2H 3H Sec. Prim. Sec. and Prim. 1.84 2.4-2.8 4.99 5.47 6.1-6.4 Prim: 0.6-0.9 219 LiBr Sec. and Prim. d m in Me2 C0 Bromides q q m - - Sec: 1.1-1.4 2H 7H 0.75H 0.25H 2H Table (10) continued

Spec. Reagent - CH 2 No. Solvent Products Aromatic . =C112 ketone

AcOK 1.7-2.8 4.21 4.44 5.74 261 in Me Olefin and Ketone m s s s 2 C0 . 9H 0.6611 0.66K o.6611 1.7-2.8 4.21 4.44 Me NOAc 5.74 4 Olefin and Ketone m 262 in Ac2 0 s s s 9H 0.8H 0.811 o.41.1

Me4NOAc 1.7-2.8 4.21 4.44 5.74 246 in Me2CO Olefin and Ketone m s s s 9H 0.85H 0.85H 0.3H 1.7-2.8 4.21 4.44 5.74 3 249 inNaNDMF Olefin and Ketone m s s s 9H 0.75H 0.75H 0.25H exposure of the above 1.80 2.65 5.74 250 Ketone q s - s mixture to 4H 511 1 air 2H

Table (10) continued

Group Spec. Reagent Products Aromatic =CH2 . -toe -CH - X No. Solvent (Ketone) X 1.84 2.2-2.9 4.21 4.44 5.74 5.51 6.16 6.67 Me0Na Prim. methyl ether, 209 d m s s s ' t d s OMe in Me0H Olefin and Ketone 2H 7H 0.25H 0.25H 0.2H 0.65H 1.3H 2H

Table (11) - Control Reactions

Group Spec. Starting Material Products Aromatic -OH X No. -CH2 X 1.7-2.8 4.31 5.41 5.41 6.4-6.7 7.07 7.10 Prim. methanesulphonate Prim. and Sec. m t s s m s s OSO2 Me 199 in chloroform methanesuiphonates 9H 0.6H 0.4H 0.8H 1.2H 1.8H 1.2H Prim. and Sec. 1.7-2.8 4.31 5.41 5.41 6.4-6.7 7.07 7.10 Sec. methanesulphonate 223 methanesuiphonates m t s s m s s OSO2 Me in chloroform (impure) 9H 0.5H 0.1H 0.2H 1H 1.5H 0.3H . 1.79 .2.54 2.67 5.48 8.06 Prim. acetate Prim. acetate d d s s s OAc 230 in acetic acid 2H 2H 5H 1 3H 3H

Table (12) - Authentic Compounds (R = 2,4-dinitrophenyl)

Grou p \ Spec. Compounds Aromatic -CH -CH2 X CH2 -CH) ppm No. X R.S.CH-CH2 OH 1.02 1.78 2.38 2.5-2.8 5.33 5.97 7.49 162 1 d q d m t d s OH 0.64 Ph 1H 1H 1H 5H 1H 2H 1H R.S.CH-CH2 OAc 0.93 1.63 2.15 2.5 5.08 5.3-5.6 7.93 163 1 d q d s q m s OAc 0.2-0.5 Ph 1H 1H 111 5H 1H 2H 3H R.S.CH-CH2 OMe 0.96 1.74 2.37 2.5-2.7 5.26 6.0-6.2 6.53 160 I d q d m q m s OMe 0.7-0.9 Ph 1H 1H 1H 5H 1H 2H 3H R.S.CH-CH2 OMs 0.96 1.64 2.26 2.4-2.7 5.04 5.2-5.5 7.06 179 1 d q d m q m s OS02 Me 0.2-0.5 Ph 1H 1H 1H 5H 1H 2H 3H R.S.CH2 -CHOH 0.91 1.61 2.31 2.58 4.88 6.55 7.5 142 1 d q d s t d broad s OH 1.7 Ph 1H 1H 1H 5H 1H 2H 1H R.S.CH2 -CHOAc 0.91 1.58 2.23 2.58 3.98 6.3-6.6 7.85 152 I d q d s t m s OAc 2.3-2.6 Ph 1H 1H 1H 5H 1H 2H 3H

Table (12) continued (R = 2,4-dinitrophenyl)

Grou Spec. Aromatic .-CH -CH2 X 4A(CH2 -CH) ppm No. Compounds X p R.S.CH2 -CHOMe 0.93 1.70 2.38 2.58 5.49 6.5-6.8 6.70 164 I d q d s q m s OMe 1.0-1.3 Ph 1H 1H 1H 5H 1H 2H 3H R.S.CH2 -CHOS02 Me 0.98 1.59 2.31 2.60 4.18 6.2-6.5 7.17 165 I d q d s t m s osol2 Me 2'.0-2.3 Ph 1H 1H 1H 5H 1H 2H 3H R.S.CH2 -CHC1* 0.90 1.41 1.92 2.2-2.6 4.50 5.88 145 I d q d m t d - - 1.38 Ph 1H 1H 1H 5H 1H 2H

* The spectrum of this compound was recorded in 4 acetone.

Table (13) - Reactions of 1-methanesulphonyloxy-1-phenyl-2-(2,4-dinitrophenylthio)ethane

p 2. Spec. Reagent Products Aromatic -CH X Gropu '.'( CH2-CH ) ppm No. Solvent -CH2 0.91 1.58 2.23 2.58 3.98 6.3-6.6 7.85 166 AcOH Sec. acetate d q d s t m s OAc - 2.3-2.6 1H 1H 1H 5H 1H 2H 3H 1.58 2.23 2.58 3.98 6.3-6.6 AcOK 0.91 7.85 169 Sec. acetate d - q d s t m s OAc 2.3-2.6 in Ac20 1H 1H 1H 5H 1H 2H 3H

Table (13) continued (R = 2,4-dinitrophenyl)

Group Spec. Reagent Products Aromatic CH=CH -CH X No. Solvent -CH2 X 0.90 1.62 2.0-2.6 2.67 ' 3.16 3.98 6.3-6.6 7.85 AcOK Sec. acetate anand 242 q q m d d t m s OAc in Me2 C0 olefin 1H 1H 6H o.6611 0.6611 o.3311 0.66H 1H

0.86 1.58 2.23 2.4-2.6 2.65, 3.14 3.98 6.3-6.6 Me4 NOAc Sec.. acetate andan 7.85 237 d q d m d d t m s OAc in Mee olefin 111 _, 1H 1H 5H 0.75H 0.75H 0.25H 0.5H 0.7H

0.91 1.58 2.23 2.58 2.65 3.15 3.97 6.3-6.6 7.84 Me NOAc SSec. c acetate and 241 d q d s d d t m s OAc in4 Ac20 olefin 1H 1H 1H 5H 0.25H 0.25H 0.7511 1.5H 2.3H

0.93 1.70 2.38 2.58 5.46 6.5-6.8 6.69 167 Me0H Sec. methyl ether d q d s - q m s OMe 1H 1H 1H 5H 1H 2H 3H

Sec. methyl ether, 0.88 1.4-1.7 2.1-2.6 2.65 3.14 5.46 6.5-6.8 6.69 5.83 Me0Na 171 olefin and q m m d d q m s s OMe in Me0H 2,4-dinitro anisole 1H 111 6H 0.3H 0.3H 0.5H 1H 1.5H 0.6H (anisole)

Purified 0.84 1.57 2.24 2.48 2.65 3.14 172 from above R.S.CH=CH.Ph d q d s d d - - - mixture 1H 1H 1H 5H 1H 1H - 1

■D

Table ( (13) continued (R = 2,4-dinitrophenyl)

Spec. Reagent Products Aromatic -CH Li■ CH2 -CH) ppm No. Solvent '''CH2 0.86 1.6-2.0 2.3-3.1 176, PhSNa R.S.Ph d m m - - - 177 in Me0H (major product) 1H 1H 6H

5.14 6.6o 173, NaN3 0.98 1.64 2.3-2.7 Sec. azide d q m t d 1.46 175 in DMF 1H 1H 6H 1H 2H

0.98 1.62 2.44 2.61 4.84 6.11 168- LiBr in Me Sec. bromide d q d s q d 1.27 2 CO 1H 1H 1H 5H 1H 2H

Table (14) - Reactions of 1-methanesulphonyloxy-2-phenyl-2-(2,4-dinitrophenylthio)ethane

Group Spec. Reagent Aromatic -CH -CH2 X . , No. Solvent Products X —C cH2 -CH) ppm

0.91 1.58 2.23 2.58 3.98 6.3-6.6 7.85 182 AcOH Sec. acetate d q d s t m s OAc 2.3-2.6 1H 1H 1H 5H 1H 2H 3H

0.93 1.70 2.38 2.58 5.49 6.5-6.8 6.7o 180 Me0H Sec. methyl ether d q d s q m s OMe 1.0-1.3 1H 1H 1H 5H 1H 2H 3H

■.0 00

Table (14) continued (R = 2,4-dinitrophenyl)

. . .. . _ Reagent Spec. Products Aromatic =CH2 . -CH -CH2 X No. Solvent L'( CH2 -CH) ppm . . 1.00 1.8-2.8 3.66 3.83 _ _ AcOK m s s - _ 181 e Olefin d in Ac 0 1H 7H 1H 1H

0.98 1.87 2.2-2.8 3.65 3.81 Me4NOAc - , 234 e Olefin d q m s s - - - in Me CO 1H 111 611 1H 1H

0.98 1.86 2.1-2.8 3.64 3.81 5.85 Me0Na Olefin and some 191 d q m s s -- - s -- in Me0H 2,4-dinitroanisole 1H 1H 611 0.9H 0.911 0.311 (anisole)

1.0-2.8 3.65 3.82 5.03 5.2-5.5 7.06 NaN3 Olefin and unreacted 187 m s q inDMF methanesulphonate 811 o.41-1* 0.411 0.611 1.2H 3H (0502 Me)

1.06 1.72 2.45 2.63 3.64 3.82 5.26 6.23 188, LiBr Prim. bromide and d d s s s t d - 0.97 190B in Me2 C0 trace of olefin q 1H 1H 111 5H 0.1H 1 0.1H 0.9H 1.8H 2 .SPh 0.98 1.80 2.3-2.7 6.40 PhSNa R.S.CH-CH 5.59 233 1 d q m - q d - 0.81 in Me0H Ph 1H 1H 11H 1H 2H (minor product) . Table (15) - Control Reactions

Spec. Starting material Products Aromatic No. ' -CH -CH2 X Group X

Prim.methyl ether in 0.96 1.74 2.37, 2.5-2.7 5.26 6.0-6.2 6.53 192 prim, methyl ether d d m methanol q q m s OMe 1H 1H 1H 5H 1H 2H 3H

1.63 2.15 Prim, acetate in acetic 0.93 2.5 5.08 5.3-5.6 7.93 193 Prim. acetate d d acid q s q m s OAc 1H 1H 1H 5H 1H 2H 3H

Prim. methanesulphonate 0.96 1.64 2.26 2.4-2.7 5.04 5.2-5.5 7.06 228 in acetone Prim. methanesulphonate d q d m q m s OSO2Me 1H 1H IH 5H 1H 2H 3H

Table (16) - Authentic Compounds Ph.S.CH=CH-CH2 X a b c

CH CH CH2 . J. Hz Spec. Group X Aromatic a b X No. isomer trans cis cis trans cis trans cis trans cis trans

2.68 3.63 4.05 5.64 7.52 ab ... 10 OH 273 s d two t d s bc . 6 cis 511 1H 1H 2H . 1H .

OH 2.67 3.51 3.64 4.06 4.o8 5.65 . 5.85 7.28 ab = 10 ' ab = 15 266, cis and s d d two t two t d d s bc = 6 bc = 5.2 277 trans 5H 0.6H 0.411 0.41.1 0.6H 0.8H 1.2H 1H 2.65 3.51 4.11 5.21 7.92 ab = 9.5 275 OAc s d two t d s bc = 6.5 cis 5H 1H 1H 2H 3H

OAc 2.63 3.47 3.54 4.10 4.17 5.21 5.40 7.93, 7.95 ab = 9.5 ab = 15 269 cis and s d d two t two t d d s s bc = 6.5 bc = 6.1 trans 5H 0.6H 0.4H 0.4H 0.6H 0.8H 1.2H 3H 2.67 3.56 4.09 5.86 6.63 ab = 10 276 O M e s d two t d ' s bc = 6 cis 5H 1H 1H 2H 3H

Table (16) continued Ph.S.CH=CH-CH2 X a b c

CH J. Hz caa b CH2' Spec. Group X Aromatic X No. isomer cis cis trans cis ' trans cis trans cis trans , trans OMe 2.64 3.48 3.54 4.08 4.13 5.84 6.03 6.62, 6.66 ab . 10 ab = 15 270 cis and s d d two t two t d 'd s s be = 6 be = 5.8 trans 5H 0.6H 0.4H 0.4H 0.6H 0.8H 1.2H 3H • 2.65 3.44 4.18 5.92 284, ab = 15 Cl s d two t d - bc = 7 298 trans 5H 1H 1H. 2H

Table (17) - Reactions of 1-(phenylthio)-3-chloroprop-1-ene

Spec. Reagent Products Aromatic -CH -c1-12 CH2 X Group X No. Solvent Ph.S.CH-CH2 -CH2 C1 2.2-2.8 4.52 6.23 7.5 HCl t • Cl 311 I m t m in CH2 C12 Cl 5H 1H 2H 2H

2.5-2.8 5.48 7.02 7.9-8.3 6.66 297B, Me0H Ph.S.CH2 -CH2 -CH(OMe)2 m t t m s (OMe)2 295 5H 1H 2H 2H 6H

Table (17) continued

CH Spec. Reagent CH 2 Group No. Solvent Products Aromatic X unsaturated sat. unsat. sat. X

Me0Na mixture of trans methyl ether 2.5-2.9 3.51 3.8-4.4 4.6-5 4.6-5 6.05 6.51, 6.68 285 OMe m d m X m d s s OMe in Me0H I and Ph.S.CH-CH.CH2 5H 0.2H 0.8H 0.6H 1.2H 0.4H 1.8H 0.6H

2.63 3.48 4.14 6.02 6.64 286 trans methyl ether (purified) s d two t d s OMe 5H 1H 1H 2H 3H a b c,d Ph.S.CH-CH=CH2 2.4-2.8 4.o6 4.78 4.86 4.91 6.48 299 I m octet d d d s OMe OMe 5H 1H 111 1H 1H 3H (purified) h bg. c d Jab=17 J =10.5 J 4 J =small bc be cd mixture of trans acetate 2.4-2.9 3.48 3.7-4.4 4.5-5 290, AcOK OAc 4.5-5 5.42 7..94 7.98 m d m m m 289 in Ace d s s OAc and Ph.S.CH-CH=CH2 with 50% impurities i

mixture of trans acetate 2.5-2.9 3.46 3.8-4.4 4.5-5 4.5-5 5.41 7.93 7.95 300 me4 NOAc OAc in Mee CO 1 m d m m m d s OAc and Ph.S.CH-CH=CH2 5H 0.5H 0.7H 0.2H 0.4H 1H 0.6H 1.5H with some impurities

Table (17) continued Ph.S.CH =CH -CH X a b 2c

CH CH CH2 . a b Group Spec. Reagent Products Aromatic X No. Solvent trans cis cis trans cis trans X

2.64 3.45 4.17 5.40 7.96 Trans acetate 293 s d two t d s OAc (purified) 5H 1H 1H , 2H 3H

trace of trans acetate 3.4-4.4 5.41 294 AcOH 2.5-2.9 3.4-4.4 7.95 OAc with impurities m m m d s

J Hz cis trans 2.65 3.47 4.25 6.22 ab=15 308 NaN3 in DMF trans azide s d two t d. bc=6 5H 1H 1H 2H

2.50 3.46 LiC1 mixture of cis and 3.53 3.8-4.3 5.75 5.93 ab=10 ab=15 312 s d d m d d in Me2 trans chlorides bc=7.5 bc=7 C0 5H 0.5H 0.5H 1H 1H 1H

NaN3 in DMF 2 . 67 6.d using above mixture of cis and 3 . 47 3 .49 3 9- 4.4 4.26 00 6.2 o ab=10 ab=15 s d d m two t 315 mixture of trans azides . d bc=7 bc=6 5H 0.5H 0.5H 1H 1H chlorides 0.5H 0.5H

0 -F-

Table (18) - Authentic compounds H4 -S CHa=CHb-CH2cX

Spec. Group X Aromatic CH CH No. isomer b CH2 X J Hz

1.87 2.63 3.5-4.0 3.5-4.0 5.62 7.43 318A ciOHs d d m m d s bc=4.5 2H 2H 1H 1H 2H 1H 1.85 2.59 3.46 3.85 5.20 7.90 319 OAc ab =9.5 cis d d d two t d s 2H 2H 1H ' 1H 2H 3H bc=6 1.87 2.61 OMe 3.53 3.85 5.85 6.626 ab=9.5 320 cis d d d two t d s 2H 2H 1H 1H 2H 3H bc=5.5 1.82 OS Me* 2.60 3.36 3.82 5.07 6.91 34o d d d two t d ab=9.S" cis s bc=5.5 2H 2H 1H 1H .2H 3H

C3 1.84 cis and 2.58 3.33 3.45 3.6-4.1 5.69 5.80 ab=9.5 ab=15 323 trans d d d d m d d - bc=5.5 bc=4.8 (ratio 1:1) 2H 2H 1H 1H 2H (cis) (trans)

Spectrum recorded at 100 MHz at 0° Table(19)- Reactions of 1-(p-nitrophenylthio)-3-methanesulphonyloxyprop-1-ene

ArS.CH=CH-CHLX (A) a b c,d ArS.CH-CH=CLL (B) I- X

Spec. Reagent CH CH CH2 Group X J Hz Products Aromatic b No. Solvent A B A B A B A B A B

OAc 1.84 2.60 3.41 3.84 5.30 332, trans acetate 7.88 AcOH d d d two t d ab=15 (A) s be=bd=5 333 2H 2H 1H 1H 2H 3H

impure mixture OAc 334 AcOK of trans acetate 1.85 2.45 3.2-4.3 4.4-4.9 3.2-4.3 3.2-4.3 5.31 4.4-4.9 7.89 7.85 in Ac2 0 A and acetate B d d m m m m d m s s *(ratio 1:2) 2H 2H

OAc cd=small acetate B 1.83 2.44 4.4-4.9 1 3.98 4.4-4.9 7.85 ab=21 336 purified from d d m octet m s bc=10 above mixture 2H 2H 1H 1H 2H 3H bd=4 .....-_ impure mixture OAc Me,NOAc of cis acetate 1.85 2.59 . 5.47 4.4-4.9 3.84 3.5-4.3 5.20 4.4-4.9 7.90 7.84 337 in A and acetate d d d m two t m d m s s B (ratio 3:1)

0 rn Table (19) continued

CH CHb CH2 Group X Spec. Reagent Products Aromatic a J Hz No. Solvent A B A B A B A B

Methyl ether B OMe and a mixture 1.8-2.1 2.4-2.7 3.5-3.8 4.4-5 3.5-3.8 4.04 5.8-6.0 4.4-5.o 6.57, 6.65 6.45 325 Me0H of cis and trans m m m m m octet m m s s s methyl ethers A 2H 2H 0.25H 0.75H 0.25H 0.75H _ 0.5H 1.5H 0.75H 2.2H

Methyl ether B OMe Me0Na and a mixture 1.8-2.1 2.4-2.7 3.5-3.8 4.4-5 3.5-3.8 4.04 5.8-6.0 4.4-5.o 6.57, 6.63 6.45 326 in Me0H of cis and trans m m m m m octet m m s s s methyl ethers A 2H 2H 0.2H 0.8H 0.2H 0.8H 0.4H 1.6H 0.6H 2.4H

trans cis cis + trans cis trans OMe trans Mixture of cis 1.88 2.63 3.47 3.55 3.6-4.1 5.85 5.94 6.57 6.63 ab=15 327 and trans methyl d d d d m d d s s bc=4.5 ethers (purified) 2H 2H 0.5H 0.5H 1H 1H 1H 1.5H 1.5H

OMe 1.89 2.45 4.4-5.0 4.04 4.4-5.0 6.45 ab-17 Methyl ether d 328 B (purified) d m octet m s bc=10 2H 2H 1H , 1H 2H 3H bd=4 -__ cd=small

NaN 1.84 2.58 3.39 3.86 5.93 ab=9 cis azide d d 338 in DMF3 A d two t d - bc=6.5 2H 2H 1H 1H 2H r H O Table (20) - Reactions of 1-(p-nitrophenylthio)-3-chloroprop-1-ene Ar.S.CH=CH-CHLOMe (A) a b c Ar.S.CH-CH=OIL (B) OMe

CH OMe CHa b CH2 Spec. Reagent Products Aromatic No. Solvent A B A B A B A B Impure mixture 1.8-2.1 2.4-2.7 3.5-3.8 4.4-5.o 3.5-3.8 4-4.5 5.8-6.0 4.4-5.0 6.57, 6.63 6.45 324 Me0H of B and cis m m m m m m m m s,s s and trans A •2H 2H (A:B, 1:1) Mixture of B 1.8-2.1 2.4-2.7 3.5-3.8 4.4-5.0 3.5-3.8 4-4.5 5.8-6.0 4.4-5.0 6.57, 6.63 6.45 324A Me0Na and cis and m m m m m m m m s,s s in Me0H trans A 2H 2H 0.3311 0.66H 0.33H 0.6611 0.66H 1.3H 1H 2H

Table (21) - Control reaction

-CH CH2 OMe Spec. a Starting Material Products Aromatic CHb No. t c c t t c 3.47 3.6-4.1 5.85 5.94 6.57 6.63 Mixture of cis 1.88 2.63 3.55 331 Cis A in methanol d d d d m d d s s and trans A 2H 2H 0.4H o.61.1 1H 1,2H 0.8H 1.2H 1.8H 109

Experimental Section

The figures in parentheses, shown throughout this section, refer to pages in laboratory notebooks. Infra-red spectra were recorded for liquid films, unless mentioned otherwise, on a Perkin-Elmer 700 instrument; n.m.r. spectra were recorded in deuteriochloroform on a Varian

A-60 instrument using tetramethylsilane as internal reference. Thin layer chromatograms were carried out using Kieslgel GF254(E. Merck Ltd.) and column chromatography with silica gel M.F.C. (Hopkin and Williams

Ltd.). Melting points were determined using a Kofler block and are uncorrected. Organic solvents were dried with magnesium sulphate.

Petroleum refers to the fraction b.p. 40-60°. The temperatures mentioned in the reaction conditions are those of the oil-bath. Unless mentioned otherwise, organic solvents were removed under reduced pressure at about 40-50° and they were purified as described in "Purification of

Laboratory Chemicals" by Perrin, Armarego and Perrin.

The following abbreviations were used:

LAH for lithium aluminium hydride

THE for tetrahydrofuran

DMSO for dimethylsulphoxide

DMF for NN-dimethylformamide 110

1-Phenyl-2-(phenylthio)ethanol, 2-phenyl-2-(phenylthio)ethanol and

their derivatives

The n.m.r. spectra of the compounds are given on pages 80 and 81.

1-Phenyl-2-(phenylthio)ethanol and 2-phenyl-2-(phenylthio)ethanol (6)

Thiophenol (12.8 g) was added to a solution of sodium (2.5 g)

in methanol (150 ml) followed by styrene oxide (14 g) at room tempera-

ture. The mixture was left for 2 hours then diluted with water and

stirred overnight at room temperature. It was then extracted with

chloroform and the organic layer was washed with 2N sodium hydroxide,

water and dried. Evaporation of the solvent gave the mixture of the

two alcohols (27 g) which were separated by column chromatography

(benzene). 1-Phenyl-2-(phenylthio)ethanol (13 g) had Rf 0.3, b.p.

135°/5 x 10 3 mm, n10 24 1.6216, v max.3400 cm-1. (Found: C, 72.93;

H, 6.14; S, 13.93. Ca1c. for C141-1140S; C, 73.01; H, 6.12; S,

2-Phenyl-2-(phenylthio)ethanol (11.5 g) had Rf 0.15 and when crystal-

lized from ether-petroleum had m.p. max. (CHOI ) 3450 cm-1. 35-360, v 3 (Found: C, 72.94; H, 6.08; S, 13.80%).

Preparation of 2-phenyl-2-(phenylthio)ethanol from mandelic acid

(i) Methyl mandelate (7)

This was prepared by esterification of mandelic acid as described

by Eliet et al.75 It had m.p. 53°(lit. m.p. 55°)

(ii) Methyl phenyl(toluene-p-sulphonyloxy)acetate (12)

This was prepared by the reaction of methyl mandelate (1 g) and

toluene--sulphonyl chloride (1.3 g) in dry pyridine (10 ml). The

mixture was kept at 0° for 12 hours and then it was poured into a

J 111 mixture of 2N sulphuric acid and crushed ice. The precipitate was filtered off and dissolved in chloroform, and the solution was washed with water and dried. Evaporation of the solvent gave the title compound (0.94 g) which when recrystallized from methanol had m.p.

90-91° (lit. m.p. 89-90°, prepared from different route76 ), T 2.28

(d; 2H, aromatic), 2.70 (s; 7H, aromatic), 4.23 (s; 1H, CH), 6.36

(s; 3H, CO CH ), 7.60 (s; 3H CH ). (Found: C, 59.94; H, 5.04; S, 2 3 , 3 9.80. Calc. for C H 0 S: C, 60.01; H, 5.04; S, 10.01%). 16 16 5

(iii) Methyl phenyl(phenylthio)acetate (13)

This was prepared by the reaction of methyl phenyl(toluene-27 sulphonylo cetate (2.5 g) and sodium thiophenate (1.5 g) in dry

DMF. The mixture was heated at 100°, under nitrogen, for 24 hours and then it was diluted with water and extracted with benzene. The benzene layer was washed with 2N sodium hydroxide, water and dried.

Evaporation of the solvent gave the title compound with some diphenyl disulphide. The product (1.6 g) was purified by column chromatography o (benzene) and when crystallized from methanol had m.p. 39-41 . (This 76 compound was described by W.A. Bonner as a crude oi1 ). T 2.51-2.92

(m; 10H, aromatic), 5.12(s; 1H, CH), 6.36(s; 3H, CH3). (Found: C,

69.80; H, 5.65; S, 12.29). C151-11402S requires C, 69.74; H, 5.46;

S, 12.41%).

(iv) 2-Phenyl-2-(phenylthio)ethanol (17)

A solution of methyl phenyl(phenylthio)acetate (0.8 g) in dry

THE' (10 ml) was added slowly to a stirred slurry of LAH (0.3 g) in dry o THE (25 ml) at 0 . After half an hour the mixture was heated under reflux for 3 hours. Then it was cooled and the excess LAH was destroyed

by dropwise addition of ethyl acetate. The mixture was then acidified and extracted with benzene. The benzene layer was washed with water 112

and dried. Evaporation of the solvent gave the title compound with

some thiophenol which was removed by column chromatography (benzene).

The alcohol (0.4 g) when crystallized from ether-petroleum had m.p.

and mixed m.p. 35-36°.

1-Acetoxy-2-phenyl-2-(phenylthio)ethane (10)

Acetic anhydride (3 ml) in pyridine (10 ml) was added, dropwise,

to a stirred solution of 2-phenyl-2-(phenylthio)ethanol (0.7 g) in

pyridine (5 ml) at room temperature and then left overnight. The

solution was then poured into a mixture of 2N sulphuric acid and crushed

ice and extracted with benzene. The benzene layer was washed with

water and dried. Evaporation of the solvent gave the acetate (0.65 g), -1 b.p. 118 /10- 4 mm, 1.5880, v 1740 cm . (Found: C, 70.49; ° max. H, 6.02; S, 11.66. C H 0 S requires C, 70.55; H, 5.92; S, 11.77%). 16 16 2

1-Acetoxy-l-phenyl-2-(phenylthio)ethane (10)

1-Pheny1-2-(phenylthio)ethanol (0.73 g) in pyridine (5 ml) when

-reacted with acetic anhydride (4 ml) in pyridine, as described above -4 22 for the isomer, yielded the acetate (0.7 g), b.p. 126°/10 mm, n D -1 1.5860, v max. 1730 cm . (Found: C, 70.69; H, 5.82; S, 11.52%).

1-Methoxy-2-phenyl-2-(phenylthio)ethane (28)

To a stirred mixture of 2-phenyl-2-(phenylthio)ethanol (1 g)

and powdered sodium hydroxide (2 g) in THE (30 ml) was added dimethyl

sulphate (2 ml) in THE (10 ml) at 45°. After 16 hours THE was dis-

tilled off and the residue was extracted with benzene. The benzene

layer was washed with water and dried. Evaporation of the solvent 4 19 afforded the methyl ether (1 g), b.p. 90°/10 mm, /ID 1.6034, v max.

1110 cm-1. (Found: C, 74.09; H, 6.64; S, 12.91. C15H160S requires

C, 73.73; H, 6.60; S, 13.12%).

113

1-Methoxy-l-phenyl-2-(phenylthio)ethane (27)

1-Phenyl-2-(phenylthio)ethanol (0.65 g) in THE (30 ml) was treated

with dimethyl sulphate (1 ml) in the presence of powdered sodium

hydroxide (1 g), as described above for the isomer. The methyl ether

22 1.5954, -1 (0.65 g) had b.p. 90°/10 4 mm, nD max. 1110 cm . (Found: C, 73.74; H, 6.43; S, 12.76%).

1-Methanesulphonyloxy-2-phenyl-2-(phenylthio)ethane (91)

Methanesulphonyl chloride (0.275 g) in dichloromethane (10 ml)

was added, dropwise, to a stirred solution of 2-phenyl-2-(phenylthio)

ethanol (0.5 g) and triethylamine (0.33 g) in dichloromethane (25 ml) at 0°. Stirring was continued for half an hour at the same temperature, then the mixture was washed with cold solutions of 2N hydrochloric acid, saturated sodium bicarbonate, water and dried. The solvent was removed under reduced pressure at 0°to yield the methanesulphonate (0.68 g) which when recrystallized from ether-petroleum had m.p. 57-57.5°. This compound was very unstable at temperatures above 0o . v max. 1340 and 1200 cm-1. (Found: C, H, 5.44; S, 21.44. C H 0 s 59.24; 15 16 3 2 requires C, 58.41; H, 5.22; S, 20.79%).

Attempted preparations of 1-methanesulphonyloxy-l-phenyl-2-(phenylthio) ethane (5o, 44, 23, 83, 38, 223) (a) 1-Phenyl-2-(phenylthio)ethanol (0.67 g) when treated with

methanesulphonyl chloride (0.44 g) using triethylamine (0.5 g)

as a base, as described for the other isomer, yielded 1-chloro-

1-pheny1-2-(phenylthio)ethane (0.68 g). This compound partially

isomerized on heating; b.p. 104° /10-4 mm, n 22 (on distilled

product, i.e. mixture of the two isomers) 1.6168. (Found: C,

67.63; H, 5.28; Cl, 13.85. recuires C, 67.62; H, 5.27;

Cl, 14.25%). 114

(b) To a stirred mixture of 1-phenyl-2-(phenylthio)ethanol (0.5 g)

and silver oxide (0.7 g) in dichloromethane was added, dropwise,

methanesulphonyl chloride (0.3 g) in dichloromethane at 0°.

After one hour the mixture was filtered and the filtrate was

washed with 2N sodium hydroxide, water and dried. The oil

obtained after evaporation of the solvent was mainly starting

material (the secondary alcohol) with about 15% of 1-pheny1-2-

(phenylthio)ethyl ether (identified by the n.m.r. spectrum, see

part (d)).

hydride (0.15 g) in dry ether (40 ml) was refluxed for 12 hours.

It was then cooled to 0° and methanesulphonyl chloride (0.19 g)

in ether (10 ml) was added to it dropwise. Stirring was continued

for one hour at 0° then it was washed with water and dried. On

evaporation of the solvent the secondary alcohol was recovered.

(d) To a stirred solution of methanesuiphonic anhydride (0.8 g) and

triethylamine (0.42 g) in dichloromethane (30 ml) was added,

dropwise, 1-phenyl-2-(phenylthio)ethanol (0.52 g) in dichloro-

methane (10 ml) at 0°. The mixture was kept for 24 hours at

0° then washed with cold solutions of 2N hydrochloric acid,

saturated sodium bicarbonate, water and dried. Evaporation of

the solvent afforded the starting material with some 1-phenyl-

2-(phenylthio)ethyl ether. The ether (15-20% yield) was separated

by column chromatography (benzene), and had b.p. 1900/5 x 10-5 mm -1 T man. cm , 2.53-2.91 (m; 20H, aromatic), 5.33-5.81 (m; 2H, CH) and 6.53-6.95 (m; 4H, CH2). (Found: C, 75.88; H, 5.89; s, 14.27.

c H S 0 requires C, 75.97; H, 5.92; s, 14.48%). 28 26 2 115

(e) Methanesulphonyl chloride (36 mg) in deuteriochloroform (2 ml)

was added, dropwise, to a stirred mixture of 1-pheny1-2-(phenyl-

thio)ethanol (69 mg) and silver oxide (45 mg) in deuteriochloro- o form at 0 . Stirring was continued for half an hour and then

the mixture was dried (MgSO4 ), filtered and concentrated to about

0.5 ml at 0°. The n.m.r. spectrum was recorded on this solution. 116

Reactions of 1-methanesulphonyloxy-2-phenyl-2-(phenylthio)ethane

Freshly prepared methanesulphonate was used for each of the following reactions. The products were identified by their n.m.r. spectra which are on pages 82-84.

(i) With acetic acid (23)

A solution of the methanesulphonate (0.5 g), acetic anhydride

(1 ml) and acetic acid (20 ml) was kept at 60° for 5 hours, then cooled to room temperature, diluted with water and extracted with benzene. The benzene layer was washed with 2N sodium hydroxide, water and dried. Evaporation of the solvent yielded 1-acetoxy-l- pheny1-2-(phenylthio)ethane (0.4 g).

(ii) With potassium acetate (86)

(a) A solution of the methanesulphonate (0.3 g) and potassium acetate

(0.3 g) in acetic anhydride (25 m1)- was stirred at 60° for 5 hours then worked up as described for the preceding experiment to afford

1-acetoxy-l-phenyl-2-(phenylthio)ethane (0.25 g).

(b) The same procedure was carried out in acetone (using 0.3 g of the methanesulphonate). The product (0.25 g) was 1-acetoxy-l- pheny1-2-(phenylthio)ethane with a trace ( 4;5%) of 1-pheny1-1-

(phenylthio)ethylene.

(iii) With tetramethylammonium acetate (95, 201)

(a) A mixture of the methanesulphonate (0.5 g) and tetramethylammonium acetate (0.4 g) in acetic anhydride (20 ml) was stirred at 40° for

5.hours then cooled to room temperature, diluted with water and extracted with benzene. The benzene layer was washed with 2N sodium hydroxide, water and dried. Evaporation of the solvent gave 1-acetoxy- l-phenyl-2-(phenylthio)ethane (0.4 g). 117

(b) The same procedure was carried out in acetone (using 0.5 g of

the methanesulphonate). Evaporation of the solvent gave a mixture

(0.35 g) of 1-acetoxy-l-phenyl-2-(phenylthio)ethane and about 25%

of 1-phenyl-1-(phenylthio)ethylene. The olefin was separated by

preparative t.l.c. plate(benzene). This compound was unstable and

when left in the air for about 5 days oxidized to b'-(phenylthio)

acetophenone. The latter when crystallized from petroleum had m.p.

50-52° (1i0m.p. 54° ), v (CHC1 ) 1685 cm-1. max. 3 Reaction of 1-phenyl-1-(phenylthio)ethylene with 2,4 dinitrophenyl

hydrazine (201)

A fresh sample of the olefin (70 mg) was added to a mixture of

2,4-dinitrophenylhydrazine (150 mg), conc. sulphuric acid (0.5 ml) and ethanol (5 ml). The mixture was stirred at 35-40° for 3 hours.

The yellow solid was filtered off and washed with hot ethanol to give acetophenone 2,k-dinitrophenylhydrazone (110 mg) which when 78 recrystallized from chloroform-petroleum had m.p. 230-239° (lit. m.p. 237° ).

(iv) With methanol (26)

A solution of the methanesulphonate (0.6 g) in dry methanol was kept at 60° for 5 hours then concentrated and extracted with benzene. The benzene layer was washed with water and dried. Evapora- tion of the solvent yielded 1-methoxy-l-phenyl-2-(phenylthio)ethane

(0.45 g).

(v) With sodium methoxide in methanol (32)

When the reaction of sodium (0.1 g) with methanol (30 ml) was complete, the methanesulphonate (0.6g) was added to it. The mixture was kept at 600 for 5 hours then concentrated and worked up, as des- 118 cribed for the preceding experiment, to afford 1-methoxy-l-phenyl-

2-(phenylthio)ethane (0.46 g).

(vi) With sodium benzylmercaptide in methanol (92)

When the reaction of sodium (0.1 g) with methanol (30 ml) was complete, benzylthiol (0.7 g) followed by the methanesulphonate

(0.5 g) were added to it and the mixture was heated at 60°, under nitrogen, for 5 hours. It was then concentrated and extracted with benzene. The benzene layer was washed with 2N sodium hydroxide, water and dried. Evaporation of the solvent gave 1-(benzylthio)-

2-pheny1-2-(phenylthio)ethane (0.58 g) which was purified by preparative t.l.c. (carbon tetrachloride). It had b.p. 120-130/10 mm

(distillation caused some decomposition). (Found: C, 74.98; H,

5.87. requires C, H, 5.99%). C21H20S2 74.95;

(vii) With lithium bromide (46)

A mixture of the methanesulphonate (1 g) and lithium bromide

(1.2 g) in acetone was kept at 50° for 5 hours. It was then concentrated and extracted with'benzene. The benzene layer was washed with water and dried. Evaporation of the solvent yielded 1-bromo- l-phenyl-2-(phenylthio)ethane (0.8 g) which when crystallized from petroleum had m.p. 65-80° (heating caused isomerization and some decomposition). (Found: C, 57.54; H, 4.35; Br, 27.29; S, 10.91.

C14H13BrS requires C, 57.34; H, 4.46; Br, 27.25; S, 10.93%).

(viii) With sodium azide (40, 42)

A mixture of the methanesulphonate (0.57 g) and sodium azide

(1 g) in DMF (40 ml) was kept at 60° for 5 hours then diluted with water and extracted with benzene. The benzene layer was washed with water and dried. Evaporation of the solvent gave 1-azido-1-iphenyl- 119

° -4 23 2-(phenylthio)ethane (0.45 g), b.p. 104/10 mm, np 1.6136, v max. -1 2100 cm . (Found: C, 65.68; H, 4.99; N, 16.19; S, 12.60. C141113SN3 requires C, 65.85; H, 5.13; N, 16.45; S, 12.55%).

Reactions of 1-chloro-l-phenyl-2-(phenylthio)ethane The general remarks given at the head of the previous section

(page 116) also apply here. The reactions were carried out under the same conditions for 7-8 hours except for methanol and acetic acid in which the mixture was left for 24'hours and in the case of tetramethylammonium acetate the reaction mixture was left for 110 hours. The products were identified by their n.m.r. spectra which are given on pages 84 and 85.

(i)With acetic acid (48) The chloride (0.45 g) afforded 1-acetoxy-l-phenyl-2-(phenylthio) ethane (0.41 g).

(ii) With tetramethylammonium acetate in acetone (58) The chloride (0.52 g) gave 1-acetoxy-l-phenyl-2-(phenylthio) ethane (0.42 g).

(iii)With methanol (57) The alcohol (0.1 g) yielded 1-methoxy-l-phenyl-2-(phenylthio) ethane (0.09 g).

(iv) With sodium methoxide in methanol (47)

The chloride (0.47 g) gave 1-methoxy-l-phenyl-2-(phenylthio) ethane (0.4 g).

(v) With sodium benzyl mercartide in methanol (59)

The chloride (0.6 g) gave 1-benzylthio-2-phenyl-2-(phenylthio) ethane (0.64 g). b.p. 120-135°710-4 mm. 120

(vi) With potassium acetate in acetic anhydride (48)

The chloride (0.3 g) gave 1-acetoxy-l-phenyl-2-(phenylthio)

ethane (0.25 g).

(vii) With lithium bromide (49)

The chloride (0.54 g) yielded 1-bromo-l-phenyl-2-(phenylthio)

ethane (0.52 g), m.p. 65-80°.

(viii) With sodium azide (44)

The chloride (0.7 g) gave 1-azido-l-phenyl-2-(phenylthio)ethane

(0.64 g), b.p. 106°/10-4 mm.

Control reactions (34, 35)

The products were identified by their n.m.r. spectra which are

given on page 85.

(i) A solution of 1-methoxy-2-phenyl-2-(phenylthio)ethane (0.32 g)

and methanesulphonic acid (3 drops) in dry methanol (30 ml) was kept

at 60° for 5 hours then worked up, as described for the reaction of

the methanesulphonate with methanol, to recover unchanged 1-methoxy-

2-pheny1-2-(phenylthio)ethane (0.28 g).

(ii) A mixture of 1-acetoxy-2-phenyl-2-(phenylthio)ethane (0.3 g),

methanesulphonic acid (3 drops), acetic anhydride (1 ml) and acetic

acid (25 ml) was kept at 60° for 5 hours then worked up, as described

for the reaction of the methanesulphonate with acetic acid, to afford

unchanged 1-acetoxy-2-phenyl-2-(phenylthio)ethane (0.27 g). 121

1-(p-Methoxypheny1)-2-(phenylthio)ethanol, 2-(p-methoxypheny1)-2-

(phenylthio)ethanol and their derivatives

The n.m.r. spectra of the compounds are given on pages 86 and 87.

p-Methoxystyrene oxide (60)

This was prepared essentially by the method described by Franzen

and Driesen47 . To a stirred mixture of anisaldehyde (26 g) and

trimethylsulphonium iodide79 (54 g) in DMSO (150 ml) was added dropwise,

under nitrogen, sodamide (11 g) in DMSO (120 ml) at 12°. After 2 hours

the mixture was worked up to give the title compound (24 g). It solidi-

fied on standing and had m.p. about 22° and b.p. 68°/5 x 10-2 mm

b.p. 51°/10 3 mm).

1-(p-Methoxyphenyl)-2-(phenylthio)ethanol and 2-(p-methoxypheny1)-

2-(phenylthio)ethanol (61, 66)

Thiophenol (15 g) was added to a solution of sodium (3 g) in

methanol (150 ml) followed by £-methoxystyrene oxide (20.5 g) at room

temperature. The mixture was left for 2 hours then diluted with water

and stirred overnight. The mixture was then extracted with benzene

and the benzene layer was washed with 2N sodium hydroxide, water and

dried. Evaporation of the solvent gave a mixture of the two alcohols

(35 g) which were separated by column chromatography (ether-petroleum,

1:3). 1-(p-Methoxypheny1)-2-(phenylthio)ethanol (first fraction, 5.2 g)

22 1.6111, v 3400 cm-l. (Found: C, H, 6.05; S, 12.22. had njo .max. 68.94; C15111602S requires C, 69.19; H, 6.19; S, 12.31%). This compound

dehydrated on distillation and gave 1-(phenylthio)-2-(p-methoxyphenyl) ethylene which when recrystallized from petroleum had m.p. 50-53°, -1 (CHC1 ) 960 cm (Trans olefin), T 2.4-2.8 (m; 7H, aromatic), v max. 3 3.13 (d; 2H, aromatic), 3.23 (s; 2H, CH-CH), 6.20 (s; 3H, OCH ). 3 122

(Found: C, 74.59; H, 5.72; S, 13.32. C15H140S requires C, 74.34;

H, 5.82; S, 13.23%). 2-(p-Methoxypheny1)-2-(phenylthiO)ethanol (second

fraction, 22.5 g) when recrystallized from ether-petroleum had m.p. -1 44-45°, v max. (CHC13) 3450 cm . (Found: C, 69.04; H, 6.19; S,

1.2.37%).

Preparation of 1-(p-methoxypheny1)-2-(phenylthio)ethanol from anisole

(i)oC -Chloro-p-methoxyacetophenone (74)

.This was prepared by the method described by Wilds and Johnson.48.

To a stirred mixture of anisole (60 g) and chloroacetyl chloride (74 g)

in carbon disulphide (120 ml) was gradually added powdered anhydrous

aluminium chloride (85 g.) at 10°, then the mixture was refluxed for

2 hours. After cooling, the solvent was decanted and the residue

hydrolyzed with ice and hydrochloric acid. The crude product obtained

by filtration (92 g) was recrystallized from methanol to give the title

compound (46 g). m.p. 90-95° (lit. m.p. 96-99). (The mother liquid

contained a mixture of the ortho and para isomers).

(ii) e.-(Phenylthio)-p-methoxyacetophenone (75)

This was prepared by reluxing the above phenacyl chloride with

thiophenol in pyridine as described by Banfield et. al 4g. It had

m.p. 88-89° (lit. m.p. 89-90°).

(iii)1-(p-Methoxypheny1)-2-(phenylthio)ethanol (77)

To a stirred mixture of 0(-(phenylthio)-mmethoxyacetophenone

(2.58 g, 0.01 M), methanol (54 ml) and water (5 ml) was added sodium

borohydride (0.38 g, 0.01 M) in methanol (5 ml) at room temperature.

Stirring was continued overnight and then the mixture was concentrated;

the residue was diluted with water and extracted with ether. The ether layer was washed with water and dried. Evaporation of the solvent gave 123

the pure alcohol (2.5 g, identified by the n.m.r. spectrum).

1-Acetoxy-1-(p-methoxypheny1)-2-(uhenylthio)ethane (78) Acetic anhydride (5 ml) in pyridine (10 ml) was added to a solution

of 1-(11.-methoxypheny1)-2-(phenylthio)ethanol (1.1 g) in pyridine at room temperature to afford the acetate (1.2 g), b.p. 150°/10 4 mm,

22 1740 cm-1. (Found: C, 67.90; H, 5.78; S, 10.60. njo 1.5811, v max. S requires C, 67.52; H, 6.00; S, 10.60%). C1718 03

1-Acetoxy-2-(p-methoxypheny1)-2-(phenylthio)ethane (72)

2-(g7Methoxypheny1)-2-(phenylthio)ethanol (0.8 g) in pyridine when reacted with acetic anhydride, as described for the above isomer, mm, 111022 yielded the acetate (0.85 g), b.p. 140°/10- 4 1.5841, v max. 1740 cm 1. (Found: C, 67:45; H, 6.31; S, 10.71%).

1-Methoxy-1-(p-methoxypheny1)-2-(phenylthio)ethane (79) To a stirred mixture of 1-(1methoxypheny1)-2-(phenylthio)ethanol

(1.1 g) and powdered sodium hydroxide (1.5 g) in THF was added dimethyl

sulphate (1.3 ml) in THF at 40° to yield the title compound (1.1 g), 4 18.5 b.p. 124°/10 mm 1.5903. (Found: C, 70.02; H, 6.54; S, 2S requires C, 70.03; H, 6.61; S, 11.68%). 11.74. C1e-1180

1-Methoxy-2-(p-methoxypheny1)-2-(phenylthio)ethane (73)

2-(17Methoxypheny1)-2-(phenylthio)ethanol (0.84 g) in THF was treated with dimethyl sulphate (1 ml) in the presence of powdered sodium hydroxide (1 g) as described for the above isomer. The methyl

ether (0.8 g) had b.p. 1300/10-4 mm, np25 1.5925. (Found: C, 69.86; H, 6.59; S, 11.94%).

1-Methanesulphonyloxy-2-(p-methoxypheny1)-2-(phenylthio)ethane (89)

Methanesulphonyl chloride (0.145 g) in dichloromethane (10 ml) 124

was added, dropwise, to a stirred solution of 2-(2.-methoxypheny1)-2-

(phenylthio)ethanol (0.3 g) and triethylamine (0.18 g) in dichloromethane

(30 ml) at 0°, to give the title compound (0.34 g) as a solid. It

was recrystallized from chloroform-petroleum and had m.p. 55-56°, max. -1 1350, 1.200 cm . This compound was very unstable at temperatures above 0°. (Found: C, 57.03; H, 5.21; S, 18.68. C1018002 requires C, 56.78; H, 5.36; S, 18.94%).

Attempted preparations of 1-methanesulphonyloxy-1-(p-methoxypheny1)-2- (phenylthio)ethane (85, 88, 90)

(i) A' mixture of 1-(1.-methoxypheny1)-2-(phenylthio)ethanol (0.8 g) and triethylamine (0.45 g) in dichloromethane when treated with methanesulphonyl chloride (0.39 g), as described for the isomer, afforded a mixture of 1-chloro-l-(p-methoxypheny1)-2-(phenylthio)ethane and 1- chloro-2-(2.-methoxypheny1)-2-(phenylthio)ethane (ratio, 3:1) with some diphenyl disulphide and other impurities. The chlorides were unstable on a t.l.c. plate and they decomposed on distillation.

(Found: Cl, 9.62. C H 15 15C10S requires 12.71%).

(ii) A mixture of 1-(p7methoxypheny1)-2-(phenylthio)ethanol (0.5 g) and sodium hydride (0.2 g) in dry ether was refluxed for 20 hours.

Then it was filtered and the filtrate was cooled to 0° and treated with methanesulphonyl chloride (0.25 g). On.working up the reaction mixture the alcohol (starting material) was recovered.

Reactions of 1-methanesulphonyloxy-2-(p-methoxyphenyl)-2-(phenylthio) ethane

The freshly prepared methanesulphonate was used for all of the following reactions which were carried out as described in detail for 125

The reactions of 1-methanesulphonyloxy-2-phenyl-2-(phenylthio) ethane,

unless mentioned otherwise. The products were identified by their n.m.r. spectra which are on pages 87 and 88.

(i) With acetic acid (80)

A solution of the methanesulphonate (0.6 g) and acetic anhydride

(1 ml) in acetic acid (25 ml) was kept for 7 days at 10° to give 1- acetoxy-1.2(p-methoxypheny1)-2-(phenylthio)ethane (0.38 g).

(ii) With potassium acetate (82)

A mixture of the methanesulphonate (0.5 g) and potassium acetate

(0.4 g) in acetic anhydride was kept at 5° for 7 days to afford 1- acetoxy-1-(2-methoxypheny1)-2-(phenylthio)ethane (0.32 g).

(iii) With tetramethylammonium acetate (96) The methanesulphonate (0.4 g) and tetramethylammonium acetate (0.25 g) in dry acetone were kept at 5° for 7 days to afford 1-acetoxy-

1-(p-methoxypheny1)-27(phenylthio)ethane (0.3 g).

(iv) With methanol (87)

The methanesulphonate (0.65 g) in methanol (30 ml) was kept at

5° for 7 days to give 1-methoxY-1-(2.-methoxypheny1)-2-(phenylthio) ethane (0.5 g).

(v) With sodium methoxide in methanol (81)

A solution of sodium (0.15 g) in methanol (30 ml) and the methanesulphonate (0.5 g) was kept at 5° for 7 days to yield 1-methoxy-1-

(R-methoxypheny1)-2-(phenylthio)ethane (0.4 g).

(vi) With lithium bromide (94)

The methanesulphonate (0.5 g) and lithium bromide (0.5 g) were stirred in dry acetone at 0° for 5 days. Working up of the reaction mixture gave a red oil (0.28 g) which was a very impure mixture of 126

1-bromo-1-(D-methoxypheny1)-2-(phenylthio)ethane and some (<5%) 1-

bromo-2-(D-methoxypheny1)-2-(phenylthio)ethane. The reaction was

repeated at -10° and the same result was obtained. The bromides

were unstable and could not be purified.

(vii) With sodium azide (97)

A mixture of the methanesulphonate (0.6 g) and sodium azide (0.4 g) in DMF was kept at 5° for 4 days to obtain 1-azido-1-(p-methoxypheny1)- -1 . 2-(phenylthio)ethane (0.35 g), b.p. 130°/10 4 mm, v max. 2150 cm (Found: C, 63.16; H, N, 14.56; S, 11.15. C H N 0S requires 5.37; 15 15 3 C, 63.13; H, 5.30; N, 14.72; S, 11.23%).

Control reactions (98)

The products were identified by their n.m.r. spectra given on page 88.

(i) A solution of 1-methoxy-2-(2.-methoxypheny1)-2-(phenylthio)ethane

(0.4 g) and methanesulphonic acid (3 drops) in methanol was kept at 5° for 7 days. Unchanged primary methyl ether was recovered.

(ii) A mixture of 1-acetoxy-2-(2.-methoxypheny1)-2-(phenylthio)ethane

(0.3 g), methanesulphonic acid (3 drops), acetic anhydride (1 ml) and acetic acid (25 ml) was kept at 10° for 7 days. Unchanged primary acetate was recovered. 127

1-(p-Nitropheny1)-2-(phenylthio)ethanol, 2-(p-nitropheny1)-2-(phenylthio)

ethanol and their derivatives

The n.m.r. spectra of the compounds are given on pages 89 and 90.

p-Nitrostyrene oxide

(a) 1,2-Dibromo-l-phenylethane (98)

This was prepared by the reaction of styrene with bromine in 8o carbon tetrachloride as-described by Fiesselmann and Sasse . It

had m.p. 69 -72° (lit., 73-74°).

(b) 1-(p-Nitropheny1)-1-nitrato-2-bromoethane (99)

1,2-Dibromo-l-phenylethane was gradually added to a stirred

mixture of conc. sulphuric acid and nitric acid at -5° to give the title compound. It had m.p. 93-95° (lit.,81 96-97°).

Hydrogen bromide was bubbled through a stirred slurry of 1-

(E-nitropheny1)-1-nitrato-2-bromoethane in hydrobromic acid (48%) at 50° to obtain the title compound. It had m.p. 85-86° (1it82,

86-87°).

(d) p-Nitrostyrene oxide (116)

This was prepared by stirring 1-(27nitropheny1)-2-bromoethanol in aqueous sodium hydroxide solution as described by Guss and Mautner83.

It had m.p. 81-84° (lit., 85-86°).

2-(Phenylthio)-2-(p-nitrophenyl)ethanol and 2-(phenylthio)-1-(p- nitrophenyl)ethanol (118)

When the reaction of sodium(0.24 g) with methanol was complete, thiophenol (0.75 g) was added, under nitrogen, followed by 2.-nitrostyrene oxide (1 g). The mixture was stirred at room temperature for

2 hours and then diluted with water and left overnight. It was then extracted with chloroform and the chloroform.layer was washed with 128

2N sodium hydroxide, water and dried. Evaporation of the solvent gave

a mixture of the two alcohols (1.75 g) which were separated by solumn

chromatography (benzene-chloroform, 1:1). These alcohols decomposed on distillation. 2-(Phenylthio)-1-(p-nitrophenyl)ethanol (first fraction, 1.08 g) had !ID20 1.6338, v -1 max. 3450 cm . (Found: C, 60.89; H, 4.91; N, 4.99; S, 11.69. C1013NO3S requires C, 61.07;

H, 4.75; N, 5.08; S, 11.64%). 2-(Phenylthio)-2-(p-nitrophenyl) ethanol (second fraction, 0.53 g) had n:3 1.6306, max. 3400 cm-l. (Found: C, 60.92; H, 5.00; N, 4.97; S, 11.53%).

1-Acetoxy-1-(p-nitrophenyl)-2-(phenylthio)ethane (131)

Acetic anhydride (4 ml) in pyridine (10 ml) was added to a solution of 1-2.-nitropheny1)-2-(phenylthio)ethanol (0.81 g) in pyridine 4 at room temperature to give the acetate (0.8 g). b.p. 177°/10/10 mm, v max. 1740 cm-1. (Found: C, 60.70; H, 4.87; N, 4.37; S, 10.21. C16H15N04S requires C, 60.55; H, 4.76; N, 4.41; S, 10.10%).

1-Acetoxy-2-(phenylthio)-2-(p-nitrophenyl)ethane (132)

2-(Phenylthio)-2-(2-nitrophenyl)ethanol (0.6 g) in pyridine when reacted with acetic anhydride, as described for the above isomer,

yielded the title compound (0.56 g). b.p. 160°/10-4 mm , V 1740 max. cm-1. (Found: C, 60.43; H, 4.88; N, 4.38; S, 10.36%).

1-Methoxy-1-(p-nitrophenyl)-2-(phenylthio)ethane (133)

To a stirred mixture of 1-(E-nitropheny1)-2-(phenylthio)ethanol

(0.8 g) and powdered sodium hydrozide (1 g) in THE was added dimethyl sulphate (1 ml) in THE at room temperature. The methyl ether (0.78 g) was purified by preparative t.l.c. (benzene). The pure compound crystallized on standing and when recrystallized from ether-petroleum had m.p. 41.5-42.5°. (Found: C, 61.97; H, 5.22; N, 4.82; S, 11.38.

C H NO S requires C, 62.27; H, 5.22; N, 4.84; S, 11.08%). 15 15 3 129

1-Methoxy-2-(p-nitrophenyl)-2-(phenylthio)ethane (134, 139)

(i) A mixture of 2-(E-nitropheny1)-2-(phenylthio)ethanol and powdered

sodium hydroxide in THE when treated with dimethyl sulphate, as des-

cribed for the above isomer, gave a red oil (low yield) which showed

several spots on t.l.c. (benzene).

(ii) A solution of diazomethane (ca. 1.2 g) in ether was added,

dropwise,, to a solution of 2-(2.-nitropheny1)-2-(phenylthio)ethanol

(0.5 g) and fluoroboric acid (40%, 2 ml) in dichloromethane (60 ml).

The solution was left at room temperature for 36 hours and then neut-

ralized with 2N sodium hydroxide, concentrated to a small volume,

washed with water and dried. Evaporation of the solvent gave an oil

which was a mixture of the title compound and unreacted alcohol.

The methyl ether (0.1 g), which was separated by preparative t.l.c.

(chloroform), crystallized on standing. It had m.p. 51-54°. (Found:

C, 62.26; H, 5.26; N, 4.71; S, 10.85%).

1-Methanesulphonyloxy-1-(p-nitropheny1)-2-(phenylthio)ethane (160)

Methanesulphonyl chloride (0.235 g) in dichloromethane (10 ml)

was added, dropwise, to a stirred solution of 1-(2.-nitropheny1)-2-

(phenylthio)ethanol (0.52 g) and triethylamine (0.3 g) in dichloro-

methane (25 ml) at 0°, to give the title compound (0.48 g). It was

crystallized from dichloromethane-petroleum and had m.p. (decomposition) o -1 55 • v (CHC1 ) 1360, 1180 cm . This compound was unstable at max. 3 temperatures above 0°. (Found: C, 50.95; H, 4.29; N, 3.81; S, 18.04.

N0s requires C, 50.98; H, 4.28; N, C15H15 2 3.96; s, 18.14%).

1-NethanesulPhonyloxy-2-(p-nitropheny1)-2-(Phenylthio)ethane (165)

2-(2.-Nitropheny1)-2-(phenylthio)ethanol (0.4 g) was treated with

methanesulphonyl chloride (0.18 g), as described for the above isomer, 130

to give the title compound (0.35 g). It was crystallied from dichloro- -1 methane-petroleum and had m.p. 78-81°, v max. (CHC1 ) 1350, 1180 cm . 3 o This compound was unstable at temperatures above 0 . (Found: C, 50.89;

H, 4.33; N, 3.89; S, 17.95%).

Reactions of 1-methanesufphonYlOxy-1-(p-nitropheny1)-2-(phenylthio) ethane

Freshly prepared methanesulphonate was used for all of the following reactions which were carried out as described for the previous series. The n.m.r. spectra of the products are on pages 90-92.

(i) With acetic acid (162)

A solution of the methanesulphonate (0.25 g) and acetic anhydride

(1 ml) in acetic acid (25 ml) was kept at 50° for 5 hours to give 1- acetoxy-1-(2-nitropheny1)-2-(phenylthio)ethane (0.21 g).

(ii) With potassium acetate (163)

(a) A mixture of the methanesulphonate (0.26 g) and potassium acetate (0.3 g) in acetic anhydride (25 ml) was kept at 10° for 15 hours to afford 1-acetoxy-1-(2.-nitropheny1)-2-(phenylthio)ethane

(0.22 g).

(b) The reaction was carried out in acetone at room temperature

(using the same quantities). The product (0.22 g) was 1-acetoxy-1-

(k-nitropheny1)-2-(phenylthio)ethane and some (<5%) 1-(phenylthio)-

1-(p7nitropheny1)ethylene.

(iii) With tetramethylammonium acetate (179)

(a) The methanesulphonate (0.1 g) and tetramethylammonium acetate

(0.1 g) in dry acetone (25 ml) were kept for 40 hours at room temperature.

The product (90 mg) was 1-acetoxy-1-(p7nitropheny1)-2-(phenylthio) ethane and some (<5%) 1-(phenylthio)-1-(u-nitroDhenyi)ethylene. 131

(b) The reaction was carried out in acetic anhydride using the

same conditions and quantities. The product (92 mg) was 1-acetoxy-1-

(27nitropheny1)-2-(phenylthio)ethane.

(iv)With methanol (161) The methanesulphonate (0.24 g) in methanol (25 ml) was kept for

5 hours at 50° to yield 1-methoxy-1-(2-nitropheny1)-2-(phenylthio)

ethane (0.2 g).

(v)With sodium methoxide in methanol (164) A solution of sodium (0.1 g) in methanol (25 ml) and the methane-

sulphonate (0.25 g) was kept for 70 hours at 0° to obtain 1-methoxy- 1-(27nitropheny1)-2-(phenylthio)ethane (0.2 g).

(vi) With lithium bromide (171)

A mixture of the methanesulphonate (0.25 g) and lithium bromide (0.3 g) in dry acetone (30 ml) was kept for 90 hours at 0°. The

product (0.15 g) was an impure mixture of 1-bromo-1-(27nitropheny1)-2- (phenylthio)ethane and 1-bromo-2-(E-nitropheny1)-2-(phenylthio)ethane

(ratio 5:2). These compounds were unstable and could not be purified.

(vii)With sodium azide (166)- A mixture of the methanesulphonate (0.3 g) and sodium azide (0.3 g)

in dry,DMF (30 ml) was kept at 0° for 48 hours to obtain 1-azido-1-

(p-nitropheny1)-2-(phenylthio)ethane (0.2 g). v max. 2120 cm-1 . (Found: C, 56.20; H, 4.02; N, 18.62; S, 10.80. S requires C1412 N4 02 C, 55.99; H, 4.03; N, 18.65; S, 10.66%).

(viii)With sodium thiophenate (172) When the reaction of sodium (0.1 g) with methanol (30 ml) was com-

plete, thiophenol (0.7 g) followed by the methanesulphonate (0.25 g) were added to it. The mixture was kept at 0° for 70 hours to give 132

1-(p-nitropheny1)-1-(phenylthio)-2-(phenylthio)ethane (0.3 g). The

product was purified by preparative t.l.c. (benzene) then crystallized

from benzene-petroleum. It had m.p. 105-107°. (Found: C, 65.37;

H, 4.65; N, 3.70; S, 17.21. C201-117NO2S2 requires C, 65.37; H, 4.66;

N, 3.81; S, 17.45%).

Reactions of 1-methanesulphonyloxy-2-(p-nitrophenyl)-2-(phenylthio)

ethane

The freshly prepared methanesulphonate was used for all of the

following reactions. The n.m.r. spectra of the reaction products are

on pages 92-94.

(i) With acetic acid (168)

The methanesulphonate (0.3 g) at 10° gave 1-acetoxy-1-(2-nitropheny1)-

2-(phenylthio)ethane (0.23 g).

(ii) With potassium acetate (168)

(a) The methanesulphonate (0.3 g) in acetic anhydride at room

temperature and at 0° decomposed and no product was obtained.

(b) The reaction was carried out in acetone at 0° (using 0.3 g of the methanesulphonate). A mixture (0.18 g) of 1-(phenylthio)-1-(117 nitrophenyl)ethylene and 2-(phenylthio)-4'-nitroacetophenone (2:1) was obtained (the ketone formed by oxidation of the olefin, see below).

(iii) With tetramethylammonium acetate (178)

(a) The methanesulphonate (0.25 g) in acetone (30 ml) at 0° gave a mixture (0.16 g) of 1-(phenylthio)-1-(Z7nitrophenyl)ethylene and 2-(phenylthio)-4'-nitroacetophenone (about 4:1). The mixture was exposed to air for 2-3 days, and the olefin became all oxidized to the ketone. The ketone was then purified by preparative t.l.c.

(benzene) and crystallized from ether-petroleum. It had m.p. 101- 133

84 103° (lit., 100-102 °), v max.(CHC13 ) 1680 cm-1. (Found: C, 61.39; H, 4.03; N, 5.22. Calc.for N303 C14H11 S: C, 61.52; H, 4.06; N, 5.12%).

(b) The reaction was carried out in acetic anhydride and the same result was obtained.

(iv) With methanol (167)

The methanesulphonate (0.3 g) at 0° afforded 1-methoxy-1-(E7nitro- pheny1)-2-(phenylthio)ethane (0.2 g).

(v) With sodium methoxide in methanol (169) The methanesulphonate (0.5 g) at 0° gave a mixture (0.32 g) of 1-methoxy-2-(27nitropheny1-2-(phenylthio)ethane (65%), 1-(phenylthio)-

1(E-nitrophenyl)ethylene (25%) and 2-(phenylthio)-4'-nitroacetophenone (10%).

(vi) With lithium bromide (171)

The methanesulphonate (0.25 g) at 0° gave a mixture (0.11 g) of the secondary and primary bromides (ratio 3:1) which were unstable and could not be purified.

(vii) With sodium azide (170)

The methanesulphonate (0.25 g) at 0° gave a mixture (0.15 g) of 1-(phenylthio)-1-(2-nitrophenyl)ethylene and 2-(phenylthio)-4'- nitroacetophenone (ratio 3:1).

Control reactions (173)

(i) A solution of 1-methanesulphonyloxy-2-(phenylthio)-2427nitro- phenyl)ethane in chloroform (ethanol free) when kept at 35-40° for half an:hour, partially (about 50%) isomerized to 1-methanesulphonyloxy-

1-(p-nitropheny1)-2-(phenylthio)ethane.

(ii) A solution of 1-methanesulphonyloxy-1-(p-nitropheny1)-2- 134

(phenylthio)ethane in chloroform (ethanol free) when kept 10 minutes o at 35 resulted in some (10-15%) isomerization and some decomposition.

(iii) A mixture of 1-acetoxy-2-(p-nitropheny1)-2-(phenylthio)ethane

(0.3 g), methanesulphonic acid (3 drops), acetic anhydride (1 ml) and

acetic acid (25 ml) was kept at room_ temperature overnight. Unchanged

primary acetate was recovered. 135

Oxidation of 1-(phenylthio)-1-(p-nitrophenyl)ethylene to 2-

(phenylthio)-41 -nitroacetophenone ' (229)

A mixture of the primary methanesulphonate (0.4 g) and

sodium azide (0.2 g) in Di1F (30 ml) was kept at 00 for 3 days

and then worked up as'described before to obtain the olefin.

The product (0.3 g) was dissolved in deuteriochloroform (ca.

2 ml) and the resulting solution was divided into three n.m.r.

tubes: A, B and C.

Nitrogen was bubbled through sample A and immediately it

was stoppered and sealed with para-film.

2,6-Di-tert-butyl-E-cresol (anti-oxidant, 5-6 mg) was added

to sample B, and it was left without a stopper (exposed to air).

Sample C was left without a stopper (exposed to air).

The n.m.r. spectra on the samples A, B and C- were recorded

after 3 hours. The spectra showed that the solutions all contained

a mixture of the olefin (90%) and some (ca. 10%) of the ketone.

The n.m.r. spectra were recorded on these samples. after 1, 2,

•4, 7 and 8 days. A graph was plotted recording the amount of

the ketone in samples A, B and C against time (page 51, graph 1).

After 7 days, benzoyl peroxide (5 mg) was added to the sample

A (which then contained 30% of the ketone) and the tube was

stoppered. The reaction was followed by recording the n.m.r.

spectra for 4 days. The formation of the ketone against time

in presence of benzoyl peroxide is shown on graph 1 (page 51 )/

sample D. 136

2-Phenyl-2-(2,4-dinitrophenylthio)ethanol 1-pheny1-2-(2,4-dinitrophenylthio)ethanol and their derivatives

The n.m.r. spectra of the compounds are given on pages 95 and 96.

1-Phenyl-2-(2,4-dinitrophenylthio)ethanol

(a) 2,2',4,41 -Tetranitrodiphenyl disulphide (108)

This was prepared by the reaction of 2,4-dinitrochlorobenzene with sodium disulphide as described by H.W. Tale 85. It had m.p. 260-280°

(lit., 280°). .

(b) 2,4-Dinitrophenylsulphenyl chloride (109)

This was prepared by treating the above disulphide with chlorine 86 as described by Kharasch et al. . It had m.p. 94-97° (lit., 9k-95°).

Reaction of 2,4-dinitrophenylsulphenyl chloride with styrene in acetic acid gave the title compound56. It was recrystallized from chloroform-petroleum and had m.p. 142-143° (lit., 143°).

(d) 1-Phenyl-2-(2,4-dinitrophenylthio)ethanol (111)

Refluxing the above chloride in dioxane in the presence of water gave the title compound which was purified by column chromatography

(chloroform) and recrystallized from chloroform-petroleum. It had m.p. 132-134° (lit.5:5134°).

2-Phenyl-2-(2,4-dinitrophenylthio)ethanol

(a) 2-Phenyl-2-bromoethanol (123)

Hydrogen bromide (48%) was added to a solution of styrene oxide, 87 in hexane to afford the title compound . It had b.p.- 94-99°/1 mm (lit.,

104/5 mm). 137

(b) 2-Phenyl-2-(2,4-dinitrophenylthio)ethanol (141)

When the reaction of sodium (0.35 .g) with methanol (100 ml) was

complete, 2,4-dinitrothiophenol (4 g) was added, under nitrogen. The

mixture was stirred at 50° for half an hour then a solution of 2-phenyl-

2-bromoethanol (2.5 g) in methanol was added to it. Stirring continued

for 6 hours and then water (10 ml) was added and left overnight at the

same condition. The warm mixture was filtered to remove the excess

2,4-dinitrothiophenol and the filtrate was concentrated and extracted

with chloroform. The chloroform layer was washed with 2N sodium hydroxide,

water and dried. Evaporation of the solvent gave an oil which was

chromatographed (chloroform) to give the title compound (1.7 g). It

was recrystallized from chloroform-petroleum and had m.p. 129-132°, -1 max. (01101 ) 3350 cm . (Found: C, 52.50; H, 4.03; N, 8.48; 3, V 3 10.02. C H N 0 14 12 2 5S requires C, 52.49; H, 3.78; N, 8.74; S, 10.01%).

1-Acetoxy-l-phenyl-2-(2,4-dinitrophenylthio)ethane (127)

Acetic anhydride (2 ml) in pyridine (5 ml) was added to a solution of 1-phenyl-2-(2,4-dinitrophenylthio)ethanol (0.4 g) in pyridine (5 ml) to give the acetate. It was recrystallized from chloroform-petroleum and had m.p. 112-113° (lit?, 113° ).

1-Acetoxy-2-phenyl-2-(2,4-dinitrophenylthio)ethane (140)

2-Phenyl-2-(2,4-dinitrophenylthio)ethanol (0.5 g) when treated with acetic anhydride (3 ml) as described for the above isomer gave the acetate (0.45 g). It was crystallized from chloroform-petroleum and -1 had m.p. 129-130°, v (CHC1 ) 1740 cm . (Found: C, 52.93; max. 3 H, 3.99; N, 7.51; S, 8.73. C161110200 requires C, 53.03; H, 3.90;

N, 7.73; S, 8.85%). 138

1-Methoxy-l-phenyl-2-(2,4-dinitrophenylthio)ethane (137)

A solution of diazomethane (ca. 2.0 g) in ether was added, dropwise, to a solution of 1-phenyl-2-(2,4-dinitrophenylthio)ethanol (0.8 g) and fluoroboric acid (40%, .2 ml) in dichloromethane (100 ml). The solution was left at room temperature for 38 hours then neutralized with 2N sodium hydroxide, concentrated to a small volume, washed with water and dried. Evaporation of the solvent gave an oil which was mainly the unreacted alcohol and some of the title compound. The methyl ether

(90 mg) was separated by chromatography (chloroform). It was crystallized from chloroform-petroleum and had m.p. 139-143°. (Found: C,

C H N 0 S requires C, 53.88; 53.65; H, 4.28; N, 8.14; S, 9.65. 15 14 2 5 H, 4.22; N, 8.34; S, 9.59%).

1-Methoxy-2-phenyl-2-(2,4-dinitrophenylthio)ethane (138)

2-Phenyl-2-(2,4-dinitrophenylthio)ethanol (0.47 g) when treated with a solution of diazomethane (ca. 1.2 g) in ether, as described for the above isomer, gave an oil which was a mixture of the title compound and unreacted alcohol. The methyl ether (0.13 g) was separated by chromatography (chloroform) and crystallized from ether-petroleum.

It had m.p. 124-126°. (Found: C, 53.94; H, 4.38; N, 8.33; S, 9.69%).

1-Methanesulphonyloxy-l-phenyl-2-(2,4-dinitrophenylthio)ethane (142)

Methanesulphonyl chloride.(0.4 g) in dichloromethane (10 ml) was added, dropwise, to a stirred solution of 1-pheny1-2-(2,4-dinitrophenylthio)ethanol (1 g) and triethylamine (0.48 g) in dichloromethane (30 ml) o at 0 to give the methanesulphonate (1.02 g), m.p. (decomposition) -1 3) 1380, 1180 cm . 75° (from dichloromethane-ether),v max. (CHC1 -(Found: C, 45.13; H, 3.49; N, 6.75; S, 16.10. C H N 0 S requires 15 14 2 7 2, C, 45.22; H, 3.45; N, 7.03; S, 16.09%). 139

1-Methanesulphonyloxy-2-pheny1-2-(2,4-dinitrophenylthio)ethane (151) 2-Phenyl-2-(2,4-dinitrophenylthio)ethanol (0.6 g) when treated

with methanesulphonyl chloride, as described for the above isomer,

gave the title compound (0.65 g) which was crystallized from dichloro-

methane-ether and had m.p. 107-107.5°, N., (CHC1 ) 1380, 1180 cm-l. max. 3 (Found: C, 45.55; H, 3.54; N, 6.73; S, 15.99%).

Reactions of 1-methanesulphonyloxy-l-phenyl-2-(2,4-dinitrophenylthio)

ethane

The freshly prepared methanesulphonate was used for all of the

following reactions. The products were identified by their n.m.r.

spectra which are on pages 96-98.

(i) With acetic acid (143)

A solution of the methanesulphonate (0.22 g) and acetic anhydride

(1 ml) in acetic acid (25 ml) was kept at 70° for 12 hours to give

1-acetoxy-l-phenyl-2-(2,4-dinitrophenylthio)ethane (0.2 g).

(ii) With potassium acetate (146)

(a) A mixture of the methanesulphonate (0.1 g) and potassium acetate

(0.1 g) in acetic anhydride was stirred at 70° for 12 hours to

obtain 1 -acetoxy -1 -phenyl -2 -(2,4-dinitrophenylthio)ethane (0.09 g).

(b) The reaction was carried out in acetone, under the same condition.

The product (0.065 g) was a mixture of 1-acetoxy-l-pheny1-2-(2,4-

dinitrophenylthio)ethane and 1-phenyl-2-(2,4-dinitrophenylthio)

ethylene (ratio 1:2).

(iii) With tetramethylammonium acetate (174)

(a) A solution of the methanesulphonate (0.2 g) and tetramethylammonium

acetate (0.2 g) in acetone was kept at 73° for 12 hours to give a

mixture (0.11 g) of 1-pheny1-2-(2,4-dinitro-rnenylthio)ethylene 14o

and 1-acetoxy-l-phenyl-2-(2,4-dinitrophenylthio)ethane (ratio 3:1).

(b) The reaction was carried out in acetic anhydride, under the same

conditions, to obtain a mixture (0.13 g) of 1-acetoxy-l-pheny1-

2-(2,4-dinitrophenylthio)ethane and some (about 25%) 1-pheny1-2- (2,4-dinitrophenylthio)ethylene.

(iv) With methanol (144)

The methanesulphonate (0.24 g) was kept in methanol (30 ml) at 70° for 12 hours to give 1-methoxy-l-phenyl-2-(2,4-dinitrophenylthio) ethane (0.21 g).

(v) With sodium methoxide in methanol (147)

(a) A solution of sodium (0.1 g) in methanol (30 ml) and the methane-

sulphonate (0.2 g) were mixed and kept at 70° for 12 hours. The product (0.10 g) was a mixture of 2,4-dinitroanisole (about 80%)

and some (about 10%) 1-methoxy-l-phenyl-2-(2,4-dinitrophenylthio)

ethane. 2,4-Dinitroanisole was separated by preparative t.l.c.

(chloroform) and crystallized from ethanol. It had m.p. 83-85° (lit.,88 86°).

(b)The reaction was carried out, using the same quantities, at room temperature. The product (0.12 g) was a mixture of 1-pheny1-2-

(2,4-dinitrophenylthio)ethylene (50-55%), 1-methoxy-l-pheny1-

2-(2,4-dinitrophenylthio)ethane (30%) and some (15-20%) 2,4-

dinitroanisole. The olefin was separated by preparative t.l.c. (chloroform) and crystallized from chloroform-petroleum. It

had m.p. 176-178° (lit.,56 m.p. 174°). (Found: C, 55.54; H,

3.45; N, 9.14; S, 10.66. Calc. for Cl4H10N204S: C, 55.62;

H, 3.33; N, 9.271 S, 10.61%). (vi) With sodium thiophenate (149)

When the reaction of sodium (0.1 g) with methanol was complete,

thiophenol (0.7 g) followed by the methanesulphonate (0.3 g) were added

to it, under nitrogen. The mixture was kept at room temperature over-

night. The product was chromatographed and two fractions were obtained:

The first fraction (0.2 g) was identified as 2,4-dinitrophenyl

phenyl sulphide which was crystallized from ether-petroleum and had 89 m.p. 119-120° (lit. 120°) . (Found: C, 52.21; H, 2.97; N, 10.16;

S, 11.63. Calc. for N 0 C12H8 2 4S: C, 52.17; H, 2.91; N, 10.13; S, 11.60%). The second fraction (30 mg) was 1-methoxy-l-pheny1-2-(2,4-dinitro-

phenylthio)ethane.

(vii) With lithium bromide (145)

The methanesulphonate (0.54 g) and lithium bromide (0.6 g) were o kept in acetone at 55 for 12 hours to yield 1-bromo-l-phenyl-2-(2,4- dinitrophenylthio)ethane (0.5 g). It was recrystallized from chloro- 6 form-petroleum and had m.p. 141-144° (lit., 142-143° ).

(viii) With sodium azide (148)

A mixture of the methanesulphonate (0.4 g) and sodium azide

(0.5 g) in DMF were kept at room temperature for 12 hours to give

1-azido-1-21=1;2-(2,4-dinitrophenylthio)ethane (0.24 g). It was o crystallized from chloroform-petroleum and had m.p. 115-116 , max. (CHC1 ) 2150 cm-1. (Found: C, 48.56; H, 3.38; N, 20.23; S, 9.10. 3 CH N 0 S requires C, 48.69; H, 3.21; N, 20.28; S, 9.28%). 11 5 4

Reactions of 1-methanesulphonyloxy-2-phenyl-2-(2,4-dinitrophenylthio) ethane

The freshly prepared methanesulphonate was used for all of the following reactions. The products were identified by their n.m.r. 142 spectra which are on pages 98 and 99.

(i) With acetic acid (153)

A solution of the methanesulphonate (0.17 g) and acetic anhydride

(1 ml) in acetic acid (25 ml) was kept at 70° for 12 hours to yield

1-acetoxy-l-phenyl-2-(2,4-dinitrophenylthio)ethane (0.14 g).

(ii) With potassium acetate (154)

A mixture of the methanesulphonate (0.25 g) and potassium acetate

(0.3 g) in acetic anhydride (25 ml)was kept at 70° for 12 hours to give

1-)oheny1-1-(2,4-dinitrophenylthio)ethylene (0.15 g). It was crystallized from carbon tetrachloride and had m.p. 95-97°. (Found: C, 55.60; H,

3.33; N, 9-15; S, 10.60%).

(iii) With tetramethylammonium acetate (174)

A mixture of the methanesulphonate (90 mg) and tetramethylammonium acetate (110 mg) in acetone was kept at room temperature for 3 days to yield 1-phenyl-1-(2,4-dinitrophenylthio)ethylene (60 mg).

(iv) With methanol (152)

The methanesulphonate (0.17 g) was kept in methanol for 12 hours at 700 to afford 1-methoxy-l-phenyl-2-(2,4-dinitrophenylthio)ethane

(0.14 g).

(v) With sodium methoxide in methanol (157)

(a) A solution of sodium (0.1 g) in methanol (30 ml) and the methanesulphonate (0.3 g) was kept for 15 hours at room temperature.

The product (0.14 g) was mainly 2,4-dinitroanisole and some (<5%)

1-phenyl-1-(2,4-dinitrophenylthio)ethylene.

o (b) The reaction was carried out at 0 for 4 days, using the sane quantities. The product (0.18 g) was mainly 1-phenyl-1-(2,4- 143

dinitrophenylthio)ethylene and some(<5%) 2,4-dinitroanisole.

(vi) With sodium thiophenate in methanol (156)

When the reaction of sodium (0.1 g) with methanol (30 ml) was com-

plete, thiophenol (0.7 g) followed by the methanesulphonate (0.3 g)

were added to it, under nitrogen, at room temperature. The product

was mainly 2,4-dinitrophenyl phenyl sulphide and some ( 410%) 1-

(phenylthio)-2-(phenyl)-2-(2,4-dinitrophenylthio)ethane which was

separated by preparative t.l.c. (benzene-petroleum, 2:1). (Found:

C, 58.40; H, 4.07; N, 6.78; S, 15.25. N204S2 requires C, 58.24; C20H16 H, 3.91; N, 6.79; S, 15.55%).

(vii) With sodium azide (155)

(a) When a mixture of the methanesulphonate (0.3 g) and sodium

azide (0.3 g) in DMF (30 ml) was kept at room temperature for 12 hours,

the methanesulphonate decomposed and no product was obtained.

(b) The reaction was carried out at 0°, using the same quantities.

After 3 hours (the mixture was becoming brown) it was worked up to

obtain a mixture (0.2 g) of 1-phenyl-l-(2,4-dinitrophenylthio)ethylene,

unreacted methanesulphonate (ratio 2:3) and some impurities.

(viii) With lithium bromide , (158)

A mixture of the methanesulphonate (0.3 g) and lithium bromide

(0.3 g) in acetone was kept at 70° for 24 hours. The product (0.25 g)

was a mixture of 1-bromo-2-phenyl-2-(2,4-dinitrophenylthio)ethane and

some (4.5%) 1-phenyl-l-(2,4-dinitrophenylthio)ethylene. The bromide

(0.18 g) was purified by preparative t.l.c. (benzene). (Found: C,

44.64; H, 3.23; N, 7.02; Br, 19.91; S, 8.40. C H BrN204S requires 14 i1 C, 43.88; H, 2.89; N, 7.31; Br, 20.85; S, 8.37%). 144

Control reactions: (159)

(a) A solution of 1-methanesulphonyloxy-2-pheny1-2-(2,4-dinitrophenyl-

, thio)ethane in dry acetone was refluxed for 1 hour. Unchanged

methanesulphonate was recovered.

(b) A solution of 1-methoxy-2-phenyl-2-(2,4-dinitrophenylthio)ethane

(0.2 g) and methanesulphonic acid (3 drops) in methanol (25 ml)

was kept at'70° for 12 hours. Unchanged methyl ether was recovered.

(0.3 g), methanesulphonic acid (3 drops), acetic acid*(25 ml)

was kept at 700 for 12 hours. Unchanged acetate was recovered.

* contained acetic anhydride (1 ml) 145

Part (2):

3-(Phenylthio)allyl alcohol and its derivatives

The compounds which are mentioned in this section were unstable o at room temperature but most of them were stable at 0 . The n.m.r. spectra of the compounds are given on pages 101 and 102.

3-(Phenylthio)ally1 alcohol and 2-(phenylthio)allyl alcohol (184)

Thiophenol (20 g) was added, dropwise, to a stirred mixture of propargyl alcohol (12 g) and powdered potassium hydroxide (0.4 g) at

125°. Stirring was continued for 2 hours at the same temperature and then the mixture was cooled to room temperature and extracted with ethyl acetate. The organic layer was washed with 2N sodium hydroxide solution, water and dried. The crude product (31 g), obtained on evaporation of the solvent, was distilled, b.p. 90-110°/0.2 mm. The distilled product (26 g) was a pure mixture of 3-(phenylthio)allyl alcohol (cis) and 2-(phenylthio)ally1 alcohol (ratio 3:2). These alcohols were unstable to column chromatography and they were separated by preparative t.l.c. (ether-petroleum, 1:1). 2-(Phenylthio)allyl 18 -1 alcohol (first fraction) had n 1.5940, v 3350, 940 (=c112 ) cm , D max w 2.4-2.8 (m, 5H, aromatic), 4.38(t, 1H, J, 1.2 Hz), 4.76(t, 1H,

1.0 Hz), 5.78(broad s, 2H, CH2 OH), 7.38(broad s, 1H, OH). (Found:

C, 64.79; H, 6.03; S, 19.09. C9H100S requires C, 65.02; H, 6.06;

S, 19.29%). Cis-3-(phenylthio)ally1 alcohol (second fraction) had -1 n 1.6058,v max 3350 cm . (Found: C, 64.73; H, 6.02; S, 19.07%). D17

2-(Phenylthio)-3-acetoxyprop-1-ene (185)

2-(Phenylthio)ally1 alcohol (0.4 g) in pyridine (5 ml) was treated with a solution of acetic anhydride (3 ml) in pyridine (5 ml) to give 146

the acetate J0.29 g). It was purified by preparative t.l.c. (benzene) 19 -1 and had n 1.5517, v 1740, 940(=CH2 T 2.4-2.8(m; D max ) cm , 5H, aromatic), 4.47( t; 1H, J, 1.2 Hz), 4.69(s, 1H), 5.36(s; ?H, CH2 OAc), 7.94(s; 3H,

OAc) . (Found: C, 63.24; H, 5.89; S, 15.19. C11H12025 requires C, 63.43; H, 5.81; 5,15.39%).

Cis-1-(Phenylthio)-3-acetoxyprop-1-ene (186)

Cis-3-(phenylthio)ally1 alcohol (0.5 g) when treated with acetic

anhydride (3 ml) in pyridine gave the cis acetate (0.45 g) which was

purified by preparative t.l.c. (benzene) and had np19 1.5663; v m ax 1740 cm-1. (Found: C, 63.29; H, 5.85; S, 15.49%). -

1-(Phenylthio)-3-methoxyprop-1-ene(cis) (187)

Dimethyl sulphate (1 ml) in THF (5 ml) was added, dropwise, to

a stirred mixture of cis-3-5phenylthio)ally1 alcohol'(0.5 g) and powdered potassium hydroxide (1 g) in THF (25 ml) to give the cis

methyl ether (0.38 g). It was purified by preparative t.l.c. (benzene).

(Found: C, 66.76; H, 6.77; S, 17.67. C10H1205 requires C, 66.63; H, 6.71; S, 17.79%).

Isomerisation of cis-3-(phenylthio)allyl alcohol (188)

A solution of sodium (0.2 g) in ethylene glycol (20 ml) and

cis-3-(phenylthio)allyl alcohol (0.2 g) was kept at 125° for 3 hours to obtain a mixture (0.18 g) of cis and trans isomers (ratio 3:2).

1-(Phenylthio)-3-methoxyprop-1-ene (cis and trans) (188)

3-(Phenylthio)allyl alcohol (mixture of cis and trans isomers

(0.2 g)) was treated with dimethyl sulphate (0.5 ml) in the presence

of powdered potassium hydroxide to give a mixture of cis and trans 147 methyl ethers (0.19 g).

1-(Phenylthio)-3-acetoxyprop-1-ene (cis and trans) (188)

3-(Phenylthio)allyl alcohol (mixture of cis and trans isomers,

0.2 g) when treated with acetic anhydride (2 ml) in pyridine gave a mixture of cis and trans acetates (0.2 g).

Attempted preparations of 1-(phenylthio)-3-methanesulphonyloxyprop-

1-ene (181, 183)

(a) Methanesulphonyl chloride (0.13 g) in dichloromethane (10 ml)

was added, dropwise, to a stirred solution of cis-3-(phenylthio)

allyl alcohol (0.166 g) and triethylamine (0.15 g) in dichloro-

methane (25 ml) at 0°. Stirring was continued for half an hour,

then the mixture was washed with cold solutions of 2N hydrochloric

acid, saturated sodium bicarbonate, water, and dried. Evaporation

of the solvent gave trans 1-(phenylthio)-3-chloroprop-1-ene (0.16 g,

see below) with some impurities.

(b) To a stirred mixture of cis-3-(phenylthio)allyl alcohol (0.15 g)

and silver oxide (0.3 g) in dichloromethane, methanesulphonyl

chloride (0.14 g) in dichloromethane was added, dropwise, at o 0 . Stirring was continued for half an hour, then the excess

silver oxide was removed by filtration and the filtrate was

washed with water and dried. On evaporation of the solvent

the alcohol was recovered.

sodium hydride (0.115.g, 60%) in dry ether (30 ml) was stirred

at room temperature for 4 hours. The mixture was then cooled to o 0 and methanesulphonyl chloride (0.16 g) in dry ether was added,

dropwise. Stirring was continued for 1 hour and then the mixture 148

was worked up to recover the alcohol.

1-(Phenylthio)-3-chlOroproP-1-ene (trans) (202)

A mixture of cis-3-(phenylthio)allyl alcohol (0.15 g) and triethyl-

amine (0.14 g) in dichloromethane (15 ml) was added, dropwise, to a

stirred solution of methanesulphonyl chloride (0.12 g) at 7-8°.

Stirring was continued for 2-3 hours at the same temperature and then

the mixture was worked up to obtain the trans chloride (0.15 g). This nD14.3 compound was unstable and could not be purified. 1.6085, v max

960 cm-1 (trans olefin). (Found: C, 58.55; H, 5.14; Cl, 16.85.

C H C1S requires C, 58.53; H, 4.91; Cl, 19.20%). 9 9

Reactions of trans 1-(phenylthio)-3-chloroprop-1-ene

The freshly prepared trans chloride was used for all of the

following reactions. The products were identified by their n.m.r.

spectra given on pages 102-104.

(i) With acetic acid (195)

A solution of the chloride (0.2 g) and acetic anhydride (1 ml)

in acetic acid (20 ml) was kept at room temperature for 2 days. The

product (0.1 g) was mainly decomposition impurities and some (ca. 10%)

trans-1-(phenylthio)-3-acetoxyprop-1-ene.

(ii) With potassium acetate (193)

A mixture of the chloride (0.4 g) and potassium acetate (0.3 g)

in acetic anhydride (25 ml) wa3 ka:n= at room temperature for 2 days.

The product (0.3 g) was an impure mixture of trans 1-(phenylthio)-

3-acetoxyprop-1-ene (ca. 15%) and 3-(phenylthio)-3-acetoxyprop-1-ene

(ca. 3026). The latter was very unstable and decomposed on a preparative

0 149

t.l.c. plate, and it was identified by comparison of the n.m.r.

spectpum of the crude product (the impure mixture of the acetates)

with the n.m.r. spectrum of 3-(phenylthio)-3-methoxyprop-1-ene (see

below). The trans acetate was purified by preparative t.l.c. (benzene) . v max 1740, 960 (trans olefin). (Found: C, 63.15; H, 5.81; S, 16.04%).

(iii) With tetramethylammonium acetate (195)

A mixture of the chloride (0.4 g) and tetramethylammonium acetate

(0.4 g) in acetone (30 ml) was kept at room temperature for 2 days.

The product (0.3 g) was an impure mixture of trans-1-(phenylthio)-

3-acetoxyprop-lene (ca. 50%) and 5-(phenylthio)-3-acetoxyprop-1-ene

(ca. 20%).

(iv) With methanol (196)

(a) The chloride (0.4 g) when kept in methanol for 2 days at room

temperature gave 1,1-dimethoxy-3.:(phenylthio)propane (0.28 g)

which was purified by preparative t.l.c. (benzene). This com- 16 pound was unstable on standing, n 1.5360. (Found: C, 62.18; D H, 7.44; S, 15.32. C111116 02S requires C, 62.23; H, 7.60; S, 15.10%).

(b) The reaction was carried out in the presence of calcium carbonate,

using the same conditions and quantities. The product (0.2 g)

was an impure mixture of 1,1-dimethoxy-3-(phenylthio)propane

(ca. 30%), a trace (<5%) of trans 1-(phenylthio)-5-methoxyprop-

1-ene and some (<5%) 3-(phenylthio)-3-methoxyprop-1-ene.

(v) With sodium methoxide (192)

A solution of sodium (0.15 g) in methanol (30 ml) and the chloride

(0.7 g) when kept at room temperature for 2 days gave a mixture 150

(0.5 g) of 3-(phenylthio)-3-methoxyprop-1-ene and trans-1-(phenylthio)-

3-methoxyprop-1-ene which were separated by preparative t.l.c. (benzene). 3-(Phenylthio)-3-methoxyprop-1-ene (first fraction, 0.32 g) had v max

1100, 1130, 940 (=CH2 ) cm-1. (Found: C, 66.43; H, 6.67; S, 17.91%).

Trans-1-(phenylthio)-3-methoxyprop-1-ene (second fraction, 0.12 g)

had v max 1100, 1130, 960 cm-1 (trans olefin). (Found: C, 66.97; H, 6.69; S, 17.72%).

(vi) With sodium azide (198)

A mixture of the chloride (0.45 g) and sodium azide (0.4 g) in dry D.M.F. (30 ml) was kept at room temperature for 2 days to obtain trans-1-(phenylthio)-3-azidoprop-1-ene (0.38 g) which was purified by preparative t.l.c. (benzene). np17 1.6008, v max 2150, 960 (trans olefin) an-1. (Found: C, 56.61; H, 4.72; N, 21.61; S, 16.97.

C H N S requires C, 56.52; H, 4.74; N, 21.97; S, 16.76%). 9 9 3

(vii)With hydrochloric acid (203) ' Hydrochloric acid was bubbled through a solution of the chloride

(0.1 g) in dichloromethane (10 ml) for -about 5 minutes at room temperature. The solution was then left at room temperature for 2 days to obtain.1,3-dichloro-1-(phenylthio)propane (80 mg). This compound was unstable on a t.l.c. plate and could not be purified.

(viii)With lithium chloride (205) The chloride (0.4 g) and lithium chloride (0.3 g) were kept in acetone at 0o for 2 days. The trod= (0.31 g) was an impure mixture of cis and trans chlorides which were unstable and could not be purified. 151

Reaction of 1-(phenylthio)-3-chloroprop-1-ene(mixture of cis and

trans) with sodium azide

The above prepared chlorides (0.3 g) when treated with sodium

azide (0.3 g) in DMF gave a mixture of cis and trans 1-(phenylthio-3- 1 azidoprop-l-ene (0.27 g), v max 2150 cm .

Reactions of 2,4-dinitrophenylhydrazine

(i) With 1,1-dimethoxy-3-(phenylthio)propane (196)

The acetal (0:13 g) was added to a mixture of 2,4-dinitrophenyl-

hydrazine (0.3 g), conc. sulphuric acid (1 ml) and ethanol (7 ml).

The mixture was stirred'at 40° for 4-5 hours. The yellow solid was

then filtered and washed with hot ethanol to give 3-(phenylthio)

propionaldehyde 2,4-dinitrophenylhydrazone (0.145 g). It was recrys-

tallized from chloroform-petroleum and had m.p. 126-127° (lit.71; 126°)

(ii) With 1-(phenylthio)-3-acetoxyprop-1-ene (cis) (200)

The acetate (0.15 g) when treated with 2,4-dinitrophenyl hydrazine

(0.3 g), as mentioned above for the acetal, gave 3-(phenylthio)propion-

aldehyde 2,4-dinitrophenylhydrazone (0.14 g). It was recrystallized

from chloroform-petroleum and had m.p. 122-126°.

(iii) With the mixture of trans-l-(phenylthio)-3-acetoxyprop-1-ene and

3-(phenylthio)-3-acetoxyprop-1-ene (199)

The crude product (0.4 g) obtained from the reaction of the chloride

with potassium acetate, when reacted with 2,4-dinitrophenylhydrazine

(0.4 g) gave an oily red solid which was chromatographed (chloroform)

to obtain 3-(phenylthio)propionaldehyde 2,4-dinitrophenylhydrazone

(0.110 g) m.p. 125-127° 152

(iv) 1-(Phenylthio)-3--methoxyprop-1-ene(trans) (204)

The methyl ether (0.1 g) gave a red solid which was chromatographed

(chloroform) to obtain 3-(phenylthio)propionaldehyde 2,4-dinitrophenyl-

hydrazone (55 mg), m.p. 126-128°.

(v) With 3-(phenylthio)-3-methoxyprop-1-ene (204)

The methyl ether (0.36 g) gave a red solid which was chromatographed

(chloroform) to obtain 3-(phenylthio)propionaldehyde 2,4-dinitrophenyl-

- hydrazone (0.22 g), m.p. 126-128°.

(vi) With 1-(phenylthio)-3-chloroprop-1-ene(trans) - (206)

The chloride (0.2 g) gave a viscous red oil which was chromato-

graphed (chloroform) to obtain 3-(phenylthio)propionaldehyde 2,4-

dinitrophenylhydrazone (0.1 g), m.p. 124-128°. 153

3-(p-Nitrophenylthio)allyl alcohol and its derivatives

The n.m.r. spectra of the compounds are given on page 105.

p-Nitrothiophenol (209)

This was prepared by the reaction of L-nitrochlorobenzene_with

sodium disulphide in ethanol . It was recrystallized from chloro-

form-petroleum and had m.p. 75-78° (lit., 750).

3-(p-Nitrophenylthio)ally1 alcohol and 2-(p-nitrophenylthio)ally1

alcohol (208, 210)

7Nitrothiophenol'(15.5 g) was added, in 12 hours, to a stirred

mixture of propargyl alcohol (7.5 g) and powdered potassium hydroxide

(0.25 g) at 130°, under nitrogen. Stirring was continued for 22 hours

and then the mixture was cooled to room temperature and extracted with

ethyl acetate. The organic layer was washed with 2N sodium hydroxide,

water and dried. Evaporation of the solvent gave a black oil (14 g)

which was chromatographed (benzene-ethyl acetate, 4:1). 2-(p-Nitro-

ylenylthio)allyl alcohol(first fraction, 2.4 g) when crystallized .

from ether-petroleum had m.p. 39-42.5°, v max (CHC1 ) 3400, 930 (=CH ) 3 2 cm 1, T 1.89(d; 2H, aromatic), 2.57(d; 2H, aromatic), 4.20(t; 1H, J,

1.5), 4.29(t; 1H, J, 1.2), 5.81(broad s; 2H, CH2OH), 7.18(broad s;

1H, OH). (Found C, 50.98; H, 4.29; N, 6.64; S, 14.98. C H NO S 9 9 3 requires C, 51.17; H, 4.29; N, 6.63; S, 15.18%). Cis-3-(p-nitrophenyl-

thio)allyl alcohol (second fraction, 7 g) when crystallized from ether-

petroleum had m.p. 60-67° (contained <5% of trans isomer), v max(CHC13)

3400 cm-1. (Found: C, 51.05; H, 4.37; N, 6.54; S, 15.39%).

1-(p-Nitrophenylthio)-3-acetoxyprop-1-ene (cis) (211)

Cis-3-(11:-nitrophenylthio)ally1 alcohol (0.18 g) in pyridine (5 154

was treated with acetic anhydride (1 ml) to give the cis acetate (0.14 g).

It was purified by preparative t.l.c. (benzene)and crystallized from

ether-petroleum, m.p. 58.5-60°, v max 1740 cm-1. (Found: C, 52.03;

H, 4.32; N, 5.52; 5,.12.64. C H N04S requires C, 52.16; H, 4.38; 11 11 N, 5.53; S, 12.66%).

1-(p-Nitrophenylthio)-3-methoxyprop-1-ene (cis) (212) •

Cis-3-(P-nitrophenyl-thio)ally1 alcohol (0.18 g) in THE (30 ml) •

when treated with dimethyl sulphate (0.4 ml) in the presence of

powdered potassium hydroxide (0.4 g) gave the cis methyl ether

(0.16 g) which was purified by preparative t.l.c. (benzene). (Found:

C, H, 4.92; N, 6.31; S, 14.22. C H NO S requires C, 53.07; 10 11 3 53.32; H, 4.92; N, 6.22; S, 14.23%). -

1-(p-Nitrophenylthio)-3-methanesullohonyloxyprop-1-ene (213)

(a) A solution of methanesulphonyl chloride (0.25 g) in dichloromethane

(10 ml) was added, dropwise, to a stirred mixture of cis-3-(2-

nitrophenylthio)ally1 alcohol (0.42 g) and triethylamine (0.3 g)

in dichloromethane (25 ml) at 0°. Stirring was continued for 1

hour and then the mixture was washed with a cold solution of 2N

hydrochloric acid, then with water and dried. Evaporation of

the solvent at 0° gave a yellow oil (0.45 g) which in 1-2 minutes

became black. In subsequent preparations the solution was con-

centrated to about 4-5 ml and the resulting solution was used

for displacement reactions.

(b) Methanesulphonyl chloride (25 mg) in deuteriochloroform (2 ml) was added, dropwise, to a stirred mixture of the alcohol (43 mg) o and triethylamine (30 mg) in deuteriochloroform (4 ml) at 0 . 155

Stirring was continued for 20 minutes then the mixture was worked o up. The solvent was concentrated to about 0.5 ml at 0 and the

n.m.r. spectrum was immediately recorded on this solution.

1-(p-Nitrophenylthio)-3-chloroprop-1-ene (214)

A mixture of cis-3-(2-nitrophenylthio)ally1 alcohol (0.211 g) and

triethylamine (0.15 g) in dichloromethane was treated with methanesul-

- phonyl chloride (0.126 g) at'room temperature. The mixture was left

for 20 hours and then worked up to obtain a mixture (0.2 g) of cis and

trans chlorides (ratio ca. 1:1). It was recrystallized from dichloro-

methane-petroleum and had m.p. 85-94°. (Found: C, 47.29; H, 3.60;

N, 6.08; Cl, 15.14. C9H8NC102S requires C, 47.06; H, 3.51; N, 6.10;

Cl, 15.43%).

Reactions of 1-(p-nitrophenylthio)-3-methanesulphonyloxyprop-1-ene

The freshly prepared solution of the methanesulphonate in

dichloromethane (<5 ml) was used for all of the following reactions.

The products were identified by their n.m.r. spectra given on page 106.

(i) With acetic acid (219)

A solution of the methanesulphonate (ca. 0.15 g) and acetic

anhydride (1 ml) in acetic acid (20 ml) was kept at room temperature

for 24 hours to obtain trans-1-(p-nitrophenylthio)-3-acetoxyprop-1-ene

(0.14 g). It was purified by preparative t.l.c. (benzene) and then

crystallized from ether-petroleum; it had m.p. 60-62°, v (CHC1 ) max 3 1740, 960 (trans olefin) cm-1. (Found: C, 52.07; H, 4.47; N, 5.49;

S, 12.40. C fi N04S requires C, 52.16; H, 4.38; N, 11 11 5.53; S, 12.66%).

(ii) With potassium acetate (220)

• A mixture of the methanesulphonate (ca. 200 mg) and potassium

acetate (300 mg) in acetic anhydride (25 ml) was kept at room tem- 156

perature for 24 hours. The product (190 mg) was an impure mixture of trans-1-(E7nitrophenylthio)-3-acetoxyprop-1-ene and 3-(27nitrophenyl- thio)-3-acetoxyprop-1-ene (ratio 1:2). The latter was very unstable and when an attempt was made to isolate it by preparative t.l.c.

(benzene) only a small amount (40 mg, first fraction) was obtained and this was contaminated with some decomposition impurities. On a second attempt to purify this acetate by t.l.c., it completely decomposed. The trans acetate ,(60 mg, second fraction) was purified by preparative t.l.c. (benzene), and showed v max 1740, 960 (trans 1 cm l ..

(iii) With tetramethylammonium acetate (221)

A mixture of the methanesulphonate (ca. 0.2 g) and tetramethylammonium acetate (0.3 g) in acetone (25 ml) was kept at room temperature for 24 hours. The product was a mixture (190 mg) of cis-142.- nitrophenylthio)-3-acetoxyprop-1-ene and 3-(27nitrophenylthio)-3- acetoxyprop-1-ene (ratio 3:1).

(iv) With methanol (216)

A solution of the methanesulphonate (ca. 0.15 g) in methanol

(20 ml) was kept at room temperature for 24 hours. The product

(0.12 g) was a mixture of 3-(2-nitrophenylthio)-3-methoxyprop-1- ene (about 75%) and 1-(27nitrophenylthio)-3-methoxyprop-1-ene (mixture of cis and trans, 25%).

(v) With sodium methoxide (227)

A solution of sodium (0.15 g) in methanol (30 ml) and the methanesulphonate (ca. 0.65 g) was kept at room te:nerature for 24 hours. The product (0.60 g) was a mixture of 3-(E7nitrophenylthio)-3-methoxyprop-

1-ene and 142-nitrophenylthio)-3-methoxyprop-1-ene which were separated 157

by preparative t.l.c. (benzene). The second fraction, 1-(-nitro-

phenylthio)-3-methoxyprop-1-ene (mixture of cis and trans, 0.11 g) -1 had v 1100, 960 cm (trans olefin). (Found: C, 53.07; H, 4.91; max N, 6.13; S, 14.45. C10H11NO3S requires C, 53.32; H, 4.92; N, 6.22; S, 14.23%). 3-(p-Nitrophenylthio)-3-methoxyprop-1-ene (first fraction,

0.4 g) had v max1100, 940 (=CH2) cm 1. (Found: C, 53.23; H, 4.67; N, 6.14; S, 14.73%). This compound when exposed to air for 5-7 days 1640, 1110, 960 was Converted into a product (0.21 g) which hadv- max -1 cm , T 1.87(d; 4H, aromatic), 2.65(d; 4H, aromatic), 3.42(d; 1.2H, J, 1.2 Hz), 3.92(d; 0.8H, J, 6 Hz), 5.17(two t; 1.2H, J, 12 and 7.5), 5.50(two t; 0.8H, J,'6 and 7.5), 6.2-6.5(m, 4H), 6.30(s, 2.4H, OMe),

6.45(s, 3.6H, OMe). It solidified on standing, and when recrystallized

from ether-petroleum had m.p. 45-60° (pure by t.l.c.). (Found: C,

53.14; H, 4.76; N, 6.24; S, 14.61. Calc. for C1oH11NO3S C, 53.32; H, 4.92; N, 6.22; S, 14.23%). Mass spectrum 17) (relative intensity), 71(100), 91(60), 108(25), 155(30), 225(30), 308(26). Recrystallization

was repeated three times and the product (30 mg) had m.p. 56-60°, -1 v max 1640, 1110, 960 cm , T 1.87(d; 4H, aromatic), 2.65(d; 4H, aromatic), 3.42(d; 2H, J, 12), 5.17(two t; 2H, J, 12 and 7.5), 6.2-6.5(m, 4H), 6.45(s, 6H, OMe), MW=258 (by Vapour Pressure Osmometer,

solvent CHC1 ). 3 (vi) With sodium azide (222)- The methanesulphonate (ca. 0.3 g) and sodiuM azide (0.3 g) were

stirred in DMF at room temperature for 24 hours. Cis-1-(p-Nitrophenyl- thio)-3-azidoprop-1-ene (0.2-g) was obtained which was purified by

-1. (Found: C, 45.70; preparative t.l.c. (benzene), v max 2120 cm H, 3.45; N, 23.95; S, 13.72. C9H8N402S requires C, 45.75; H, 3.41; N, 23.71; S, 13.57%). 158

Reactions of 1-(p-nitrophenylthio)-3-chloroprop-1-ene

(i) With methanol (215)

The chloride (60 mg) when kept in methanol (15 ml) for 2 days at

room temperature gave a mixture (40 mg) of.3-(p-nitrophenylthio)-3-

methoxyprop-1-ene (ca. 50%) and 1-(1.-nitrophenylthio)-3-methoxyprop-1- ene (50%, mixture of cis and trans isomers).

(ii) With sodium methoxide (215)

A solution of sodium (25 mg) in methanol (20 ml) and the chloride

(60 mg) when kept at room temperature for 2 days gave a mixture (45 mg)

of 3-(2.7nitrophenylthio)-3-methoxyprop-1-ene (ca. 65%) and 1-(27

nitrophenylthio)-3-methoxyprop-1-ene (ca. 35%, mixture of cis and trans

isomers).

Control reaction (218)

A mixture of cis-1-(2-nitrophenylthio)-3-methoxyprop-1-ene (80 mg)

and methanesulphonic acid (2 drops) in methanol (20 ml) was kept at

room temperature for 2 days. The product (70 mg) was a mixture of cis

and trans isomers (ratio 3:2). 159

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