Organic compounds of sulphur, selenium, and tellurium vol 2

Contents Chapter 1 Aliphatic Organo-sulphur Compounds, Compounds with Exocyciic Sulphur Functional Groups, and their Selenium and Tellurium Analogues phosphorus, and Organotin Compound

A Specialist Periodical Report

Selenium, and Tellurium

Senior Reporter

D mHI Reid, Department of Chemistry, The University, St Andrews

Reporters

G C Barrett, Oxford Polytechnic

R J S Beer, The University of Liverpool

F DUUS, Odense University, Denmark

S Gronowitz, University of Lund, Sweden

A Wm Johnson, University of North Dakota, U.S.A

D N Jones, The University, Shefleld

F Kurzer, Royal Free Hospital School of Medicine, University of London

G Prota, University of Naples, Italy

@ Copyright 1973

The Chemical Society

Burlington House, London, W I V OBN

ISBN : 0 85186 269 1 Library of Congress Catalog Card No 77-23818

Organic formulae composed by Wright's Symbolset method

PRINTED IN GREAT BRITAIN BY JOHN WRIGHT AND SONS LTD., AT THE STONEBRIDGE PRESS, BRISTOL

Preface

The aims and structure of this second Volume of ‘Organic Compounds of Sulphur, Selenium, and Tellurium’ remain those set out in the Preface to Volume 1

Two changes in the coverage are announced First, a review of the Theoretical Aspects of Organosulphur, Organoselenium, and Organo- tellurium Compounds has been omitted from this volume A review of the

subject, covering the four-year period beginning April 1970, will appear in

Volume 3 Secondly, an extended chapter on the chemistry of Thiophen and Related Compounds, which could not be reviewed in time for inclusion

in Volume 1, takes its place in this volume, and covers the three-year period April 1969 to March 1972 Reviewing of all other material covered

in this volume is for the two-year period April 1970 to March 1972

D H R

Contents

Chapter 1 Aliphatic Organo-sulphur Compounds, Compounds

with Exocyciic Sulphur Functional Groups, and their Selenium and Tellurium Analogues

phosphorus, and Organotin Compounds 8

Addition of Thiols to Multiple Bonds

Protection of SH Groups in Synthesis

Spectroscopic and Related Properties of Thiols

Reactions of Thiols with Organoboron, Organo-

Reactions of Unsaturated Sulphides

Skeletal Rearrangements of Unsaturated Sulphides

Naturally Occurring Organo-sulphur Compounds

vi Contents

5 Sulphoxides

Preparation

Spectroscopic Properties of Sulphoxides

Resolution and Racemization of Sulphoxides

7 Sulphenic Acids and their Derivatives

Sulphenic Acids and Sulphenate Esters

Sulphenamides

Sulphenyl Halides

Sulphenyl Protecting Groups

8 Thiocyanates and Isothiocyanates

Sulphonamides and Related Compounds

11 Disulphides, Trisulphides, and their Oxy-sulphur Analogues

Preparation of Disulphides, Hydrodisulphides, and Oligosulphides

By Intramolecular Displacement Reactions

By Cycloadditions involving Thiocarbonyl Com- pounds

By Cycloadditions involving Sulphenes

BY Cvcloadditions involving Thiet 1.1-Dioxides

9 Structure and N.M.R Properties of Thietan Derivatives

10 1,3=Dithietans and 1,3-Diselenetans

11 1,ZThiazetidines

12 1,3-Thiazetidines and 1,2,3-0xathiazetidines

13 1,2-Oxathietans and 1,2,3-Dioxathietans

Chapter 3 Saturated Cyclic Compounds of Sulphur and

Properties and Reactions

Oxides and Dioxides

Sulphimides and Sulphoximides

2 Compounds with Two Sulphur or Selenium Atoms in the Ring; their Oxy-sulphur Analogues

Cyclic Disulphides and Cyclic Diselenides

Formation Properties and Reactions Analogues

Formation Properties and Reactions

1 ,5-Dithiocans Formation

1,3-Dithiolans, 1,3-Dithians, and their Selenium

1,4-Dithians, 1,4-Diselenans, 1,4-Dithiepans, and

Pronerties and Reactions

3 Compounds containing Three or More Sulphur Atoms

4 Compounds containing Sulphur or Selenium and other

Penicillins, Cephalosporins, and Related Compounds 191

Chapter 4 Thiocarbonyl, Selenocarbonyl, and Tellurocarbonyl

Sulphines Sulphenes Thioamides Derivatives of Thioamides Thioureas

Thiono- and Dithio-acids and Derivatives Selenocarbonyl Compounds

0 ther Physical Properties

Chapter 5 Ylides of Sulphur, Selenium, Tellurium, and

Reactions of Sulphonium Ylides

Sulphonium Ylides as Reaction Intermediates

3 Oxysulphonium Ylides

Synthesis and Properties

Reactions of Oxysulphonium Ylides

5 Four- and Five-membered Ring Compounds

Chapter 7 Thiophens and their Selenium and Tellurium

Application of the Hammett Equation

The Structures and Reactions of Hydroxy- and Mercapto-thiophens and their Simple Derivatives Side-chain Reactivities

Rearrangement Reactions

Biheterocyclics

Thiophen Analogues of Porphyrins

Reactions at the Thiophenic Sulphur

Polymers from Thiophen Derivatives

Naturally Occurring Thiophens

Thiophens of Pharmacological Interest

Thiophen Derivatives of Analytical Interest

3 Thienothiophens, their Benzo-derivatives, and Analogous Compounds

Synthesis

Theoretical Studies and Physical Properties

Substitution Reactions

Non-classical Thienothiophens

4 Benzothiophens and their Benzoannelated Derivatives

Synthesis of Benzothiophens by Ring-closure Re- Theoretical Studies and Physical Properties

Thiophen Analogues of Anthracene

Thiophen Analogues of Phenanthrene

Thiophen Analogues of Helicenes

Thiophen Analogues of Fluorene

Thiophen Analogues of Tropylium Ions and Related Miscellaneous Thiophen Analogues of Polycyclic Compounds

xiv Contents

478

Thiophen Analogues of Isoquinoline and Related

0 ther Pyridine-fused Thiophen-con t aining Sy s terns

7 Thiophens Fused to Rings containing Two Nitrogens 480

Pyrazole- and Imidazole-fused Systems 480

Miscellaneous Rings containing Several Nitrogens 485

8 Miscellaneous Fused Systems

Thiazole-fused Systems

Pyrylium-fused Systems

Thiapyrylium-fused Systems

Other Fused Systems

9 Selenophens and Tellurophens

2 Structural and Theoretical Studies 497

3 Synthesis, Properties, and Reactions of 6a-Thiathio-

4 Compounds Structurally Related to 6a-Thiathiophthen 505

Chapter 9 1,2- and 1,3-Dithioles

Contents

3 1,ZDithiolium Salts

4 1,3-Dithioles and Related Systems

Chapter 10 Thiopyrans and Related Compounds

6 Thiochromans and Related Compounds

7 Thio- and Seleno-coumarins

8 2-Thioisocoumarins, Dithioisocoumarins, and Related Compounds

9 Thioxanthones, Selenoxanthones, and Related Com- pounds

10 Peri-Fused Naphthothiopyrans

11 Complex Thiopyran and Selenopyran Derivatives

Chapter 11 Thiepins and Dithiins

By D H Reid

1 Thiepins

2 Dithiins

1 ,ZDithiins

1,4-Dithiins and 1,4-Diselenins

Benzo- and Dibenzo-l,4-dithiins

From Chlorosulphonyl Isothiocyanates and Olefins From a-Amino-ketones or fl-Cyano-enamines and

(Type B) From 3,3’-Dit hiodipropionamides (Type C)

From Phenylcysteine (Type C)

From Vilsmeier Salts (Type C)

From 1,2-Dithiolans (Type C)

From Thiazoles

3 Physical Properties

4 Chemical Properties

Free-radical and Photolytic Reactions

Nitration and Halogenation

Diazo tizat ion

Metallation

Miscellaneous Substitution Reactions (mostly

Nucleophilic Ring Cleavage

S-Oxides and -Dioxides

Complexes

Some Biological Properties

Conversion into 1,2,3-Thiadiazoles

Nucleophilic) Base-catalysed Dimerization

5 Condensed Ring Systems

2,l -Benzisothiazoles

Synthesis Electrophilic Substitution Synthesis

Mass Spectra Chemical Properties Nucleophilic Substitution and Ring Fission Complexing

Hantzsch’s Synthesis (Type A, S-C-N + C-C)

Other Type A (S-C-N + C-C) Syntheses

2-Thiazoline Pep t ides

Acid Cyclic)

From Thiirans From 1,4-Thiazines by Ring Contraction From Thiocarbonylamino-acid Silyl Esters From Enamines and Mercaptocarboxylic Acids From Keten, Carbodi-imide, and Sulphur Dioxide Physical Properties

Synthesis from Quinones and Thioureas 658

Michael Reaction Azido benzo thiazoles Acylation

Alkylation and Acylation by Free-radical Re- actions

Alkylation and Arylation Acylation

Heterocyclic Carbenes Nucleophilic Substitution Silyl benzothiazoles Polymethine Dyes Polymers

Metal Complexes Biochemical Aspects Physiological Activity Condensed Ring Systems Benzoselenazoles

2 Structures Comprising Two Five-membered Rings (5,5)

Thiazolo[4,3-b] benzot hiazoles

Thiazolo [3,2-a]pyrrolo [2,3-d]pyrimidines

6 Structures Comprising One Five-membered and Two Six-membered Rings (5,6,6)

[ 1,3]Thiazino [2,3-b] benzo thiazoles

Pyrimido [2,1 -b] benzot hiazoles

0 ther React ions Properties

From Thiocarbonohydrazide From Thiosemicarbazides and (Thio)phosgene Oxidation of Thiosemicarbazones

Syntheses from Dithiocarbazates Synthesis from Acylhydrazines Synthesis from 1 -Thiocyanato-2,3-diazabuta- 1,3- dienes

Mesionic 1,3,4-Thiadiazoles

Chemical Properties

Synthesis Properties 1,3,4-Thiadiazoio [3,2-a]pyridines 1,3,4-Thiadiazolo [3 ,Za]pyrimidines

7 1,2,5-Selenadiazole and Condensed Ring Systems 756

1,2,5-SeIenadiazolo[3,4,-b(and c)]pyridines 756 Naph t ho [2,3 -d]-2,1,3 -selenadiazole 757

Introductory Review

Important general principles concerning the structure of aliphatic organo- sulphur compounds have been surveyed (I, 18-20).* The essentials of

of experimental data on bivalent sulphur compounds (I, 18) Structural consequences of interactions between lone pairs or between lone pairs and polar bonds have been outlined Preferred conformations for a-sulphonyl, a-sulphinyl, and m-sulphenyl carbanions are those involving maximum gauche interactions of the pyramidal carbanion with the lone pairs on sulphur or with S-0 polar bonds The skew conformation of the disul- phide grouping is an example of gauche lone pair-lone pair interactions General reinforcement is given to the idea that the disposition of d-orbitals does not determine conformational preferences Understanding of these interactions will assist the interpretation of physical and chemical pro- perties of organosulphur compounds and their oxygen and nitrogen analogues Stereochemical reaction cycles involving sulphoxides, sul- phimides, and sulphoximides (I, 317, 318) and for sulphinimides and

related compounds (I, 527) have filled gaps in sulphur functional group

chemistry and provided new knowledge of the stereochemical aspects of reactions at a sulphur atom in general The high affinity of both phos- phorus and boron for sulphur can result in extrusion of sulphur from a variety of compounds on treatment with tervalent phosphorus and boron compounds The oxathiolan-5-one obtained by treatment of thiobenzilic acid with benzaldehyde or a ketone loses carbon dioxide and sulphur when warmed with tris(diethy1amino)phosphine to give 1,l -diphenylalkenes ( I ,

60) The same reagent converts cystine derivatives into lanthionines (I,

123), while triethylphosphine converts disulphides (R-S-S-But) into sulphides (R-S-Et) (I, 124) Trialkylboranes show synthetic pos-

sibilities, converting disulphides into sulphides in free-radical chain reac- tions (I, 120) Thioboranes have been used to transform a sulphenate

ester into an unsymmetrical sulphide (I, 122), and aldehydes and ketones

into the corresponding thioacetals and thioketals (I, 217, 218)

Interest in small-ring organosulphur compounds has in the past received much impetus from the synthetic potential attending the loss of sulphur or its oxides from compounds to furnish olefins, acetylenes, or cycloalkanes, and a recent, elegantly conceived, potential synthesis of highly hindered

* Italicized numerals in brackets refer to chapter numbers, ordinary numerals to reference numbers

xxvi Introductory Review

olefins involves the desulphurization by tervalent phosphorus compounds

of thiirans formed in situ from dihydrothiadiazoles (2, 4, 5 ) or 1,3-oxa- thiolan-5-ones (2, 5) Thermal loss of sulphur dioxide from thiiran 1,l -dioxides to give olefins, well documented and exploited synthetically, did not occur in some exceptional cases (2, 36, 38), fission of the thiiran carbon-carbon bond occurring instead The recently synthesized phenyl- and alkyl-substituted thiiren 1,l-dioxides (2, 40, 41) and diphenylthiiren

1 -oxide (2, 42) displayed remarkable thermal stability when compared

with their saturated analogues, and diphenylthiiren 1-oxide was more stable than the corresponding dioxide Interest in the reactions and elec- tronic structure of these interesting heterocycles will doubtless develop rapidly The carefully investigated thermolysis and photolysis of thietan 1,l-dioxides (2, 62, 63, 82, 84, 89, 90) and thiet 1,l-dioxides (2, 82) occurs non-stereoselectively and gives mixtures of products, but the stereo- specificity of butyl-lithium-induced fragmentation of thietanium salts

(2, 63) and of the base-catalysed isomerizations of 2,4-diphenylthietan

1-oxide (2, 96) and the corresponding dioxide (2, 96, 98) are interesting

developments which should receive stimulation from the ready availability

of thietan systems by a variety of synthetic routes

Stereochemical aspects of organosulphur chemistry are investigated most conveniently with saturated cyclic compounds, and in this area the role of sulphinyl oxygen in thian 1-oxides (3, 90), cyclic thiolsulphinates

(3, 125, 126), cyclic sulphinates (3, 125, 221), and cyclic sulphites (3, 177,

258-270) in determining the conformational behaviour of compounds containing these groups has been elucidated Investigations of the con- figurational integrity of sulphur-stabilized carbanions in cyclic sulphonium salts (3, 63, 64), 1,3-dithians (3, 146), lY3,5-trithians (3, 205), cyclic sul-

phoxides (3, 108), cyclic sulphones (3, 107), and cyclic sulphonates (3, 228)

have made important contributions to this developing area, the salient features of which have been discussed in a significant paper (3, 191) The exploitation of the synthetic versatility of substituted 1,3-dithians should receive further impetus from the recent availability of methods for their

formation (3, 130), utilization (3, 147-152), and hydrolysis (3, 157-161), whilst the cheletropic loss of sulphur dioxide on heating 3-thiabicyclo- [3,1 ,O]hexane 3,3-dioxide derivatives and related 6-oxa- and 6-aza- analogues leads stereospecifically to 1,5-dienes, substituted divinyl ethers, and substituted divinyl carbamates (3, 36, 110) The intermediacy of

sulphenic acid derivatives in the rearrangement of penicillin sulphoxides

to deacetylcephalosporins, and in the thermal stereomutation of penicillin

sulphoxides, has been elegantly demonstrated (3, 283-286) and skilfully exploited (3, 286-293)

Although thioaldehydes belonging to certain classes of heterocyclic compounds have been isolated and characterized (Volume 1, p 184), all attempts to prepare aliphatic thioaldehydes have so far proved unsuccessful However, monomeric thioformaldehyde has recently been generated at low

Introductory Review xxvii pressure in a radiofrequency discharge tube by the reaction of methane with small sulphur-containing molecules, such as carbon disulphide and hydrogen sulphide (4, 25), or by the reaction of dimethyl sulphide with sulphur hexafluoride (4, 26) Thioformaldehyde thus produced has a

half-life of a few minutes Cleavage of a/3-unsaturated sulphides with alkali metals in liquid ammonia produces enethiols, the tautomeric forms

of aliphatic thioaldehydes and thioketones (4, 2, 21) The enethiol tauto- mers of thioaldehydes are stable and show no tendency to tautomerize spontaneously, but with base they form high-boiling polymers Thioketone enethiols equilibrate spontaneously with the thiocarbonyl form Metal complexes of thiocarbonyl compounds are the subject of growing interest Two of the more interesting reactions involve the trapping of unstable

thioaldehydes as their nickel(rz) complexes (4, 32, 33) Theoretically and

mechanistically significant is the reaction of thiobenzophenone with Grignard and organolithium reagents (4, 84) The direction of addition is the opposite to that taken by benzophenone Thus phenyl-lithium gives benzhydryl phenyl sulphide Monomeric thioketens are unstable com- pounds, and most of the literature has been concerned with these com- pounds as transient intermediates Raasch (4, 6) now describes the stable

bis(trifluoromethyl)thioketen, an orange-red liquid obtained by thermolysis

of its dimer It undergoes a variety of cycloaddition reactions involving the thiocarbonyl function The first stable thiocarbonyl ylides have been isolated (4, 126) from the reaction of 1,2-dithiole-3-thiones with bis-

(toluene-psulphony1)diazomethane The intermediacy of thiocarbonyl

ylides had previously been deduced (4, 124, 125) from the formation of cycloaddition products during the thermal decomposition of 1,3,4-thia- diazolines in the presence of diethyl azodicarboxylate and dimethyl acetylenedicarboxylate Sulphenes are very reactive species and have hitherto escaped detection Flash thermolysis of chlorosulphonylacetic

acid has now been shown to give sulphene, which was trapped at - 196 "C

(4, 132) and characterized by its i.r spectrum and by its reaction with hydrogen chloride to form methyl sulphonyl chloride

Application of the sulphonium salt ligand-exchange reaction to sul-

phonium ylide synthesis provides a route (5, 13-17) to diphenylsul- phonium ylides which possess some advantages over the more readily

available dialkylsulphonium ylides A major limitation in the use of

oxysulphonium ylides is the scarcity of ylides other than methylides Johnson (5, 72) has now devised a high-yield synthesis of phenyldimethyl- amino-oxysulphonium methylide potentially expandable for the prepara- tion of higher alkylides Data on the structure of iminosulphuranes come from X-ray crystallographic structure determinations of N-(toluene-p-

sulphonyl)iminodiphenylsulphurane, the corresponding dimethyl com- pound, and related structures (5, 146-149) A study of the reactions of

sulphoximine ylides (5, 145-147) suggests that these compounds have considerable potential for reactions requiring stereochemical control

xxviii Introductory Review

The key step in a new approach to thiabenzenes (6, 5 ) involves the reduction of the readily available thiabenzene 1-oxides (6, 6, 7) with tri- chlorosilane In contrast to earlier views on the structure of thiabenzenes and their 1-oxides (Volume 1, p 309), the results of recent lH n.m.r

spectroscopic studies and studies of the basicity of thiabenzenes and their 1-oxides are interpreted in terms of ylide.structures in which two orthogonal and non-conducting hybrid d-orbitals on positively charged sulphonium or oxysulphonium sulphur overlap weakly with the ends of the n-system of a pentadienyl carbanion (6, 5, 9) Cram (5, 10) has developed an elegant general synthesis of heterocyclic compounds containing the sulphoximine function as part of a ring, including 2,4-diazathiabenzene 1-oxides lH

n.m.r spectral studies indicate that ring-current effects do not operate significantly in these compounds

A large amount of work continues to be carried out on thiophen and

its derivatives Considerable progress has been made in the past few years

on the quantitative aspects of electrophilic substitution reactions of thiophens and benzothiophens, increasing our knowledge of the differences

in reactivity of five-membered heterocyclic compounds (7, 88, 362) The mechanism of the now celebrated photochemical rearrangement of mono-

and di-substituted thiophens has been elucidated by Wynberg (7, 146, 146a)

in terms of valence-bond isomerizations Thienyl-lithium derivatives continue to find use in the synthesis of otherwise inaccessible compounds, for example fluorothiophens (7, 59e, 96a), and the rings of 3-lithio-2- methyl-thiophen and -selenophen open spontaneously in boiling ether to give vinylacetylenes (7, 129-13 1) A detailed description of the synthesis

and physical and chemical properties of tellurophen has been published (7, 584)

It is now becoming evident that 6a-thiathiophthens comprise only one

of a potentially large number of structurally related heterocyclic systems Members of several of these systems have recently been synthesized and, in some cases, their structures determined by X-ray crystallography These include the 6a-selenathiophthens (8, 3 l), the 6a-selenaselenophthens (8, 33), isothiazolo[5,1 -e]isothiazoles (8, 40), dibenzo derivatives of 1,6-dioxa-6a- thiapentalene (8, 41, 42), 3,4-diaza-6a-thiathiophthens (8, 34, 3 9 , 1,6-

dioxa-6a-thia-2,5-diazapentalenes (8, 49), 1,6a-dioxa-6a-selena-2,5-diaza-

pentalenes (8, 46-48), 1,6-dioxa-6a-tellura-2,5-diazapentalenes (8, 46), and

6a-selena-1,2,5,6-tetra-azapentalenes (8, 46) Of especial interest theoreti- cally are two ‘extended’ 6a-thiathiophthens containing five sulphur atoms

(8, 28) The array of sulphur atoms in these compounds is nearly linear,

and the S - S distances fall into the range normal for 6a-thiathiophthens

(8, 16, 17) From the limited information available, position 3 in 6a-

thiathiophthen is more reactive than position 2 towards electrophiles; the results of theoretical studies agree with these experimental results

New, long-lived, sulphur-containing radicals based on the 1,3-dithiole system have been characterized spectroscopically (9, 29, 54), and in one

Introductory Review xxix

case (9, 55) a cation-radical salt was isolated Bis-thiopyrylium salts have also been obtained and reduced to stable cation-radical salts (10, 43) Thiepins are predicted to be antiaromatic (11, 2), and previous studies have shown that annelated thiepins extrude sulphur readily, doubtless by valence isomerization into benzene sulphides and cheletropic elimination

of sulphur Attempts to isolate simple thiepins not stabilized by conjuga- tion have been unsuccessful A stable thiepin has now been synthesized by

employing steric effects to prevent valence isomerization (If, 3) Interesting cycloaddition and electrocyclic reactions of thiepin derivatives are reported

Thermal cycloaddition of sulphur monoxide to cyclo-octatetraene leads to a

2,7-sulphur-bridged-2,7-dihydrothiepin which, when irradiated, produces thiabarbaralene (11, 5, 6) Addition of sulphur dioxide to vinyldiazo- methane gives initially a thiiran 1,l-dioxide which undergoes a Cope rearrangement into a 4,Sdihydrothiepin 1 ,I-dioxide (11, 7, 8)

The exploration of novel preparative routes commands much attention

in isothiazole chemistry Especially interesting are the reactions of 3-phenyl- 1,2,4-oxathiazol-5-one with acetylenic esters which afford isothiazoles in

high yield (12, 7) The reaction is envisaged as a 1,3-dipolar addition of

benzonitrile N-sulphide, produced as a transient intermediate, to the dipolarophilic dimethyl acetylenedicarboxylate or propiolic ester Iso- thiazoles are also produced by photoisomerization of thiazoles (12, 19)

Nitrenes may be implicated in the thermal decomposition of 2-azidoaryl

thioketones into benzoisothiazoles (12, 51)

A large volume of work continues to be published in the area of thiazole chemistry Physicochemical aspects continue to receive their share of attention, and interest in meso-ionic compounds has been sustained Asinger and Offerman’s versatile synthesis provides routes to reduced

thiazoles (13, 212-217) Other notable methods employ thiirans (13, 218,

219), thiocarbonylamino-acid silyl esters (13, 220), and enamines (13, 221)

as starting materials Reduced thiazoles play an important role in peptide and protein studies (13, 234-239), and generate interest because of their occurrence as structural units in compounds of physiological interest, such as the antibiotics bacitracin A (23, 147 - 149) and thiostrepton Benzothiazole derivatives have been employed to separate amidines for the

first time into their syn- and anti-isomers (14, 49) The reaction of citric

acid with penicillamine provides an interesting entry into the thiazolo-

[3,2-a]pyridine system (14, 152)

In the field of thiadiazole chemistry the study of meso-ionic compounds

stimulates interest (15, 98-1 13) The parent thiadiazoles have been

obtained for the first time only in recent years; they have now been joined

by 1,3,4-~elenadiazole (15, 120), whose physical properties have been compared with those of relevant analogues in studies of bonding in these systems The nature of the products formed in the photolysis of 1,2,3- thiadiazoles is accounted for in terms of a transient thiocarbene inter-

mediate (15, 10)

xxx Introductory Review

A number of mechanistically important papers have appeared which

deal with the deoxygenation of 2-nitrophenyl aryl suIphides with triethyl phosphite and the thermolysis of aryl 2-azidophenyl sulphides These reactions involve a novel molecular rearrangement and lead to pheno-

thiazines via nitrene intermediates Studies have now been made of sul-

phides in which the essential ortho-positions are blocked (16, 66, 67); hydroaromatic intermediates are involved In certain cases 1,sthiazepines result (17, 8, 9) The group of amphoteric pigments from red mammalian

hair and bird feathers that are known as trichosiderins have recently been shown to contain the hitherto unknown 2,2’-bi-(2W-l,bbenzothiazine)

chromophore, which arises biogenetically by a new metabolic pathway involving as the key step the 1,6-addition of cysteine to dopaquinone, produced by enzymic oxidation of tyrosine (17, 46-50)

electron nuclear double resonance

electron spin resonance

nuclear magnetic resonance

optical rotatory dispersion

parts per million

A I i p h ati c Organo-s u I p h u r Co m po u n ds,

Compounds with Exocyclic Sulphur Functional

Groups, and their Selenium and Tellurium

Analogues

BY G C BARRETT

1 General

For every literature report, describing a new detail of the properties of

sulphur functional groups, there now appears a matching publication in which an implication of new knowledge is followed through, enriching broad areas of organic synthesis and reaction mechanism This process, the putting to use of knowledge acquired for its own sake, is well illustrated

in the literature from which this Chapter is built

Text-books and Reviews.-Volumes 1-111 of a detailed coverage of sulphur chemistry augment the sparse textbook coverage in this field; analytical aspects are exhaustively covered.2

Reviews cover the topics : alkynethiolates in synthesis ;aa oxygen-exchange reactions of sulphoxides;3b sulphonyldiazomethanes ;3c C- S bond

~leavage;~" acyl isothio~yanates;~~ radical reactions of sulphur com- pounds;3f addition of sulphenyl halides to 01efins;~" s ~ l p h e n a r n i d c s ; ~ ~ mercaptoethylation of amines ;4c sulphur as a chiral centre ;6a stereo- chemistry of SV and Svl compounds ; 5 b reductive cleavage of sulphides, synthetic uses of alkene- and alkyne-thiolates, and thio-Claisen rearrange- ments;6C nucleophilic displacements at sulphur in disulphides ; 6 a aromatic

'Sulphur in Organic and Inorganic Chemistry', ed A Senning, Marcel Dekker, New York, 1971

e.g 'The Analytical Chemistry of Sulphur and its Compounds', ed J H Karchmer, Wiley, New York, 1972; 'Instrumental Methods of Organic Functional Group Analysis',

ed S Siggia, Wiley, New York, 1972

Quart Reports Surfur Chem., 1970, 5 ; (a) p 1, J F Arcns, L Brandsma, P J W Schuijl, and H E Wijers; (b) p 53, S Oae; (c) p 67, A M Van Leusen and J Strating;

( d ) p 125, R Mayer; (e) p 175, J Goerdeler; (f) p 305, W A Pryor, J P Stanley, and T.-H Liu

' Mech Reactions SuZfur Compounds, 1970,5; (a) p 87, D R Hogg; (b) p 93, C Brown and B T Grayson; (c) p 103, D L Johnson and D D Reynolds

Internat J Sulfur Chem., B, 1971,6; (a) p 65, C K Ingold; (b) p 69, K K Andersen;

(c) p 85, L Brandsma, P J W Schuijl, D Schuijl-Laros, J Meijer, and H E Wijers;

(d) p 103, J P Danehy; (e) p 123, H Cerfontain and C W F Kort; (f) p 137, F Montanari; (g) p 149, S Braverman; (h) p 159, J P Danehy; (i) p 177, I B Douglass

2 Organic Compounds of Sulphur, Selenium, and Tellurium

sulphonation ;5e neighbouring-group participation by sulphinyl oxygen ;sf

rearrangement of allylic sulphinates to sulphones, and related sigmatropic rearrangements ;58 conversion of thiols into disulphides via sulphenyl

iodides ;sh methanesulphenyl chloride as an electrophile;si nucleophilic attack at 6 b elimination and addition reactions of sulphur compounds;6c ~ynthesis,~" oxidation, reduction, and addition reactions of sulphenyl halides ; 7 b s 7c sulphonylnitrenes ;* protonation of sulphur functional groups ;9 synthesis of sulphinyl chlorides, solvolysis of organosulphur trichlorides, chlorinolysis of disulphides in AcOH or Ac20 ;lo insertion of

SO2 and SO, into metal-carbon bonds;ll free-radical addition of thiols

to unsaturated compounds ;12, l3 stereochemistry of polysulphides;l*

modification of -SH and - S - S - groupings in proteins;l6 broad possi- bilities of the use of organic sulphur compounds in synthesis.16

Spectroscopic studies (n.m.r., i.r., u.v., m.s.) of o-hydroxyphenyl alkyl sulphides, sulphoxides, and sulphones l7 have been reported, bringing together basic correlations, including hydrogen-bonding effects, into one review

Important general principles of structure have been surveyed,18-20

based on molecular orbital considerations The essentials of d-p, d-sp3, and d-d interactions have been set out, providing a background for the

interpretation of experimental data on bivalent sulphur compounds.18 Wolfe and co-workers l9, 2o have collected data from the literature con- cerning the conformations adopted by groupings in which lone pair- lone pair or lone pair-polar bond interactions may occur Preferred con- formations for a-sulphonyl-, -sulphinyl-, and -sulphenyl-carbanions,

R1-X- CH-R2, are those involving maximum gauche interactions of

the pyramidal carbanion with the S - 0 polar bond(s) or lone pairs on

sulphur; the skew conformation of the disulphide grouping is an example

of gauche lone pair-lone pair interactions There is a satisfying generality

to the principle (the stabilization of an axial l-hydroxy-group in a pyranose

Internat J Sulfur Chem., C, 1971, 6; (a) p 3, J L Kice; (b) p 17, D R Hogg and

P W Vipond; (c) p 41, C J M Stirling

' E Kuehle, Synthesis; (a) 1970, 561; (b) 1971, 563; (c) 1971, 617

R A Abramovitch and R G Sutherland, Fortschr Chem Forsch., 1970, 16, 1

G A Olah, A M White, and D H O'Brien, Chem Rev., 1970,70,561; G A Olah,

A T Ku, and J A Olah, J Org Chem., 1970,35, 3904, 3908

l o M.-L Kee and I B Douglas, Org Prep Procedures, 1970, 2, 235

l1 W Kitching and C W Fong, Organometallic Chem Rev., 1970, AS, 281 ; A Wojcicki,

Accounts Chem Res., 1971,4, 344

l2 K Griesbaum, Angew Chem Internat Edn., 1970, 9, 273

l 3 D I Davies, Chem SOC Special Publ., No 24, 1970, p 201

l4 R Rahman, S Safe, and A Taylor, Quart Rev., 1970, 24, 208

l6 A N Glazer, Ann Rev Biochem., 1970,39, 101

E Block, J Chem Educ., 1971, 48, 814

l7 A 0 Pedersen, G Schroll, S 0 Lawesson, W A Laurie, and R I Reed, Tetrahedron,

1970,26,4449

la D L Coffen, Records Chem Progress, 1969,30, 275

l9 S Wolfe, A Rauk, L M Tel, and I Z Csizmadia, J Chem SOC (B), 1971, 136

S Wolfe, Accounts Chem Res., 1972, 5 , 102

A lipha t ic 0 rgano -sulp h ur Compounds e t c 3 sugar - the ‘anomeric effect’ - is a further example), and for sulphur compounds it gives general reinforcement to the idea that the disposition

of d-orbitals does not determine conformational preferences

2 Thiols

Methods employed for the synthesis of new thiols RSH are mainly those which have already proved themselves The properties and reactions of compounds of this class are well documented, and although new data do not upset existing foundations, there are many points of interest

Preparation.-For those interested in the past, the report,21 that irradiation

(185 and/or 254 nm) of mixtures of CH,, C2H6, NHS, HaO, and H2S gives

cysteine and cystine, among other products, will give a basis for speculation

on developments in pre-biotic Earth history Among well-tried procedures, the preparation of naphthalene-2-thiol from 2-naphthol is notable; the thionocarbamate RO CS NMe,, obtained from the reaction of the phenol

with Me,N CS- C1, gives the thiol on pyrolysis.22

Routes of widest applicability involve nucleophilic displacement of halide or toluene-p-sulphonate, or disulphide cleavage, or the less widely used reduction of thione to thiol 2-Benzamido-2-mercaptopropionic acid

(1) has been prepared 23 from 2-phenyl-4-methyloxazol-5(4H)-one (2),

Me

SH

though the corresponding route from the thiazolone failed at the last

stepe4 The trifunctional grouping -NH-CR(S-)- CO- is a feature

of the structure of gliotoxin and related natural products (see Vol 1,

p 104) p-Chlorolactic acid serves as starting material for the synthesis of a-hydroxy-analogues of S-benzylcysteine ; reaction 25 with benzylmercaptan

is followed by debenzylation with Na-NH, in an efficient route to the mercapto-acid (3),26 and D- and L-isomers are available in this way.2s

ra M S Newman and F W Hetzel, Org Synthesis, 1971, 51, 139

23 1 D Rae and P M Pojer, Tetrahedron Letters, 1971, 3077

l4 I D Rae and B N Umbrasas, Austral J Chem., 1971, 24, 2729

D B Hope and M WBlti, J Chem SOC ( C ) , 1970,2475

M Wsilti and D B Hope, J Chem SOC (C), 1971,2326

4 Organic Compounds of Sulphur, Selenium, and Tellurium

3-Mercapto-4-phenylcyclobutene-1 ,2-dione (4) is even more acidic than its oxygen analogue (the latter has pK' = 0.37 k 0.04) but can be liberated from its pyridinium salt with conc hydrochloric as pale yellow crystals

P h

pyridine '

0

Nucleophilic replacement reactions (by AcS-, Ph- CO S-, MeS-, and

PhCH,S-) with methyl 0-toluene-p-sulphonyl-L-lactate and sodium L-2-chloropropionate give 2-acylthio- and 2-alkylthio-~-propionic acids and esters.28 Extensive racemization accompanies the use of excess thio- acetate or thiobenzoate, due to further S N ~ replacement reactions, as observed for LiAlH, reduction of ~-(2-methylthio)propionic acid or its methyl ester Diborane reduction gives optically pure ~-(2-methylthio)- propanol, however.28 This work28 includes a new synthesis of (+)-2-

mercaptopropionic acid, though by known methods, and establishes the

D configuration for this isomer

Adamantanone with PzS5 gives the corresponding thione, which can be

reduced to the thiol with sodium b o r ~ h y d r i d e ; ~ ~ success in this example should not be taken as an indication of a similar result in other cases, in gener a1

A simple method for reducing diselenides to alkylselenols RSeH by

warming with aq H3P02 at 80-100 "C gives high yieldsao Other cleavage reactions, exposing as a thiol group a sulphur atom that was present in some other form, include further details on the ring-opening of 4H- thiopyran-4-thiones by sulphide or hydroxide ions,31 the demonstration

of the existence of equal amounts of thiol and thiazoline isomers in solutions

of S-(2-aminoethyl)isothiowea at pH 4.2 [i.e (9, (6), and (7) in equilib-

r i ~ m ] , ~ ~ and some novel reactions of penicillin d e r i ~ a t i v e s ~ ~ - ~ ~ The epimerization at C(6) in penicillins (8) may be accounted for by /3-elimination,

giving (9), which gives back the epimer mixture in the reverse step,33

though enethiolate or enolate intermediates are alternative pos~ibilities,~~ with the enethiolate (10) as a likely intermediate in the conversion of a

O7 A H Schmidt, W Reid, P Pustolemsek, and H Dietschmann, Angew Chem Znternat Edn., 1972, 11, 142

as L N Owen and M B Rahman, J Chem SOC (C), 1971, 2432

J W Griedanus, Canad J Chem., 1970, 48, 3530, 3593

ao M Schmidt and H D Block, Chem Ber., 1970, 103, 3348

a1 J G Dingwall, D H Reid, and J D Symon, J Chem SOC ( C ) , 1971, 2412

32 M D Hallas, P B Reed, and R B Martin, Chem Comm., 1971, 1506

ss S Wolfe, W S Lee, and R Misra, Chem Comm., 1970, 1067

34 J R Jackson and R J Stoodley, J.C.S Perkin Z, 1972, 895

B G Ramsay and R J Stoodley, J Chem SOC ( C ) , 1971, 3859

Aliphatic Organa-sulphur Compounds etc 5

1,6-anhydro-3-deoxy-3-benzyl thio-p-~-al tropyranose (major product) and

1,6-anhydro-2-deoxy-2-benzylthio-/3-~-glucopyranose, the latter giving

2-thio-/3-~-glucopyranose through further reactions 36 (the benzylthio- sugars result from di-equatorial and di-axial epoxide ring-opening of a 2,3-epoxide, respectively) Complementary routes to 2-thio-~-glucose and -mannose3' involve addition of PhCH,SH to the olefinic double bond in

~-arabino-3,4,5,6-tetra-acetoxy-l -nitrohex- 1 -ene, in the presence of pyridine ;

elaboration of S-benzyl-1,2-O-isopropylidene-5-thio-~-xylose into I-thio- L-xylitol 38 illustrates the satisfactory removal of protecting groups, just the aspect of any synthesis of a multi-functional compound which must go

well to justify the route

The use of N-(benzoylthiomethy1)piperidine hydrochloride (1 2) as a

reagent for introducing a mercaptomethyl group into an active-methylene position has been d e m ~ n s t r a t e d ; ~ ~ dimedone gives (1 3) N-Methylation of sulphonamides is the net result of mercaptomethylation in this way followed

by reductive desulphurization using Raney nickeL3@

36 E Hardegger and W Schuep, Helv Chim Acta, 1970, 53, 951

37 P Wirz and E Hardegger, Helv Chim Acta, 1971, 54, 2017

38 P Wirz, J Stanek, and E Hardegger, Helv Chim Acta, 1971, 54, 2027

3a E E Smissman, J R J Sorenson, W A Albrecht, and M W Creese, J Org Chenr.,

6 Organic Compounds of Sulphur, Selenium, and Tellurium

A convenient synthesis 40 of benzene-l,2-dithiol (14), and another invol-

ving replacement of the NH2 group by SH to give the biologically impor-

tant 4-thiouridine and its analogues from cytidines (but in low yield)41

[e.g (1 5 ) + (1 6)] illustrate additional synthetic methods

+

KOH glyme I

Spectroscopic and Related Properties of Thio1s.-The n.m.r absorption of the thiol proton moves to lower field in the order PhCH2-SH, Ph,CH-SH,

Ph&* SH;42 corresponding hydrotrisulphides RSS- SH show the opposite

sequence,42 due to over-riding inductive and anisotropic effects within the cumulative sulphur chain

The ultraviolet c.d of 2-(R)-mercaptopropionic acid is dominated by the

n -+ v* Cotton effect (near 220 nm) of the carboxy-group, while the

S-methyl homologue shows, in addition to the positive n + (T* thioether Cotton effect at 238 nm, a weak negative c.d maximum at 271 nm, ascribed

to electrostatic coupling of the carboxyl and thioether t r a n ~ i t i o n s ~ ~

40 S Huenig and E Fleckenstein, Annalen, 1970, 738, 192

41 T Ueda, M Imazawa, K Miura, R Iwata, and K Odajima, Tetrahedron Letters,

1971, 2507

42 S Kawamura, T Horii, and J Tsurugi, Bull Chem SOC Japan, 1971, 44, 2878

P M Scopes, R N Thomas, and M €3 Rahman, J Chem SOC ((3, 1971, 1671