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A Specialist Periodical Report

Saturated Heterocyclic Chemistry
Volume 3

A Review of the Literature Published
during 1973
Sen ior Reporter

M. F. Ansell, Queen Mary College, London
Reporters
D. J. Maitland, University of Bradford
J. M. Mellor, University of Southampton
A. E. A. Porter, University of Stirling
B. Walker, Queen’s University, Belfast

0 Copyright

I975

The Chemical Society
Burlington House, London, W I V OBN.

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ISBN: 0 85186 562 3

Library of Congress Catalog Card No. 72-83454

Printed in Northern Ireland at The Universities Press, Belfast

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Fore word
The third volume of this Specialist Periodical Report reviews developments
in the field of Saturated Heterocyclic Chemistry for the period JanuaryDecember 1973. The format of the Report follows that of Volume 2,
except for the omission of the chapter on Medium-sized Rings. It is intended
to remedy this unfortunate omission by including a two-year Report (1973
and 1974) in Volume 4.
The production of this volume is due to the skill and patience with which
the contributors have compiled their Reports and the expert assistance of
the Chemical Society Editorial Staff. I express to all of them my sincere
thanks.
M. F. Ansell

April 1975

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Contents
Chapter I


Three-membered Rings

1

By D. /. Maitland

1 Introduction
2 Oxirans
Formation
Direct Insertion
Oxygen atom insertion
Carbon atom insertion
Cyclization of Halohydrin
Darzens Reaction
Metal-cata1y sed Epoxidation
Miscellaneous
Reactions
Ring-opening
Electrophilic
Nucleophilic
Dipolar cycloaddition
Rearrangement
Ring Retention
Miscellaneous
3 Aziridines
Format ion
Direct Insertion of Nitrogen or Carbon Atoms
Cyclization
Ring Contraction
Formation via Azirines

Reactions
Ring-opening
Electrophilic and nucleophilic
Dipolar cycloaddition
Rearrangement
Ring Retention

4 Thiirans
Formation
Carbon Atom Insertion
Sulphur Atom Insertion
Cyclization
Miscellaneous
Episulphoxides
V

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1
1
1
1
1
12
16
19
22
24
28
28

28
32
40
41
45
46

49
49
49
51
59
60
62
62
62
65
69

70
73
73
73
77
77
77
79


vi


Contents
Reactions
Ring-opening
Desulphurization
Ring Expansion
5 Rings containing More than One Heteroatom
Formation
Diaziridines
Oxaziridines
Azaphosphiridines
Thiadiaziridine 1,l-Dioxides
Reactions
Diaziridines
Oxaziridines
Thiadiaziridine 1,l-Dioxides

Chapter 2

Four-membered Rings
By B. 1. Walker

1 Introduction
2 Physical Methods
Magnetic Resonance
Miscellaneous
3 Formation
Oxetans
Cyclization
[2 21 Cycloaddition

Miscellaneous
Azetidines
Cyclization
12 21 Cycloaddition
Ring Contraction
Miscellaneous
Rings containing More than One Heteroatom
Cyclization
[2 21 Cycloaddition
Miscellaneous
4 Reactions
Oxetans
Ring-opening
Rearrangement
Miscellaneous
Azet idines
Ring-opening
Rearrangement
Miscellaneous

+

+
+

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80
80
81

82
82
82
82

84
84
85
85
85
87
90

92
92
92
92
94
94
94
94
96
99
100
100
103
112
113
117
117

118
121
122
122
122
125
126
127
127
128
131


vii

Contents

Chapter 3

Rings containing More than one Heteroatom
Ring-opening

136
136

Five- and Six-membered Rings and
Related Fused Systems

138


By A. E. A. Porter

1 Introduction
2 Conformational Analysis of Reduced Heterocycles
General
Oxygen-containing Rings
Nitrogen-containing Rings
Phosphorus-containing Rings
Sulphur-containingRings

138
138
138
139
144
151
154

General
Nitrones
Nitrile Imines
Nitrile Oxides
Nitrile Ylides
Azides and Diazoalkanes
Miscellaneous
[4 + 21 Cycloaddition
Oxygen-containing Rings
Nitrogen-containing Rings
Rings containing both Oxygen and Nitrogen


158
158
158
159
161
161
163
165
166
166
166
168
169

4 General Chemistry of Saturated Heterocycles
Oxygen containing Rings
Tetrahydrofurans
Dihydrofurans
Lactones
Miscellaneous Furanoid Derivatives
1,ZDioxolans
1,3-Dioxolans
Ozonides
Tetrahydropyrans
Dihydropyrans
Dihydropyrones
Fused Pyrans
1,ZDioxans
lY3-Dioxans
1,4-Dioxans

Miscellaneous

170
170
170
172
174
176
177
177
179
180
181
183
184
184
185
185
185

3 Cycloaddition Reactions
[3 21 Cycloaddition

+

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Contents


viii
Nitrogen-containing Rings
Pyrrolidines
Pyrrolidones
Dihydropyrroles
Pyrazolines
Imidazolines
Triazolines
Tetrazolines
Piperidines
Piperidones
Tetrahydropyridines
Dihydropyridines
Quinoline Derivatives
Isoquinoline Derivatives
Aza-steroids
Fused Systems
Hexahydropyridazines
Tetrahydr opyridazines
Dihydropyridazines
Cinnoline Derivatives
Phthalazine Derivatives
Pyrimidine Derivatives
Piperazines
Dihydropyrazines
Piperazinediones
Fused Pyrazines
1,2,4-Triazines
1,3,5-Triazines
Condensed Triazines

Tetrazines
Fused Tetrazines
Rings containing both Oxygen and Nitrogen
Isoxazole Derivatives
Oxazole Derivatives
Fused Oxazoles
Dioxazoles
Oxadiazoles
1,2-Oxazines
1,3-0xazines
Fused 1,3-Oxazines
1,4-0xazines
Dioxazines
Oxadiazines
Miscellaneous Fused Systems

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186
186
189
190
194
197
200
202
202
204
205
207

208
209
210
21 1
212
212
213
213
214
214
216
217
218
221
222
223
223
224
226
226
226
229
236
236
237
238
239
241
242
243

244
245


ix

Contents

Chapter 4 Bridged Systems
By 1. M. Mellor

248

1 Introduction

248

2 Physical Methods

248

3 Nitrogen Compounds
Synthesis
Mannich-type Reactions
Routes via Electron-deficient Nitrogen Species
Cycloadditions
Miscellaneous Reactions
Reactivity

254

255
255
256
257
264
266

4 Cryptates

272

5 Oxygen Compounds
Synthesis by Cycloaddition
Miscellaneous Syntheses

274
274
277

6 Sulphur Compounds

28 1
28 1
283

Synthesis by Cycloaddition
Miscellaneous Syntheses

7 Miscellaneous Compounds


286
288

Author Index

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1
Three-membered Rings
BY D. J. MAITLAND

1 Introduction

This chapter reports on developments in the chemistry of three-membered,
saturated heterocyclic ring compounds. As is usual in such Reports a certain
degree of selectivity has been necessary. However, in general the author has
tried to steer as neutral a course as possible, not being swayed by his own
special interests, as can so easily happen. A break has been made with a
pattern set in earlier Reports, in that a separate section on ‘Physical Methods’
has not been compiled. It is this author’s opinion that as such techniques are
now almost routine tools in most chemical laboratories they no longer merit
special attention, an opinion substantiated by the fact that almost every
paper published today includes in the discussion a report on the application
of various physical methods to the problem in question.

2 Oxirans

In the M.T.P. review series three-membered ring compounds have been
reviewed.l The synthesis, reactivity, and synthetic applications of a$epoxy-ketones have been summarized.2 Reviews have been published on the
synthesis and characteristics of epoxides3 and arene oxides: selectivity in
the reactions of epoxides,6 and the electrocyclic ring-opening reactions of
bicyclic aziridines with oxirans.6
Formation-Direct Insertion. Oxygen atom insertion. The most common
reaction in this category is the oxidation of alkenes to epoxides by organic
peroxy-acids. However, some other reactions which involve either molecular
D. R. Marshall, in ‘Heterocyclic Compounds’, ed. K. Schofield, M.T.P. International
Review of Science, Organic Chemistry, Series One, Vol. 4, Butterworths, London,
1973, p. 1.
T. Iizuka, Yuki Gosei Kagaku Kyokui Shi, 1973, 31, 271 (Chem. A h . , 1974, 80,
59 803u).

‘

Y. Tanaka, A. Okada, and I. Tomizuka, Epoxy Resins: Chem. Technol., 1973,9-134,
7 3 7 - 4 0 (Chem. Abs., 1974,80, 82 507J).
D. M. Jerina, H. Yagi, and J. W. Daly, Heterocycles, 1973, 1, 267.
D. N. Kirk, Chem. and Ind., 1973, 109.
K. Matsumoto, Kaguku No Ryoiki, 1973, 27, 148 (Chem. A h . , 1973,79,42 253w).

1

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Saturated Heterocyclic Chemistry

2


oxygen or ozone have been reported. Hexaflu~ropropylene~
has been epoxidized (79 %) by reaction with oxygen at 200 "C over a silica catalyst, activated
either by pre-treatment with hexafluoropropylene or by pre-treatment with
1M hydrochloric acid8 followed by washing and treatment with hexafluoropropylene. Tetrafluoroethylene and chlorotrifluoroethylene were also
successfully epoxidized at 25 "C by a variation of the same te~hnique.~
The conversion of styrene into 1-phenyl-1,2-epoxyethane, without serious
competition from polymerization, has been achieved by the oxidationlo
of styrene at 120 "C and 83 or 160 mmHg partial pressure of oxygen or by
heating styrene, t-butyl hydroperoxide, or di-t-butyl peroxidell in chlorobenzene at 120 "C.
While investigating the thermal cycloreversion of the bicyclo [3,1,O]hex-2ene system, Padwa and Brodsky12 found that when exo,exo-3,4,6-triphenylbicyclo[3,1,O]hex-2-ene (1) was heated for 48 h at reflux temperature in
xylene, the major product was the oxiran (2). Similar treatment of the
exo,endo-isomer (3) gave a 2:2:1 mixture of (l), (2), and the oxiran (4).

A, 02-xylene

Ph
Ph'

Ph

*Ip
Ph

A, 02-mesitylene

'

Ph


H35-/$;+u)+~2
Ph
(4)

(3)

Heating (1) or (3) at 160°C under nitrogen afforded a 16:l equilibrium
mixture of (1) and (3). Thus the oxirans must be formed by therrnal epoxidation of the olefins by molecular oxygen, and the reactions can be rationab
ized in terms of a biradical intermediate formed by cleavage of the cyclopropane ring.
A continuous process for the preparation of epichlorohydrin has been
G . M. Atkins, jun., U.S.P.3 775 439/1973.

* R. J. Cavanaugh, U.S.P.3 775 438/1973.
* R. J. Cavanaugh and G. M. Atkins, jun., U.S.P.3 775 440/1973.

l o M. E. Pudel, L. G. Privalova, Z . K. Maizus, and I. V. Kalechits, Neftekhimiya, 1973,

13, 669 (Chem. Abs., 1974,80,95 624v).
P. Koelewijn, B.P. 1 304 403/1973.
l a A. Padwa and L. Brodsky, Tetrahedron Letters, 1973, 1045.
l1

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Three-memberedRings
3
reported. l-Chloroprop-2-ene in dimethyl phthalate containing 10-12 %
acetaldehyde is oxidized13 by air in a flow system at 150-160 "C.
The reaction of ozone with encumbered allenes at -78 "C in dichloromethane has recently been studied.14 1,1,3-Tri-t-butylalleneon treatment with

two equivalents of ozone afforded the corresponding diepoxide (5), which
rearranged to 2,2,4-tri-t-butyl-1-oxacyclobutan-3-one
(6) on standing. One
equivalent of ozone gave the diepoxide ( 5 ) as the principal product and the

allene oxide (7) in low yield. Neither 1,l-di-t-butylallene (8) nor 1,3-di-tbutylallene (9) gave an oxiran when treated with ozone. The allene (8)
afforded di-t-butyl ketone and 2,2-di-t-butylcyclopropanonewhereas (9) gave
exclusively pivaldehyde. The degree of substitution of the allene is obviously
a critical factor.
But

-

But

But

-c-

H

But
(8)

-H

(9)

The epoxidation of allenes by organic peroxy-acids has also been studied
by Crandall et a1.l5 The products are rationalized in terms of an initial

epoxidation of the allene (lo), followed by competitive partitioning of the
monoepoxide (1 1) between valence isomerism to the related cyclopropanone
(12) and further oxidation of (11) to a dioxaspiropentane derivative (13)
(Scheme 1). The cyclopropanones may react further with the peroxy-acid
to yield /3-lactones (14)or undergo oxidative decarbonylation to the corresponding olefins (15), which are usually transformed into their epoxides (16)
under the reaction conditions. The dioxaspiropentanes may also add carboxylic acids, yielding a-acyloxy-a'-hydroxy-ketones (17). An excess of
peracetic acid in buffered methanol gave (18) and (19) as the major products
from tetramethylallene. A small quantity of the lactone (20) was also detected, the a-acetoxy-ketone (18) arising by acetoxylation of the epoxyallene.
Under the same conditions 1 ,l-dimethylallene gave analogous products.
Under acid conditions, tetramethylallene upon epoxidation gave the amethoxy-ketone (21)as the only product (Scheme 2).
Sh. K. Kazimov, A. S. Rzaeva, G. Z. Ponomareva, Khim. Prom., 1973,49,824 (Chem.
Abs., 1974, 80, 70 613c).
l4 J. K . Crandall and W. W. Conover, J.C.S. Chem. Comm., 1973, 340.
l5 J. K. Crandall, W. H. Machleder, and S. A. Sojka, J. Org. Chem., 1973, 38, 1149.
la

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4

Saturated Heterocyclic Chemistry

R\A

\o/

R

R


R,

/-C-C

R /c-c\R

‘**R

I

R

\c=c/
’R

II
\ IC\ /R

+ HOAc + COz

‘.R

0

Me
H-C

“


I

Me

Me

I

Me

Me,

,c-c

Me

/ O \ p
M
‘e

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I

Me-C-C-Me

I

I 1


Me Me


Three-membered Rings

5

\iu- -n(o*c
0

0-

>=f?
)
-

(11;R = Me)

\

Cyclonona-l,2-diene with excess peracetic acid in buffered methanol
affords the epoxide (22), the lactone (23), cyclo-octene, and the a-acyloxya'-hydr oxy-ketone (24).

oo

4-Oxoisophorone (25) when epoxidized16with hydrogen peroxide (30 %)
affords oxabicycloheptanedione (26), which with 20 % sulphuric acid yields

2-hydroxy-3,5,5-trimethylcyclohex-2-en-1,4-dione.


(25)

(26)

@-Unsaturated f-alkoxy-ketones (27) can be converted into the corresponding epoxides (28) in good yield by treatment at 40 "C (with one equivalent of alkaline hydrogen per0xide.l' Excess alkaline hydrogen peroxide
effects destructive oxidation, affording formic acid, acetone, and a B-alkoxycarboxylic acid.

16

17

D. L. Roberts and B. P. Bonita, U.S.P. 3 775 437/1973.
I. G. Tishchenko and V. V. Berezovskii, Vesti Akad. Navuk belarusk. S.S.R.,Ser.
khim., Navuk, 1973, 113 (Chem. Abs., 1973,79,4939s).

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6

Saturated Heterocyclic Chemistry

Olefins can be epoxidized in high yield and with high selectivity by hydrogen
peroxide in the presence of fluoro(ha1ogeno)acetonecatalysts.l*Thus oct-1-ene
was epoxidized (100 %) in the presence of hexafluoroacetone. Similarly
effective were Cl,CCOCCl,F and ClF,CCOCFCl,. Propylene, ally1 alcohol,
trans-stilbene, and 1,5-cyclo-octadiene were similarly epoxidized in high
yield.
Fluoro-oxirans have been preparedlg by the epoxidation of RCF=CF,
at -20 OC with hydrogen peroxide in methanolic potassium hydroxide.

Substituted cyclohexenes20with an olefinic side-chain undergo selective
epoxidation with peracetic acid to afford the corresponding epoxycyclo-ol)cyclohex-1-ene (29) gave the
hexane. Thus 2,6,6-trimethyl-l-(but-3-en-l
epoxycyclohexane (30).

Cyclohex-3-ene-l-carboxylates(31), obtained by treatment of the appropriate cyclohexenecarboxylicacid with R1CO2CH,CH2Clin xylene containing
aqueous potassium hydroxide, afford21 the corresponding oxirans (32) on
treatment with 50 % peracetic acid in chloroform.

oR2
C02CH2CH20COR1

~ ~ O z C H 2 C H 2 0 C OMeC03H-CHC'3+
R 1
0

Treatment of endo-tricyclo[5,2,1,02~6]deca-3
,8-dienes with t-butyl hydroperoxide or peracetic acid affords a mixture of epoxides22which can be
separated by steam-distilling the product mixture to isolate the diepoxyendo-tricyclo[5,2,1,02*6]decane.The residual monoepoxide mixture is then
distilled in the presence of 0.1 % bis-(l-naphthy1)amine to give 3,4-epoxyendo-tricyclo[5,2,1 ,02*6]dec-8-ene
(33) and the 8,9-epoxy-isomer.
l8 L.

Kim, Ger. Offen 2 239 681/1973 (Chem. Abs., 1973,78, 159 400n).
A. Y.Zapevalov, I. P. Kolenko, and V. S. Plashkin, Zhur. org. Khim., 1973, 9, 2013
(Chem. Abs., 1974, 80,47 722d).
2o E. Kovats, G. Ohloff, E. Demole, and M. Stoll, Swiss P. 536 834/1973 (Chem. Abs.,
1973,79,91 972p).
a1 B. F. Pishnamazzadeand A. K. Mamishov, Zhur. org. Khim., 1973,9,715 (Chem. A h . ,
1973,79, 31 748k).

29 H. Fuerst, H. G. Hauthal, and D. Schied, East Ger. P. 98 925/1973, (Chern. Abs.,
1974,80,70 67th).

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7

Three-membered Rings

(3 3)

Epoxidation of 1 -(p-methoxybenzyl)-2-methyl-l,2,3,4,5,6,7,8-octahydroisoquinoline (34) with performic acid23affords the isomeric epoxides (35)
and (36) and the two diols (37)and (38) (Scheme 3). Hydrolysis of the epox-

CH2C6H,0Me-p
(34)

I

I

CHnCsH40Me-p

CH2CsHtOMe-p

(36)

&HC)
Le'


(35)

cj?-JMe

CH~C~H~OM~-~

;

HO

CHpCeH40Me-p

(37)

(38)

Scheme 3

ides (35) and (36) with 10% sulphuric acid affords quantitative conversion
into the diols (37) and (38), respectively, in a ratio of 1 :15. Therefore formation of the cis-epoxide (36) predominates. Chemical evidence shows that
performic acid exclusively attacks from the side cis to the 1-substituent.
Interpretation of this result is difficult, but it has been shown that the aminogroup in the isoquinoline ring does not particularly participate in the formation of the epoxides, and a particular role of the ArCH, group in the transition state would be suggested. The transition state (39) for the formation of
23

M. Onda, Y. Sugama, H. Yokoyama, and F. Tada, Chem. and Pharm. Bull. (Japan),
1973, 21, 2359.

2


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Saturated Heterocyclic Chemistry

(39)

(36), with intramolecular hydrogen-bonding as depicted in the formula, may
depress the activation energy for ( 3 9 , leading to predominant formation of
(36). The competitive reactions of (35) and (36) have also been examined.
The peroxy-acid oxidation of cyclo-octatetraene oxide2* yields the bisoxirans (40), (41), and (42) and the trisoxiran (43), which is unchanged on
heating at 255 "C for 20 h (Scheme 4). The oxirans (44) and (45) result on

Do+
,00+
.o

&-

0
m-ClC6H4COf

(40)

(40)

(41)

67 %


24 %

0
(42)
9%

+ (41) + (42) +
(43)

Scheme 4

thermal treatment (200 "C)of (41) and (42) respectively. Despite the requirement for high thermal activation, the bond relocations of (41) and (42)
proceed entirely along symmetry-allowed pathways. The n.m.r. spectra of
these compounds are discussed.

a4

A. G. Anastassiou and E. Reichmanis, J. Org. Chem., 1973, 38, 2421.

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Thee-membered Rings

9

7

Me


\
c=c
/
\
Et

Me

I

CHzCH2O(CH2)S- C- 0

/

\

0

\

(46)

/!HZ

CH2

The epoxyoxatridecenoate (48), a pesticide,25is obtained as a mixture of
(E)- and (2)-isomers by treating the unsaturated ester (47) with rn-chloroperbenzoic acid. The acetal (46), prepared from (2)-4-methylhex-3-enol and
5-bromo-2,2-ethylenedioxypentane,on acid hydrolysis followed by reaction
with dimethyl methoxycarbonylmethylphosphonate affords the unsaturated

ester (47).
When @-unsaturated ketones are treated with peroxy-acids, attack
usually occurs at the carbonyl group and epoxidation of the double bond is
rare. However, it has recently been reported that oxidation of 2,3,4,5,6hexamethylcyclohexa-2,5-dienonewith m-chloroperbenzoic acid26 affords
2,3-epoxy-2,3,4,4,5,6-hexamethylcyclohex-5-enone(49) and on further
oxidation cis-2,3 :5,6-diepoxy-2,3,4,4,5,6-hexamethylcyclohexanone.
Irradiation of the monoepoxy-ketone (49) through a Vycor filter affords the

(49)
25
26

(50)

D. Hainaut and J. P. Demoute, Fr. Demande, 2 174 666/1973; ibid., No. 2 172 847/
1973 (Chem. A h . , 1 9 7 4 , 8 0 , 82 617v; 82 618w).
H. Hart, M. Verma, and I. Wang, J. Org. Chem., 1973, 38, 3418.

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Saturated Heterocyclic Chemistry

10

single photoisomer 5-acetyl-2,3,4,4,Ppentamethylcyclopent-2-enone (50).
Irradiation of the diepoxy-ketone gives only starting material.
The epoxidation of acid-sensitive olefins, or olefins yielding acid-sensitive
epoxides, is typically conducted in the presence of a buffer such as sodium
carbonate, sodium bicarbonate, or disodium hydrogen phosphate. Such solid

buffer-solid systems have proved to be unsuitable for certain compounds.
For example the epoxide (52), derived from 6-methylhept-Sen-2-one (51),
is known to undergo very facile rearrangement to 1,3,3-trimethyl-2,7dioxabicyclo[2,2,l]heptane (53) when heated or treated with acid. Thus

treatment of (5 1) with rn-chloroperbenzoic acid and sodium bicarbonate
affords a mixture of (52) and (53). A simple procedure for the rn-chloroperbenzoic acid epoxidation of such acid-sensitive olefins2' has been reported.
The method, which employs a biphasic solvent mixture of dichloromethane
and 0.5M sodium bicarbonate solution, was used to epoxidize the ydunsaturated ketone (Sl), affording 85% conversion into (52) with no concurrent formation of the bicyclo-compound (53). An olefinic acetal (54) and
olefins containing enol-ester moieties, Me,~CHCH,CH,C(OAc)==CH,
and Me,C=CHCH,CH=C(OAc)Me, were similarly epoxidized. The system
can also be used to epoxidize less reactive olefins (e.g. hex-l-ene) and shows
good selectivity in the epoxidation of a trisubstituted double bond in preference to a disubstituted double bond. Limonene with one equivalent of the
peroxy-acid gave 1,2-epoxy-p-rnenth-8-ene
in 85 % yield.
Epoxycyclopentanes (55) have been prepared by epoxidation of the appropriate cyclopentenes with monoperphthalic acid.28

(55)

(54)

27
28

W. K. Anderson and T. Veysoglu, J . Org. Chem., 1973,38,2267.
S . A. Nesterenko, D. A. Pisanenko, and S. V. Zavgorodnii, Zhur. org. Khim., 1973,
9,758 (Chem. A h . , 1973,79,31 747j).

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Three-memberedRings

11

MeCH=CH-CH=CHCONRlR*
(56)

Me
0
x
0
Me

Reagents: i, Phthalic anhydride-H,O,-NH,CONH,EtOH

; ii, Me,CO-FeCl,

Scheme 5

Substituted amides of sorbic acid (56) when treated with phthalic anhydride-hydrogen peroxide in ethanol containing urea afford29 the corresponding epoxyhexenamides (57) (Scheme 5). Hydrogenation of 4,5-epoxyNN-diethylhex-2-enamide (57; R1 = R2 = Et) in the presence of Raney
nickel gives NN-diethylhexanamide and 5-hydroxy-NN-diethylhexanamide.
The epoxide (57; R1 = R2 = Et) condenses with acetone in the presence of
ferric chloride to give the hexenamide cyclic acetal (58).
Syntheses30 for disparlure [cis-7,8-epoxy-2-methyloctadecane(61)], a
sexual attractant of the gypsy moth (Purthetria dispar L.), have been reported
by two independent groups. The syntheses differ only slightly in their routes
from 1-bromo-5-methylhexane to the key intermediate 2-methyloctadec-7yne (59). In one, reaction is with dodec-1-yne in the presence of sodium
hydride, in the other with lithium dodecylide. Oxidation of the olefin (60) to
the oxiran (61) is achieved with perphthalic acid. Sheads and Beroza31 have
synthesized a tritium-labelled disparlure (~is-7,8-epoxy-2-methy1[7,8-~H,]octadecane) and report an improved method for preparing the intermediate

2-methyloctadec-7-yne.
Oxiran derivatives, (62) and (63), of p-aminoacetophenone which exhibit
juvenile hormone activity2 have been prepared by the reaction of N-trifluoroacetyl-p-aminoacetophenone with geranyl bromide and citronellyl
L. P. Glushko, M. M. Kremlev, Yu. Yu. Samitov, and T. M. Malinovskaya, Ukrain.
khim. Zhur., 1973,39, 807 (Chem. Abs., 1973,79, 126 173h).
A. A. Shamshurin, M. A. Rekhter, and L. A. Vlad, Khim. prirod. Soedinenii, 1973,
9, 545 (Chem. Abs., 1974, 80, 36 927y); B. G. Kovalev, R. I. Ishchenko, V. A.
Marchenko, and M. P. Filippova, Zhur. org. Khim., 1973,9,6 (Chem. Abs., 1973, 78,
84 127t).
31 R. E. Sheads and M. Beroza, J. Agric. Food Chem., 1973, 21, 751.
xt2 Z. Machkova, L. Dolejs, and F. Sorm, Coil. Czech. Chem. Comm., 1973,38, 595.

29

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Saturated Heterocyclic Chemistry

+ Br(CH&CHMe2

Me(CH2)gC-CLi

(59)

Me(CH2)9C-C(CH&CHMe2

Me(CHB)sCH=CH(CH2)4CHMez (60)
!-HO.p


CsH 4. CO,H

bromide respectively, followed by oxidation of the resulting unsaturated
derivatives with perphthalic acid in diethyl ether. Masking of the aminogroup of the intermediate N-(3,7-dimethylocta-2,6-dienyl)-p-aminoacetophenone and N-(3,7-dimet hyloct-6-enyl)-p-aminoacetophenonewith the
trifluoroacetyl group is essential for successful epoxidation of the alkenyl
chain, since compounds with an unprotected amino-group afford mixtures
of products which are difficult to resolve. The trifluoroacetyl group is readily
removed with alcoholic sodium hydroxide at 35 "C affording (62) and (63)
in 57 % and 72 % yields respectively.

NHR

(62)

R

(63)

R = (CH&CHMe(CH2)2CH-CMeB

= CH2CH=CMe(CH2)2CH-CMea

\o/

'0'

Carbon atom insertion. The reactions of various sulphur-stabilized carbanions
with aldehydes and ketones continue to provide useful routes to epoxides.
Dimethyl sulphoximine, prepared from dimethyl sulphoxide, on dialkylation
affords NN-dimethylamino- and NN-diethylamino-dimethyloxosulphonium

fluoroborates as stable, white, crystalline s0lids.3~Treatment of the latter
with sodium hydride in a variety of aprotic solvents, in particular dimethyl
sulphoxide, gives the corresponding methylides (64; R = Et or Me). These
0
0

II
1

Me-SLMe

BF4-

NaH-DMSO,

-DMF, or -THF
+

II

Me-S+CHI-

I

NRB

NRt
C. R. Johnson and P. E. Rogers, J. Org. Chem., 1973, 38, 1793.

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Three-memberedRings

13

ylides have proved to be effective nucleophilic methylene-transfer reagents.
Reactions with aldehydes and ketones afford epoxides, whereas reactions
with c$-unsaturated ketones give cyclopropyl compounds as the major
products. A certain degree of selectivity is observed: diethylaminomethyloxosulphonium methylide with 4-t-butylcyclohexanonegave only the (2)-epoxide,
a similar stereospecificity having previously been reported for dimethyloxosulphonium methylide, whereas dimethylsulphonium methylide gave predominantly the (E)-epoxide.
A general procedure for the synthesis of epoxy-alkylated and -acylated
heterocycles has been reported by Taylor et al.34The oxirans (65) (R1 = 2-

quinolyl, 4-quinolyl , 1-isoquinolyl, 4-quinazolinyl, 2-benzoxazolyl, 1,3dimethyl-2,4-dioxo-6-pyrimidinyl;
R2 = Et or Ph, R3 = H; or R2 = R3 =
Me) were prepared in 17-70 % yields by treating the appropriate aryl methyl
sulphone (RISO,Me) or aryl chloride with diphenylmethylsulphonium
tetrafluoroborate or diphenylmethylsulphonium perchlorate followed by
reaction with the ketone (R2R3CO).
One disadvantage of base-promoted reactions of sulphur-stabilized
carbanions with aldehydes or ketones is the possibility of side-reactions
(hydrolysis of the sulphonium salt or Cannizzaro or aldol reactions etc.).
However, it has been reported that if a biphasic system is used these sidereactions do not occur. Thus, by stirring a heterogeneous mixture of lauryldimethylsulphonium chloride (66) and a carbonyl compound in benzeneaqueous sodium hydroxide, oxirans have been synthesized in high yields.35
Typically, acetophenone gave an 85% yield of the oxiran (67). It has also
been reported that trimethylsulphonium iodide reacts with benzaldehyde in a
two-phase system (dichloromethane-aqueous sodium hydroxide) to form
2-phenyloxiran in excellent yield, but only if tetrabutylanimonium iodide is
present.36 The latter is considered to be acting as a phase-transfer reagent,
transferring the anionic reactant from the aqueous to the organic phase.

Cinnamaldehyde afforded an equally smooth conversion into 2-styryloxiran,
but ketones gave only low yields (18-36 %) of oxirans. Trimethyloxosulphonium iodide and benzaldehyde afforded 2-phenyloxiran (in only 2 0 30 % yield) and 2,6-diphenyl-l,4-oxathian4-oxide (68) (12 %). With apunsaturated ketones no oxirans were formed, but instead cis-trans mixtures
of cyclopropane derivatives.
s4

35
s6

E. C. Taylor, M. L. Chittenden, and S. F. Martin, Heterocycles, 1973, 1, 59.
Y. Yano, T. Okonogi, M. Sunaga, and W. Tagaki, J.C.S. Chem. Comm., 1973, 527.
A. Merz and G. Markl, Angew. Chem. Internat. Edn., 1973,12,845.

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