Heterocyclic Chemistry Volume 2

A Review of the Literature Abstracted Between July 1979 and June 1980

By H. Suschitzky, O. Meth-Cohn

The Royal Society of Chemistry

Copyright © 1981 The Royal Society of Chemistry
All rights reserved.
ISBN: 978-0-85186-813-4

Contents

Chapter 1 Three-Membered Ring Systems By T. J. Mason, 1,
Chapter 2 Four-Membered Ring Systems By R. C. Storr, 51,
Chapter 3 Five-Membered Ring Systems By G. V. Boyd, P. A. Lowe, and S. Gronowitz, 73,
Chapter 4 Six-Membered Ring Systems By S. D. Carter, G. W. H. Cheeseman, and G. P. Ellis, 223,
Chapter 5 Seven-Membered Ring Systems By J. T. Sharp, 331,
Chapter 6 Eight-Membered and Larger Ring Systems By G. M. Brooke, 3591,
Chapter 7 Bridged Systems By J. M. Mellor, 381,
Author Index, 411,

CHAPTER 1

Three-Membered Ring Systems

BY T. J. MASON

1 Oxirans

The interest of Eastern European chemists in oxirans has been evident for many years, and from such sources have come a number of reviews on the production of these important raw materials. While concentrating mainly on ethene and propene oxides, one review deals more specifically with the types of heterogeneous catalysts employed in the processes. The latest edition of the Kirk-Othmer Encyclopedia contains an entry on epoxidation.

An extensive article on the importance of chalcone oxides in ftavonoid chemistry contains 346 references. Other specialised reviews have appeared on the chemistry of juvenile hormones (up to 1974), epoxy-sulphones, and epoxy-derivatives of dicyclopentadiene.

The important safety aspects of the use of oxiran in high-pressure bench-scale experiments have been considered.

Preparation. — Catalytic Oxidation of Alkenes to Oxirans, using Oxygen or Oxygen-containing Gases. The mechanism for the conversion of the phenol (1) into the epoxy-quinol (4) by molecular oxygen in ButOK-ButOH has been investigated (Scheme 1). The first step is the formation of hydroperoxide (2), which is converted into hydroperoxide (3) via a π-complex intermediate; the yield of (4) increases with temperature.

Photo-oxygenation of cyclohepta-3,5-dienone that is sensitized with tetraphenylporphyrin leads initially to the 3,6-endoperoxide; this, on reduction with di-imide, gives (5), from which (6) and (7) were obtained, via photolysis at 300 nm in CDCl3 and subsequent deoxygenation with PPh3 in CH2Cl2, at 0°C, respectively. Photo-oxidation of 3-methylfuran in CH2Cl2 at 0°C, with methylene blue as the sensitizer, led directly to the epoxy-ketones (8) and (9), together with some diepoxide.

Dye-sensitized oxygenation of vinylsilanes yields β-silylated allylic alcohols via epoxysilane intermediates and provides a new synthesis of allylic alcohols from saturated ketones (Scheme 2). The vinylsilanes (10; R = H) and (10; R = Me), prepared from the corresponding cyclohexanone benzenesulphonylhydrazone, react with singlet O2 to give the intermediates (11) (not isolated); these open regiospecificall y to (12), from which (13) may be obtained on reaction with Bun4N+F-. Calculations indicate the possible role of silicon in directing the opening of the oxiran ring.

The kinetics of oxidation of ethene at 490 — 620 K, using Ag catalysts supported on pumice, have been reported. 15 Total oxidation to CO2 and H2O accompanies formation of oxiran, apparently with similar activation energies. Ethene has also been oxidized, using complex catalysts derived from silver carboxylates and heterocyclic compounds, 78.5% selectivity being obtained using the catalyst from silver acetate and 2-methyl-2-oxazoline. Epichlorohydrin may, however, be obtained directly from allyl chloride in the liquid phase, using simply silver nitrate in dimethyl phthalate.

The epoxy-alcohol (15) (76%) was obtained from (14), using the cyclopentadienyl-vanadium catalyst [(C5H5)V(CO)4] in solution at 50°C. Under similar reaction conditions, a catalyst prepared by exchange of V4+ and Cu2+ with an Na–X–zeolite resin furnished a mixture of (15) and (16) in 46% and 40% yields respectively.

The 1 : 1 complex formed between ZnCl2 and tetramethyl-2-tetrazene reacts with cyclo-octene and oxygen to give solely the oxiran, whereas with styrene the reaction goes further, the intermediate oxiran ring being opened regiospecifically to produce the amino-alcohol PhCH(OH)CH2NMe2.

Oxidation of Alkenes to Oxirans by Peroxy-acids. The mechanism of the reaction of m-chloroperbenzoic acid with double bonds has been investigated through a study of the epoxidation of a series of cycloal kenes (of ring sizes 5, 6, 7, 8, and 12) and substituted cyclohexenes. The second-order rate constants were determined in CHCl3 at 0 — 30°C, and the data support a 1,3-dipolar cycloaddition reaction.

Factors that affect the stereoselectivity of epoxidations with peroxy-acids have been probed. A remarkable change in selectivity has been observed when a β-carbonyl group is introduced into the lanost-9(11)-ene skeleton. While (17; R = H) yields only α-epoxide on treatment with 3-ClC6H4 CO3H, the presence of the carbonyl group in (17; R2 = O) produces a ratio of β- : α-epoxides of 3:1 in CHCl3, which falls to 1:1 in more polar solvents. Undoubtedly there must be considerable steric influence in this reaction, but it is thought that the carbonyl group acts largely through a polar effect, reducing the rate of epoxidation of (17; R = H) by a factor of 300. Mono-epoxidation of the substituted cyclohexa-1,4-dienes (18; R1 = Me, R2 = CO2Me or CH2OH) and (18; R1 = H, R2 = CO2 Me) with 3-ClC6H4CO3H demonstrates a predominant steric control of epoxidation rather than, as previously suggested, a cis-directing eff ect by allylic methoxycarbonyl groups. 24 The diene (18; R1 = Me, R2 = CO2Me) gave a 55:45 mixture of epoxides, with the predominant isomer having the oxiran ring cis to the methoxycarbonyl group. The product distribution reflects the slightly smaller bulk of this group compared with methyl. The steric argument is reinforced with the observation that monoepoxidation of (18; R1 = H, R2 = CO2 Me) yields a 35 : 65 ratio of products in favour of oxiran trans to the more bulky CO2 Me group. High stereoselectivity was obtained from the epoxidation of (19) to a 9:1 ratio of epoxides in which (20) predominated.

The presence of base in the oxidizing media dramatically affects the distribution of epoxide products. In the oxidation of cholesterol acetate with the new reagent pentafluoroperbenzoic acid, a 65:35 mixture of α- : β-epoxides was obtained (almost quantitative yield) in CH2Cl2 at 25°C; this changed to a quantitative yield of solely the α-epoxide when Na2CO3 was added to the reaction mixture. The sesquiterpene lactone (21; R1R2 = a bond) gave the cyclized product (22) on oxidation with 3-ClC6H4CO3H in CH2Cl2, but when the same reaction was run under biphasic conditions, using CH2Cl2 and aqueous NaHCO3, it gave the epoxide (21; R1R2 = O) that is the precursor to (22).

A biphasic system has also been used for the generation of the new reagent O-ethylperoxycarbonic acid (23). Ethyl chloroformate in CH2Cl2 that is in contact with an aqueous phase containing 30% H2O2 generates (23) at the interface. The reaction has the advantages that the conditions may be maintained by buffering within the pH ranges 6.8 — 4.5 (Na2HPO4) and 9.5 — 8.8 (Na3PO4) and also yields high-purity products. Cyclo-octene oxide is formed in 85% yield from the cycloalkene.

Interest has been shown in the oxides of dicyclopentadiene, as noted earlier, with reports of epoxidations using permaleic, perphthalic, and peracetic acids. The mechanism of oxidation of trans-stilbene by peroxomonophosphoric acid (H3PO5) in a number of solvents has been investigated. A report on the epoxidation of a number of methoxy- and hydroxy-substituted cinnamaldehydes (24; R1 = R2 = R3 = H, MeO, or OH) concludes with the suggestion that the most effective oxidant is 3-ClC6H4CO3H in CHCl3.

Oxidation of Alkenes to Oxirans, using Peroxides. Two reviews in this area have been published, one dealing with new methods for the catalytic epoxidation of alkenes using hydrogen peroxide and the other with selective oxidation of alkenes and alkynes with t-butyl hydroperoxide.

The direct oxidation of alkenes to oxirans by hydrogen peroxide is, of course, only possible when a catalyst is used. In the past the main choice of catalyst has been oxides of the metals of Groups 5a, 5b, 6a, or 6b. In 1978, however, Sharpless put the use of arylseleninic acids as catal ysts on a firm practical footing. Using the nitrophenylseleninic acids (25; R1 = H, R2 = NO2 ) and (25; R1 = R2 = NO2), 95% preparative yields of cyclo-octene oxide were obtained from the alkene in CH2Cl2 with 30% H2O2.

A new and more selective catalyst is (26; R = OH); this is a stable oxidizing agent in its own right, which may be stored for stoicheiometric use or else used catalytically with H2O2 for inexpensive, large-scale epoxidations. The reagent, after oxidizing an alkene, forms hexafluoroacetone hydrate (26; R = H), which readily regenerates (26; R = OH) under the reaction conditions. The efficiency of the system is demonstrated by the 90% conversion of cyclohexene into its epoxide in 15 minutes at 0°C, while its selectivity in the oxidation of (27) to (28) (90%) in 12 h at room temperature contrasts sharply with the mixtures of products obtained using other epoxidation techniques.

Another new group of catalyst systems for direct epoxidations by hydrogen peroxide is the arsonated polystyrenes. Using a triphasic system of CHCl3, 30% H2O2, and the catalyst (in the form of beads), slow but selective epoxidations of simple alkenes have been achieved (e.g. 90% of cyclo-octene oxide after 2 days at 70°C). The catalyst is removed from the system by straightforward filtration, and may be recycled.

On treating ethyl orthoformate or acetone dimethyl ketal with 90% H2O2, α-hydroperoxy-ethers (29) are generated. With structural similarities to peroxo-acids, these compounds are capable of oxygen transfer, and comprise a new class of epoxidation reagents. The simple experimental procedure of dissolving cyclopentene in ethyl orthoformate and adding 90% H2O2 results in a 95% yield of the epoxide.

The kinetics and mechanism of the epoxidation of allyl chloride by H2O2 in ethanol, using molybdate catalysts, have been investigated. The reaction has been found to be of first order in both ally! chloride and the catalytic species H2MoO4 and of zero order in H2O2. Supported molybdenum catalysts, prepared by precipitating MoO(OH)3 onto silica, were also effective in the epoxidation of the same substrate with cumyl peroxide.

A group of Russian workers has produced a series of technical reports, currently to number 11, that deal with the epoxidation of cyclohexene by ethylbenzene hydroperoxide, using molbydenum catalysts. The reports explore the effects of modifications of the catalyst on reaction efficiency. The use of molybden um catal ysts in the oxidation of cyclohexene by cumyl peroxide has been studied, using i.r. and e.s.r. spectroscopy. E.s.r. spectroscopy has also been used to investigate the decomposition of ethylbenzene hydroperoxide in the presence of molybdenum naphthenate.

Whitham has reported the stereochemical aspects of the epoxidation of cis– and trans-5-t-butykyclohex-2-en-1-ol when catalysed by [VO(acac)2](Scheme 3). The trans-alcohol was found to be oxidized 34 times faster than the cis-alcohol, the enone (32) being the ma jor product from the latter reaction. These results provide a justification for the proposed intermediate complex (30), since the steric demands of the transition state that leads to the epoxide (31) would be better satisfied for the axial alcohol.

Synthesis of Oxirans by Halohydrin Cyclizations and Related Reactions. The synthesis of precocene 1-epoxide (33; R1R2 = O) has been achieved via the bromohydrin cyclization route. Several previous attempts at this preparation had failed, probably owing to the ready cleavage of the oxiran ring; this is to some extent borne out by the fact that the bromohydrin (33; R1 = OH, R2 = Br) gave a ring-opened methoxy-alcohol on treatment with anhydrous K2CO3 in MeOH. The required oxiran (33; R1R2 = O) was isolated in 88% yield from cyclization of the bromohydrin, using NaH in THF at room temperature. A convenient one-pot preparation of α-halogeno-epoxides (35; R = Cl or Br) from (34), avoiding the need to isolate the intermediate halohydrin, involves the treatment of (34) in ether sequentially with NaOH in aqueous methanol and then NaBH4. A yield of 59% for the chloro-oxiran (35; R = Cl) was obtained by using this procedure.

Treatment of steroidal bromohydrins with ‘Ag2O’ tends to give ring-contracted nor-aldehydes when the bromine is equatorial but epoxides or ketones if the bromine is axial. 5β-Bromocholestane-3β,6β-diol (36) has both the 19-methyl and 6-hydroxyl groups trans, and coplanar with the bromine, and thus in competition for its displacement. Treatment of this bromchydrin with Ag2 0 gave 80% of the expected β-epoxide (37) together with 8% of (38), which is the product of a Westphalen rearrangement. The epoxyphosphorane oxides (39; R1 = Me, Ph, or OMe; R2, R3 = H or Me) have been prepared from the parent alkene via its chlorohydrin almost quantitatively.

Industrial interest has been shown in the generation of oxirans from vicinal hydroxy-acetates (by elimination of acetic acid at temperatures of around 400°C) or from vicinal diols (through conversion into hydroxy-esters in situ and subsequent cyclization).

Synthesis of Oxirans via Attack of a Carbanion on the Carbonyl Group of Aldehydes and Ketones. In the past, this section has been entitled ‘Darzens and Related Reactions’; however, with the advent of the now commonly used sulphur ylides, e.g. Me2[??]-[??]H2 (Corey’s reagent), the new title was necessary. Corey has shown the sulphur ylide reagents to be of use in the synthesis of relatively unstable oxirans such as (42), which is air- and acid-sensitive and which is stored at –78°C in frozen benzene, under argon. This material has been synthesized from (40; X = OH) in 35% yield, via the reaction of (40; X = [??]Me2) with aldehyde (41). The last stage in thE synthesis of the trichothecatriene derivative (43) involves the use of Me2[??] — [??]H2 on its exo-methylene precursor, the yield being 18%.

Alternative sulphur reagents that may be used to cause epoxidation are the N-(p-tolylsulphonyl)sulphilimines (44; X = H); they are produced (by a phase-transfer-catalysed process) from the trihydrate of Chloramine-T (the sodium salt of N-chlorotoluene-p-sulphonamide) with a solution of PhSCH2R in CH2Cl2. The lithiated materials (44; X = Li, R = H) or (44; X = Li, R = Ph) react with PhCHO to give quantitative yields of styrene and stilbene respectively.

A Darzens-type condensation has been employed in the synthesis of (46) by the reaction of 9-chloroftuorene anion (45) with PhCHO. A two-phase system was used to prepare (E)-(47; R = H, Cl, or NO2) almost exclusively, via a Darzens reaction of the substituted benzaldehyde with PhCOCH2Br in the presence of a quaternary ammonium salt as catalyst.

(Continues…)Excerpted from Heterocyclic Chemistry Volume 2 by H. Suschitzky, O. Meth-Cohn. Copyright © 1981 The Royal Society of Chemistry. Excerpted by permission of The Royal Society of Chemistry.
All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.
Excerpts are provided by Dial-A-Book Inc. solely for the personal use of visitors to this web site.