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A novel method has been developed for the synthesis of substituted cycloheptatrienes, involving the cycloaddition of substituted cyclopropenes to substituted thiophene 1,1-dioxides followed by expulsion of sulfur dioxide from the cycloadduct. The scope and limitations of the reaction have been investigated and its mechanism is discussed. Attempts to extend this reaction principle to the synthesis of 1-heterocycloheptatrienes were unsuccessful.

Three series of novel crown ethers have been prepared in which polyether rings of various sizes are linked to a benzene ring through the 1,3- or 1,4-positions or to a furan ring through the 2,5-positions. They were synthesized from the corresponding α,γ- or α,δ-bis(halomethyl)-substituted aromatics by reaction with polyethylene glycol disalts or from the disalts of bis(hydroxymethyl)-substituted aromatics by reaction with polyethylene glycol ditosylates. Both 1:1 (2−67 % yield) and 2:2 (6−30% yield) cyclic reaction products were formed. The fact that the above compounds, which may contain up to 31 ring atoms, are obtained in such high yields without operating at high dilution is connected with the relationship between the chain length of the polyethylene glycol and the diameter of the cation used in the synthesis (template effect).

The influence of substituents in close proximity to crown ether cavities, on the stability of complexes of the crown ethers with t-butylammonium salts, has been investigated. Crown ethers with intra-annular donor substituents (2–4) were prepared by the reaction of 2-acetylresorcinol (1) with polyethylene glycol ditosylates and subsequent modification of the acetyl group. Crown ethers with substituents above and below the plane of the crown ether 0 atoms were synthesized by the reaction of 2,2'-dihydroxy-1,1'-biphenyls with polyethylene glycol ditosylates. Chloromethylation of 5,5'-dimethyl-1,1'-biphenyl crown ethers (6) yielded 4,4'-bis(chloromethyl)-1,1'-biphenyl crown ethers (10). 3,3'-Disubstituted-1,1'-biphenyl crown ethers (13–24) were synthesized by the reaction of 3,3'-diallyl-2,2'-dihydroxy-1,1'-biphenyl (12) with polyethylene glycol ditosylates. The allyl groups of 13 were isomerized with sodium hydride to propen- 1-yl groups. Ozonolysis of 13 and 14 gave the corresponding dialdehydes (15 and 18) which were converted into other 3,3'-disubstituted biphenyl-20-crown-6 derivatives (RCH2COOMe, CH2COOH, CH2OH, CH2Cl, CH2OMe, OH and Me) by standard operations. The thermodynamic stability of the complexes of these functionalized crown ethers with t-butylammonium hexafluorophosphate has been studied in deuterochloroform in competition experiments with m-xyleno-18-crown-5 and benzo-15-crown-5 as the reference compounds. The nature of the 2-substituents in the crown ethers 2 and 3 has little effect on the stability of the complexes. The stability of the complexes of 3,3'-disubstituted biphenyl crown ethers depends of ringsize and the size and nature of the substituents. The most stable complexes are those of 24 (R = Me) and 14 (R=CH=CHMe). The Me groups in 24 represent the optimum between relief of O-O repulsion in the polyether ring and steric hindrance of complexation. The propen-1-yl substituents of 14 stabilize the complex because they provide extended π-electron donor stabilization. Substitution at the 4- and 4'-positions of the aryl groups has little effect on the stability of the complexes.

Two types of novel crown ethers in which a polyether chain is linked, via C atoms, with two adjacent C atoms of an aromatic or heteroaromatic ring have been synthesized by reaction of α,β-bis(halomethyl)-substituted aromatics with polyethylene glycolates. Both 1:1 and 2:2 cyclic reaction products were formed, in yields varying from 1 to 53% and from 0 to 24%, respectively. The relatively high yields of these macrocyclic polyethers (rings containing from 11 to 34 atoms), obtained without operating at high dilution, depend both on the chain length of the glycol and on the nature of the cation. This can be explained in terms of a “template” effect of the cation in the cyclization step. Experimental evidence supporting such an effect was obtained from the relationship between the 1:1 product selectivity and the glycol chain length for cations with different ionic radii (L + , Na + and K + ). Furthermore, a correlation has been established between the ratio of the yields of 1:1 and 2:2 cyclic products from the reaction of 1,2-bis(bromomethyl)benzene and dipotassium triethylene glycolate and the ratio of the relative complexation constants of these compounds with potassium salts.

1-Hydroxyazetidines (5), prepared by reductive cyclization of O-benzyl-β-tosyloxy omines 1 and subsequent debenzylation, can be oxidized selectively either to four-membered cyclic nitrones (6 and 7) or to 1,4-diacetoxy-2-azetidinones (9).

3,4 - Di(methoxycarbonyl) - 5 - pyrrolidinobenzo[b]thiepin 5 is synthesized by a [2+2]cycloaddition of 3 - pyrrolidinobenzo[b]thiephene 3 to dimethyl acetylenedicarboxylate, with subsequent ring opening of the cyclobutene moiety in the intermediate 6,7-di(methoxycarbonyl)-5-pyrrolidino - 2 - thiabenzo[b]bicyclo[3.2.0]hepta - 3,6 - diene 4 (detectable by PMR spectroscopy at −30°C). Hydrolysis of the pyrrolidino group in 5 affords 3,4 - di(methoxycarbonyl) - 5 - hydroxybenzo[b]thiepin 8. Peracid oxidation of 5 yields the corresponding 1,1-dioxide. The benzo[b]thiepins are thermally unstable and (depending on the substituents) either extrude sulphur or rearrange to a 4-mercapto-1-naphthol, probably via the thianorcaradiene as the intermediate. The kinetics of the latter reaction are discussed. On being irradiated, the benzo[b]thiepins isomerize to 2-thiabenzo[b]bicyclo[3.2.0]hepta-3,6-dienes.

Monocyclic thiepins have been synthesized by reaction of (4-methyl-) 3-pyrro-lidinothiophenes 1 with dimethyl acetylenedicarboxylate at − 30°C. A [2+2] cycloaddition, yielding 6,7-di(methoxycarbonyl)-(4-methyl)-5-pyrrolidino-2-thiabicyclo[3.2.0]hepta-3,6-diene 2 is followed by isomerisation into 3,4-di(methoxycarbonyl)-(6-methyl-)5-pyrrolidinothiepin 3 . The predicted antiaromatic character of this class of compounds is borne out by the readiness with which they eliminate sulphur at − 30°C to give the corresponding benzene. The reaction product of dicyanoacetylene and tetramethylthiophene, recently claimed to be an unusually stable thiepin, is shown to be a 2-thiabicyclo[3.2.0]hepta-3,6-diene. Its structure allows the observed thermal rearrangement at 140°C to be interpreted as a symmetry-allowed antara,antara Cope rearrangement.

The decomposition of thiirene 1,1-dioxides into sulphur dioxide and the corresponding acetylenes is catalysed by certain transition metal complexes [Pd0 Pt0 and Ir1]. The metal complexes of the substrate are key intermediates in the decomposition. A possible pathway is suggested.

Publisher Summary Cycloaddition reactions have adequately demonstrated their usefulness as direct and elegant routes for the synthesis of heterocyclic compounds. This chapter deals with intermolecular and intramolecular reactions of heterocyclic compounds, where the two reacting π-electron systems constitute a part of one heterocyclic molecule. In the first type of reaction, two σ -bonds are formed, whereas in the second type, either one σ -bond and a new π-bond are created via electrocyclization of a conjugated diene system or two σ -bonds are formed from two isolated π-bonds. The chapter also emphasizes the scope and application of (2 + 2)-cycloadditions for the synthesis of heterocycles along with the relevant theoretical considerations. The impact of (2 + 2)-cycloaddition and (2 + 2)-cycloreversion reactions of heterocyclic compounds on organic chemistry can be clearly illustrated by several examples, such as various members of the important β -lactam antibiotics; penicillin and cephalosporin C, as well as structurally related heterobicyclic compounds, have been obtained by (2 + 2)-cycloaddition of heterocycles with ketenes.

A novel method has been developed for the synthesis of substituted cycloheptatrienes, involving the cycloaddition of substituted cyclopropenes to substituted thiophene 1,1-dioxides followed by expulsion of sulfur dioxide from the cycloadduct. The scope and limitations of the reaction have been investigated and its mechanism is discussed. Attempts to extend this reaction principle to the synthesis of 1-heterocycloheptatrienes were unsuccessful.

Three series of novel crown ethers have been prepared in which polyether rings of various sizes are linked to a benzene ring through the 1,3- or 1,4-positions or to a furan ring through the 2,5-positions. They were synthesized from the corresponding α,γ- or α,δ-bis(halomethyl)-substituted aromatics by reaction with polyethylene glycol disalts or from the disalts of bis(hydroxymethyl)-substituted aromatics by reaction with polyethylene glycol ditosylates. Both 1:1 (2−67 % yield) and 2:2 (6−30% yield) cyclic reaction products were formed. The fact that the above compounds, which may contain up to 31 ring atoms, are obtained in such high yields without operating at high dilution is connected with the relationship between the chain length of the polyethylene glycol and the diameter of the cation used in the synthesis (template effect).