Hetarynes

The examples 4-6 illustrate these nomenclature systems as well as the 

Finally, the caveat about reading too much into structural formulas is particularly to be emphasized in the hetaryne series since heteroatoms would be expected to have a pronounced effect on the relative extent to which canonical 

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Methyl-5-aminothia2ole-4-carboxylic acid is diazotized with isoamyl nitrite in the presence of furan in 1.2-dichloroethane to give a mixture of products 163 (53%), 164 (33%). 165 (11%), and 166 (3%) (Scheme 104) (334). This reactivity experiment was carried out to examine the possibility of the occurrence of 4,5-dehydrothiazole (hetaryne). Hetaryne intermediates seem not to be involved as an intermediate in the reaction. The formation of 163 through 166 can be rationalized in terms of the intermediacy of 166a. 

Prior to 1960 little work had been done on reactions of heterocyclic compounds involving hetarynes, i.e. intermediates with a triple bond in the nucleus containing the hetero atom. Since then interest in hetarynes has grown and investigations in this area are developing rapidly using information available from carbocyclic aryne chemistry. Therefore, a short survey of the chemistry of arynes is presented before summarizing typical problems encountered in hetaryne chemistry. 

Hetarynes can be expected to differ from carbocyclic arynes in several respects, i.e. ... 

Since unsubstituted hetarynes are usually asymmetric, their participation in a reaction can manifest itself in the occurrence of a rearrangement. 

The properties of a hetaryne in which the C = C bond is adjacent to the hetero atom may differ considerably from those of its isomer(s). 

The action of nucleophiles on a monosubstituted heterocyclic compound may generate isomeric hetarynes. 

These characteristic properties of hetarynes will be discussed in the section on pyridines, which have been investigated more extensively than other hetarynes. 

This review covers the hterature up to the beginning of 1963. Papers published before the era of aryne chemistry that merely give incidental information on reactions which might proceed via hetarynes are not included. 

By treating 3-bromo- (27, X = Br) or 3-chloropyridine (27, X = Cl) with lithium piperidide (2.2 equivalents) and piperidine (2.8 equivalents) in boiling ether, mixtures of 3- (29, Y = NC5H10) and 4-piper-idinopyridine (34, Y = NC5H10) were obtained in 85-90% total yield. In both reactions the ratio of the 3- to 4-piperidino compounds was 48 52. Support for the hetaryne mechanism as the sole pathway for these reactions comes from the fact that increasing the amounts of lithium piperidide and piperidine to 5 and 10 equivalents, respectively, scarcely changed the composition of the reaction products. If addition-elimination had occurred concomitantly with reaction via the hetaryne, more of the 3-piperidino compound would have been formed, since the reconversion of the hthium intermediate 30 into 27 by piperidine would be accelerated by the enhancement of the concentration of this substance. 

Apparently only one hetaryne containing oxygen as a hetero atom, 2,3-dehydrocoumarone (98), has been described thus far. It was formulated by Stoermer and Kahlert as an intermediate containing a triple bond in its hetero ring system as eaHy as 1902 and was probably the first aryne mentioned in the hterature of organic... 

Two hetarynes containing sulfur as a hetero atom have been mentioned in the literature. The first thiaaryne, 2,3-thianaphthyne (105), may have been handled by Komppa and Weckman in 1933. On heating 3-bromothianaphthene (104) with a solution of potassium hydroxide in ethanol at 200°, a reaction mixtime was obtained consisting of unchanged starting material (4%), thianaphthene (65%), and 2-hydroxyfhianaphthene (106, 15%). The course of the reaction... 

The second thiaaryne is the 2,3-hetaryne derived from thiophene (108). It was obtained by Wittig and Wahl34 by heating bis-(3-... 

As might be expected, hetaryne chemistry has been growing at an increasing rate since this review was written. When reading the proof we felt inclined to summarize the latest developments which have come to our attention. 

The existence of some curious intermediates related to hetarynes has... 

In an extensive investigation of the behavior of halogeno-pyridines and -quinolines towards potassium amide in liquid ammonia, tendencies to react according to the hetaryne type and other mechanisms were compared. The following results may be mentioned. 3-Fluoropyridine does not react via 3,4-pyridyne, but yields fluoro derivatives of 4,4 - and 2,4 -bipyridine. 3,6-Dibromopyridine is converted first into 6-bromo-3,4-pyridyne and not into 6-amino-3-bromopyridine. 2-Bromoquinoline yields 2-methylquinazoline together with 2-aminoquinohne. ... 

Finally, the elimination-addition mechanism has been proposed to explain the course of the weU-known Tschitschibabin reaction, but this extension of hetaryne chemistry has been rightly objected to by several authors. 

During this period of time we, and a number of other research groups, have been investigating the reactions of highly halogenated aiynes and hetarynes with aromatic hydrocarbons, for the reasons outlined in the introduction. In a reaction of pentafluorophenylmagnesium chloride with ethylene oxide in the presence of benzene, it was shown that, as well as 3-pentafluorophenylethanol (23) a by-product of molecular formula C12H6F4 was produced 43>. 

A common synthetic use of heterocyclic carbanions is as precursors of heterocyclic arynes (hetarynes), although the intermediacy of the latter species can often only be inferred from the structure of the isolated products [65AG(E)543, 65AHC(4)121 67MI1 71AG(E)20 82T427], However,... 

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