Other Syntheses

Other Syntheses.—A high yield of 2-phenyl benzothiazole is obtained when benzaldehyde, benzyl alcohol, benzyl benzoate, or thiobenzanilide is heated 185 °C) with aniline and sulphur in HMPA.  

In addition to the more conventional approaches discussed above, several attempts have been made to synthesize azaindoles by other routes, some of which have been successful. For convenience these have been separated into those leading directly to azaindoles (this section) and those involving oxygenated intermediates (Section III,G). 

During their early investigations of harmine, Perkin and Robinson attempted a synthesis of what they thought to be isoharman. The 2-quinolone amide (74) was cyclized with phosphoryl chloride to a chloro compound (75), which gave 2.ff-pyrrolo[2,3-6]quinoline (76, R = H) with tin and hydrochloric acid, and its 3-methyl derivative (75, R = Me) with methylmagnesium iodide. The name quinindole  

Bernstein et al. synthesized 6-amino-2,3-diphenyl-7-azaindole (77) in 89% yield by heating nearly equimolar amounts of 2,6-diaminopyridine, its hydrochloride salt, and benzoin at 185°. 

Cookson condensed 3-hydroxyimino-l-methyl-4-piperidone with ethyl acetoacetate in the presence of zinc to give ethyl 4,5,6,7-tetrahydro-2,6-dimethyl-6-azaindole-3-carboxylate, which was oxidized with mercuric acetate to the 6,7-dihydro compound. 

Herz and Murty tried a similar cyclization with i r-(3-p3U idyl)-aminoacetal and its iV -oxide, but the former gave an intractable tar 

Datwyler, R.Ott-Longoni, E.Schopp, and M.Hesse, Helv. Chim. Acta, 1981, 64, 1959 

Tokuyama, K.Shimada, M.Uemura, and J.W.Daly, Tetrahedron Lett., 1981, 23, 

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Besides the classical heterocydization and ammonolysis methods some other syntheses have been developed to prepare secondary and tertiary... 

Other Syntheses. Acryhc acid and other unsaturated compounds can also be made by a number of classical elimination reactions. Acrylates have been obtained from the thermal dehydration of hydracryhc acid (3-hydroxypropanoic acid [503-66-2]) (84), from the dehydrohalogenation of 3-halopropionic acid derivatives (85), and from the reduction of dihalopropionates (2). These studies, together with the related characterization and chemical investigations, contributed significantly to the development of commercial organic chemistry. 

Other syntheses utilise a-bromo or a-iodo compounds, which condense on heating with copper (44). 

Other syntheses involve preformed quinoline systems in standard syntheses, including examples in the pyrimido[4,5-fe]quinoline (e.g. 200 201) (71JHC111>, pyrimido[4,5-clquinoline (e.g. 202 203) (62JCS1671) and pyrimido[5,4-c]quinoline (e.g. 204 205) (78JMC295> series. 

A-Substituted polypyrazoles can also be obtained by using A-alkylhydrazines, and it should be noted that these polymers consist of a random mixture of head-to-head and head-to-tail structures. Other syntheses of polypyrazoles have been described in the literature. Thus polyphenylene pyrazoles (742) and (743) occurred when m- or p-diethynyl-benzene (DEB) reacted with 1,3-dipoles such as sydnones or bis(nitrilimines) (Scheme 64). 

A number of other syntheses were discussed by Takeuchi and Furusaki and the most common involved reaction of hydroxylamine with selected a,/3-unsaturated ketones to give isoxazolidine-3- or -5-ols, which exist in equilibrium with an open-chain counterpart (77AHC(21)207). A similar equilibrium was observed in the reaction of a,/3-unsaturated ketones with N-hydroxyurea. The geometric orientation of the ring substituents was studied as a dynamic process (Scheme 158) (75TL2337). 

Oxiranes react with iodotrimethylsilane to give silylated halo alcohols e.g. 60) which can be converted to allylic alcohols (Scheme 53) (80JOC2579, 80TL2329) cf. other syntheses of allylic alcohols (Sections 5.05.3.2.2, 5.05.3.4.3(0 and Hi)). 

Other syntheses of oxiranes which are occasionally useful and involve a species (64) are the dehydration of 1,2-diols (Scheme 69) (78TL5153, 7808(58)12) and the reductive coupling of aldehydes (Scheme 70) (B-73MI50500). 

The present procedure, based on the last method, is relatively simple and uses inexpensive starting materials. Step A exemplifies the 2 + 2 cycloaddition of dichloroketene to an olefin, " and the specific cycloadduct obtained has proved to be a useful intermediate in other syntheses. Step B has been the subject of several mechanistic studies, and its yield has been greatly improved by the isolation technique described above. This synthesis has also been extended to the preparation of various tropolone derivatives. " ... 

A number of other syntheses of coniine have been effected, of which that of Diels and Alder is of special interest. The initial adduct of pyridine and methyl acetylenedicarboxylate, viz., tetraraethylquinolizine-1 2 3 4-tetracarboxylate (IX) on oxidation with dilute nitric acid is converted into methyl indolizinetricarboxylate (X). This, on hydrolysis and decarboxylation, furnishes indolizine, the octahydro-derivative (XI) of which, also known as octahydropyrrocoline, is converted by the cyanogen bromide method (as applied by Winterfeld and Holschneider to lupinane, p. 123) successively into the broraocyanoamide (XII), cyanoaraide (XIII) and dZ-coniine (XIV). A synthesis of the alkaloid, starting from indolizine (pyrrocoline) is described by Ochiai and Tsuda. ... 

Other syntheses of tropic acid have been accomplished by Spiegel, Miiller, Wislicenus and Bilhiiber, Chambon and Natarajan and Swamina. ( > Of these, the most interesting is the reduction of ethyl formylphenylacetate (VIII) CHO. CHPh. COOC Hj in moist ethereal solution by aluminium amalgam to ethyl tropate, from which the acid (IX) HO. CHj. CHPh. COOH, is obtainable by hydrolysis with baryta. 

The results of other syntheses effected by the general methods outlined above are given in the following table with reference numbers —... 

Since then other syntheses have been effected of hordenine and its homologues and derivatives. 

In a comprehensive review of this subject Schopf (1937) gave a preliminary description of a number of other syntheses of this kind, including that of teloidine, already referred to. Suggestions for other alkaloidal syntheses were also made and the conditions under which such reactions might take place in plants discussed. 

The method is that of DePuy and co-workers.1 2 No other syntheses of 1-arylcyclopropanols have been reported. 

Besides the oxidative and transition-metal-catalyzed condensation reactions discussed above, several other syntheses were developed to generate PPP and PPP derivatives. 

The approach makes use of a bipyrroledicarbaldehyde 54 and a tripyrranedicarboxylic acid 55 which are condensed with subsequent decarboxylation in the presence of acid and oxygen. The presence of oxygen, as in many other syntheses of porphinoid macrocycles, is necessary to adjust the oxidation level of the chromophore which is in sapphyrins a 2271-aromatic cyclically conjugated system. Many sapphyrins 56 with different substitution patterns have been synthesized according to this general scheme. As in all McDonald-type condensations at least one of the components has to be symmetric because otherwise mixtures of constitutional isomers would be formed. 

Some insect pheromones are internal ketals. We have already mentioned multistriatin (pp T 2 and 99) and frontalin p 193). Brevicomin (22) is another example. Disconnection of the ketal gives (23) containing a 1,2-diol. Among other syntheses, hydroxy-lation of protected enone (24) by epoxidation and acid catalysed rearrangement gives brevicomin stereo-specifically,... 

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