Derivatives of 4-halocrotonic acids, convenient reactants in the synthesis of heterocycles. (Review)

Abstract

Literature data are reviewed.ft." the first time on tile use of 4-halocrotonic acid derivatives in the synthesis of five-and six-memhered heterocvcles containing one or several heteroatoms in the ring, attd their atmelated attalogs.Keywords: enethiolatonitriles, condensed pyridines and pyrimidines, crotOnic acid derivatives, cascade heterocyclization.Functionally substituted crotonic acids possess a high synthetic potential, especially for obtaining various types of heterocycles. In this respect a special place is held by derivatives of 4-hatocrotonic acid containing functional groupings Z such as ester, nitrile, or carboxyl, and chlorine or bromine atoms as halogen. ,,,,~,tlal~['~ZSubstituted 4-halocrotonic acids contain several reaction centers predetermining the type of interactions in which they may participate.1. Halogen atom, readily reacting by nucleophilic substitution. 2. Methylene group in the vinylogic position to an electron-withdrawing Z group. 3. Double bond activated towards nucleophilic addition and cycloaddition by the presence of the conjugated Z group.4. Substituent R (from hydrogen atom and hydrocarbon radicals to functional groups analogous to the Z group}.5. Electron-withdrawing group Z able to being subjected to nucleophilic attack.Conversions in which derivatives of 4-halocrotonic acid are involved have been classified by us according to the reaction center participating in the reaction. Since the halogen atom is practically always subjected to nucleophilic substitution the main accent in this review is directed towards the reactions proceeding at other reaction centers.

Thienopyridines: synthesis, properties, and biological activity

“…106 It was also demonstrated 107 that the reactions can be performed under analogous conditions not only with pyridine 128 but also with 2 chloro 3 formylpyridine N oxide or 2 bromo 3 (1,3 dioxolan 2 yl)pyridine N ox ide. The latter reactions produce the corresponding thieno [b] [2,5]naphthyridine N oxides, which can also be prepared by oxidation of the parent systems with m chloroperoxybenzoic acid.…”

“…Six isomeric thienopyridine structures characterized by different annelation modes are known: thieno[2, 3 b]pyri dine (1), thieno [3,2 b]pyridine (2), thieno[2, 3 c]pyridine (3), thieno [3,2 c]pyridine (4), thieno [3,4 b]pyridine (5), and thieno [3,4 c]pyridine (6). The first four thieno pyridines were studied in most detail.…”

“…In an alternative procedure for the preparation of dithienopyridines 255-257, acetal 258 is used instead of aldehyde 252, and the reaction mixture is then treated with hydrochloric acid; however, this procedure af fords the target products (Scheme 78) in lower yields (27-63%). 160b The tricyclic skeleton of thieno[3,2 c] [1,5]naphthyri dine 9 N oxide (259) was constructed 140 in two ways: by condensation of aldehyde 252 with pyridine N oxide 198 or (in lower yield) by the modified Suzuki reaction of the latter with 3 formylthiophene 2 boronic acid (260) (Scheme 79).…”

“…64b6,9 Dihydropyrido[3´,2´:4,5]thieno[3,2 d]pyrimidines were successfully prepared by the reaction with the use of the corresponding 1,4 dihydropyridine 2 thiolates 19 in stead of thiones 7. 62a,86a This approach made it possible to synthesize pyrimidothieno[2,7]naphthyridine deriva tive 85 starting from tricyclic structure 86 (Scheme 25).…”

Synthesis of pyrido[2',3':3,4]cyclopenta-[1,2-c]isoquinoline, a new heterocyclic system

“…We note that this is the first report of malononitrile 4 used for the synthesis of a condensed cyclopentane ring. This compound has been previously employed as an alkylating agent for the preparation of heterocycles [5].…”