Ring closure heterocyclic compounds

Heterocyclic ring closure of o-hydroxylated or o-acylated styrene, stilbene, and stilbazole derivatives. This group includes miscellaneous methods, the final stage of which involves ring closure of compounds as in Eq. (2). Starting from o-acyloxystilbenes, the reaction provides... 

Polyfluorinated a-diketones react with 1,2-diainino compounds, such as ortlio-phenylenediamine, to give 2,3-substituted quinoxalmes [103] Furthermore, the carboxyl function of trifluoropyruvates offers an additional electrophilic center. Cyclic products are obtained with binucleophiles [13, 104] With aliphatic or aromatic 1,2-diamines, six-memhered heterocycles are formed Anilines and phenols undergo C-alkylation with trifluoropyruvates in the ortho position followed by ring closure to form y-lactams and y-lactones [11, 13, 52, 53, 54] (equation 23). 

Once formed, 7 and 8 undergo a Michael reaction that gives rise to ketoenamine 9. Ring closure, to form 10, and loss of water then afforded 1,4-dihydropyridine 11. The presence of 9 and 10 could not be detected thus ring closure and dehydration were deduced to proceed faster than the Michael addition. This has the result of making the Michael addition the rate-determining step in this sequence. Conversely, if the reaction is run in the presence of a small amount of diethylamine, compounds related to 10 could be isolated. Diol 20 has been isolated in an unique case (R = CFb). Attempts to dehydrate this compound under a variety of conditions were unsuccessful. Stereoelectronic effects related to the dehydration may be the cause. In related heterocyclic ring formations, it has been determined that dehydration (20 —> 10) is about 10 times slower than diol formation (19 —> 20). Therefore, one would expect 20 to... 

As shown by Heindel and Corley (1979), ring closure also takes place if the nucleophilic nitrogen is part of a heterocycle, as in the diazotization of 5-amino-3-methyl-2-H-l,2,4-benzothiadiazine-l, 1-dioxide (6.50). In the tricyclic compound 6.51 formed initially, the thiadiazinedioxide ring is opened rapidly in water, forming 1-acetyl-7-aminosulfonyl-l-i/-benzo-l,2,3-triazole (6.52). 

Pyrazolopyrazoloquinoline derivatives can be prepared by treatment of pyrazolidin-3-one with 2-chloroquinoline-3-carbaldehyde, which gives firstly the zwitterionic compound 283. Reduction with sodium borohydride followed by ring closure in basic media gives the fused tricyclic heterocycles (Scheme 77) <1991T9599>. 

Five-membered ring heterocycles can be the result of cycloaddition reactions of ADC compounds acting as 2n components with 1,3-dipoles, or as 47t components in cheletropic reactions. They can also result from nucleophilic attack on the ADC compound, followed by ring closure of the initial adduct. 

This chapter deals with thermal ring-closure reactions of dienes and polyenes resulting in carbocyclic compounds the formation of heterocycles is mentioned only occasionally. The account is highly selective, concentrating on recent work, since two comprehensive general reviews have appeared1,2. Other pertinent reviews are cited at appropriate places in the text. 

Catalysed alkylation of tosylmethylisocyanate (TOSMIC) [63, 64] has extended its versatility in the preparation of l, 4-dicarbonyl compounds and as a l, 3-dipolar precursor for the synthesis of heterocyclic compounds. The alkylation reactions should not be conducted in carbon disulphide, as nucleophilic attack by the methylene group on the carbon disulphide leads, after ring closure and S-alkylation, to a 4-alkylthio-1,3-thiazole system [65]. 

Since in the synthesis of heterocyclic compounds the ring closure usually involves the formation of the carbon-heteroatom bond, in the retrosynthetic analysis the first bond to be disconnected is the carbon-heteroatom bond (Cf. heuristic principle HP-8), either directly or after the pertinent (FGI or FGA) functional group manipulation. For instance, compound 17 -which is the starting material for Stork s synthesis of Aspidosperma alkaloids [30]- may be disconnected as shown in Scheme 6.11. 

Gamez-Montaho et al. described an Ugi variation where the carboxylic acid was replaced with an amide [68]. The amide oxygen is nucleophilic enough to effect ring closure to oxazole intermediates 44, which then undergo aza-Diels-Alder reaction with the double bond of the allylic amine component to form oxa-bridged heterocycles 45, which can either be isolated as a separate class of compounds or converted to pyrrolopyridines 46 by treatment with TEA (Scheme 8). 

The two reaction modes of the Michael adducts 145 demonstrate two general principles for the possible preparation of ordinary size heterocyclic compounds from the chlorocyclopropylideneacetates 1,2. Thus, either the heterocycles 153 can be formed by Michael addition of a bidentate nucleophile 150 onto the chloro ester 1-Me and subsequent ring closure of the intermediate 151 [26] by nucleophilic substitution of the chlorine atom at the newly formed sp carbon center adjacent to both the carbonyl and the cyclopropyl group (Route B in Scheme 48). Alternatively, the intermediate 151 can cyclize by nucleophilic attack on the ester moiety to give heterocycles of type 152 (Route A in Scheme 48) [26]. 

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