A-Amino heterocycles

Other A-amino heterocycles upon oxidation with DIB were converted through nitrenes into aziridines [64],... 

The reaction of a-mercapto-A-amino heterocycles with acylating agents leads to fused 1,3,4-thiadiazoles. In general, the dehydration step is carried out with phosphorus oxychloride. The method has been used to prepare imidazo[2,l-6][l,3,4]thiadiazoles (63LA(663)113) and s-triazolo[3,4-6][l,3,4]thiadiazoles (64CI(L)1919> (equation 29). 

Thiocyanates 55a,h with A-amino heterocycles produced N,N -linked isothiazolium salts 67a-c (06ZN(B)464, Scheme 17, see also Scheme 19). 

However, when 36 was heated with a-amino heterocycles or with cyclic 1,3-dicarbonyl or potential 1,3-dicarbonyl compounds, 3-heteroarylp)rr-azol derivatives were obtained. In this manner 36 afforded, when heated with 2-aminopyridine and 3-amino-lH-pyrazol in acetic acid under reflux for 2 h and 5 h, respectively, 3-(5-ethoxy-l-phenyl-lH-pyrazol-3-yl)-4H-pyrido[l,2-fl]pyrimid-4-one (38) and 6-(5-ethoxy-l-phenyl-lH-p5rrazol-3-yl)pyrazolo[l,5-fl]pyrimid-7(lH)-one (39) in 70% and 77% 5deld, respectively. Similarly, 36 afforded with cyclicjS-dicarbonyl compounds, such as 4-hydroxy-6-methyl-2H-pyran-2-one and 5,5-dimethylcyclohexane-l,3-dione by heating in acetic acid for 4 h and 8 h, respectively, the corresponding 3-(5-ethoxy-l-phenyl-lH-pyrazol-3-yl)-7-methyl-2H,5H-pyrano[4,3- 7]pyran-2,5-dione (40) and 3-(5-ethoxy-l-phenyl-IH-pyrazol-3-yl)-7,7-dimethyl-7,8-dihydro-2H-chromene-2,5-dione (41) in 26% and 82% yield, respectively (Scheme 15). 

Oxidation of Hydrazones, Alkylhydrazones, A-Amino Heterocycles, A-Aminophthalimidates, and Aldazines. The oxidation of hydrazones to diazo compounds is not a generally useful reaction but it was uniquely effective in the oxidation of a triazole derivative (eq 36). ... 

A general synthetic route to N-bridgehead condensed heterocyclic structures incorporating a 1,2,4-thiadiazole ring consists of the interaction of an a-amino-heterocyclic compound with chlorothioformyl chloride (84) or ethyldithiocarbonyl chloride (85). The reaction is widely applicable, as shown. 

A novel method for preparing amino heterocycles is illustrated by the preparation of 2-amino-5-methylthiophene (159). In this approach vinyl azides act as NH2 equivalents in reaction with aromatic or heteroaromatic lithium derivatives (82TL699). A further variant for the preparation of amino heterocycles is by azide reduction the latter compounds are obtained by reaction of lithio derivatives with p- toluenesulfonyl azide and decomposition of the resulting lithium salt with tetrasodium pyrophosphate (Scheme 66) (82JOC3177). 

Cyclization reactions effected by intramolecular attack of the heteroatom on a nitrile group provide a useful source of 2-amino heterocycles. Some illustrative examples are depicted in Scheme 16. 

Hexafluoroacetone and certain perfluorinated or partially fluorinated ketones, aldehydes, and imines react with a-functionalized carboxylic acids (e.g., a-amino, a-At-methylamino [S3, 84], a-hydroxy [S5], and a-mercapto [Sd] acids) to give five-membered heterocyclic systems (equation 13). 

Recently the Bohlmann-Rahtz synthesis has received greater attention. Baldwin has employed this method for the construction of heterocyclic substituted a-amino acids. Exposure of alkynyl ketone 39 to 3-aminocrotoyl ester 40 resulted in the Michael product 41. Thermolysis then gave rise to the desired pyridyl-P-alanines 42. 

G. Amino Group as Part, of a Fused Heterocyclic Ring. . . 426... 

In spite of the fact that the vast majority of quaternizations of amino-heterocyclic compounds are reported as occurring on the ring nitrogen atom only, it seems quite likely that salt formation may also take place on the exocyclic nitrogen in other cases but that it has been overlooked in the absence of a test such as was available for 4. 

Heterocyclizations by reactions of electrophilic carbenes with a-amino acids derivatives 97T3425. 

Aziridine esters are a- and -amino acid derivatives at the same time. A characteristic reaction of a-amino acids is their reaction with triethylboron to give boroxazolidines. We showed that aziridinecarboxylic acids exhibit the expected behavior in their reaction with triethylboron, viz., that they form stable boroxazolidines 34 (Scheme 19) [29]. These boron heterocycles can be reconverted into the free amino acids by treatment with 8-hydroxyquinoline. 

Kricheldorf HR (1987) a-Amino acid N-carboxyanhydrides and related heterocycles. Springer, Berlin... 

At the present time, the coupling is usually done via an activated ester (see Section 3.4). The coupling reagent and one of several A-hydroxy heterocycles are first allowed to react to form the activated ester, followed by coupling with the depro-tected amino group. The most frequently used compounds are A-hydroxysuccinimide, 1-hydroxybenzotriazole (HOBt), and l-hydroxy-7-azabenzotriazole (HOAt).47... 

In other words, a synthetic route to polypeptides which requires only HCN and water is presented preformed a-amino acids are not necessary. According to Matthews, the pyrolysis of cyanide polymers can give nitrogen-containing heterocycles with purine and pyrimidine structures in other words, the HCN world ... 

Amino-8-cyano-3-methyl-4-oxo-6/7-[l,2,4]triazino[3,4-7][l,3,4]thiadiazine 16 when reacted with phenacyl bromide in the presence of triethylamine in acetonitrile afforded a novel heterocyclic system 27 (Equation 1) <2004IJH181>. 

The regio- and stereochemical outcome of the intermolecular 1,3-dipolar cycloaddition of an azomethine ylide generated by the decarboxylative condensation of an isatin with an a-amino acid was unambiguously determined by a single-crystal X-ray study of the spirocyclic heterocycle 49 (R1 =4-Br, R2 = H, X = CH2) <1998TL2235>. 

Using a semiempirical SCF MO it approximation, the tautomerism of several amino heterocycles has been studied (70JA2929). From the theoretical heats of atomization of the tautomers of 4-aminoimidazole (181a-d), it was suggested that there would be a slight predominence of 1-//-4-... 

Strecker aldehyde are generated by rearrangement, decarboxylation and hydrolysis. Thus the Strecker degradation is the oxidative de-amination and de-carboxylation of an a-amino acid in the presence of a dicarbonyl compound. An aldehyde with one fewer carbon atoms than the original amino acid is produced. The other class of product is an a-aminoketone. These are important as they are intermediates in the formation of heterocyclic compounds such as pyrazines, oxazoles and thiazoles, which are important in flavours. 

Substituted derivatives of l-(tetrahydrobenzo[b]thiophen-2-yl-3-carboxylate)-5-phenyl-6-thio-l,2,4-triazin-4-one have been synthesized by heterocyclization reactions of different hydrazones obtained from 2-amino-tetrahydrobenzo[b]thiophene-3-carboxylate with phenyl isothiocyanate <00PS275>. Reaction of 5-methyl isothiosemicarbazide with a-amino acid vicinal tricarbonyl reactive substrates 1 and 2 yields 1,2,4-triazine substituted a-amino acids, as an equimolar mixture of regioisomers 3a/3b and 4a /4b, respectively <00JCS(P1)299>. 

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