2- pyrazine hydrolysis

Most pteridines are degraded to pyrazines and when they do yield pyrimidines, these may well be the ones from which they were made. However, some useful preparations of pyrimidines from pteridines are known. Thus, reduction of pteridin-7(8//)-one (732) and subsequent hydrolysis yields N-(4-aminopyrimidin-5-yl)glycine (733) (52JCS1620) and hydrolysis of 5,8-dimethylpteridine-6,7(5Ff,8Ff)-dione (734) gives dimethyl-... 

Nitro groups have been reduced to amino groups, whilst amino groups in the 3- and 6-positions of pyrido[2,3-f ]pyrazines and in the 5-position of the [3,4-f ] isomers have been hydrolyzed to the corresponding hydroxy derivatives with alkali. Protected amino groups have been liberated by hydrolysis or reduction in deazapteridine syntheses. 

Imidazo[ 1,5-a]pyrazine, 1 -bromo-3-methyl-hydrolysis, S, 625 reactivity, 5, 625... 

A side chain carboxyl group in perhydropyrido[l,2-a]pyrazines was obtained from an ester group by acidic or alkalic hydrolysis. A side chain carboxyl group was converted into a carboxamide group by the treatment with an amine in the presence of 1-hydroxybenzotriazole (OOJAP(K)OO/ 86659). 

Ethoxycarbonylmethyl-3-(2-formylethyl)pyrazine (334) (freshly liberated from its acetal) gave a separable mixture of ethyl 6-hydroxy-5,6,7,8-tetrahydro-5-quinoxalinecarboxylate (335) its dehydration product, ethyl 7,8-dihydro-5-quinoxalinecarboxylate (336, R = Et), and the hydrolysis product, 7,8-dihy-dro-2-quinoxalinecarboxylic acid (336, R = H) [NaH, Et20, 0°C, 2 h 15%, 37%, and 37%, respectively when the aqueous workup was carried out at 0°C, product 335 predominated]. " ... 

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. 

The vinyl triflate of Komfeld s ketone has been subjected to Heck reactions with methyl acrylate, methyl methacrylate, and methyl 3-(Af-rerf-butoxycarbonyl-lV-methyl)amino-2-methylenepropionate leading to a formal synthesis of lysergic acid [259]. A similar Heck reaction between l-(phenylsulfonyl)indol-5-yl triflate and dehydroalanine methyl ester was described by this research group [260]. Chloropyrazines undergo Heck couplings with both indole and 1-tosylindole, and these reactions are discussed in the pyrazine Chapter [261], Rajeswaran and Srinivasan described an interesting arylation of bromomethyl indole 229 with arenes [262]. Subsequent desulfurization and hydrolysis furnishes 2-arylmethylindoles 230. Bis-indole 231 was also prepared in this study. 

One of the very few exceptions to the rule that the acidity of the complexed ligand exceeds that of the free ligands involves the Ru(II) complexes shown in Table 6.5. It is believed that back bonding from the filled iig orbitals of Ru(II) to unoccupied tt-antibonding orbitals of the ligands more than compensates for the usual electrostatic effects of the metal that makes the nitrogen less basic. This tt-bonding is less likely with the Ru(III) complex and its is lower than that for the protonated pyrazine (see also Sec. 6.3.3. for the effects of Ru(II) and Ru(III) on hydrolysis of nitriles). ... 

PIPERAZINES AND PYRAZINES The classical synthetic method for constructing 2-aminopyrazines is illustrated by the synthesis of ampifzine (117), a CNS stimulant. Condensation of aminomalonamide and glyoxal leads to pyrazine 114. Hydrolysis to the acid and decarboxylation gives 2-hydroxypyrazine (115). Reaction with PCl produces chloride 116, and heating with dimethylamine completes... 

Pd-catalyzed cyanation of 2-methylpyrido[3,4- ]pyrazine 95 with Zn(CN)2 in the presence of Pd2(dba)3 and dppf gave the 5-cyano derivative 96 (dba = dibenzylideneacetone). Amination, without using any base, with benzylamine converted 95 into adduct 97 in excellent yield. Hydrolysis of 95 in aqueous formic acid provided the 5-oxo derivative 98 (Scheme 4) <2003H(60)925>. 

A tetrahydropyrido[3,4-/)]pyrazine nucleus was constructed from 2,3-dimethylpyrazine 687 by chlorination with A-chlorosuccinimide (NCS) to give 2,3-bis(chloromethyl)pyrazine 688, followed by cyclization with diethyl acet-amidomalonate to pyridopyrazine 689. Hydrolysis and decarboxylation of 689 in hydrochloric acid, then esterification by action of thionyl chloride in methanol gave methyl 5,6,7,8-tetrahydropyrido[3,4-. ]pyrazine-7-carboxylate hydrochloride 690 (Scheme 32) <2003BMC433>. 

Attempts to prepare 2,3,5,6-tetraaminopyrazine (91) by Hoffman degradation of the diamide (88) were unsuccessful. This is apparently due to both intermolecular and intramolecular urea formation from the intermediate isocyanate giving a mixture of products, which upon attempted hydrolysis to 91 undergo a significant amount of attack on the pyrazine ring (70UP1). 

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