Subject pyrazines

The number of simple alkylated pyrazines and the food products with which they are associated are enormous and a few examples are listed in Table 5. Fuller reviews on this subject are available (73MI21400). 

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. 

The preparation of biologically active [l,2,4]triazolo[l,5- ]pyrazines has been reported recently. The reaction routes are shown in Scheme 50. Dowling et al. reported <2005BML4809> the synthesis of aryl-substituted derivatives 411. The first step was the transformation of the 2-aminopyrazine compound 409 to an amidine 410, which was subjected... 

Relatively few new papers have appeared on synthetic procedures for the title ring system. Some of these follow established methodologies. Thus, three reports appeared where 2-hydrazinopyrazines - or their derivatives - were subjected to ring closure to give [l,2,4]triazolo[4,3- ]pyrazines. These products - with yields and references - are shown in Table 14. 

Thus, ketone enolates easily substitute chlorine in position 2 of the electrophilic nucleus of pyrazine (1,4-diazabenzene), and even in the dark, the reaction proceeds via the Sj l mechanism (Carver et al. 1981). It is expected that the introduction of the second chlorine in the ortho position to 4-nitrogen in the electrophilic nucleus of pyrazine promotes the ion-radical pathway even more effectively. However, 2,6-dichloropyrazine in the dark or subjected to light reacts with the same nucleophiles by Sr.,2 and not S nI mechanism (Carver et al. 1983). The authors are of the opinion that two halogens in the pyrazine cycle facilitate the formation of a-complex to the extent that deha-logenation of anion-radicals in solution and a subsequent nucleophilic attack of free pyrazine radical become virtually impossible. Thus, the reaction may either involve or exclude the intermediate a-complex, and only special identification experiments can tell which is the true one. 

It is a major challenge to keep our coverage of this immense field up to date. One strategy is to publish Supplements or new Parts when merited by the amount of new material, as has been done, inter alia, with pyridines, purines, pyrimidines, quinazolines, isoxazoles, pyridazines and pyrazines. The chemistry and applications to synthesis of 1,3-dipolar cycloaddition reactions in the broad context of organic chemistry were first covered in a widely cited two-volume treatise edited by Prof. Albert Padwa that appeared in 1984. Since so much has been published on this fascinating and broadly useful subject in the intervening years, we felt that a Supplement would be welcomed by the international chemistry community, and we... 

Amino acids may also undergo thermal degradation, which is almost always coupled with some other food components, particular sugars. The major types of volatile compounds formed from amino-sugar interactions include Strecker degradation aldehydes, alkyl pyrazines, alkyl thiazolines and thiazoles and other heterocycles [35, 36]. As the subject has mainly relevance for baked and roasted vegetable food products, this subject will not be discussed in further detail. 

Heating with phosphoryl chloride converted 1 -hydroxy-3-phenyl-2( 1H )-pyrazinone (52) into the 2,5-dichloro derivative (53) via the 5-monochIoro species. It had been expected that chlorination would take place at C-6, but this occurred only to a minor extent. The observed chloride attack /3 to the oxygen function might be accounted for in terms of the sequence illustrated in Scheme 46 (86JHC149). Reaction mechanisms have been proposed to explain the observed a- and /3-chlorination when 2- and 3-substituted pyrazine Af-oxides are subjected to the Meisenheimer reaction. /3-Chlorination was rationalized in terms of electron withdrawal by the unoxidized nitrogen atom [84JCR(S)318] (Scheme 46). 

Substrate Ji-deficiency is, apparently, a critical factor. Thus, dibromovinyl derivatives of monocyclic azines, e.g. pyrimidine 92, pyrazine 93 and quinoline 94 are not subjected to this reaction (01H2139). On the contrary, lumazines 95 and pyrimidopyridazines 97 form the corresponding thiophenes 96 and 98 (Scheme 29) (03RCB1403, 05JHC413). 

Pyrazines form diquaternary salts on treatment with triethyloxonium fluoroborate. Using this reagent the 1,4-diethylpyrazinium difluoro-borates of pyrazine, 2,5-dimethyl-, and 2,6-dimethylpyrazines have been obtained in 96, 97, and 46% yield, respectively. The reaction is subject to considerable steric hindrance since the yield of diquaternary salt from tetramethylpyrazine is only 6%. The diquaternary salts are extremely reactive substances and that of the parent compound is shown by ESR measurements to be readily reducible to the radical cation [Eq. (7)].150... 

Very few imidazo[4,5-b] pyrazines have been reported in the literature1-3 and no good general method has been available for preparing compounds in this most interesting heterocyclic class. We have found that the Curtius reaction of a 3-aminopyrazine-2-carboxylic acid azide (Scheme I) proceeds with intramolecular cyclization to provide, in good yield, a wide variety of the subject compounds. We will report here only the 6-substituted 5-chloro-l, 3-dihydro-2tf-... 

After an oral dose of 3 g to one subject, a peak serum concentration of 134 pg/ml was attained in 1 hour the serum concentration of pyrazine-2-carboxylic acid was 20 to 30 pg/ml after the first hour and the concentration of 5-hydroxypyrazine-2-carboxylic acid ranged between 3 and 8 M-g/ml over a period of 12 hours (J. Roboz et al., ibid.). 

An large number of pyrazines were subjected to X-ray crystallographic analysis. Those in the realm of metal complexes included [/i-2,3,5,6-tetrakis(2-pyridyl)pyrazine]bis[chloroplatinum(II)] bis[trichloro(dimethyl sulfoxide-ir5)platinate(II)] 152 <03AX(E)411>, tetraaqua-1,2,4,5-benzenetetracarboxylato(pyrazine)dicobalt(II) dihydrate <03AX(E)841>, polymeric... 

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