Methylpyrazines

Figure C3.3.6. Doppler-line profiles for molecules scattered into the CO COO O J= 72) state by collisions with hot methylpyrazine molecules as depicted by the equations above each half of the figure. The energy of methylpyrazine...

Methylpyrazine reacts with sodamide in liquid ammonia to generate the anion, which may be alkylated to give higher alkylpyrazines (Scheme 10) (61JOC3379). The alkylpyrazines have found extensive use as fiavouring and aroma agents (see Section 2.14.4). Condensation reactions with esters, aldehydes and ketones are common, e.g. methyl benzoate yields phenacylpyrazine in 95% yield, and reactions of this type are summarized in Scheme 11. 

Bromination using NBS has been used to provide acetylpyrazine derivatives from the corresponding ethylpyrazines. Bromination of 2-ethyl-3-methylpyrazine gives 2-bromoethyl-3-methylpyrazine in quantitative yield this may be oxidized using the sodium salt of 2-nitropropane or with pyridine AT-oxide to yield 2-acetyl-3-methylpyrazine in yields of 66 and 25% respectively (Scheme 14). 

The ease of oxidation varies considerably with the nature and number of ring substituents thus, although simple alkyl derivatives of pyrazine, quinoxaline and phenazine are easily oxidized by peracetic acid generated in situ from hydrogen peroxide and acetic acid, some difficulties are encountered. With unsymmetrical substrates there is inevitably the selectivity problem. Thus, methylpyrazine on oxidation with peracetic acid yields mixtures of the 1-and 4-oxides (42) and (43) (59YZ1275). In favourable circumstances, such product mixtures may be separated by fractional crystallization. Simple alkyl derivatives of quinoxalines are... 

Side chain reactivity is also enhanced and is typified by the difference in reactivity of 2-methylpyrazine and 2-methylpyrazine 1,4-dioxide towards anion formation and subsequent condensation reactions. 2-Methylpyrazine undergoes condensation with benzal-dehyde at 180 °C, with zinc chloride catalysis, to yield the styrylpyrazine (58), whereas the corresponding reaction of 2-methylpyrazine 1,4-dioxide proceeds at 25 °C under base catalysis (67KGS419). 

Methylpyrazine-2-carboxylic acid p-(/3-Aminoethy )benzenesulf onamide... 

CjjHjjOj 35363-65-6) see Dimethisterone methyl pyrazine-2-carboxylate (QH N202 6164-79-0) see Pyrazinamide 5-methyl-2-pyrazinecarboxylic acid (QHfiN202 5521-55-1) see Adpimox Glipizide 5-methylpyrazine-2-carboxylic acid see under 5-methyl-2-pyrazinecarboxylic acid... 

Lonza, for example, has commercialized processes for highly chemo- and regioselective microbial ring hydroxylation and side-chain oxidation of heteroaromatics (see Fig. 2.32 for examples) (Kiener, 1995, 1999). The pharmaceutical intermediate 5-methylpyrazine-2-carboxylic acid, for example, is manufactured by microbial oxidation of 2,5-dimethylpyrazine. Many conversions of the type shown in Fig. 2.32 would not be possible by conventional chemical means. 

It has been discovered that direct chlorination of pyrazines can be accomplished and this has also been used to make candidate drugs. For example, when 2-methylpyrazine (120) is heated with chlorine in carbon tetrachloride, a mixture of the 3-chloro (121) and the 6-chloro derivatives result. After separation, 121 is heated with piperidine to give modaline (122), an antidepressant. 6... 

Methylpyrazine-2- Acipimox Anti-lipolytic Oxidation Pseudomonas putida Single-stage fermentation [6]... 

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