Amination of pyrazines

There is one report describing the oxidative amination of pyrazine, using potassium amide as nucleophile, liquid ammonia at — 35°C as solvent and... 

Pyrazine is aminated to 2-aminopyrazine with sodium amide in liquid ammonia at room temperature (606), in solvents such as dioxane or pyridine at room temperature or above (yields to 16%), or in the absence of added solvent at 50-55 (yields 36-60%) (607). N.m.r. evidence has been obtained for the anionic a complex (2) in the amination of pyrazine (608). 3-Substituted 1-methylpyrazinium ions... 

R = Me) have been synthesized by A/-amination of pyrazine derivatives with hydroxylamine-D-sulfonic acid (H2NOSO2H) as the potassium salt, and later addition of hydriodic acid (610). 

A -Amination of pyrazine 1-oxide and 2,5-dimethylpyrazine 1-oxide has been effected with hydroxylamine-O-sulfonic acid and hydriodic acid to give 4-aminopyrazinium 1-oxide iodide (40, R = = H) and 4-amino-2,5-dimethyl-... 

The direct amination of pyrazine and alkylpyrazine has been discussed in Sections IV. 1C and 1V.2C (8), respectively. 

Treatment of a-hydroxy-ketones or -aldehydes with ammonium acetate (65BSF3476, 68BSF4970) results in the formation of dihydropyrazines, presumably by direct amination of the hydroxyketone followed by self-condensation (79AJC1281). Low yields of pyrazines have been noted in the electrolysis of ketones in admixture with KI and ammonia, and again it appears probable that the a-aminoketone derived by way of the a-iodoketone is the intermediate (69CI(L)237>. 

Analogous photoadditions have been observed on irradiation of pyrimidine and purine bases in ethers and amines. Irradiation of 1,3-dimethylur-acil (314) in tetrahydrofuran leads to the formation of 5- and 6-(tetrahydro-furan-2-yl)-5,6-dihydrouracils 315 and 316.261 Similarly, solvent adducts arising by way of initial hydrogen abstraction have been obtained on irradiation of pyrazine derivatives in diethyl ether or tetrahydrofuran.262 The... 

The reaction is one of the few examples of a degenerate ring transformation in pyrazine chemistry. Extensive investigations on the amination of 2-chloroquinoxaline have shown that in the formation of the 2-amino compound no Sn(ANRORC) process is involved (72RTC850). 

The Chichibabin amination of phenylpyrazine with N-labeled potassium amide/liquid ammonia gave two products, 3-amino- and 5-amino-2-phenylpyrazine in both products the label is only present in the amino group, and no label was found to be incorporated into the pyrazine ring (82MI1). This result proves that in the aminodehydrogenation of phenylpyrazine, no Sn(ANRORC) mechanism is involved. This result is confirmed by the fact that amination of phenylpyrazine in the presence of the radical scavenger azobenzene, a compound that has been found to prevent the Sn(ANRORC) mechanism in the Chichibabin amination of 4-phenylpyrimidine, still yields both aminopyrazines. 

Although there have been few new developments in the period since 1993, halogenopyrazines 42 have been convenient precursors for a variety of pyrazine derivatives. For example, the halogenopyrazines 42 are cyanated by palladium-catalyzed cross-coupling with alkali cyanide or by treatment with copper cyanide in refluxing picoline, to yield cyanopyrazines 48. Alkoxypyrazines 49 are produced by treatment with alkoxide-alcohol, and aminopyrazines 50 are prepared by amination with ammonia or appropriate amines. The nucleophilic substitution of chloropyrazine with sodium alkoxide, phenoxide, alkyl- or arylthiolate is efficiently effected under focused microwave irradiation <2002T887>. 

The formation of pyrazines in foods has been reviewed extensively by Mega and Sizer (50). Temperature and pH are very important factors in the formation of specific pyrazines. Forty-two pyrazines have been identified in meat from various sources by these authors. MacLeod and Seyyedain-Ardebili (20) listed 49 pyrazines found in beef by various investigators. Ching (19) identified 28 pyrazines in her studies of sugar-amine reactions simulating beef flavor. 

Several mechanisms have been reported for pyrazine formation by Maillard reactions (21,52,53). The carbon skeletons of pyrazines come from a-dicarbonyl (Strecker) compounds which can react with ammonia to produce ot-amino ketones as described by Flament, et al. (54) which condense by dehydration and oxidize to pyrazines (Figure 6), or the dicarbonyl compounds can initiate Strecker degradation of amino acids to form ot-amino ketones which are hydrolyzed to carbonyl amines, condensed and are oxidized to substituted... 

The cooked aroma of E paclfica (Pacific krill) is fishy and relatively unacceptable. Its GC profile is quite different than that of other samples, because N,N-dimethyl-2-phenylethyl amine was a principal volatile component while only small quantity of pyrazine and thialdine were observed (see Table I). This amine was not produced by cooking, it occurs in vivo (27). Volatiles from both raw and boiled (85°C, 90 min) E. pacifica were prepared by steam distillation under reduced pressure (20 Torr). 

P. E. Koehler and G. V. Odell, Factors affecting the formation of pyrazine compounds in sugar-amine reactions, J. Agric. Food Chem., 1970, 18, 895-898. 

Pork fat contains more unsaturated fatty acids than beef and its linoleic acid content is double that in beef. Heat produced volatiles in red meat fats are listed in Table IV. The presence of pyrazines in the volatiles of beef fat is due to the presence of nitrogenous compounds in the fat amounting to 0.1-0.2%N, (Kjeldhal method). These compounds might be proteins, peptides, amino acids, and amine moities in polar lipids. Such compounds... 

Aminopyrazines are conveniently prepared from carboxamido-pyrazines by application of the Hofmann reaction (see Section V,B). Thus, Camerino and Palamidessi prepared aminopyrazine in 80% yield from carboxamidopyrazine.312 Aminopyrazine may also be prepared from the reaction of pyrazine with sodamide in liquid ammonia,313 and 3-amino-2,5-dimethylpyrazine is the product of amination of 2,5-dimethylpyrazine with sodamide in dimethyl-aniline.311 The ammonolysis of halopyrazines also represents a useful preparative procedure for aminopyrazines (see Section V,C). This reaction proceeds most easily in the case of fluoro compounds for example, fluoropyrazine is converted into aminopyrazine in 70% yield by treatment with concentrated aqueous ammonia at room temperature for 3 days,299 whereas the corresponding reaction with chloropyrazine has been carried out in a sealed tube at 150°.147 Alkaline hydrolysis of 2,4-dihydroxypteridines followed by decarboxylation yields aminopyrazines 315 thus, high-temperature alkaline hydrolysis of 7-methyl-2,4-dihydroxypteridine (7-methyIlumazine) gives, after decarboxylation of the intermediate pyrazinecarboxylic... 

Comparative A -oxide activation was likewise observed when other amines such as hexylamine, aniline, benzylamine, piperidine, and dimethylamine were used. It was also noted, in every example studied, that amination of the chloropyrazine A -oxide or alkylchloropyrazine 7V-oxide at elevated temperatures in a sealed vessel gave mixtures containing greater or lesser amounts of deoxygenated halogeno-pyrazine or aminopyrazine (921). Similar enhanced activation by theTV-oxide group was observed when 3-chloro-2,5-dimethylpyrazine and its 1-oxide in reaction with various amines were compared, although dialkyl substitution further retarded overall aminolysis (793,921). 

High-speed Pd-catalyzed amination of 2-chloropyrazine with 2V-methylaniline under temperature-controlled microwave heating produced 2-(7V-methyl-7V-phenyl)pyrazine in high yield (151) [73]. 

---