Tetra pyrazine

Classic A/-heterocychc ligands, eg, bipyridyl (bipy), terpyridyl, imidazole, pyrazine, phenanthroline, piperazine (including alkyl- and aryl-substituted derivatives), and polypyrazol-l-yl-borates (bis, tris, and tetra), have all been found to coordinate Th(IV) chlorides, perchlorates, and nitrates. The tripodal hydrotris(pyrazolyl)borates, HBPz, have been used to stabilize organometaHic complexes (31). Bis-porphyrin Th(IV) "sandwich" complexes have been... 

Direct halogenation of quinoxaline appears to be of limited value but pyrazine may be chlorinated in the vapor phase to give monochloropyrazine at 400 °C or at lower temperatures under catalytic conditions 72AHC(14)99, and at higher temperatures tetra-chloropyrazine formation occurs in high yields. Mention has already been made of direct chlorination (see Section 2.14.2.1) of phenazine. 

The fusion of a benzene ring to pyrazine results in a considerable increase in the resistance to reduction and it is usually difficult to reduce quinoxalines beyond the tetrahydroquinoxa-line state (91). Two possible dihydroquinoxalines, viz. the 1,2- (92) and the 1,4- (93), are known, and 1,4-dihydroquinoxaline appears to be appreciably more stable than 1,4-dihydropyrazine (63JOC2488). Electrochemical reduction appears to follow a course anzdogous to the reduction of pyrazine, giving the 1,4-dihydro derivative which isomerizes to the 1,2- or 3,4-dihydroquinoxaline before subsequent reduction to 1,2,3,4-tetra-hydroquinoxaline (91). Quinoxaline itself is reduced directly to (91) with LiAlH4 and direct synthesis of (91) is also possible. Tetrahydroquinoxalines in which the benzenoid ring is reduced are well known but these are usually prepared from cyclohexane derivatives (Scheme 30). 

Ring reductions in the pyridopyrazine series have been achieved with a wide variety of agents, and may lead to di- or tetra-hydro derivatives, usually in the pyrazine ring. 

Second only to sulfur-based systems, nitrogen complexes are relatively well represented in the structural literature with 41 complexes reported. Of these, 25 are with I2 as the electron acceptor, 11 are with the interhalogen IC1, three are with Br2, and two are with IBr. As expected, in every case the halogen bond forms between the nitrogen and the softest halogen atom, i.e., iodine, in all of the complexes except those with dibromine. Most N I2 complexes, and all N Br2, N IBr, and N IC1 complexes are simple adducts, mode A. Exceptions for the diiodine complexes include bridging mode (B) observed for diazines, such as pyrazine [86], tetramethylpyrazine [86], phenazine, and quinoxaline [87], and for 9-chloroacridine [89] and the 1 1 complex of diiodine with hexamethylenetetramine [144] and amphoteric bridging mode (BA) observed for 2,2 -bipyridine [85], acridine [89], 9-chloroacridine [89], and 2,3,5,6-tetra-2/-pyridylpyrazine [91]. The occurrence of both B and BA complexes with 9-chloroacridine, and of B and A complexes and an... 

The versatility of the quinolyl derivative (295) is exemplified in the complex [Ru(295-A,A )(295-A,A, A")C1]. The coordination behavior of (295) has been compared with those of (296) and (297) and factors influencing didentate vs. tridentate preferences have been examined. Perchlorate salts of [Ru(tpy)L)] " and [RUL2] where L = (298)-(300) have been synthesized and characterized, and their properties compared with those of [Ru(tpy)2] ". Complexation of Ru with 2,6-bis(4 -phenyl-2 -quinolyl)pyridine (L) affords [RUL2] , spectrosccmic properties of which have been discussed. " The bis(7 -methyl)-derivative of this ligand, L, has also been prepared and incorporated into the complexes [M(L )2f, [ (L CIs] (M = Ru, Os), and [Ru(L )(tppz)] + where tppz = 2,3,5,6-tetra(2 -pyridyl)pyrazine. Related cyclometallated complexes have also been studied. All the complexes luminesce at 77 K and [M(L )2] (M = Ru or Os), [Ru(L )(L )] , and two of the cyclometallated species are luminescent at room... 

In the reaction of ammonia with l,3,4,5-tetra-0-benzoyl-/3-n-fructopyranose, a significant proportion of benzoic acid was formed, indicating that the ammonolysis of the sugar ester occurred to a certain extent through acyloxy-group rupture. As neither the formation of imidazole nor of pyrazine derivatives (see Section VI,3, p. 124) re-... 

Pteridones behave electrochemically akin to quinoxaline, the pyrazine ring being reduced. In the first, reversible step of 6-methyl-2-amino-4(3//)-pteridone (225 R = H), a 5,8-dihydro derivative (226) is formed, which in a pH-dependent reaction tautomerizes to the more stable 7,8-dihydro compound 227 227 is reduced in acidic and neutral solution to the 5,6,7,8-tetra-hydro derivative 228, which may be oxidized to a quinonoid dihydro compound (229) 227 is formed on tautomerization of 229358-362 [Eq. (126)]. 

Tetra-r-butylpyridazine (34) is converted into its Dewar isomer (35) when irradiated in pentane with UV light of wavelength > 300 nm. Irradiation of this product at shorter wavelengths, or thermolysis, gives rise to further reaction (91TL57). Irradiation of 4-amino-2,6-dimethylpyrimidine gives the acyclic amino imine via the Dewar pyrimidine as shown in Scheme 2a. The photoisomerization of perfluoropyridazines to pyrazines is considered also to involve Dewar diazine intermediates. 

Pyrazine is chlorinated at 400°C to give a mixture of mono-, di-, tri- and tetra-chloropyrazines, presumably by a free radical mechanism. 

The treatment of l-(carboxylmethyl)-4-oxo-l,4-dihydropyridine-2-carboxamide 330 with (COCl)2 in the presence of catalytic amount of DMF at room temperature for 1.5 h afforded l,3,8-trioxo-l,2,3,4-tetra-hydro-8H-pyrido[l,2-fl]pyrazine-7-carboxamide 331 (06WOP2006/ 000824). 

The formation of some pyrroles, pyrrolines, pyrrolidines, pyridines, and tetra-hydropyridines were considered above. Next come the pyrazines, a very important group of odorants. Pyrazines have been reviewed periodically by Maga.231-233 Vemin and Parkanyi216 have tabulated 26 pyrazines, as well as 11 6,7-dihydro-(5//)-cyclopentapyrazines and 9 5,6,7,8-tetrahydroquinoxalines from 15 systems. 

Pyrazines occur naturally, although not in appreciable quantities. Fusel oil contains 2,5-dimethyl-, 2,5-diethyl-, trimethyl-, and tetra-methylpyrazine. The last compound has been isolated from cultures of Bacillus natto and B. subtilis and from fermented soybeans.4-6 Emimycin (pyrazine-2-one-4-oxide), a powerful antibiotic, has been obtained from Streptomyces No. 2020-1.7,8... 

The self-condensation of two molecules of an a-aminoketone to a 2,5-dihydropyrazine and subsequent oxidation represents an important method for the preparation of 2,5-disubstituted and 2,3,5,6-tetra-substituted pyrazines. The second step may proceed spontaneously in the presence of air, or be carried out with oxidizing agents such as hydrogen peroxide or mercuric chloride. The required a-aminoketones are by no means easily accessible intermediates and an alternative route to tetrasubstituted pyrazines has been developed which involves... 

Pyrazinetetracarboxylic acid is converted into tetra(trifluoro-methyl)pyrazine by the action of sulfur tetrafluoride [Eq. (13)].244... 

Methylated 1,4-dihydropyrazines (1,2,4-tri-, 1,2,4,5-tetra-, and 1,2,4,6-tetramethyl) as well as imidazolines have been isolated from the reaction of sucrose with methylamine at high temperatures (120°-260°), for prolonged reaction periods (18 hours) and in the presence of ammonium phosphate as catalyst. 1,4-Dihydropyrazines are also isolated from the reaction of sucrose and ethanolamine sucrose-ammonia interaction yields a wide range of pyrazines and imidazoles.369-372... 

Dithiinopyrazines have been obtained by the cyclizations of 2,3-dichloro-pyrazine with 1,2-dimercapto compounds (Scheme 24) (75USP3853901) and double 1,4-dithiine annelation has been observed in the reaction of tetra-chloropyrazine with 1,2-dimercapto-1,2-dicyanoethylene (Scheme 24) (75USP3843644 75USP3853901). 

In each subsection, any examples of syntheses that lead directly to pyrazines usually precede any that afford di-, tetra-, or hexahydropyrazines (piperazines) in that order. Examples of any pre-1978 syntheses in each broad category may be located from the cross-references (e.g., H 49) to appropriate subsections in Barlin s parent volume.1686 Less comprehensive reviews of primary syntheses in the pyrazine series have appeared in recent years.743,1287,1426,1677... 

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