2- pyrazine, with

Reaction of 2-(benzisoxazol-3-yl)-7-[2-(3,3-tetramethylenegluta-rimido)ethyl]perhydropyrido[l,2- ]pyrazine with sodium bis(trimethyl-silyl)amide in THF at -70°, then with (+)-(camphorsulfonyl)oxaziridine gave a diastereomeric mixture of 7-[2-(2fl-hydroxy-3,3-tetramethyleneglu-trimido)ethyl] derivatives (93MIP1). 

Wall M C, Lemoff A and Mullin A S 1998 An independent determination of superoollision energy loss magnitudes and rates in highly vibrationally exoited pyrazine with . = 36,000 to 41,000 om J. Rhys. Chem. at press... 

Substitution of two carbon atoms of a benzene ring by tervalent nitrogen atoms may occur in three ways, giving rise to pyridazines (see Chapter 2.12), the pyrimidines (see Chapter 2.13) and the pyrazines, with the nitrogen atoms occupying a 1,2-, 1,3- or 1,4-disposition respectively. 

It would appear that this type of addition may not be confined to the addition of NH2 in liquid ammonia, since it has been observed that treatment of 2-chloro-3-dichloromethyl-pyrazine with an excess of methoxide results in the introduction of a methoxy group into the 6-position of the pyrazine ring (Scheme 9) (68TL5931). This reaction is best rationalized in terms of addition of the methoxide ion at the 6-position, followed by loss of chloride ion from the dichloromethyl side chain. 

No systematic study of the mass spectra of pyridopyrazines has been noted, but those of 2,3-dialkyl and 2,3-diaryl derivatives have been recorded 750MS97), and mass spectrometry has been used in the elucidation of problems in the reactions of pyrido[2,3-f ]pyrazines with amide ion (including use of and derivatives) (79JHC305), and of pyrido[2,3-f ]pyrazinium salts with indoles (78ZOR431). The mass spectra of some 1-deazaflavins have been recorded (74JCS(P1)1965). 

Oxidation of 8-hydroxylperhydropyrido[l,2-u]pyrazines with SOs-pyr-idine complex at 0°C in DMSO in the presence of NEts afforded 8-0x0 derivatives (00JAP(K)00/86659). 

Maldotti (96) studied the kinetics of the formation of the pyrazine-bridged Fe(II) porphyrin shish-kebab polymer by means of flash kinetic experiments. Upon irradiation of a deaerated alkaline water/ethanol solution of Fe(III) protoporphyrin IX and pyrazine with a short intense flash of light, the 2 1 Fe(II) porphyrin (pyrazine)2 complex is formed, but it immediately polymerizes with second-order kinetics. This can be monitored in the UV-Vis absorption spectrum, with the disappearance of a band at 550 nm together with the emergence of a new band due to the polymer at 800 nm. The process is accelerated by the addition of LiCl, which augments hydrophobic interactions, and is diminished by the presence of a surfactant. A shish-kebab polymer is also formed upon photoreduction of Fe(III) porphyrins in presence of piperazine or 4,4 -bipyridine ligands (97). 

Stereostructures of a co-crystal of (li )-l- 4-[(9aA)-perhydropyrido[l,2- ]pyrazin-2-yl]phenyl -2-phenyl-7-hydroxy-l, 2,3,4-tetrahydroisoquinoline with ERa-LBD301-553/C — S triple mutant <2005JME364> and iV-[2-(4-hydroxyphenyl)ethyl]-a-propyl-3-[(4-hydroxyphenyl)methyl]-l,4-dioxo-l,2,3,4,ll,l la-hexahydro-67/-pyrazino[l,2- ]isoquinoline-3-acetamide with fructose-1,6-biphosphatase <2003JBC51176> were determined by X-ray crystallography. The structure of a complex formed from 3-[( -methylphenyl)amino]-4-[(4-methylphenyl)imino]-4//-pyrido[l,2-tf]pyrazine with sodium bis(trimethylsilyl)amide and (norbornadiene)Mo(CO)4 in THF was characterized by single crystal X-ray diffraction <1995JPR38>. 

H NMR spectra of a 1 2 adduct of pyrazine with 2,2-pentamethylene-l-boraadamantane are temperature dependent implying an equilibrium between two rotamers 17a and 17b in solutions (Figure 5) <20040L313>. 

Corsaro and co-workers studied the reaction of pyridazine, pyrimidine, and pyrazine with benzonitrile oxide and utilized H NMR spectral analysis to determine the exact structure of all the cyclized products obtained from these reactions <1996T6421>, the results of which are outlined in Table 1. The structure of the bis-adduct product 21 of reaction of pyridazine with benzonitrile oxide was determined from the chemical shifts of the 4- and 5-isoxazolinic protons at 3.76 and 4.78 ppm and coupled with the azomethine H at 6.85 ppm and with the 5-oxadiazolinic H at 5.07 ppm, respectively. They determined that the bis-adduct possessed /(-stereochemistry as a result of the large vicinal coupling constant (9.1 Hz). Similarly, the relative stereochemistry of the bis-adducts of the pyrimidine products 22-25 and pyrazine products 26, 27 was determined from the vicinal coupling constants. 

A test library with three novel p38a inhibitory activity has been prepared, among them pyrazolo[3,4-c/]pyrimidine and pyrazolo[3,4-h]pyrazine with potent in vivo activity <06BMCL262>. A convenient route for the synthesis of pyrazolo[3,4-<7]pyrimidine involving Friedlander condensation of 5-aminopyrazole-4-carbaldehyde with formamide or benzamide has been reported <06JHC1169>. A facile synthesis of pyrazolo[3,4-<7]pyrimidines and pyrimido[4,5-<7]pyrimidin-4-one derivatives has been published <06SC2963>. 

Relevant examples of enantioselective hydrogenation of aromatic N-heterocycles are given below. Scheme 16.21 shows the hydrogenation of a 2-ester substituted piperazine to the corresponding 2-substituted pyrazine with a catalyst... 

Ring Synthesis of Fused Pyridazines, Pyrimidines, and Pyrazines with Oxygen, Sulfur,... 

Another experiment used cod liver oil, crude krill extract, and the krill odor components trimethylamine and pyrazine, with phenylethanol (rose odor) as control. Several procellariiform species were attracted to krill extract. The krill odor components attracted giant petrels, cape petrels, blue petrels, Antarctic petrels, Kerguelen petrels, and black-browed albatrosses. Cape petrels were more attracted to trimethylamine than to pyrazine and cod liver oil hut blue petrels responded most to cod liver oil (Nevitt, 1999). 

The H, and NMR spectra of mono-, di-, and trisubstituted pyrazines with acetyl, alkyl, alkoxy, and methylthio substituents were reported <2000MRC907>. The assignment of chemical shifts to the ring carbons and nitrogens were verified by H, and H, correlation spectra, respectively. In the proton spectra of monosubstituted pyrazines, the /(h,h) coupling constants are V(h-s, h-6) = 2.49-2.83 Hz, h-S) = 0.27-0.36 Hz,... 

The pyrazine ring is stable toward permanganate oxidation, and this explains a variety of pyrazinecarboxylic acids that have been prepared from quinoxalines or benzo-fused quinoxalines. In contrast, alkyl side chains on pyrazines are effectively oxidized by permanganate, selenious acid, selenium dioxide, or dichromate to afford the corresponding carboxylic acids (Section 8.03.7.1). Oxidation of pyrazines with hydrogen peroxide or percarboxylic acids gives pyrazine A -oxides and/or A, A -dioxides (Section 8.03.5.2). 

Treatment of 6-amino-3-phenylpyrido[2,3-/)]pyrazine with allyl isothiocyanate afforded the thioureido derivative... 

Pyrazine 168 underwent cross-coupling with propyne in the tri-o-tolylphosphine, and copper(l) iodide to provide 170. The isocyanate or methyl chloroformate and sodium hydride to give An isolated example of the synthesis of chiral pteridines from a (Scheme 33). 2-Isothiocyanatopyrazine-3-carboxylates have been isothiocyanatopyrazine-2-carboxylate 172 reacted with R)- —) provided the pteridine derivative 173 and uncyclized pyrazine with pyridine precursors afforded pyrido[2,3 Pytitnidines. 

The reaction of pyrazine with phenyllithium in THF or TMEDA at -45°C leads quantitatively to 102, as shown by the H-NMR spectrum. The assignment of the structure is made possible by comparison with the amino anaIog31. Both H- and l3C-NMR spectra of 102 are rather poorly diagnostic because they consist of broad signals. 

Early publications on [VO(/3-diketonato)2] have been reviewed.355 More recently, complexes with benzoyl m-nitroacetanilide, benzoyl acetanilide545 and l,l -(l,3-phenylene)-bis(butane-1,3-dione546 have been synthesized. Other [VO(/S-dik)2] adducts have been isolated, for example [VO(acac)2] adducts with a series of pyridine N-oxides547 and several pyridine carboxamides, 48 and [VO(bzac)2] adducts with pyridine, methylamine, isoquinoline and 4-picoline.549 Equilibrium constants of 1 1 and 2 1 adducts of pyrazine with [VO(tfacac)2] have been determined (equation 38).550 In the 2 1 complex, the pyrazine bridge between two equatorial sites of adjacent vanadium atoms promotes a weak exchange interaction. The nitroxide radical 2,2,6,6-tetramethylpiperidinyl N-oxide also forms an adduct with [VO(hfacac)2] in which there is a strong interaction between the electrons on the metal and nitroxide.551... 

Mass spectrum from V. J. Angelico, S. A. Mitchell, and V. H. Wysocki, "Low-Energy Ion-Surface Reactions of Pyrazine with Two Classes of Self-Assembled Monolayers, Anal. Chem. 2000, 72, 2603. 

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