Ring contraction pyrazine rings

In a series of reactions with potassium amide in liquid ammonia, 6-chloropyrido[2,3-f)]pyrazine gave reduction and ring contraction (Section 2.15.13.3), the 6-bromo analogue underwent only reduction, whilst the 6-fluoro derivative gave only the 6-amino substitution product (79JHC305). 

Wentrup and co-workers have carried out systematic flash vacuum thermolysis studies with a series of fused tetrazoles. Investigations of the isomeric tetrazolo[l,5- ]pyrazine 17 and tetrazolo[l,5-f]pyrimidine 20 showed that, in both cases, ring contraction takes place to afford imidazoles in high yields, but isotope labeling experiments revealed that the mechanisms of the openings of the two ring systems are different <2002JOC8538>. 

In contrast, 3-tert-butyI-6-chIoropyrido[2,3-6]pyrazine rapidly reacts with KNHj-NHj to yield a ring contraction product, 2-tm-butyl-l//-imidazo[4,5-6]pyridine (Scheme 4). The transformation is reminiscent of the ring contraction undergone by 2-methylthio-4,6,7-triphenyIpteridine to yield 6,8-diphenyI-2-methyIthiopurine.120 Although no ff-adduct could... 

The investigations on the pyrido[2,3-6]pyrazine ring were inspired by the related pteridine ring, of importance in natural products. Pteridines are very reactive systems with both liquid ammonia and KNH2 in liquid ammonia, but in neither medium have anionic (j-adducts ever been detected. Such adducts presumably form initially and rapidly evolve toward covalent amination and ring contraction products.119,121... 

Ring contractions of six- or seven-membered fused systems have sometimes been used to synthesize azapentalenes. Taylor et a/.158 found that triazolo[4,3-a]pyrazines (164) rearrange in acid to imidazotriazoles 165 following initial fission of the six-membered ring at the point shown (164). The kinetics,58b of this reaction have revealed the intermediacy of covalently hydrated species. 

The acid-catalysed hydrolysis of die cyclic diazotiiiolactone, 4-diazoisochroman-3-one (159) to a ring-contracted product involves protonation of the diazo carbon in the slow step.133 A variable-temperature NMR sriidy has been undertaken to study the reaction of the pyrazine (160) giving (161a R = OH, Me, H). Spectral evidence has been obtained supporting the involvement of the dihydroimidazopyrazine ring system (161b).134 Work by Edward and co-workers on the alkaline hydrolysis of strychnine and some of its derivatives was dealt with earlier.21... 

The 1,5-quinonoid 6,6,7,7-tetramethyl-6,7-dihydro-8f/-pterin (146) reveals interesting reactivity towards nucleophiles due to the blocked 6-position. Solvolysis with OH leads via ring contraction to 2-amino-5,5,6,6-tetramethyl-5,6-dihydroimidazo(4,5-6)pyrazine (145) and O-methylhydroxyl-... 

In the course of the polymerization of DSP (a), the a-axis is contracted by 11% and the b-axis is elongated by 13% whereas the c-axis is contracted only by less than 2%. In order for the reaction to occur between the intermolecular double bonds of the diolefin (Fig. 11), these double bonds must approach each other from the van der Waals separation distance (3.939 A) to the bond length of cyclobutane ring (1,56 A). However, the center of the pyrazine ring which is the center of gravity of the monomer unit does not move as much along the c-axis. The approach of the first two double bonds results in a close contact of another double bond in the same molecule with the double bond of an... 

Distillation of l,2,3,4-tetrahydropyrido[3,2-ii]pyrimidine-2,4-dione (384) with zinc dust caused a reductive rearrangement to imidazo[4,5-h]pyridine (385) (56JCS1045). Reaction of 6-chloropyrido[2,3-h]pyrazines (386) with potassium amide in liquid ammonia resulted in attack at C-2 giving (387), with ring contraction to (388) involving loss of chlorine to give imidazo[4,5-h]pyridine or 2-substituted derivatives thereof (389) (79JHC305). 

Much literature has appeared describing ring contractions of pyrimidines, pyrazines, and triazines into imidazoles, and the field has been reviewed. ... 

Deoxygenation of pyrazine endoperoxides with triphenylphosphine induces ring contraction to imidazoles (Equation (79)) <83CC399>. 

Besides ring contraction to give 177-imidazo[4,5-A]pyridines 3 (cf. Section 7.2.3.1.2.1.), several 6-halo-2,3-disubstituted pyrido[2,3-A]pyrazines 1 undergo dehalogenation on treatment with potassium amide in liquid ammonia to yield pyrido[2,3-A]pyrazines 2.34... 

The reactions of pyrido[2,3- ]pyrazines and potassamide in liquid ammonia have been further investigated. A ratio of 1 3 of the product of dechlorination (361) to that of ring-contraction (362) is obtained from 6-chloropyrido[2,3-/ ]-pyrazine (360). Labelling experiments revealed the exclusive elimination of C-2 during the formation of the imidazole ring (Scheme 139). ... 

---