Ring contraction imidazoles

A novel ring contraction of 6-azauraciIs yields imidazole derivatives . Azauracil-5-yl-isatin 33 is converted through its thiosemicarbazone 34 to 6-(6-azauracil-5-... 

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>. 

Similar amide-induced ring contractions have been reported when heating 2,3-diphenylquinoxaline with potassium amide at 140°C, 2-phenylbenz-imidazole being obtained (65JOC2858). A quinazoline-benzimidazole transformation has also been reported when heating 6-bromoquinazoline with ammonia. 2-Bromoquinazoline is a probable intermediate (74RC1233). 

Attempted displacement of the 2-O-imidazole-1 -sulfonyl ester of methyl 3,4,6-tri-O-rhethyl 3-D-galactopyranoside with azide ion led to the formation of the corresponding 2,5-arihydro sugar [86], as illustrated in Scheme 17. The predominance of a ring-contraction... 

The 8ir-electron anions derived from 1,3,5-oxadiazines (30) (75AG(E)581) are unstable and readily ring contract to give imidazolones (141 Scheme 9). The related anions from 1,3,5-thiadiazines (100 Scheme 1) also ring contract to give imidazoles in high yield... 

The synthesis of target imidazoles can be also realized by photoinduced ring-contraction of the pyrimidine nucleus. For example, significant yield of 4(or 5)-acetylimidazoles 64 are isolated from the photolysis, at 254 nm in methanol or benzene, of 4-substituted 2,6-dimethyl-pyrimidine-N-oxides 62 (Scheme 12.18) [43],... 

Moreover, 4(or 5)-heteroarylmethyl-imidazoles 67 can be obtained by a photo-induced ring-contraction of 4-heteroaryl-substituted l,4(or 3,4)-dihydropyrimi-dines 65 easily prepared by reaction of the corresponding pyrimidine with hetero-aryllithium (Scheme 12.19). The irradiations were performed in acetone in a Rayonet preparative photoreactor equipped with RUL 300 lamps, and the products isolated in 43-57% yields. The reaction was determined by the anion-stabilizing effect of the heteroaryl group R1, which affects the thermal development of the bicyclic intermediate 66 [44]. 

When the 6-position is unsubstituted, oxidative degradation is most common, and peracetic acid treatment leads to ring contraction to form 2,4-disubstituted imidazoles and their N-oxides (81H573). For example, 2-methyl-4-phenylpyrimidine (28) reacts in this way with peracetic acid, but with m-chloroperbenzoic acid in chloroform, pyrimidine N-oxides were formed as well (Scheme 12). Even pyrimidine itself gave the oxide in 48% yield under these latter conditions 2-methylpyrimidine gave 55% of the N-oxide (81H573). 

At that time it was suggested that the isomerization occurred by way of an initial photo-ring contraction to an undetected 2-(A-methylimino)-2//-azirine intermediate (2) and subsequent ring expansion to the observed product, 1-methylimidazole (3). Although the intermediacy of acylazirines has been adequately demonstrated in the analogous isoxazole-to-oxazole phototransposition, such iminoazirines have not been detected in a pyrazole to imidazole isomerization, and thus, this mechanistic suggestion has never been experimentally substantiated. 

By ring contraction. Photolysis of l,4-dimethyl-3,5,6-triphenyl-4,5-dihydro-l,2,4-triazinium iodide 516 gave l-methyl-2-phenylphenanthro[9,10-r/]imidazole 517 in 90% yield. 

Imidazoles from condensed heterocycles 4.08.2.3 Ring Contractions... 

When treated with potassium amide in liquid ammonia, chloropyrazines undergo ring contraction to imidazoles. The reaction has synthetic importance and resembles similar reactions of pyridines and pyrimidines (Section 4.08.2.3.1). As before, labelling experiments have been utilized to establish the origins of the nitrogen atoms in the products, and complex... 

Heteroaryl-substituted 1,4- or 3,4-dihydropyrimidines undergo ring contraction to imidazoles on irradiation. In addition to other products of irradiation of N-(6,7-methylenedioxyquinazolin-3-io)amidates (78), triazolines (79) arising by rearrangement of the dimers (80), known to be present in significant amounts in acetone solution, are also obtained. ... 

Such synthetic approaches can only be valid if the other heterocycles are readily available, or if their transformations lead to imidazoles difficult to make by other means. It is certainly important to be able to aromatize imidazolines since a number of ring-synthetic procedures lead to reduced imidazoles. 4-Aminoisoxazoles are sources of a-acylaminoenaminones which cyciize with bases to give 4-acylimidazoles. Oxazole-imidazole conversion has largely historical importance, but it is also implicated in some ring-synthetic procedures (e.g. the Bredereck method, see Chapter 5). Transformations of benzofuroxans into 2-substituted benzimidazole iV-oxides have some synthetic importance. Few, if any, ring contractions appear to have major application. 

There are considerable data available on imidazole formation by ring contractions of pyrimidines, pyrazincs and triazines [15, 43, 59-61]. Few of the reactions, however, have synthetic potential except perhaps for the thermolytic conversions of azidopyrimidines and azidopyrazines into 1-cyano-substituled imidazoles, and the reactions of chloropyrimidines and chloropyrazines with potassium amide in liquid ammonia to give 4- and 2-cyanoimidazoles, respectively. Ring contractions of quinoxaline 1-oxides may also have some applications. 

The few examples of photochemical ring contractions of l,3-dia7,ines into imidazoles have no obvious synthetic importance [68]. 

Chloropyrazines undergo ring contraction when treated with potassium amide in liquid ammonia. The reactions resemble those of pyridines and pyrimidines, and may be useful for making 2-cyanoimidazoles despite the formation of product mixtures and low yields. For example, 2-chloropyrazine is converted into a mixture of 2-aminopyrazine (15%), imidazole (14-15%) and 2-cyanoimidazole (30-36%) [82]. In a similar experiment, 2-cyano-4-phenylimidazole (19%) can be obtained 83J. 

Under reducing regimes some 1,3,5- and 1,2,4-triazines ring contract to imidazoles [84-86], but there is no obvious synthetic importance. When a-halogenooximes react with amidines, they appear to form AH-... 

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

When the dihydro-1,2,4-triazinone 76 is heated at 180°C with red phosphorus and hydroiodic acid, there is rupture of the 1,2-bond and subsequent ring closure to give 4,5-diphenylimidazolin-2-one (77) (see Scheme 17) and reductive ring contractions to imidazoles (81) have also been reported " in the 1,3,5-triazine series. A further interesting ring contraction is that which occurs when 4H-l,3,5-thiadiazines (78) are treated with aliphatic amines at room temperature. The triarylimidazoles (81) may be formed by initial formation of the 1,3,5-thiadiazine anion (79) which probably loses sulfur... 

---