2- Methyl-6-substituted-pyrimidine-1-oxides

Substituted pyrimidine N-oxides such as 891 are converted analogously into their corresponding 4-substituted 2-cyano pyrimidines 892 and 4-substituted 6-cya-no pyrimidines 893 [18]. Likewise 2,4-substituted pyrimidine N-oxides 894 afford the 2,4-substituted 6-cyano pyrimidines 895 whereas the 2,6-dimethylpyrimidine-N-oxide 896 gives the 2,6-dimethyl-4-cyanopyrimidine 897 [18, 19] (Scheme 7.6). The 4,5-disubstituted pyridine N-oxides 898 are converted into 2-cyano-4,5-disubsti-tuted pyrimidines 899 and 4,5-disubstituted-6-cyano pyrimidines 900 [19] (Scheme 7.6). Whereas with most of the 4,5-substituents in 898 the 6-cyano pyrimidines 900 are formed nearly exclusively, combination of a 4-methoxy substituent with a 5-methoxy, 5-phenyl, 5-methyl, or 5-halo substituent gives rise to the exclusive formation of the 2-cyanopyrimidines 899 [19] (Scheme 7.6). The chemistry of pyrimidine N-oxides has been reviewed [20]. In the pyrazine series, 3-aminopyrazine N-ox-ide 901 affords, with TCS 14, NaCN, and triethylamine in DMF, 3-amino-2-cyano-pyrazine 902 in 80% yield and 5% amidine 903 [21, 22] which is apparently formed by reaction of the amino group in 902 with DMF in the presence of TCS 14 [23] (Scheme 7.7) (cf. also Section 4.2.2). Other 3-substituted pyrazine N-oxides react with 18 under a variety of conditions, e.g. in the presence of ZnBr2 [22]. 

Polystyrene-bound isothiuronium chloride, which is readily prepared from chloro-methyl polystyrene and thiourea, has been used as a starting material for the preparation of various substituted pyrimidines (Entries 9-11, Table 15.28). After oxidation to the corresponding sulfones, nucleophilic cleavage with amines proceeds smoothly to yield substituted 2-aminopyrimidine derivatives (see Section 3.8). 

In an efficient microwave-assisted solution or solid-phase protocol (07Mn2) for 2-amino-4-arylpyrimidine-5-carboxylate derivatives (Scheme 27), 22 (X = S, R = H) was S-alkylated with methyl iodide to 2-methylthiodihydropyrimidines 34, which was sequentially oxidized first with manganese dioxide and then with Oxone to 2-methylsulfonyl-pyr-imidines 66 as precursors of 2-substituted pyrimidines 67 via displacement of the reactive sulfonyl group with N, O, S, and C nucleophiles (Scheme 27). However, direct displacement of the S-methyl group of 34 with nitrogen nucleophiles provided 2-amino-l,4-dihydropyrimidines 68. 

Some unusual syntheses of substituted 2,2 -bipyridines deserve mention. Tetracyclone (tetraphenylcyclopentadienone) on heating with picolinonitrile at 215°C affords 3,4,5,6-tetraphenyl-2,2 -bipyridine, whereas 5-methyl-2,2 -bipyridine and some polysubstituted 2,2 -bipyridines are obtained by the oxidative degradation of the antibiotic streptonigrin. 5-Aldehydo-6-amino-2,2 -bipyridines are obtained by acid hydrolysis of pyrido[2,3-[Pg.311]

The oxidative desulfurization-fluorination of methyl A,-alkyl-A,-pyridyl(or pyrimidin-yl)dilhiocarbamates produces the corresponding (trifluoromethyl)amino-substituted pyridines (or pyrimidines) 5.69... 

Methylsulfonyl)-3-phenyl-3//-l,2,3-triazol[4,5-d]pyrimidine 176 was prepared by the reaction of 175 with sodium methyl sulfide, followed by oxidation with potassium permanganate in acetic acid. A nucleophilic substitution reaction on 176 with potassium cyanide gave 182, but the same reaction did not take place on 175. Treatment of 176 with sodium methoxide... 

Syntheses from precursors of types (405) and (406) are rare, and of type (407) are unknown. One example of the first of these is the oxidative cyclization of pyrimidine (408) to the glycosyl pyrimidotriazine (409) (Equation (68)) <82MI 720-01). An interesting example of the second type is the cyclization of the 6-chloropyrimidine (411). In the presence of air this affords 2-methyl-fervenulone (412) by straightforward intramolecular nucleophilic substitution of the chlorine atom. Pyrolytic cyclization of compound (411), however, affords the isomeric 1-methyl product (413), possibly via a diaziridine intermediate (Scheme 33) <75JOC232i>. 

A number of densely substituted 3-aminothiophene derivatives, including several fused systems, have been obtained by cyclization reactions of suitable acrylonitriles or similar precursors with ethyl mercaptopyruvate in the presence of a base, as illustrated by the conversion of the pyridine-1-oxide 4 into the pyridothiophene 5 <05JHC661>. Similar annulations involving 2-amino-4,6-dichloropyrimidine-5-carboxaldehyde and methyl mercaptoacetate leading to thieno[2,3-t/]pyrimidine derivatives have also been reported <05JHC1305>. 

In a palladium-mediated oxidative coupling reaction, alkenes such as methyl acrylate, acrylonitrile, or styrenes cyclize with 6- [(diinethylainino)methylene]amino -l,3-dimethyluracil to give the corresponding 6-substituted pyrido[2,3-[Pg.128]

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