Johnson reaction

Both thermal and Hilbert-Johnson reactions occur quite readily in 2- and 4/6-alkoxyquinazolines. For example, distillation of 2,4-bis-/3-diethylaminoethoxyquinazoline in vacuo yields l,3-bis-/3-diethylaminoethylquinazolin-X4(l/J,3H )-dione (60JCS3546). A complicated example is furnished by heating a tetramethoxybipyrimidine with methyl iodide to give four separable products progressively (81AJC1157). 

The rearrangement of 2- or 4/6-alkoxypyrimidines, either by thermal means or by the Hilbert-Johnson reaction, also leads to iV-alkylpyrimidinones the former method is of little preparative value but the Hilbert-Johnson reactiop is quite important. The processes are outlined in Section 2.13.2.2.7/. 

Quinazoline, 2,4-bis(/3-diethylaminoethoxy)-Hilbert-Johnson reaction, 3, 93 Quinazoline, 2-chloro-4-(p-chlorophenylthio)-synthesis, 3, 137 Quinazoline, 6,8-dichloro-chlorosulfonation, 3, 76 Quinazoline, dihydrosynthesis, 3, 108, 124 Quinazoline, 2,4-dimethyl-Mannich reactions, 3, 78 Quinazoline, 4-ethoxy-1-oxide... 

Because activated 4-0-trimethylsilylated-2, 3, 5 -0-acyluridines such as 3 are also obtained as reactive intermediates in the Friedel-Crafts-catalyzed silyl-Hilbert-Johnson reaction [59, 59 a] of persilylated uracils or 6-azauracils such as 227 with sugars such as l-0-acetyl-2,3,5-tri-0-benzoyl-/9-D-ribofuranose 228 in the presence of SnCl4, treatment of the reactive intermediate 229 with a large excess of pyrrolidine neutralizes the SnCLi. used and aminates 229 to afford the protected 6-aza-cytidine 230, although in 57% yield only [49, 59] (Scheme 4.20). 

The most frequent side effects are diplopia, drowsiness, ataxia, and headache. Rashes are usually mild to moderate, but Stevens-Johnson reaction has also occurred. The incidence of the more serious rashes appears to be increased in patients who are also receiving valproic acid and who have rapid dosage titration. Valproic acid substantially inhibits the metabolism of lamotrigine. 

The synthesis of uracil analogs was achieved by a Hibert Johnson reaction or by its trimethylsilyl modification using 2,4-diethoxyuracil. Other 5-... 

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