Synthesis of 1‐Aminocodeine as a Synthon for Other Codeine Derivatives

Abstract

The first nitration of codeine by using bismuth nitrate pentahydrate under mild reaction conditions is described. The resulting 1‐nitrocodeine was reduced to 1‐aminocodeine, a key precursor for the synthesis of the azo derivative and several hydrazones. Structures of both 1‐nitrocodeine and 1‐aminocodeine were unequivocally determined by single‐crystal X‐ray analysis. The reported preliminary synthetic study lays the groundwork for the synthesis of modified codeine derivatives with potential biological activity.

Synthesis and reactions of pyrazolo[5,1-c][1,2,4]triazine-3-carbothioamides

“…Compounds 5a,b were purified by recrystallization from appropriate solvents. (60), 236 (51), 142 (23), 116 (16), 73 (25), 58 (22), 43 (24), 42 (22) (13), 187 (27), 172 (11), 156 (22), 142 (55), 134 (100), 130 (13), 115 (60), 102 (46), 89 (53), 77 (28), 63 (14), 51 (17), 42 (26), 29 (5) (7), 156 (20), 142 (15), 128 (14), 115 (75), 103 (6); 89 (13), 77 (10), 68 (10), 44 (38), 39 (10) (53), 251 (23), 157 (24), 142 (55), 115 (65), 89 (10), 77 (14), 36 (40)…”

Synthesis and Modification of Morphine and Codeine, Leading to Diverse Libraries with Improved Pain Relief Properties

“…With the aim to synthesize azo and hydrazone derivatives of codeine, Cankar et al used 11 as a starting material [ 46 ]. Initially, a novel nitration process was developed using bismuth nitrate pentahydrate (instead of nitric acid) as a mild nitrating agent with a 69% yield.…”

“…The possibility of radical intermediates in such reactions led the scientists to apply high temperature and microwave (MW) induction as successful optimizations (Scheme 8), and a mechanism was proposed for this reaction with radical intermediates, supported by DFT (Density Functional Theory) calculations. With the aim to synthesize azo and hydrazone derivatives of codeine, Cankar et al used 11 as a starting material [46]. Initially, a novel nitration process was developed using bismuth nitrate pentahydrate (instead of nitric acid) as a mild nitrating agent with a 69% yield.…”

Chemistry of Pyrazole-3(5)-Diazonium Salts (Review)*

“…These transformations also involved the formation of hydrazones 79, which either after specific treatment stage (or sometimes spontaneously) transformed into 4-amino derivatives of pyrazolo [5,1- Hetarylacetonitriles have been used for the construction of pyrazolotriazine 3-azolyl and 3-azinyl derivatives 81 from pyrazole diazonium salts [156][157][158][159][160][161][162]. There are examples of pyrazole diazonium salts 1 reacting with amides or hydrazides of cyanoacetic acid [92,128,[163][164][165] as well as its thioamide [166].…”