Chiral 1,2,4-triazoles: stereoselective acylation and chlorination

Acyl groups are transferred from diverse N- and O-acyl derivatives of chiral 3,5-bis-(1-hydroxyethyl)-[1,2,4]-triazole to amino acid esters enantioselectively, with 7% to 68% ee, depending on the temperature conditions and nature of the reagents. Thionyl chloride replaced the hydroxyl groups of (S)-1-[4-amino-5-((S)-1-hydroxy-ethyl)-[1,2,4]-triazol-3-yl]-ethanol 3 stereospecifically with inversion, as confirmed by X-ray analysis, which also revealed unusual crystal structures with asymmetric units comprising three molecules of 4-amino-3,5-bis(R-1-chloroethyl)-1,2,4-triazole 5 and four of 3,5-bis((R)-1-chloroethyl)-1H-1,2,4-triazole 6.

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3,5-Bis-((R)-1-chloroethyl)-1H-[1,2,4]triazoleC9H9Cl2N3[α]D25=+52 (c 2, CH2Cl2)Absolute configuration: (R)

[3,5-Bis-((R)-1-chloroethyl)-[1,2,4]triazol-1-yl]-(4-nitrophenyl)-methanoneC13H12Cl2N4O3[α]D25=-112 (c 2, CHCl3); [α]D25=-198 (c 2, CH2Cl2)Absolute configuration: (R)

(1S,1′S)-1,1′-(1-Benzoyl-1H-1,2,4-triazole-3,5-diyl)-bis(ethane-1,1-diyl)dibenzoateC54H48N6O11[α]D25=+66.8 (c 2, CH2Cl2)Absolute configuration: (1S,1′S)

(1S,1′S)-1,1′-[(1-(p-Nitrobenzoyl)-1H-1,2,4-triazole-3,5-diyl)]-bis(ethane-1,1-diyl)-bis(p-nitro-benzoate)C27H20N6O11[α]D25=+87.5 (c 2, CH2Cl2)Absolute configuration: (1S,1′S)

(1S,1′S)-1,1′-(1-Acetyl-1H-1,2,4-triazole-3,5-diyl)-bis(ethane-1,1-diyl)diacetateC12H17N3O5[α]D25=-131.9 (c 2, CH2Cl2)Absolute configuration: (1S,1′S)

4-Nitrobenzoic acid 1-[5-(1-4-nitrobenzoyloxy-ethyl)-2H-1,2,4-triazol-3-yl]-ethyl esterC20H17N5O8[α]D25=+36.6 (c 2, CH2Cl2)

(1S,1′S)-1,1′-(1H-1,2,4-Triazole-3,5-diyl)-bis-(ethane-1,1-diyl) diacetateC20H32N6O9[α]D25=-156 (c 2, CH2Cl2)Absolute configuration: (1S,1′S)