Synthesis of 1,2,4-oxadiazoles (a review)

Polycyclic N-Heterocyclic Compounds. Part 62: Reaction of N-(Quinazolin-4-yl)amidine Derivatives with Hydroxylamine Hydrochloride and Anti-platelet Aggregation Activity of the Products

“…After our work with aliphatic ring-fused amidines, we focused our attention on the aromatic ring-fused amidines (4). As shown in Chart 2, the requisite amidines 4 starting materials were synthesized by the same method as described above for amidines 3.…”

“…58, No. 3 producing various N- [2-(3-alkyl(or aryl) [1,2,4]oxadiazol-5-yl)cyclohexen-1-yl (or phenyl)]formamide oximes (7, 10) through the reaction of N- (5,6,7,8-tetrahydroquinazolin-4-yl)amidines (3) or N-(quinazolin-4-yl)amidines (4) with hydroxylamine hydrochloride via a ring cleavage of a pyrimidine component accompanied with a ring closure of 1,2,4-oxadiazole. Compound 7e showed considerable inhibitory activity against platelet aggregation comparable to clinically used Cilostazol.…”

“…1,2,4-Oxadiazoles 4) are usually prepared by 1) Paal-Knorr type ring closure of O-acylamide oximes, 5) 2) reaction of imide equivalents with NH 2 OH, 6) 3) ring closure of N-acyl NЈ-substituted amidines, 7) or 4) 1,3-dipolar cycloaddition of nitriles and nitrile oxides. 8) Additionally, we have reported the pyrimidine ring opening reaction accompanying the formation of the 1,2,4-oxadiazole ring to give N- [2-([1,2,4]oxadiazol-5-yl)cycloalken-1-yl]formamide oximes (1) by the reaction of tricyclic N-(aliphatic ring-fused pyrimidin-4-yl)amidine (2) or its amide oxime with hydroxylamine hydrochloride (Fig.…”

Synthesis of Novel 3‐Aryl‐5‐dichloromethyl‐Δ2‐1,2,4‐oxadiazolines

“…The chemistry, properties, and applications of heterocyclic compounds comprising a 1,2,4-oxadiazole ring have been thoroughly reviewed [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15], showing that this nucleus confers a wide variety of biological and pharmacological activities. Regarding oxadiazolines, 4,5dihydro-1,2,4-oxadiazoles (Δ 2 -1,2,4-oxadiazolines) are distinguished as substances of significant synthetic [5,[16][17][18][19] and biological [20][21][22][23][24][25][26] interest.…”

1,2,4‐ and 1,3,4‐Oxadiazole Synthesis by Palladium‐Catalyzed Carbonylative Assembly of Aryl Bromides with Amidoximes or Hydrazides

“…Subsequent reaction with, for example, activated esters, acid chlorides or nitriles then leads to the 1,2,4-oxadiazoles. [15] Only few carbonylative approaches exist for the transformation of aryl iodides or iodonium salts into 1,2,4-oxadiazoles with CO and amidoximes. However, these procedures are extremely limited to the substrate scope, and there are no examples of the similar reaction starting from aryl bromides.…”