Novel Regioselective Hydroxyl‐Alkylation of 4,5‐Diphenylimidazole‐2‐thione and a Competitive Intramolecular Ring Closure of the S‐Hydroxyalkyl‐imidazoles to Imidazo[2,1‐b]thiazines and Thiazoles. Role of Catalyst, Microwave Irradiation, and Solid Support.

Abstract

Nucleic acids U 0700Novel Regioselective Hydroxyl-Alkylation of 4,5-Diphenylimidazole-2-thione and a Competitive Intramolecular Ring Closure of the S-Hydroxyalkyl-imidazoles to Imidazo[2,1-b]thiazines and Thiazoles. Role of Catalyst, Microwave Irradiation, and Solid Support. -For the preparation of acyclonucleoside analogues, the alkylation of imidazole derivatives (I) with alkanols (II) is carried out. The reaction proceeds regioselectively and under microwave irradiation in short time. The use of bentonite as solid support leads to similar results.Excess (II) leads to bisalkylated products. In the case of (Ic) imidazothiazine (IVc) is also formed which is obtained via ring closure of monoalkylated product (IIIc). -(EL ASHRY*, E. S. H.; RASHED, N.; AWAD, L. F.; RAMADAN, E.; ABDEL-MAGGEED, S. M.; REZKI, N.; Nucleosides, Nucleotides Nucleic Acids 26 (2007) 5, 423-435; Dep. Chem., Fac. Sci., Alexandria Univ., Alexandria 21321, Egypt; Eng.) -Schulze 47-199

Regioselectivity of the reactions of 4,5‐diphenylimidazole‐2‐thione with 1‐chloro‐2,3‐epoxy‐propane and 1‐bromo‐propene, efficient precursors for imidazo[2,1‐b]thiazine and thiazole. Effect of microwave and solid support

“…The predominance of the thione form of 1 over the respective thiol form has been confirmed in a former work [22]. The higher electron density on the sulfur atom than the nitrogen atom could lead to the conclusion that the sulfur atom should have more nucleophilic capability to react regioselectively with 1-chloro-2,3-epoxypropane (2) to give 4.…”

“…Similar results were also obtained when KOH was replaced by K 2 CO 3 either under conventional or MW conditions. The preferential alkylation of the thioimidazole 1 at the sulfur atom has been due to its higher nucleophilicity [22]. Accordingly, it can be concluded that the formation of the imidazothiazine 3 could be through the formation of the thiolate anion intermediate to give 4, which underwent an intramolecular ring closure via a nucleophilic attack of the imidazole nitrogen on the oxirane carbon atom.…”

“…Thus, the regioselective alkylation of 1 [22], to give 4 could take place via displacement of the chlorine atom or opening the epoxide ring to give the anionic transition states TS-1 which could be cyclized to 4. If a proton transfer has taken place to give TS-2, it could be cyclized to 3, which also formed via TS-3 from 4.…”

Synthesis, reactions, and biological activity of 4,5-diarylimidazole-2-thiones (Review)

“…Hydrazinolysis of compound 127 gave the hydrazide 128, whose condensation with aromatic aldehydes and isatin gave the corresponding hydrazones 129 and 130 [51]. Cyclization of 131 (R = H, i-Pr, R 1 = Et, Pr, Ph) in the presence of sodium hydroxide afforded triazoline-5-thiones 132 or cyclized into 1,3,4-thiadiazoles 133 in the presence of sulfuric acid [91].…”

Synthesis of 4-amino-5-(3-chlorobenzo[b]thien-2-yl)-3-mercapto-1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles and triazolo[3,4,b][1,3,4]thiadiazines under classical and microwave conditions

“…16 Continuing our efforts directed toward the synthesis of new heterocyclic compounds with anticipated biological activities, we have investigated a green chemistry approach for the synthesis of heterocycles combining the benzothiophene and triazolothiadiazole or triazolothiadiazine rings. Much attention has been recently directed in our laboratory to use microwave (MW) in organic synthesis, [17][18][19][20][21][22][23][24][25][26][27] as a result of its extensive popularity as a powerful tool for rapid and efficient synthesis of a variety of organic compounds. It has not only been used to dramatically accelerate organic reactions, but also to improve both the yields and selectivity [28][29][30] .…”