An approach to the cyclopeptide alkaloids (phencyclopeptines) via heterocyclic diamide/dipeptide equivalents. Preparation and N-alkylation studies of 2,4(5)-disubstituted imidazoles

Abstract

2,4(5)-Disubstituted imidazoles containing a variety of substituents have been prepared via a modified literature procedure. An extensive study regarding the site of N-alkylation is reported which demonstrates that a strong preference exists for 1,2,4-trisubstituted products with little or no formation of the corresponding 1,2,5-trisubstituted isomers. The relationship of imidazoles with this substitution pattern to the phencyclopeptines is disclosed in

Synthesis of 1,2,4,5‐Tetrasubstituted Imidazoles Using Sulfuric Acid ([3‐(3‐Silicapropyl)sulfanyl]propyl]ester as a Recyclable Solid Acid

“…The most well‐known and classical method for the preparation of these compounds involves four‐component condensations of a 1,2‐diketone derivative with an aldehyde, primary amine, and ammonium acetate in refluxing HOAc, which is known to have poor yields and long reaction times . Improvements occurred using other acidic conditions, such as heteropolyacid , silica gel , zeolite , alumnia , NaHSO 4 ‐SiO 2 , HClO 4 · SiO 2 , molecular iodine [16a,b], FeCl 3 · 6H 2 O [17a,b], BF 3 .SiO 2 , InCl 3 · 3H 2 O , K 5 CoW 12 O 40 · 3H 2 O , copper acetate , trifluroacetic acid , L ‐proline , zeolite‐supported reagents , mercaptopropylsilica (MPS) , Bronsted acidic ionic liquid , and MCM‐41 or p ‐TsOH under microwave‐irradiated, solvent‐free, or classical conditions. However, most of these synthetic methods suffer from some serious drawbacks, such as laborious and complex workup and purification, significant amounts of waste materials, strongly acidic conditions, and occurrence of side reactions, poor yields, and the use of expensive reagents.…”

An Efficient Synthesis of 2,4,5‐Trisubstituted and 1,2,4,5‐Tetrasubstituted Imidazoles Using Dihydroquinolines as Novel Organocatalyst

“…Through condensation reaction, different methods are used that include α‐hydroxyketone/1,2‐diketone with an aldehyde and ammonium acetate, in the presences of catalyst such as silica‐supported sulfuric acid (Scheme a), refluxing in acetic acid, ionic liquids, InCl 3 .H 2 O, NiCl 2 .6H 2 O/Al 2 O 3 (Scheme b), ceric ammonium nitrate, and microwave irradiation for the synthesis of 2,4,5‐trisubstituted imidazoles. Similarly, via condensation reaction, α‐hydroxyketone/1,2‐diketone with an aldehyde, amine, and ammonium acetate, in the presence of catalysts such as DABCO, N‐sulfamic acid, silica gel/NaHSO 4 , molecular iodine, BF 3 ‐SiO 2 , ionic liquid, copper acetate, potassium dodecatugstocobaltate trihydrate, and heteropoly acids, gave 1,2,4,5‐tetrasubstituted imidazoles. However, most of these methods have suffered some limitations such as longer reaction time, use of hazardous chemicals with often expensive acid catalysts, long reaction time, lengthy work‐up and purification procedures, unsatisfactory product yields, significant amounts of waste materials which limit their use under the aspect of environmentally benign processes.…”

Microwave-assisted solvent-free synthesis and luminescence properties of 2-substituted-4,5-di(2-furyl)-1H-imidazoles

“…Many methods for the synthesis of highly substituted imidazoles have been reported so far (Schubert & Stodolka, 1963;Stoeck & Schunack, 1974;Lipshutz, & Morey, 1983;Tsuji et al, 1983;Consonni et al, 1991;Evans & Lundy, 1992;Claiborne et al, 1998). Some of them involve fussy treatment, long reaction times and relatively low yields.…”