Imidazoles aldehydes

Aldehyde Imidazole Potassium fluoride Oxalyl chloride Methyl magnesium bromide Acetic anhydride Sodium hydrogen carbonate Hydrogen hydrochloride Lithium hydroxide Tetrabromomethane Tetramethylammonium acetate Benzylchlorobis(triphenyl-phosphine)palladium (II)... 

The protocol for the preparation of solid supported imidazoles 220 and 221 involved the condensation of resins 215 or 217 with a large excess of 1 -dicarbonyl compounds, NH,OAc and primary amines or aldehydes. Imidazoles of type 222 were prepared in a similar manner by replacing primary amines with NH OAc. Following resin cleavage with 20% TFA afforded imidazoles 223,224 and 225 in high yields and purities ( Scheme 4.3.3). 

The photochemical addition of azirines to the carbonyl group of aldehydes, ketones, and esters is also completely regiospecific (77H(6)143). Besides the formation of the isomeric oxazolines (50) from (39) and ethyl cyanoformate, there is also formed the imidazole (51) from addition to C=N in the expected regioselective manner. Thioesters lead to thiazolines (52), while isocyanates and ketenes produce heterocycles (53). 

The aldehyde functionality present in 3-phenyl-2H-azirine-2-carbox-aldehyde reacts selectively with amines and with Qrignard and Wittig reagents to give a variety of substituted azirines. These azirines have been used, in turn, to prepare a wide assortment of heterocyclic rings such as oxazoles, imidazoles, pyrazoles, pyrroles, and benzazepins. ... 

It is possible to use the enhanced electrophilicity in condensation reactions with aldehydes in the presence of amines to form imidazoles [77] (equation 16). 

The existence of imidazole-4-aldehyde (232) in the enolic form 233 was postulated on the basis of chemical evidence," but the infrared spectrum indicates the presence of a carbonyl group and absence of a hydroxyl group, suggesting that structure 232 should... 

Bei der Herstellung von Aldehyden iiber die 1-Acyl-imidazole wird die Carbonsaure mit l-[Imidazolyl-(l)-carbonyI]-imidazol umgesetzt und das erhaltene Imidazol-Derivat ohne Isolierung zum Aldehyd reduziert5 ... 

Die Reduktion von Imidazol-carbonsauren bzw. deren Amiden an einer Quecksilber-Kathode bleibt gleichfalls auf der Aldehyd-Stufe stehen6 ... 

A number of microwave-assisted multicomponent methods for the synthesis of imidazoles have been reported [68-71 ]. The irradiation of a 1,2-diketone and aldehyde with ammonium acetate in acetic acid for 5 min at 180 °C in a single-mode reactor provides alkyl-, aryl-, and heteroaryl-substituted imidazoles 39 in excellent yield (Scheme 14) and this method has been used for the rapid and efficient preparation of two biologically active imidazoles, lepidiline B and trifenagrel [68]. 

This transformation can also be carried out under solvent-free conditions in a domestic oven using acidic alumina and ammoniiun acetate, with or without a primary amine, to give 2,4,5-trisubstituted or 1,2,4,5-tetrasubstituted imidazoles, respectively (Scheme 15A) [69]. The automated microwave-assisted synthesis of a library of 2,4,5-triarylimidazoles from the corresponding keto-oxime has been carried out by irradiation at 200 ° C in acetic acid in the presence of ammonium acetate (Scheme 15B) [70]. Under these conditions, thermally induced in situ N - O reduction occurs upon microwave irradiation, to give a diverse set of trisubstituted imidazoles in moderate yield. Parallel synthesis of a 24-membered library of substituted 4(5)-sulfanyl-lff-imidazoles 40 has been achieved by adding an alkyl bromide and base to the reaction of a 2-oxo-thioacetamide, aldehyde and ammonium acetate (Scheme 15C) [71]. Under microwave-assisted conditions, library generation time was dramatically re-... 

The synthesis of imidazoles is another reaction where the assistance of microwaves has been intensely investigated. Apart from the first synthesis described since 1995 [40-42], recently a combinatorial synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles has been described on inorganic solid support imder solvent-free conditions [43]. Different aldehydes and 1,2 dicarbonyl compounds 42 (mainly benzil and analogues) were reacted in the presence of ammonium acetate to give the trisubstituted ring 43. When a primary amine was added to the mixture, the tetrasubstituted imidazoles were obtained (Scheme 13). The reaction was done by adsorption of the reagent on a solid support, such as silica gel, alumina, montmorillonite KIO, bentonite or alumina followed by microwave irradiation for 20 min in an open vial (multimode reactor). The authors observed that when a non-acid support was used, addition of acetic acid was necessary to obtain good yields of the products. 

An analogous approach starting from monoximes 44 derived from 1,2 diketo derivatives was described in 2004 [44]. Reaction with different aldehydes in the presence of NH4OAC in acetic acid at 200 °C under microwave irradiation for 20 min gave the corresponding trisubstituted imidazoles 45... 

The cyclization of 1,2-dicarbonyl compounds with aldehydes in the presence of NH4OAC to give imidazoles was employed in a combinatorial study that compared conventional and microwave heating in the preparation of a library of sulfanyl-imidazoles (Scheme 15). The study employed an array of expandable reaction vessels that could accommodate a pressure build-up system for heating without loss of volatile solvents or reagents. A 24-membered library of imidazoles (48 and 49) was prepared in 16 min instead of the 12 h required using conventional heating [45]. 

Ketones and aromatic aldehydes undergo facile addition reactions with CDI (A) or better with A -sulfmyldiimidazole (B) to give diimidazolylmethanes and N-alkylene-imidazoles, depending on the presence of hydrogen atoms a to the carbonyl group ... 

Hydroxymethylation (formaldehyde) of nitro-imidazole 76 affords 77, which is oxidized to aldehyde 78. To prepare the other fragment for this convergent synthesis, reaction of epichlorohydrin with morpholine leads to the aminoepoxide 79, which is reacted with hydrazine to afford 80. Reaction of this substituted hydrazine with dimethyl carbonate affords oxazolinone 81 by sequential ester interchange reactions. Condensation of 81 with aldehyde 78 affords the antitricho-... 

One-pot multi-bond-forming reactions are one of the ways to address the ever growing demand for efficiency in organic synthesis. Rosini and coworkers have developed (tandem) processes for the synthesis of a highly functionalized tricyclic system. The reaction is simply performed by bringing together, at room temperature, a-bromo aldehydes, ethyl nitroacetate, and chlorodimethylvinylsilane in the presence of imidazole as the base (Eq. 8.83).134... 

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