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Novel Synthesis of Substituted Imidazoles

IP.com Disclosure Number: IPCOM000029568D
Publication Date: 2004-Jul-07
Document File: 4 page(s) / 53K

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Abstract

Oxidation of an aldehyde by air in the presence of ammonia generates a substituted imidazole as the major or primary product with the formation of a lesser amount of amide as a by-product. For example, heating a solution of propionaldehyde in aqueous ammonia under 500 psi of air generates 2 ethyl 4 methylimidazole as the major product along with a smaller amount of propionamide. The ratio of imidazole to amide products depends on reaction conditions such as temperature and aldehyde concentration. The yield of imidazole can be at least 75% and the imidazole:amide ratio can be at least 9:1. This novel reaction produces commercially valuable imidazoles in good yield in a single step from very inexpensive starting materials, namely, aldehyde, air and ammonia.

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Novel Synthesis of Substituted Imidazoles

Anonymous

SUMMARY

                   Oxidation of an aldehyde by air in the presence of ammonia generates a substituted imidazole as the major or primary product with the formation of a lesser amount of amide as a by-product.  For example, heating a solution of propionaldehyde in aqueous ammonia under 500 psi of air generates 2‑ethyl‑4‑methylimidazole as the major product along with a smaller amount of propionamide.  The ratio of imidazole to amide products from aldehyde reaction depends on reaction conditions such as temperature and aldehyde concentration.  The yield of imidazole can be as high as at least 75% and the imidazole:amide ratio can be at least as high as 9:1.  This novel reaction produces commercially valuable imidazoles in good yield in a single step from very inexpensive starting materials, aldehyde, air, and ammonia.

RESULTS AND DISCUSSION      

                        Air autoxidation of 6-hydroxyhexanal (6HH) to 6-hydroxycaproic acid (HCA) proceeds at high rate at temperatures near 100°C. We discovered that running the reaction in the presence of ammonia led to the incorporation of nitrogen into the products.  Heating a solution of 10% 6HH in aqueous ammonia at 100°C under 500 psi of air led to the formation of two primary products, one of which was identified as 6-hydroxycaproamide (HCAm).  The other major product was shown by GC mass spec to have a molecular weight 226, consistent with a molecular formula of C12H22N2O2.  The product ratio based on GC area percent is: HCAm:C12H22N2O2 = 0.58:1.

                        Running the reaction at lower temperature in the presence of sodium persulfate as an initiator increased the yield of C12H22N2O2.  With 10% 6HH and about 1% sodium persulfate in aqueous ammonia and 500 psi of air at 80°C, the product ratio was found to be HCAm:C12H22N2O2 = 0.26:1.  The reaction was virtually complete after one hour.  Running at 80°C without initiator and a higher 6HH concentration (20%) improved the C12H22N2O2 yield significantly; the HCAm:C12H22N2O2 ratio was now 0.11:1.  This reaction was very clean with few by-products.  The yield of C12H22N2O2, assuming a GC response factor equal to that for HCAM, was 75%.

                        The C12H22N2O2 material was sufficiently pure to interpret the NMR data.  The 13C NMR showed a total of 12 different carbon atoms with one peak in the carbonyl region with a shift similar to amide, two olefinic carbons, only two allylic carbons, and two primary alcohols.  1H NMR showed the presence of only one olefinic proton, a singlet, and two allylic triplets.  A structure was not easily assigned based on these data.  Anticipating that structural assignment would be easier with a simpler molecule, we ran a model experiment, oxidizing propionaldehyde in the presence of ammonia.  By analogy, we expected t...