Imidazole -5-carbaldehyde

Imidazole-4-carbaldehyde, 5-mercapto-1 -phenyl-reactions, 5, 444 Imidazolecarbaldehydes oxidation, 5, 437 Imidazole-2-carbaldehydes condensation reactions, 5, 436 deacylation, 5, 93 decarbonylation, 5, 436 oximes, 5, 436 reactions, 5, 93... 

The synthesis of losartan potassium (1) by the process research chemists at Merck is outlined in the following (Griffiths et ak, 1999 Larsen et al., 1994). Phenyltetrazole (8) is protected as the trityl phenyltetrazole 9 (Scheme 9.3). Ortho-lithiation of 9 followed by quenching with triisopropyl borate afforded boronic acid 10 after treatment with aqueous ammonium chloride. Reaction of glycine (11) with methyl pentanimidate (12) in a methanol/water mixture yielded (pentanimidoylamino) acetic acid (13), which underwent a Vilsmeier reaction with phosphorous oxychloride in DMF followed by hydrolysis to give imidazole-4-carbaldehyde 14 in moderate yield. 

Scheme 9.3. Synthesis of boronic acid 10 and imidazole-4-carbaldehyde 14.

Imidazole-2-carbaldehyde, 1-phenyl-dipole moment, 5, 351 (71CHE801) Imidazole-4-carbaldehyde pKa, 5, 384 (B-76MI40701, 70AHC(12)103, 80AHC(27)241>, 386 <80AHC(27)241, 70AHC(12)103>... 

Treatment of the thiazolium sail (249) with base gives the imidazo[2,1 -b]thiazole (250) (64CPB813). Bromination of the hydrochloride of (251) in the presence of KOAc proceeds with simultaneous cyclization to give 3-oxo-6-bromomethyl-2,3,5,6-tetrahydroimidazo[2,l-6]thiazoles (252) (73CHE395). Imidazole-4-carbaldehyde reacts with vinyltriphenylphos-phonium bromide in the presence of NaH to give 5H-pyrrolo[l,2-c]imidazole, presumably via an allenic intermediate (equation 47). Imidazole-2-carbaldehyde reacts analogously... 

The selective UV absorption of imidazole-4-carbaldehyde has been referred to resonance structures such as (92), which are improbable in the cation. In addition, a hydroxymethylene form can be excluded. 

A selection of syntheses illustrates the potential of these procedures. For example, the synthesis of l-methylimidazole-5-carbaldehyde (1) (Scheme 7.2.1) illustrates the uses of blocking groups and regiospecific metallation [25]. In this particular sequence around 10-15% of the regioisomer is formed at the quenching stage, resulting in a small amount of 1-mcthyl-imidazole-4-carbaldehyde as a contaminant. 

Ando N, Terashima S (2010) A novel synthesis of the 2-amino-lH-imidazol-4-carbaldehyde derivatives and its application to the efficient synthesis of 2-aminoimidazole alkaloids, oroidin, hymenidin, dispacamide, monobromodispacamide, and ageladine A. Tetrahedron 66 6224-6237... 

The same group developed a copper-catalyzed unprecedented intramolecular dehydrogenative aminooxygenation (IDA) process that produces imidazo[l,2-a]pyridine-3-carbaldehydes and 1,2-disubstituted imidazole-4-carbaldehydes... 

---