125572-33-0Relevant academic research and scientific papers
Palladium(0)-catalyzed phenylation of imidazo[4,5-b]pyridines
Grivas,Lindstrom
, p. 467 - 471 (1995)
The tetrakis(triphenylphosphine)palladium(0)-catalyzed coupling of benzeneboronic acid with 2-chloro, 6-bromo and 6-bromo-2-chloro derivatives of 1- and 3-methylimidazo[4,5-b]pyridines to novel 2-phenyl-, 6-phenyl- and 2,6-diphenylimidazo[4,5-b]pyridines is described. The phenylation of imidazo[4,5-b]pyridines containing labile hydrogens was not successful.
Synthesis and decomposition of an ester derivative of the procarcinogen and promutagen, PhIP, 2-amino-1-methyl-6-phenyl-1H-imidazo[4,5-b]pyridine: Unusual nitrenium ion chemistry
Nguyen, Thach-Mien,Novak, Michael
, p. 4698 - 4706 (2008/02/10)
(Chemical Equation Presented) The food-derived heterocyclic amine (HCA) carcinogen 2-amino-1-methyl-6-phenyl-1H-imidazo[4,5-b]-pyridine, PhIP, is often generated in the highest concentration of the HCAs formed during broiling and frying of meat and fish. Although it is considered to be an important contributor to human cancer risk from exposure to HCAs, the chemistry of PhIP metabolites that presumably react with DNA to initiate carcinogenesis has received only cursory attention. We have synthesized the ester derivative N-pivaloxy-2-amino-1-methyl-6-phenyl-1H-imidazo[4,5-b]pyridine, 1b, and investigated its chemistry in aqueous solution. Although 1b was too unstable to isolate, we could characterize it by NMR methods in DMF-d7, a solvent in which it is stable at -40°C. It decomposed rapidly in aqueous solution, but its conjugate acid, 1bH+, is not reactive. The nitrenium ion, 2, was trapped by N3- to form the unusual tetrazole adduct, 16. In the absence of N3-, the expected hydration products of 2 were not detected, but the reduction product, 12, was detected. Although such products are often taken as evidence of triplet nitrenium ions, the efficient trapping of 2 by N3- indicates that it is a ground state singlet species. The product 12 appears to be generated by reduction of an initially formed hydration product of 2. An alternative addition-elimination mechanism for the formation of 12 does not fit the available kinetic data. The selectivity of 2, measured as kaz/k s, the ratio of the second-order rate constant for its reaction with N3- and the first-order rate constant for its reaction with the aqueous solvent, is (2.3 ± 0.6) × 104 M -1, a value that is in the middle of the range of k az/ks of 10-106 M-1 observed for nitrenium ions derived from other HCAs. The mutagenicity of aromatic amines (AAs) and HCAs, measured as the log of histidine revertants per nanomole of amine, log m, in Salmonella typhimurium TA 98 and TA 100 correlates with log(kaz/ks) for a wide variety of carbocyclic and heterocyclic amine mutagens including PhIP. Previously developed linear regression models for mutagenicity that include log(kaz/k s) as an independent variable predict log m for PhIP with good accuracy in both TA 98 and TA 100. Quantitative carcinogenicity data are less strongly correlated with log(kaz/ks), so prediction of the carcinogenicity of PhIP and other HCAs or AAs based primarily on log(k az/ks) is less successful.
An easy photochemical approach to the synthesis of the food-borne carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
Bavetta, Fabio S.,Caronna, Tullio,Pregnolato, Massimo,Terreni, Marco
, p. 7793 - 7796 (2007/10/03)
Mutations induced by substances formed during food cooking are a field of growing interest; for a better comprehension of the mechanism of action of these carcinogens, simple routes to their synthesis are needed. In this letter we describe an easy method for 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP) synthesis, starling from the commercially available 2,3- diaminopyridine 1 via the 2-amino-3-methylamino-5-phenylpyridine 5 formation. The key step of this approach is the one pot synthesis of 5 performed by photolysis of 2-amino-5-iodo-3-(N-methyl-N-tosylamino)pyridine 4 to obtain simultaneous phenylation and tosyl group removal. Compound 5 was then used as an intermediate to obtain the 1-methyl 6-phenylimidazo[4,5-b]pylidine 6 which was aminated to afford PhIP in good overall yields.
A convenient route to the imidazo[4,5-b]pyridines
Harada, Kenichi,Choshi, Tominari,Sugino, Eiichi,Sato, Koichi,Hibino, Satoshi
, p. 213 - 218 (2007/10/02)
The reaction of the acroleins possessing a leaving group, derived from alkenyl sulfides by Vilsmeier reaction, with 4-amino-1-methylimidazole provided a new and convenient route to the imidazo[4,5-b]pyridines, the reaction mechanisms of which were examined by a deuterium labelled experiment.
