279692-00-1Relevant articles and documents
Synthesis of pyrazinamide analogues and their antitubercular bioactivity
Wati, First A.,Adyarini, Prisna U.,Fatmawati, Sri,Santoso, Mardi
, p. 2157 - 2163 (2020/10/02)
The Yamaguchi reaction is widely and generally applied to synthesize esters and lactones. It involves 2,4,6-trichlorobenzoyl chloride as the Yamaguchi reagent, 4-dimethylaminopyridine, and triethylamine. Pyrazinamide is a crucial first-line drug for tuberculosis treatment, therefore their analogues are interesting in organic synthesis. In general, the synthesis pyrazinamide analogues involve reaction of pyrazine-2-carboxylic acids with thionyl chloride to yield the corresponding acyl chlorides, which on treatment with amines gave pyrazine-2-carboxamides. However, thionyl chloride is listed under the Chemical Weapons Convention and releases toxic sulfur oxide when react with carboxylic acid. We successfully synthesized series of pyrazinamide analogues using the Yamaguchi reaction. The synthesis involved reaction of pyrazine-2-carboxylic acid with various aliphatic and aromatic amines in the presence of Yamaguchi reagent and 4-dimethylaminopyridine. The yield of the pyrazine-2-carboxamides and the reaction time depended on the type of the amine (aliphatic vs aromatic), substitution pattern, and number of substituents on the aromatic amines. N-(4-chlorophenyl)pyrazine-2-carboxamides can be prepared by this method in 81% yield; N-(2-ethylhexyl)pyrazine-2-carboxamide and N-(4-fluorobenzyl)pyrazine-2-carboxamide showed the best activity against Mycobacterium tuberculosis H37Rv (6.25 μg/mL). This result could lead to find more active pyrazinamide analogues.
Strengthening N...X halogen bonding via nitrogen substitution in the aromatic framework of halogen-substituted arylpyrazinamides
Khavasi, Hamid Reza,Hosseini, Mahdieh,Tehrani, Alireza Azhdari,Naderi, Soheila
, p. 4546 - 4553 (2014/05/20)
The importance of N...X halogen bonding in a series of N-(5-halo-2-pyridinyl)pyrazine-2-carboxamides has been investigated by different methods. The results show that when nitrogen is substituted for carbon in the aryl backbone of the parent compound, it can affect the electron accepting ability of bromine and iodine substituents. Thus, a stronger halogen bond can be formed. This journal is the Partner Organisations 2014.
Effect of halogen bonding interaction on supramolecular assembly of halogen-substituted phenylpyrazinamides
Khavasi, Hamid Reza,Tehrani, Alireza Azhdari
, p. 3222 - 3235 (2013/06/27)
A series of halogen-substituted phenylpyrazinamides have been synthesized and crystallographically characterized in order to investigate the effect of halogen bonding interaction on supramolecular assembly of N-phenylpyrazine-2- carboxamide derivatives. The notable feature in crystal structures of meta- and para-iodinated, brominated and chlorinated compounds is that there is a tendency to form a halogen bonding synthon between adjacent halophenyl and prazine/halophenyl rings. Influence of these halogen bonding interactions on supramolecular assemblies have been discussed with the help of geometrical analysis and theoretical calculations. The X...N halogen bonding distances are 2.2-7.7% shorter than the sum of the van der Waals radii of the nitrogen and halogen atoms. Also, theoretical methods show the N...X halogen bonding energies within a range of -9.43 to -23.67 kJ mol-1. Our studies show that the selection of halogen atom as well as the position of substitution on phenylpyrazinamide compound may be important for crystal design based on halogen bonding.
