Intramolecular hydrogen bond stabilization of hemiaminal structures, precursors of imidazo[1,2-a]pyridine

Synthesis and evaluation of novel heteroaromatic substrates of GABA aminotransferase

“…42–46 Hemiaminals have also been shown to be stabilized by both intermolecular and intramolecular hydrogen bonding. 47–50 The hemiaminal formed during product hydrolysis ( 35 , Scheme 7) is stabilized by the electron-withdrawing nature of the heterocyles and potentially favorable interactions within the active site. On the basis of the secondary isotope effect observed for [ D 2 ]-5a , and the known stability of aryl substituted hemiaminals, the breakdown of this intermediate may be rate limiting, leading to a normal secondary isotope effect (change in hybridization from sp 3 to sp 2 ), which may supercede the expected primary isotope effect from C-H(D) bond cleavage.…”

Stable hemiaminals from axially chiral pyridine compounds

“…Yield: 0.043 g (43%), yellow colored solid, mp: 64-66 C. 1 H NMR (400 MHz, CDCl 3 ): for major isomer δ 8.42-6.34 (m, 8H, ArH), 5.82 (d, 1H, CH at C-4, J = 0.8 Hz), 5.12 (br, 1H, OH), 3.56 (qd, 1H, CH at C-5, J = 0.8 Hz and J = 7.2 Hz), 1.48 (d, 3H, CH 3 , J = 7.2 Hz) ppm and for minor isomer δ 8.43-6.72 (m, 8H, ArH), 5.96 (d, 1H, CH at C-4, J = 5.2 Hz), 5.29 (br, 1H, OH), 3.86 (qd, 1H, CH at C-5, J = 5.2 Hz and J = 7.2 Hz), 1.54 (d, 3H, CH 3 , J = 6.8 Hz ppm. 13 (8) This compound was synthesized according to the general procedure using Compound 4 (0.1 g, 0.32 mmol), LiAlH 4 (0.018 g, 0.48 mmol) and 10 mL THF. Yield: 0,038 g (38%), yellow colored solid, mp: 112-115 C. 1 H NMR (400 MHz, CDCl 3 ): for major isomer δ 8.06-6.60 (m, 6H, ArH), 6.27 (br s, 1H, OH), 5.26 (s, 1H, CH at C-4), 3.50 (q, 1H, CH at C-5, J = 7.2 Hz), 2.21 (s, 3H, CH 3 on N-3 aryl group), 2.09 (s, 3H, CH 3 on iminoaryl group), 1.21 (d, 3H, CH 3 at C-5, J = 7.2 Hz) ppm and for minor isomer δ 8.06-6.60 (m, 6H, ArH), 6.27 (br s, 1H, OH), 5.26 (s, 1H, CH at C-4), 3.60 (dq, 1H, CH at C 5 , J = 6.8 Hz and J = 11.2 Hz), 2.29 (s, 3H, CH 3 on N-3 aryl group), 2.09 (s, 3H, CH 3 on iminoaryl group), 1.54 (d, 3H, CH 3 at C-5, J = 6.8 Hz) ppm and for trace isomer δ 8.06-6.60 (m, 6H, ArH), 6.27 (br s, 1H, OH), 4.82 (s, 1H, CH at C-4), 3.94 (dq, 1H, CH at C 5 , J = 6.8 Hz and J = 11.2 Hz), 2.51 (s, 3H, CH 3 on N-3 aryl group), 2.31 (s, 3H, CH 3 on iminoaryl group), 1.33 (d, 3H, CH 3 at C-5, J = 6.8 Hz) ppm.…”

“…Their isolation was monitored by using nuclear magnetic resonance spectroscopy in many research, [1][2][3] and their transformation kinetics to related compounds were reported. 4,5 The presence of π-conjugation, 4 electron-withdrawing groups, 6 pyridine ring 7 on the structure, and intramolecular H-bonding [8][9][10] was found to have an important role in the stabilization of these molecules. Suni et al obtained a stable hemiaminal as a single crystal from the condensation reaction of di-2-pyridyl ketone with 4-cyclohexyl-3-thiosemicarbazide and the X-ray diffraction result showed that the intramolecular hydrogen bonding interactions affect the stability of the molecule.…”

Синтез и фармакологическая активность трифторметилсодержащих имидазо[1,2-<i>a</i>]бензимидазолов

“…Ïðè äîáàâëåíèè â ðåàêöèîííóþ ñìåñü òðèýòèëàìèíà ïðîèñõîäèò çíà-÷èòåëüíîå îñìîëåíèå, è ïîâûñèòü âûõîä ñîåäèíåíèé 2 òàêèì ïóòåì íå óäàåòñÿ. Îòìåòèì ñóùåñòâåííîå îòëè-÷èå ðåàêöèîííîé ñïîñîáíîñòè 2-àìèíîáåíçèìèäàçîëîâ ïî ñðàâíåíèþ ñ 2-àìèíîïèðèäèíîì è 2-àìèíîáåíçòèàçîëîì, îáðàçóþùèõ ñ 1-áðîì-3,3,3-òðèôòîðàöåòîíîì ñ âûñîêèì âûõîäîì ñòàáèëüíûå öèêëè÷åñêèå àìè-íàëè òèïà À [22,23], êîòîðûå â íàøåì ñëó÷àå çàôèêñèðîâàòü íå óäàëîñü.…”