Reactions of N-chlorosuccinimide with 4-phenyl-1,4-dihydropyridines

Experimental and Theoretical Studies of Bromination of Diethyl 2,4,6‐Trimethyl‐1,4‐dihydropyridine‐3,5‐dicarboxylate

“…The next step, the formation of methoxy intermediate 3b, is evidenced in the 1 H NMR spectra by the simultaneous decline of the resonances from C2, C6, and C4 methyl groups of intermediate 2, (2) to 325.15 ppm (3b) evidence the retention of sp 2 hybridization for C2 carbon and N1 nitrogen and sp 3 one for C3 carbon atom. In the literature, the similar methoxybromination of the C5 C6 bond was observed in reactions of 3,4-dihydropyridine-2(1H)ones with NBS [38], and in reactions of 2 equiv of N-chlorosuccinimide with 2,6-dimethyl-3,5-dialkoxycarbonyl-4-aryl-1,4-dihydropyridine in methanol leading to 2,6-dimethyl-3,5-dichloro-6methoxy-3,4,5,6-tetrahydropyridines [37].…”

“…Slight changes from intermediate 2 to derivative 3b for 13 C2 resonances from 165.29 ppm ( 2 ) to 157.01 ppm ( 3b ), as well as 13 C3 from 59.44 ( 2 ) to 66.85 ( 3b ) and for 15 N1 signal from 311.35 ppm ( 2 ) to 325.15 ppm ( 3b ) evidence the retention of sp 2 hybridization for C2 carbon and N1 nitrogen and sp 3 one for C3 carbon atom. In the literature, the similar methoxybromination of the C5C6 bond was observed in reactions of 3,4‐dihydropyridine‐2(1H)ones with NBS , and in reactions of 2 equiv of N‐chlorosuccinimide with 2,6‐dimethyl‐3,5‐dialkoxycarbonyl‐4‐aryl‐1,4‐dihydropyridine in methanol leading to 2,6‐dimethyl‐3,5‐dichloro‐6‐methoxy‐3,4,5,6‐tetrahydropyridines .…”

“…Next steps are the formation of the exocyclic double bond and subsequent rearrangements IM5 → IM6 and IM6 → 4b . It is worth to underline that 1,4‐DHPs with exocyclic double bonds as in IM4 and IM6 are formed relatively easy and were isolated in several reactions of chlorination of 1,4‐DHPs .…”

“…Then fast elimination of NHS leads to the formation of intermediate 2 . The subsequent attachment of the methanol molecule to the N1C2 bond produces the intermediate 3a , which is relatively long‐lived one and can be characterized by all kinds of NMR spectra and in some cases could be even isolated, for example, in chlorination reactions . One can assume that the conversion of 3a to 4a proceeds through the detachment of the methanol molecule leading from 3a to the corresponding IM2 , followed by a suprafacial ‐sigmatropic rearrangement of IM2 to 4a .…”

Physical-chemical and in silico Studies of 1,4-dihydropyridine Derivatives

“…Next, methanol is attached to the N1=C2 bond of the SP1 molecule, forming intermediate SP2'. Similar observations have been described for chlorination reactions [21]. It can be assumed that the transformation of intermediate product SP2' to 2a' occurs with the separation of a methanol molecule from compound SP2', forming the possible corresponding intermediate SP3', followed by [1,3]-sigmatropic rearrangement to monobromated product 2a'.…”