The deoxydative substitution reactions of nicotinamide and nicotinic acid N‐oxides by 1‐adamantanethiol in acetic anhydride

Abstract

The reaction of nicotinamide N‐oxide with 1‐adamantanethiol in acetic anhydride yielded a mixture of 2‐and 6‐(1‐adamantylthio)nicotinamides (49%, in the ratio of 24:1) and 2‐, 5‐, and 6‐(1‐adamantylthio)nicotino‐nitriles (18%, in the ratio of 79:1:20). From a reaction of nicotinic acid N‐oxide with 1‐adamantanethiol, there was isolated 2‐(1‐adamantylthio)nicotinic acid as the only sulfide in 23% yield. Carbonsulfur bond cleavage took place when 2‐(1‐adamantylthio)nicotinic acid, or the corresponding amide or nitrile, were boiled with concentrated hydrochloric acid to furnish 2‐mercaptonicotinic acid and 1‐chloroadamantane, quantitatively. The reaction of nicotinamide N‐oxide alone in acetic anhydride at 135° formed N‐acetyl‐2‐hydroxynicotinamide (61%), 2‐hydroxynicotinonitrile (0.5%) and N,N‐diacetyl‐2‐acetoxynicotinamide (0.8%).

Synthesis of Pyridine and Dihydropyridine Derivatives by Regio- and Stereoselective Addition toN-Activated Pyridines

“…Initial studies involved the addition onto N -acyl pyridinium species, and later studies were made on the addition of thiols onto pyridine N -oxides. The first account involved the addition of 1-adamantanethiol onto nicotinamide N -oxide . The reaction was found to be mostly selective for the 2-position, although in total six products were observed, many of them being formed as a result of side-reactions following the amide activation with Ac 2 O (Scheme ) .…”

“…The first account involved the addition of 1-adamantanethiol onto nicotinamide N -oxide . The reaction was found to be mostly selective for the 2-position, although in total six products were observed, many of them being formed as a result of side-reactions following the amide activation with Ac 2 O (Scheme ) . The reaction was simultaneously studied on 3-picoline N -oxide using tert -butyl mercaptan and 1-adamantanethiol, which also led to a mixture of regioisomers .…”

Elucidating the Structure-Activity Relationships of the Vasorelaxation and Antioxidation Properties of Thionicotinic Acid Derivatives

“…1-Adamantylthionicotinic acid derivatives 6 - 8 were obtained [ 14 ] from the reaction of nicotinic acid, nicotinamide and nicotinonitrile N -oxides with 1-adamantylmercaptan in boiling acetic anhydride. The structures of analogs 6 - 8 was confirmed by IR and 1 H-NMR spectral data and their melting points.…”

“…The tested compounds were 2-(1-adamantylthio)nicotinic acid ( 6 ), 2-(1-adamantylthio)- nicotinamide ( 7 ) and 2-(1-adamantylthio)nicotinonitrile ( 8 ). They were prepared as previously described [ 14 ] and characterized as follows: compound 6: 1 H-NMR (DMSO-d 6 ): δ2.22-1.73 (m, 15H, 1-Adm), 7.18 (dd, 1H, J = 7.78, 4.82 Hz, H-5), 8.06 (d, 1H, J = 7.78 Hz, H-4), 8.56 (d, 1H, J = 4.82 Hz, H-6); compound 7: 1 H-NMR (CDCl 3 ): δ2.13-1.70 (m, 15H, 1-Adm), 6.60 (br, CONH 2 ), 7.18 (dd, 1H, J = 7.21, 4.72 Hz, H-5), 8.18 (dd, 1H, J = 7.21, 1.81 Hz, H-4), 8.53 (dd, 1H, J = 4.72, 1.81 Hz, H-6) and compound 8: 1 H-NMR (CDCl 3 ): δ2.25-1.75 (m, 15H, 1-Adm), 7.08 (dd, 1H, J = 7.21, 4.72 Hz, H-5), 7.80 (dd, 1H, J = 7.21, 1.81 Hz, H-4), 8.58 (dd, 1H, J = 4.72, 1.81 Hz, H-6).…”

“…In this context, 1-adamantyl-thionicotinic acid analogs 6 - 8 ( Figure 2 ) are interesting target molecules. The target compounds 6 - 8 were prepared as described previously [ 14 ] and evaluated for vasorelaxant and antioxidative activities.…”