There is no evidence in the literature for the elimination of alkanols from 2,3-dihydropyridines
containing an alkoxy substituent on an sp2-hybridized carbon atom, in fact from alkoxyethene or 1-alkoxy-
1-propene fragments either in the presence of superbases or under any other conditions. In contrast to examples
reported in the literature of aromatization of dihydropyridines, which generally have an oxidative nature [4], the
5-alkoxy-2-(alkylsulfanyl)-2,3-dihydropyridines are not aromatized when stored in air nor when heated.
It was found that the reaction we have discovered has a general nature and, in combination with our
development of a one-pot system route to the dihydropyridine nucleus from aliphatic isothiocyanates and
alkoxyallenes [1, 2], may become the main overall strategy for synthesizing a novel class of functionally
substituted pyridines and, in fact, to 2-alkyl-6-(alkylsulfanyl)pyridines. High reactivity, biogenic and other
useful properties of the alkylsulfanyl group are well known [5-8].
1H and 13C NMR spectra were taken using CDCl3 on a Bruker DPX-400 spectrometer (400 and 100
1
MHz respectively) and 2D HMBC H and 13C NMR spectra on a Bruker AV-400 spectrometer (400 and 100
MHz respectively) using HMDS as internal standard. GLC analysis was performed on an Agilent 6890N
chromatograph.
THF was purified by dispersed KOH (~ 50 g/l), refluxing and distilling over Na in the presence of
benzophenone under an argon atmosphere. DMSO was dehydrated by distillation from t-BuOK. Methoxyallene
was prepared using method [9]. The butyl lithium (~ 1.6 M solution in hexane) and the other reagents and
solvents used were commercial preparations. Liquid nitrogen was used for cooling.
5-Methoxy-2-methyl-6-(methylsulfanyl)- 2,3-dihydropyridine (1). A mixture of methoxyallene (9 g,
128.6 mmol) in THF (10 ml) was added with vigorous stirring under an argon atmosphere to a solution of BuLi
(104 mmol) in hexane (65 ml) and THF (80 ml) at -100ºC. Stirring was continued for 10 min holding the
temperature at -55 to -50ºC, the product was cooled to -100ºC, and ethyl isothiocyanate (9 g, 103.4 mmol) was
added. The temperature increased to -55ºC and MeI (21.6 g, 152.1 mmol) was added. Cooling was removed, the
temperature was allowed to increase to 0ºC, cold water (150 ml) was added, and the product was vigorously
stirred, and the organic layer was separated. The products from the aqueous fraction were extracted with pentane
(250 ml) and the combined organic fraction was washed with water (2 x 50 ml) and dried over K2CO3. Solvent
was removed on a rotary evaporator with a temperature bath at 60-70ºC. The residue obtained (16.1 g, 91%) was
a liquid which GLC data and NMR spectra showed to contain 77% of the 2,3-dihydropyridine 1 and 21% of the
pyrrole 2. The products were dissolved in pentane (50 ml) and the solution was vigorously shaken with cold
hydrochloric acid (1M, 20% excess, 0ºC) and the layer separated. The "acid" aqueous layer was treated with
concentrated aqueous KOH solution to neutrality and the product was extracted with diethyl ether (450 ml) and
dried over K2CO3. Removal of solvent at reduced pressure gave the 2,3-dihydropyridine 1 (11.65 g, 65%) as a
clear liquid which contained 98% of the main product (GLC data). Distillation in vacuo gave compound 1 (9 g,
53%) with a purity of 99% (GLC data), bp 91-92ºC (1 mm Hg), and nD20 1.5376. 1H NMR spectrum, , ppm (J,
Hz): 5.02 (1H, dd, 3J = 5.4, 3J = 3.8, H-4); 3.58 (3H, s, OCH3); 3.58 (1H, m, H-2); 2.29 (3H, s, SCH3); 2.60 (2H,
3
m, H-3); 1.29 (3H, d, J = 6.8, CH3). 13C NMR spectrum, , ppm: 160.01 (C-6); 147.98 (C-5); 98.09 (C-4);
54.68 (OCH3); 53.68 (C-2); 28.58 (CH3); 21.98 (C-3); 11.43 (SCH3). Found, %: C 55.57; H 7.74; N 7.81;
S 18.79. C8H13NOS. Calculated, %: C 56.10; H 7.65; N 8.18; S 18.72.
2-Methyl-6-(methylsulfanyl)pyridine (3). t-BuOK (0.27 g, 2.41 mmol) was added in one portion with
vigorous stirring to a solution of the 2,3-dihydropyridine 1 (0.83 g, 4.85 mmol) in DMSO (3 ml) at room
temperature. Rapid self-heating of the reaction mixture occurred to 45ºC and water (15 ml) was added after
35 min. The product was extracted with diethyl ether (410 ml) and the extracts were washed with water (320 ml),
and dried over MgSO4. Solvent was evaporated under reduced pressure and the residue (0.62 g of a light-yellow
oil) was chromatographed on alumina with petroleum ether as eluent to give the pyridine 3 (0.56 g, 83%) as
22
1
3
3
colorless, mobile liquid with nD 1.5719. H NMR spectrum, , ppm (J, Hz): 7.34 (1H, dd, J = 7.9, J = 7.5,
3
3
13
H-4); 6.93 (1H, d, J = 7.9, H-5); 6.78 (1H, d, J = 7.5, H-3); 2.51 (3H, s, SCH3); 2.47 (3H, s, CH3). C NMR
1537
Nedolya
