Cyclocondensation of a Baylis-Hillman adduct with amidines

Full text of DOI:10.1007/s10593-009-0311-x

Chemistry of Heterocyclic Compounds, Vol. 45, No. 5, 2009
CYCLOCONDENSATION OF A BAYLIS-
HILLMAN ADDUCT WITH AMIDINES
M. A. Shramko1, D. V. Dar'in1, and P. S. Lobanov1*
Keywords: Baylis-Hillman adducts, 5-benzylpyrimidines, dinucleophiles, cyclocondensation.
Baylis-Hillman adducts [1, 2] are polyfunctional compounds with high synthetic potential. They contain
three electrophilic centers and so can react with different nucleophilic reagents including dinucleophiles to form
cyclic systems.
We have studied the reaction of the acetylated adduct 1 (prepared from 4-chlorobenzaldehyde and
methylacrylate [3]) with the benz- and acetamidines 2a,b and with S-methylisothiourea (2c).
Me
O
N
OAc
NH
N
CO2Me
NH
NH
O
+
+
R
H2N
2a–c
R
Cl
Me
Cl
Cl
1
4
3a–c
2, 3 a R = Ph, b R = Me, c R = SMe
The reaction with benzamidine 2a and S-methylisothiourea 2c gave good yields of the pyrimidines 3
only. In the case of the acetamidine 2b a mixture of the pyrimidines 3b (main product) and 4 (4:1, determined
1
by the comparison of the integrated intensities of the aromatic proton multiplets in the H NMR spectra) was
obtained in overall yield 47%. Only the pyrimidine 3b could be isolated in a pure state. The reason for this
reactivity will be the subject of a later and detailed investigation.
1H and 13C NMR spectra were recorded on a Bruker DPX 300 instrument (300 and 75 MHz
1
respectively) using DMSO-d6 as solvent. The residual signals for DMSO-d5 at 2.50 for the H nucleus and for
DMSO-d6 at 39.7 ppm for the 13C nucleus were used as internal standards.
Cyclocondensation of Adduct 1 with 1,3-Dinucleophiles (General Method). A mixture of methyl 2-(α-
acetoxy-4-chlorobenzyl)acrylate (1) (1 mmol), the dinucleophile (amidines 2a and 2b as their hydrochlorides and 2c
as its sulfate, 1.5 mmol), and anhydrous potassium carbonate (2.4 mmol) in dry DMSO (3 ml) was stirred vigorously
at 70ºC to completion of the reaction. Solvent was removed in vacuo (1 mm Hg) and the residue was
_______
* To whom correspondence should be addressed, e-mail: pslob@mail.ru.
1St. Petersburg State University, St. Petersburg 198504, Russia.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 776-778, May, 2009. Original
article submitted February 17, 2009.
0009-3122/09/4505-0615©2009 Springer Science+Business Media, Inc.
615

diluted with cold water (30 ml) and extracted twice with ethyl acetate. The organic phase was washed with
saturated NaCl solution, dried over sodium sulphate, and the ethyl acetate was distilled off. Pure material was
separated by column chromatography (with the exception of 3a), eluting with a mixture of methylene chloride
and acetone (3:1) in a gradient regime gradually increasing the proportion of acetone to 100%.
5-(4-Chlorobenzyl)-2-phenylpyrimidin-4(3H)-one (3a). Reaction time 2 h. Dilution of the reaction
mixture with water gave crystals which were filtered off and recrystallized from tert-butyl methyl ether. Yield
69%; mp 187ºC. 1H NMR spectrum, δ, ppm: 3.74 (2H, s, CH2); 7.32 (4H, m, ClC6H4); 7.51 (3H, m, C6H5); 7.95
13
(1H, s, H-6); 8.09 (2H, m, C6H5); 12.53 (1H, s, NH). C NMR spectrum, δ, ppm: 32.87 (CH2); 125.76 (C-5);
128.40, 129.06, 129.46, 131.36, 131.61 132.31, 133.17, 139.38 (Ar); 152.29 (C-6); 156.89 (C-2); 163.68 (C-4).
Found, %: C 68.75; H 4.58; N 9.51. C17H13ClN2O. Calculated, %: C 68.64; H 4.71; N 9.27.
5-(4-Chlorobenzyl)-2-methylpyrimidin-4(3H)-one (3b). Reaction time 4 h. Yield 34%; mp 167ºC.
1H NMR spectrum, δ, ppm: 2.48 (3H, s, CH3); 3.61 (2H, s, CH2); 7.27 (4H, m, ArH); 7.74 (1H, s, H-6); 12.40
(1H, s, NH). 13C NMR spectrum, δ, ppm: 28.86 (CH3); 32.81 (CH2); 125.05 (C-5); 129.08, 131.34, 131.67,
139.69 (Ar); 152.71 (C-6); 158.92 (C-2); 162.95 (C-4). Found, %: C 61.35; H 4.76; N 11.91. C12H11ClN2O.
Calculated, %: C 61.41; H 4.72; N 11.94.
6-(4-Chlorophenyl)-2,5-dimethylpyrimidin-4(3H)-one (4). An analytically pure sample could not be
obtained. 1H NMR spectrum, δ, ppm: 1.94 (3H, s, 5-CH3); 2.28 (3H, s, 2-CH3); 7.52 (4H, m ArH); 12.45 (1H, s,
NH).
5-(4-Chlorobenzyl)-2-methylsulfanylpyrimidin-4(3H)-one (3c). Reaction time 2 h. Yield 52%; mp
171ºC. 1H NMR spectrum, δ, ppm: 2.05 (3H, s, SCH3); 3.60 (2H, s, CH2); 7.28 (4H, m, ArH); 7.79 (1H, s, H-6);
12.64 (1H, s, NH). 13C NMR spectrum, δ, ppm: 15.64 (SCH3); 33.62 (CH2); 126.41 (C-5); 128.86, 129.41,
131.37, 138.52 (Ar); 152.71 (C-6); 160.74 (C-2); 163.20 (C-4). Found, %: C 54.13; H 4.09; N 11.97.
C12H11ClN2OS. Calculated, %: C 54.03; H 4.16; N 10.50.
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