Addition of organolithium and grignard reagents to pyrimidine-2(1H)-thione: Easy access to 4-substituted 3,4-dihydropyrimidine-2(1H)-thiones

Article abstract of DOI:10.1080/10426500903110066

Organolithium and Grignard reagents are added to pyrimidine-2(1H)-thione, yielding 4-substituted 3,4-dihydropyrimidine-2-(1H)-thiones. Since the synthetic procedure can be performed on a multigram scale, and since pyrimidine-2(1H)- thione as well as the m

Full text of DOI:10.1080/10426500903110066

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Addition of Organolithium
and Grignard Reagents to
Pyrimidine-2(1H)-thione: Easy
Access to 4-Substituted 3,4-
Dihydropyrimidine-2(1H)-
thiones
Jacek G. Sośnicki a
a Szczecin University of Technology, Institute of
Chemistry and Environmental Protection , Szczecin,
Poland
Published online: 22 Jul 2009.
To cite this article: Jacek G. Sośnicki (2009) Addition of Organolithium and
Grignard Reagents to Pyrimidine-2(1H)-thione: Easy Access to 4-Substituted 3,4-
Dihydropyrimidine-2(1H)-thiones, Phosphorus, Sulfur, and Silicon and the Related
Elements, 184:8, 1946-1957, DOI: 10.1080/10426500903110066
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Phosphorus, Sulfur, and Silicon, 184:1946–1957, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500903110066
Addition of Organolithium and Grignard Reagents to
Pyrimidine-2(1H)-thione: Easy Access to 4-Substituted
3,4-Dihydropyrimidine-2(1H)-thiones
´
Jacek G. Sosnicki
Szczecin University of Technology, Institute of Chemistry and
Environmental Protection, Szczecin, Poland
Organolithium and Grignard reagents are added to pyrimidine-2(1H)-thione, yield-
ing 4-substituted 3,4-dihydropyrimidine-2-(1H)-thiones. Since the synthetic proce-
dure can be performed on a multigram scale, and since pyrimidine-2(1H)-thione
as well as the majority of organometallic reagents are readily available, the pro-
cess described provides an easy access and complementary to other methods to
4-substituted 3,4-dihydropyrimidine-2-(1H)-thiones.
Keywords 3,4-Dihydropyrimidine-2(1H)-thiones; Grignard reagents; nucleophilic addi-
tion; organolithium reagents; pyrimidine-2(1H)-thione
INTRODUCTION
In the last two decades, 3,4-dihydropyrimidine-2(1H)-thiones were rec-
ognized as valuable pharmacophores, which show a wide range of phar-
macological activities,1 including calcium channel modulation activity
(e.g., 1, SQ 32547, Figure 1)2 and anticancer activity (monastrol, 2,
Figure 1),3 as well as novel low molecular weight molecules with high
cell permeability4 and biological activities of other type.5–7
A large majority of 3,4-dihydropyrimidine-2(1H)-thione derivatives
were synthesized according to the three-component protocol developed
by Biginelli in 1893 (Scheme 1).8 To the present date, a number of im-
provements have been introduced in order to enhance the efficiency of
this reaction,9,10 including an enantioselective approach.11–13 However,
due to limited application to the aromatic or unsaturated aldehydes,
Received 13 December 2007; accepted 12 August 2008.
Dedicated to Professor Marian Mikolꢀajczyk, CBMiM PAN in Lꢀ o´dz´, Poland, on the
occasion of his 70th birthday.
Address correspondence to Dr. Jacek G. Sos´nicki, Szczecin University of Technol-
ogy, Institute of Chemistry and Environmental Protection, Al. Piasto´w 42, PL–71065
Szczecin, Poland. E-mail: sosnicki@ps.pl
1946

Grignard Reagents and Pyrimidine-2(1H)-thione
1947
FIGURE 1 Biologically active representatives of the 3,4-dihydropyrimidine-
2(1H)-thione family.
the Biginelli reaction suffers from the lack of the attachment of the
optional substituent at C-4.
Another
method
of
synthesizing
3,4-dihydropyrimidine-
2(1H)-thiones involves the condensation reaction between
functionalized amines with either 4-isothiocyanato-2-pentanone or
3-isothiocyanatobutanal.5–7,14 The synthesis of 3,4-dihydropyrimidine-
2(1H)-thiones by the reaction of derivatives of pyrimidine-2(1H)-
thiones with organometallic nucleophiles has been given less attention;
it has been limited only to N-substituted 4,6-dimethyl species.15
Exploring the concept of the use of simple precursors in the syn-
thesis of functionalized piperidine-2(1H)-(thio)ones, we have recently
reported that organolithium reagents can be added to pyridine-2(1H)-
thione (commercially available as 2-mercaptopyridine) yielding 4- or
6-substituted dihydropyridine-2-thiones,16,17 while standard Grignard
reagents were insufficiently reactive in these reactions.
Taking into account a more pronounced electron deficiency in the
pyrimidine than in the pyridine ring,18 we investigated the reaction of
organometallic reagents with pyrimidine-2(1H)-thione (commercially
available as 2-mercaptopyrimidine). We anticipated that addition of the
organometallic reagents to pyrimidine-2(1H)-thione would take place
SCHEME 1 Biginelli aryl-3,4-dihydropyrimidine-2(1H)-thiones synthesis.

1948
J. G. Sos´ nicki
SCHEME 2 Synthesis of 4-substituted 3,4-dihydropyrimidine-2(1H)-thiones
5.
much easier than to pyridine-2(1H)-thione, and that the preparation of
3,4-dihydropyrimidine-2(1H)-thione could be achieved also using Grig-
nard reagents. In order to check the scope and the limitations of the ad-
dition and to demonstrate the possibilities of introducing a substituent
at C-4, a variety of alkyl, aryl, allyl, and vinyl organolithium compounds
as well as Grignard reagents were tested in these reactions.
RESULTS AND DISCUSSION
As expected, pyrimidine-2(1H)-thione 4 affords 4-substituted 3,4-
dihydropyrimidine-2(1H)-thiones (5) from the reactions with both
organolithium and Grignard reagents. The results and conditions of
the reactions are presented in Table I. An amount of 2–3 equivalents
of the organometallic reagent with respect to 4 was required in or-
der to obtain product 5 in optimum yields. The first equivalent of RM
converted 4 into the metallated salt 4M, and the second one induced
addition (Scheme 2, Table I).
In general, the reactions were performed at 0◦C in THF or in DEE
as solvents. However, in some cases the reaction was initiated at a
low temperature, which was subsequently raised. All 4-substituted
3,4-dihydropyrimidine-2(1H)-thiones were obtained in good yields and
on a multigram scale. In the case of 1-methyl-2-propenylmagnesium
chloride, the addition afforded an inseparable 70:30 mixture of two
diastereomers (Table I).
It should be emphasized that the products did not require labor-
consuming purification. The protocol applied, sufficient to obtain the
product in pure state, consisted of an extraction using ethyl acetate,
simple filtration of the solution through the pad of Celite under reduced
pressure, and subsequent crystallization of the white solid.
As far as the reactivity of the organometallic reagents is concerned,
it should be noted that the organometallic compounds used showed

Grignard Reagents and Pyrimidine-2(1H)-thione
1949
TABLE I Reaction Conditions and Yields of 5 Obtained by the
Addition Reaction of 4 with Organolithium and Grignard Reagents
Reaction Equivalents Yields
5
a
RM
Solventd
Temp. [◦C] Time [min]
RM
[%]
THF/DEE
0
0
0
0
0
15
15
15
30
15
3
80
a
b
b
c
THF
3
3
3
3
3
30
84
31
99
98
THF/hexane
THF
DEE/hexane
DEE/pentane
d
−78
15
15
−78 to −40
e
DEE/pentane
−78
20
30
2.5
92
−78 to r.t.
f
f
THF/pentane −78 to r.t.
30
30
2.1
2.2
75
99
THF
0
g
THF
0
15
2.2
78e
h
THF
0
60
15
2.5
96
0 to r.t.
i
DEE/pentane
−78
30
30
2.5
80
−78 to r.t.
j
THF
THF
0
0
30
30
2.5
2.6
96
63
k
l
l
DBE/DEE
DEE/THF
−78 to −20
30
30
2.1
2.5
95
40
0
(Continued on next page)

1950
J. G. Sos´ nicki
TABLE I Reaction Conditions and Yields of 5 Obtained by the
Addition Reaction of 4 with Organolithium and Grignard
Reagents (Continued)
Reaction
Equivalents Yields
5
RM
Solventd
THF
Temp. [◦C] Time [min]
RM
[%]
m
−78 to 0
30
2.1
70
n
THF/pentane
−30
60
15
2.2
55
−30 to r.t.
aRLi obtained by the reaction of RX (X = I, 5d, X = Br, 5i) with 2 equiv. of
t-BuLi.19
bAllyllithium prepared from AllylBu3Sn (see the Experimental section).
c1,1-Dimethylallyl substituent is present in the product.
dTHF – tetrahydrofuran; DEE – diethylether; DBE – dibuthylether.
eObtained as 70:30 mixture of diastereomers.
different reactivity regarding the addition to pyrimidine-2(1H)-thione.
Alkyl and aryl organolithium nucleophiles were more effective than the
corresponding Grignard reagents, thus the majority of products 5 with
alkyl and aryl substituents were prepared using organolithium com-
pounds, both commercially available and prepared according to known
methods. On the other hand, allyl- and vinylmagnesium reagents are
very reactive and afford products in good or very good yield; this applies
particularly to allylmagnesium reagents. Since preparation of allyl-
lithium reagents often requires expensive and toxic starting materials
(e.g., organotin derivatives), the use of allyl Grignard reagents seemed
to be a good alternative for these reactions.
The structures of all products 5 were determined on the basis of 1D
1
1
NMR (1H, 13C, 13C-DEPT) and 2D NMR (1H, H COSY, 13C, H HET-
COR) spectroscopy, IR spectroscopy, mass spectrometry, and elemental
1
analysis. H NMR spectroscopy showed the characteristic signals of
CH-4, appearing in the region of 3.7–5.4 ppm as a broad singlet or
as a broad multiplet. The signals of CH-5 and CH-6 are present at
4.8–5.1 ppm and near 6.0 ppm, respectively. Analysis of the multiplets
showed that in all cases CH-5 and CH-6 protons are coupled and
that the value of coupling constant (J) is about 8.0 Hz.
In summary, we have described an efficient access to 4-substituted
derivatives of 3,4-dihydropyrimidine-2(1H)-thione obtained by the
reaction between organolithium and/or Grignard reagents with

Grignard Reagents and Pyrimidine-2(1H)-thione
1951
unsubstituted pyrimidine-2(1H)-thione. Due to complementary re-
activity of both reactants, alkyl, aryl, allyl and vinyl substituents
were introduced at C-4. Since this synthetic procedure can be per-
formed on a multigram scale, and since pyrimidine-2(1H)-thione 4 and
most of organometallic reagents used are readily available, the pro-
cess described provides a new and easy way to obtain 4-substituted
3,4-dihydropyrimidine-2-(1H)-thione derivatives, which complements
other methods.
EXPERIMENTAL
Melting points were determined on a Boetius hot stage apparatus.
1H and 13C NMR spectroscopic measurements were performed with
a Bruker DPX 400 spectrometer equipped with a 5 mm 1H/BB–inverse
probehead, operating at 400.13 and 100.62 MHz, respectively. TMS was
used as internal reference. Two-dimensional spectra were acquired us-
ing standard Bruker software. Mass spectra (70 eV) were recorded with
an HP 6890 (Hewlett-Packard) GC-MS spectrometer equipped with a
mass detector HP 5973. Elemental analyses were performed with Eu-
roEA 3000 series, EuroVector CHNS-O Elemental Analyzer.
Starting Compounds
Pyrimidine-2(1H)-thione 4, butyllithium (2.5 M in hexane), tert-
butyllithium (1.7 M in pentane), phenyllithium (2.0 M in Bu2O), hexyl-
lithium (2.3 M in hexane), 2-thienyllithium (1.0 M in THF), allylmag-
nesium chloride (2.0 M in THF), and 1-methyl-2-propenylmagnesium
chloride (0.5 M in THF) were purchased from Aldrich. Methyl-
lithium (1.6 M in Et2O) was purchased from Acros Organics. Isobutyl-
lithium was prepared from appropriate iodoalkane and 2.0 eq of
tert-butyllithium.19 The same procedure was applied for the synthe-
sis of cyclopentenyllithum; however here 1-bromocyclopentene was
used. 3,3-Dimethylallylmagnesium bromide was prepared as described
earlier.20 3-(2-Methylthienyl)lithium was obtained by treatment of 2-
methylthiophene with butyllithium in equimolar ratio at −30◦C in
THF and stirred over 1 h. Allyllithium reagents were prepared by
stirring the appropriate allyltributyltin compound (1.0 eq) with 1.0
eq of butyllithium at r.t. for 30 min. All reagents were prepared un-
der argon prior to use. Solvents (THF and DEE) were purified over
sodium in argon atmosphere according to a standard procedure prior to
use.

1952
J. G. Sos´ nicki
Preparation of 3,4-Dihydropyrimidine-2(1H)-thiones: General
Procedure
To a cooled and stirred solution of 0.029 mol of pyrimidine-2(1H)-thione
(4) in dry solvent (50–70 mL) (see Table I), a portion of 0.059–0.088 mol
of RM solution (see Table I) was added via syringe over 3 min under
argon. The mixture was stirred at the temperature and for the period
specified in Table I. After quenching with aqueous saturated NH4Cl
(15 mL), the water layer was extracted with ethyl acetate (2 × 150 mL)
and the combined organic layers were dried over MgSO4. Filtration
through a 1 cm pad of Celite followed by concentration of the filtrate
in vacuo and crystallization from the appropriate solvent yielded 4 as
white solid in all cases.
4-Methyl-3,4-dihydropyrimidine-2(1H)-thione (5a)
1
White solid, mp 137–139◦C from n-hexane:ethyl acetate; H NMR
(400.13 MHz, CDCl3): δ =1.32 (d, J = 6.4 Hz, 3H, CH3), 4.23 (br s,
1H, CH-4), 4.85 (d, J = 7.7 Hz, 1H, CH-5), 5.96 (dd, J = 7.2, 4.8 Hz,
1H, CH-6), 7.44 (br s, 1H, NH), 8.54 (br s, 1H, NH);13C NMR (100.63
MHz, CDCl3): δ = 24.5 (CH3), 48.0 (CH-4), 105.1 ( CH-5), 122.1 ( CH-
6), 174.6 (C-2); MS (EI, 70 eV) m/z: 128 (100), 113 (94), 79 (14), 68 (15),
60 (7), 41 (9); IR (KBr pellet, cm−1):νmax = 3204, 2968, 2928, 1674, 1584,
1504, 1436, 1302, 1220, 1192, 736, 638; Anal. Calcd. for C5H8N2S: C
46.84; H 6.29; N 21.85; S 25.01; Found: C 46.85; H 6.33; N 21.79; S
24.90.
4-Butyl-3,4-dihydropyrimidine-2(1H)-thione (5b)
White solid, mp 91–93◦C from n-hexane:ethyl acetate; 1H NMR
(400.13 MHz, CDCl3): δ = 0.91 (t, J = 7.1 Hz, 3H, CH3), 1.27–1.43 (m,
4H, CH2), 1.54–1.64 (m, 2H, CH2), 4.09–4.15 (m, 1H, CH-4), 4.86 (d of
quintets, J = 7.9, 1.6 Hz, 1H, CH-5), 5.99 (ddd, J = 7.9, 4.6, 1.0 Hz,
1H, CH-6), 7.22 (br s, 1H, NH), 8.46 (br s, 1H, NH); 13C NMR (100.63
MHz, CDCl3): δ = 14.0 (CH3), 22.5 (CH2), 26.1 (CH2), 37.8 (CH2), 52.3
(CH-4), 103.7 ( CH-5), 122.6 ( CH-6), 175.0 (C-2); MS (EI, 70 eV) m/z:
170 (M+., 32), 126 (3), 113 (100), 79 (9); IR (KBr pellet, cm−1):νmax
3192, 2956, 2928, 1570, 1498, 1312, 1218, 1180, 754, 650; Anal. Calcd.
for C8H14N2S: C 56.43; H 8.29; N 16.45; S 18.83: Found: C 56.36; H
8.35; N 16.44; S 18.91.
=
4-Hexyl-3,4-dihydropyrimidine-2(1H)-thione (5c)
White solid, mp 94–96◦C from n-hexane:ethyl acetate; 1H NMR
(400.13 MHz, CDCl3): δ = 0.88 (t, J = 7.0 Hz, 3H, CH3), 1.25–1.42
(m, 8H, CH2), 1.53–1.61 (m, 2H, CH2), 4.08–4.15 (m, 1H, CH-4), 4.86 (d

Grignard Reagents and Pyrimidine-2(1H)-thione
1953
of quintets, J = 8.0, 1.6 Hz, 1H, CH-5), 5.98 (ddd, J = 8.0, 4.5, 0.8 Hz,
1H, CH-6), 7.04 (br s, 1H, NH), 8.27 (br s, 1H, NH); 13C NMR (100.63
MHz, CDCl3): δ = 14.1 (CH3), 22.6 (CH2), 24.0 (CH2), 29.0 (CH2), 31.7
(CH2), 38.2 (CH2), 52.3 (CH-4), 103.7 ( CH-5), 122.6 ( CH-6), 175.2
(C-2); MS (EI, 70 eV) m/z: 198 (30), 113 (100), 79 (6), 41 (4); IR (KBr
pellet, cm−1) :νmax = 3196, 2960, 2856, 1678, 1570, 1498, 1380, 1316,
1216, 1178, 754; Anal. Calcd. for C10H18N2S: C 60.56; H 9.15; N 14.12;
S 16.17; Found: C 60.61; H 9.18; N 14.03; S 16.22.
4-Isobutyl-3,4-dihydropyrimidine-2(1H)-thione (5d)
White solid, mp 160–163◦C from EtOH; 1H NMR (400.13 MHz,
CDCl3): δ = 0.92 (d, J = 6.6 Hz, 6H, CH3), 1.42 (quintet, J = 6.8 Hz,
1H, CHH), 1.56 (quintet, J = 6.8 Hz, 1H, CHH), 1.79 (septet, J = 6.7
Hz, 1H, CH), 4.12 (br s, 1H, CH-4), 4.89 (br d, J = 7.9 Hz, 1H, CH-5),
5.97 (dd, J = 7.9, 4.6, Hz, 1H, CH-6), 6.85 (br s, 1H, NH), 8.07 (br s,
1H, NH); 13C NMR (100.63 MHz, CDCl3): δ = 22.3 (CH3 or CH), 22.8
(CH3 or CH), 23.3 (CH3 or CH), 47.4 (CH2), 50.5 (CH-4), 104.2 ( CH-5),
122.4 ( CH-6), 175.3 (C-2); MS (EI, 70 eV) m/z: 170 (34), 113 (100), 79
(10); IR (KBr pellet, cm−1):νmax = 3208 br, 2956, 1676, 1572, 1492, 1464,
1384, 1302, 1214, 1168, 756, 648; Anal. Calcd. for C8H14N2S: C 56.43;
H 8.29; N 16.45; S 18.83; Found: C 56.38; H 8.22; N 16.53; S 18.90.
4-tert-Butyl-3,4-dihydropyrimidine-2(1H)-thione (5e)
White solid, mp 245–246◦C from EtOH; 1H NMR (400.13 MHz,
CDCl3): δ = 0.93 (s, 9H, CH3), 3.67–3.71 (m, 1H, CH-4), 4.94 (d of
quintets, J = 8.1, 2.0 Hz, 1H, CH-5), 6.07 (ddd, J = 8.1, 4.6, 0.7 Hz,
1H, CH-6), 6.52 (br s, 1H, NH), 7.61 (br s, 1H, NH); 13C NMR (100.63
MHz, CDCl3): δ = 24.6 (CH3), 37.2 (C(CH3)3), 62.0 (CH-4), 101.1 ( CH-
5), 123.4 ( CH-6), 176.1 (C-2); MS (EI, 70 eV) m/z: 170 (M+., 27), 113
(100), 79 (10); IR (KBr pellet, cm−1): νmax = 3212, 2964, 1678, 1566,
1490, 1304, 1218, 1182; Anal. Calcd. for C8H14N2S: C 56.43; H 8.29; N
16.45; S 18.83; Found: C 56.51; H 8.19; N 16.39; S 18.91.
4-Allyl-3,4-dihydropyrimidine-2(1H)-thione (5f)
1
White solid, mp 100–102◦C from n-hexane:ethyl acetate; H NMR
(400.13 MHz, CDCl3): δ = 2.27–2.43 (m, 2H, CH2), 4.14–4.20 (m, 1H,
CH-4), 4.87 (d of quintets, J = 8.0. 1.6 Hz, 1H, CH-5), 5.15 (m, 2H,
CH2), 5.69–5.81 (m, 1H, CH), 6.00 (ddd, J = 8.0, 4.7, 1.3 Hz, 1H,
CH-6), 7.16 (br s, 1H, NH), 8.51 (br s, 1H, NH); 13C NMR (100.63
MHz, CDCl3): δ = 42.6 (CH2), 51.6 (CH-4), 103.1 ( CH-5), 119.8 ( CH2),
122.9 ( CH-6), 132.0 ( CH), 175.1 (C-2); MS (EI, 70 eV) m/z: 154 (6),
113 (100), 79 (14); IR (KBr pellet, cm−1): νmax = 3212, 1676, 1568, 1496,

1954
J. G. Sos´ nicki
1314, 1216, 1178, 912, 740; Anal. Calcd. for C7H10N2S: C 54.51; H 6.54;
N 18.16; S 20.79; Found: C 54.45; H 6.62; N 18.15; S 20.69.
4-(1-Methylallyl)-3,4-dihydropyrimidine-2(1H)-thione (5g)
White solid. Crystallization from n-hexane:ethyl acetate enriched
the quantity of the major isomer from 70:30 to 80:20; NMR data of
the major isomer were obtained from the spectra of 80:20 diastereomer
1
mixture. H NMR (400.13 MHz, CDCl3): δ = 1.07 (d, J = 6.9 Hz, 3H,
CH3), 2.29–2.39 (m, 1H, 4-CH), 4.08–4.13 (m, 1H, CH-4), 4.85 (dm, J =
8.1 Hz, 1H, CH-5), 5.17 (dt, J = 17.2, 1.3 Hz, 1H, CHH), 5.21 (dt,
J = 10.6, 1.3 Hz, 1H, CHH), 5.78 (ddd, J = 17.2, 10.6, 6.6 Hz, 1H,
CH), 6.04 (ddd, J = 8.1, 4.6, 1.3 Hz, 1H, CH-6), 6.61 (br s, 1H, NH),
8.00 (br s, 1H, NH); 13C NMR (100.63 MHz, CDCl3): δ = 13.1 (CH3),
43.9 (CH-4), 56.4 (CH-4), 101.9 ( CH-5), 117.3 ( CH2), 123.5 ( CH-6),
138.2 ( CH), 175.9 (C-2); MS (EI, 70 eV) m/z: 168 (M+., 2), 113 (100),
79 (11); IR (KBr pellet, cm−1): νmax = 3208 br, 2972, 1678, 1568, 1492,
1216, 1180, 916, 752. Anal. Calcd. for C8H12N2S: C, 57.11; H, 7.19; N,
16.65; S, 19.06; Found: C, 57.03; H, 7.16; N, 16.74; S, 18.99.
4-(1,1-Dimethylallyl)-3,4-dihydropyrimidine-2(1H)-thione (5h)
White solid, mp 227–229◦C from EtOH; 1H NMR (400.13 MHz,
CDCl3): δ = 1.01 (s, 3H, CH3), 1.04 (s, 3H, CH3), 3.78–3.82 (m, 1H,
CH-4), 4.91 (d of quintets, J = 8.1, 1.8 Hz, 1H, CH-5), 5.14 (d, J =
17.4 Hz, 1H, CHH), 5.19 (d, J = 10.8 Hz, 1H, CHH), 5.71 (dd, J =
17.4, 10.8 Hz, 1H, CH), 6.08 (ddd, J = 8.1, 4.6, 1.3 Hz, 1H, CH-6),
6.52 (br s, 1H, NH-3), 7.95 (br s, 1H, NH-1); 13C NMR (100.63 MHz,
CDCl3): δ = 20.4 (CH3), 22.3 (CH3), 43.3 (4C(CH3)2), 60.2 (CH-4), 100.2
( CH-5), 115.3 ( CH2), 123.8 ( CH-6), 143.1 ( CH), 175.8 (C-2); MS
(EI, 70 eV) m/z: 182 (M+., 1), 113 (100), 79 (9); IR (KBr pellet, cm−1):
νmax = 3208 br, 2928, 1678, 1566, 1498, 1308, 1218, 1184, 916. Anal.
Calcd. for C9H14N2S: C 59.30; H 7.74; N 15.37; S 17.59; Found: C 59.39;
H 7.69; N 15.40; S 17.63.
4-Cyclopent-1-enyl-3,4-dihydropyrimidine-2(1H)-thione (5i)
White solid, mp 166–168◦C from EtOH; 1H NMR (400.13 MHz,
CDCl3): δ = 1.92 (quintet, J = 7.5 Hz, 2H, CH2), 2.27–2.42 (m, 4H,
CH2), 4.74 (br s, 1H, CH-4), 4.87 (dm, J = 7.8 Hz, 1H, CH-5), 5.62
(br s, 1H, CH), 6.02 (ddd, J = 7.9, 4.8, 1.3 Hz, 1H, CH-6), 6.93 (br s,
1H, NH), 8.35 (br s, 1H, NH); 13C NMR (100.63 MHz, CDCl3): δ = 23.2
(CH2), 30.7 (CH2), 32.2 (CH2), 52.7 (CH-4), 102.4 (CH-5), 122.6 ( CH-
6), 127.6 ( CH), 144.3 ( C), 175.1 (C-2); MS (EI, 70eV) m/z: 180 (M+,
100), 151 (12), 120 (11), 93 (24); IR (KBr pellet, cm−1): νmax = 3188 br.,

Grignard Reagents and Pyrimidine-2(1H)-thione
1955
2988, 2940, 2844, 1676, 1580, 1492, 1284, 1216, 1180, 740, 628; Anal.
Calcd. for C9H12N2S: C, 59.96; H, 6.71; N, 15.54; S, 17.79; Found: C,
60.02; H, 6.82; N, 15.64; S, 17.66.
4-Vinyl-3,4-dihydropyrimidine-2(1H)-thione (5j)
1
White solid, mp 155–157◦C from n-hexane:ethyl acetate; H NMR
(400.13 MHz, CDCl3): δ = 4.58 (br s, 1H, CH-4), 4.89 (dm, J = 7.9 Hz,
1H, CH-5), 5.18 (dt, J = 10.0, 0.7 Hz, 1H, CHH), 5.22 (dt, J = 17.1,
0.9 Hz, 1H, CHH), 5.85 (ddd, J = 17.1, 10.0, 7.1 Hz, 1H, CH), 6.00
(ddd, J = 7.9, 4.8, 1.5 Hz, 1H, CH-6), 6.66 (br s, 1H, NH), 7.90 (br s,
1H, NH); 13C NMR (100.63 MHz, CDCl3): δ = 55.0 (CH-4), 102.5 ( CH-
5), 116.6 ( CH2), 122.4 ( CH-6), 137.7 ( CH), 175.3 (C-2); MS (EI, 70
eV) m/z: 140 (100), 113 (44), 80 (32), 53 (8); IR (KBr pellet, cm−1): νmax
3192 br, 2988, 1678, 1580, 1498, 1220, 1180, 984, 932, 736, 640; Anal.
Calcd. for C6H8N2S: C, 51.40; H, 5.75; N, 19.98; S, 22.87; Found: C,
51.44; H, 5.77; N, 20.06; S, 22.94.
=
4-Isopropenyl-3,4-dihydropyrimidine-2(1H)-thione (5k)
1
White solid, mp 136–138◦C from n-hexane:ethyl acetate; H NMR
(400.13 MHz, CDCl3): δ = 1.80 (s, 3H, CH3), 4.57 (br s, 1H, CH-4), 4.84
(d of quintets, J = 7.8, 1.7 Hz, 1H, CH-5), 4.86 (s, 1H, CHH), 4.92
(s, 1H, CHH), 6.04 (ddd, J = 7.8, 4.7, 1.0 Hz, 1H, CH-6), 7.07 (br
s, 1H, NH), 8.54 (br s, 1H, NH); 13C NMR (100.63 MHz, CDCl3): δ =
17.4 (CH3), 58.4 (CH-4), 102.4 ( CH-5), 112.9 ( CH2), 122.9 ( CH-6),
145.0 ( C), 175.0 (C-2); MS (EI, 70 eV) m/z: 154 (79), 139 (4), 113 (100),
94 (19), 79 (14); IR (KBr pellet, cm−1): νmax = 3200, 2984, 1676, 1566,
1492, 1438, 1214, 1176, 912, 762; Anal. Calcd. for C7H10N2S: C 54.51;
H 6.54; N 18.16; S 20.79; Found: C 54.46; H 6.47; N 18.21; S 20.80.
4-Phenyl-3,4-dihydro-pyrimidine-2(1H)-thione (5l)
1
White solid, mp 185–186◦C from n-hexane:ethyl acetate; H NMR
(400.13 MHz, CDCl3): δ = 4.98 (d of quintets, J = 8.0, 1.5 Hz, 1H, CH-
5), 5.13–5.16 (m, 1H, CH-4), 6.07 (ddd, J = 8.0, 4.7, 1.5 Hz, 1H, CH-
6), 6.91 (br s, 1H, NH), 7.31–7.42 (m, 5H, C6H5), 8.15 (br s, 1H, NH);
13C NMR (100.63 MHz, CDCl3): δ = 56.6 (CH-4), 103.8 ( CH-5), 121.9
( CH-6), 126.9 (C6H5), 128.6 (C6H5), 129.1 (C6H5), 142.3 (C6H5), 174.4
(C-2); MS (EI, 70eV) m/z: 190 (100, M+.), 189 (45), 130 (68), 115 (9), 113
(38), 103 (15), 77 (19); IR (KBr pellet, cm−1): νmax = 3160, 2976, 1674,
1566, 1490, 1284, 1210, 1174, 764, 698; Anal. Calcd. for C10H10N2S:
C 63.13; H 5.30; N 14.72; S 16.85; Found: C 63.20; H 5.27; N 14.81; S
16.79.

1956
J. G. Sos´ nicki
4-Thiophen-2-yl-3,4-dihydropyrimidine-2(1H)-thione (5m)
White solid, mp 181–183◦C from EtOH; 1H NMR (400.13 MHz,
CDCl3): δ = 5.09 (d of quintets, J = 7.9, 1.6 Hz, 1H, CH-5), 5.26–
5.45 (m, 1H, CH-4), 6.12 (ddd, J = 7.9, 4.8, 1.5 Hz, 1H, CH-6), 6.82 (br
s, 1H, NH), 6.99 (dd, J = 5.0, 3.6 Hz, 1H, CH-4arom), 7.01 (dd, J = 3.6,
1.2 Hz, 1H, CH-3arom), 7.33 (dd, J = 5.0, 1.2 Hz, 1H, CH-5arom), 7.79
(br s, 1H, NH); 13C NMR (100.63 MHz, CDCl3): δ = 51.4 (CH-4), 103.1
( CH-5), 122.5 ( CH-6), 125.3 (C4H3S), 126.6 (C4H3S), 127.1 (C4H3S),
146.1 (C4H3S), 174.5 (C-2); MS (EI, 70 eV) m/z: 196 (M+., 100), 195
(29), 163 (9), 153 (7), 136 (80), 109 (10); IR (KBr pellet, cm−1): νmax
3160 br, 2976, 1672, 1566, 1490, 1220, 1176, 996, 758. Anal. Calcd. for
C8H8N2S2: C 48.95; H 4.11; N 14.27; S 32.67; Found: C 49.00; H 4.09;
N 14.31; S 32.78.
=
4-(2-Methylthiophen-3-yl)-3,4-dihydropyrimidine-2(1H)-thione
(5n)
White solid, mp 195–198◦C from EtOH; 1H NMR (400.13 MHz,
CDCl3): δ = 2.46 (d, J = 0.9 Hz, 3H, CH3), 5.06 (d of quintets, J = 7.9,
1.7 Hz, 1H, CH-5), 5.31–5.34 (m, 1H, CH-4), 6.09 (ddd, J = 7.9, 4.8,
1.4 Hz, 1H, CH-6), 6.63 (d of quartets, J = 6.6, 1.0 Hz, 1H, CH-4arom),
6.77 (d, J = 3.4 Hz, 1H, CH-5arom), 6.82 (br s, 1H, NH), 7.87 (br s, 1H,
NH); 13C NMR (100.63 MHz, CDCl3): δ = 15.5 (CH3), 51.6 (CH-4), 103.2
( CH-5), 122.4 ( CH-6), 125.0 (C5H5S), 126.1 (C5H5S), 141.5 (C5H5S),
143.7 (C5H5S), 174.3 (C-2); MS (EI, 70 eV) m/z: 210 (100), 209 (24), 195
(5), 177 (10), 167 (5), 150 (77), 136 (12), 118 (12); IR (KBr pellet, cm−1):
νmax = 3188 br, 2984, 1678, 1578, 1494, 1276, 1222, 1178, 800, 772, 732.
Anal. Calcd. for C9H10N2S2:C 51.40; H 4.79; N 13.32; S 30.49; Found:
C 51.38; H 4.85; N 13.33; S 30.60.
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