The dramatic effect of thiophenol on the reaction pathway of ethyl 4-chloromethyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate with thiophenolates: Ring expansion versus nucleophilic substitution

Article abstract of DOI:10.1016/j.tetlet.2010.07.098

Ethyl 4-methyl-2-oxo-7-phenylthio-2,3,6,7-tetrahydro-1H-1,3-diazepine-5- carboxylate and/or ethyl 6- methyl-2-oxo-4-(phenylthiomethyl)-1,2,3,4- tetrahydropyrimidine-5-carboxylate were obtained in the reaction of ethyl 4-chloromethyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate with PhSNa or PhSK with or without PhSH, depending on the reagent ratio, reaction time, or temperature, as a result of ring expansion and/or nucleophilic substitution. The reaction pathway was affected strongly by the basicity-nucleophilicity of the reaction media. The results obtained were confirmed by reactions of 4-mesyloxymethyl-6-methyl-5-tosyltetrahydropyrimidin- 2-one with PhSNa/PhSH and ethyl 4-chloromethyl-6-methyl-2-oxo-1,2,3,4- tetrahydropyrimidine-5-carboxylate with NaCN/HCN or NaCH(COOEt)₂ CH₂(COOEt)₂.

Full text of DOI:10.1016/j.tetlet.2010.07.098

Tetrahedron Letters 51 (2010) 5056–5059
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Tetrahedron Letters
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The dramatic effect of thiophenol on the reaction pathway of ethyl
4-chloromethyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
with thiophenolates: ring expansion versus nucleophilic substitution
Anastasia A. Fesenko a, Ludmila A. Trafimova a, Dmitry A. Cheshkov b, Anatoly D. Shutalev a,
*
a Department of Organic Chemistry, Moscow State Academy of Fine Chemical Technology, 86 Vernadsky Ave., 119571 Moscow, Russian Federation
b State Scientific Research Institute of Chemistry and Technology of Organoelement Compounds, 38 Entuziastov shosse, 111123 Moscow, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
Ethyl 4-methyl-2-oxo-7-phenylthio-2,3,6,7-tetrahydro-1H-1,3-diazepine-5-carboxylate and/or ethyl 6-
methyl-2-oxo-4-(phenylthiomethyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate were obtained in the
reaction of ethyl 4-chloromethyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate with
PhSNa or PhSK with or without PhSH, depending on the reagent ratio, reaction time, or temperature,
as a result of ring expansion and/or nucleophilic substitution. The reaction pathway was affected strongly
by the basicity–nucleophilicity of the reaction media. The results obtained were confirmed by reactions
of 4-mesyloxymethyl-6-methyl-5-tosyltetrahydropyrimidin-2-one with PhSNa/PhSH and ethyl 4-chloro-
methyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate with NaCN/HCN or NaCH(COOEt)2/
CH2(COOEt)2.
Received 6 May 2010
Revised 7 July 2010
Accepted 16 July 2010
Available online 22 July 2010
Keywords:
1,2,3,4-Tetrahydropyrimidin-2-ones
2,3,4,5-Tetrahydro-1H-1,3-diazepin-2-ones
Ring expansion
Ó 2010 Elsevier Ltd. All rights reserved.
Nucleophilic substitution
Ring expansion reactions are widely used in organic chemistry,1
particularly in the synthesis of nitrogen-containing heterocycles.1,2
An important example of one-carbon ring expansion is the trans-
formation of tetrahydropyrimidines 1 into tetrahydro-1,3-diaze-
pin-2-ones 2 by treatment with nucleophilic reagents (Scheme 1).3
It was postulated3 that diazepinones 2 form via the cyclopropane-
containingbicyclicintermediates4(Scheme1)whichresultfrompro-
tonabstractionfromtheN(1)Hgroupundertheactionofnucleophiles
followed by intramolecular nucleophilic substitution of chlorine in
anions3. Clearly, thisreactiondependsnotonlyonthenucleophilicity
but also on the basicity of the nucleophile. For example, direct nucle-
ophilic substitution of chlorine resulting in pyrimidines 5 cannot be
excluded a priori under certain reaction conditions. However, the
influence of reaction conditions on the reaction of compounds 1 with
nucleophiles remained unexplored.3 Therefore, study of the effect of
the nucleophilicity and basicity of the nucleophile, reagent ratio, sol-
vent, time, and temperature on the reaction of compounds 1 with
nucleophiles is interesting. In this research we used the readily avail-
able pyrimidinone 6 as the starting material and PhSNa or PhSK as
nucleophileswhichdemonstratestrongnucleophilicityandrelatively
low basicity.4 The nucleophiles were generated by the treatment of
PhSH with NaH or KOH in an appropriate solvent.
(Scheme 2). According to the 1H NMR spectrum, the crude material
contained 3 mol% of tetrahydropyrimidinone 8, a product of nucle-
ophilic substitution of chlorine in 6 (Table 1, entry 1). Diazepinone
7 formed with complete selectivity under similar conditions in the
reaction of 6 with PhSNa (1.10 equiv) in dry THF (rt, 7 h) (entry 2),
however, 9 mol% of starting material 6 was recovered. When EtOH
was used as the solvent, the rate of the reaction of 6 with PhSK
(1.10 equiv) decreased dramatically (conversion of 6 was only 8%
after7 h at rt), andtheselectivityalsodecreased (7:8 = 7:1)(entry3).
The reaction of 6 with PhSNa (1.08 equiv) in dry MeCN at rt for
7 h yielded diazepinone 7 as the product of ring expansion
Scheme 1. Two possible pathways for the reaction of pyrimidines 1 with nucleo-
philic reagents: ring expansion or nucleophilic substitution.
* Corresponding author. Tel.: +7 495 936 8908; fax: +7 495 936 8909.
E-mail address: shutalev@orc.ru (A.D. Shutalev).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.07.098

A. A. Fesenko et al. / Tetrahedron Letters 51 (2010) 5056–5059
5057
Scheme 2. Reaction of pyrimidine 6 with PhSNa or PhSK.
Table 1
Reactions of pyrimidine 6 with PhSNa or PhSK
Entry
Solvent
Base
Molar ratio of 6:PhSH:base
Molar ratio of 6:PhSNa:PhSH or 6:PhSK:PhSH
Conditions
Molar ratioa of products 7:8:6
1
2
3
4
5
6
7
8
MeCN
THF
EtOH
NaH
NaH
KOH
NaH
NaH
NaH
NaH
NaH
NaH
NaH
NaH
NaH
NaH
KOH
NaH
NaH
1.00:1.08:1.09
1.00:1.10:1.10
1.00:1.13:1.10
1.00:2.02:1.10
1.00:2.21:1.05
1.00:3.00:1.10
1.00:3.00:1.10
1.00:3.29:1.10
1.00:3.32:1.10
1.00:2.24:1.05
1.00:2.20:1.10
1.00:3.26:1.08
1.00:4.43:1.10
1.00:2.23:1.10
1.00:2.01:2.00
1.00:3.31:1.10
1.00:1.08:0
1.00:1.10:0
rt, 7 h
rt, 7 h
rt, 7.5 h
rt, 7 h
rt, 7.2 h
rt, 7 h
Reflux, 7 h
rt, 47.9 h
rt, 72.7 h
rt, 48.2 h
Reflux, 8 h
Reflux, 8.1 h
Reflux, 8.1 h
rt, 7 h
97:3:0
91:0:9
7:1:92
48:43:9
9:61:30
0:35:65
15:85:0
1:93:6
1.00:1.10:0.03
1.00:1.10:0.92
1.00:1.05:1.16
1.00:1.10:1.90
1.00:1.10:1.90
1.00:1.10:2.19
1.00:1.10:2.22
1.00:1.05:1.19
1.00:1.10:1.10
1.00:1.08:2.18
1.00:1.10:3.33
1.00:1.10:1.13
1.00:2.00:0.01
1.00:1.10:2.21
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
EtOH
9
0:97:3
6:89:5
10
11
12
13
14
15
16
33:67:0
16:84:0
11:89:0
16:6:78
93:7:0b
11:89:0
MeCN
MeCN
rt, 7 h
Reflux, 29 h
a
According to 1H NMR data of the crude products.
83 mol% of 7 + 8 and 17 mol % of bis-diazepinone 9.
b
Thiophenol (PhSH) strongly affected the ratio of 7:8 and the rate
solvents (MeCN or THF) and highly basic reaction media without
PhSH, the thiophenolate-anion acts as a base and abstracts a pro-
ton from N(1)H to give anion 3 (R = Et, R1 = Me) (see Scheme 1),
which further affords diazepinone 7. Addition of PhSH inhibits an-
ion 3 formation and therefore causes a decrease in the amount of
diazepinone 7. Probably, in this case, compound 6 reacts with
PhSNa via an SN2 mechanism, resulting in pyrimidine 8. Since chlo-
rine is a rather poor leaving group, the rate of reaction is low, and
heating at reflux or a long reaction time is necessary for comple-
tion of the reaction. The low rate of reaction of 6 with PhSK in EtOH
can be explained by the decreased basicity and nucleophilicity of
PhSK in a polar protic solvent.
In continuation of this research we used 4-mesyloxymethyl-5-
tosyltetrahydropyrimidine (10) as the starting material in a reac-
tion with PhSNa in the presence of PhSH. We found that 10 readily
reacted with PhSNa in MeCN to give 4-phenylthio-6-tosyltetrahy-
dro-1,3-diazepinone (11) (Scheme 3).8 As expected, when com-
pound 10 was reacted with PhSNa/PhSH (1:1.08:2.47) in MeCN
(rt, 23.7 h), pyrimidinone 12 formed along with diazepinone 11
(12:11 = 56:44). The amount of 12 increased up to 92% in this reac-
tion, when a 1:1.24:3.82 ratio of the reagents was used (MeCN, rt,
42.4 h).9
of the reaction. The amount of pyrimidine 8 increased with a rise in
the amount of PhSH in the reaction of 6 with PhSNa (1.05–
1.10 equiv) in MeCN at rt for 7 h (entries 1, 4–6). Pyrimidine 8
formed with complete selectivity when 1.90 equiv of PhSH was
used (entry 6). However, the reaction rate decreased significantly
with an increase in the amount of PhSH (entries 1, 4–6).
The extent of conversion of compound 6 in the reaction with
PhSNa in the presence of PhSH (1.90–2.22 equiv) increased with
reaction time or temperature. Indeed, the reaction of 6 with PhSNa
(1.10 equiv) in refluxing MeCN in the presence of PhSH (1.90 equiv)
was complete in 7 h, while the selectivity of the reaction decreased
significantly (entry 7). However, the selectivity remained high at rt
and over long reaction times (entries 8 and 9).
A relationship between the ratio of 7:8 and the amount of PhSH
was also observed at rt and over long reaction times (entry 8 vs entry
10), refluxing the reaction mixture (entry 11 vs entry 12 vs entry 13),
and when EtOH was used as the solvent (entry 3 vs entry 14).
On using a greater excess of the nucleophile PhSNa (2.00 equiv),
bis-diazepinone 95 (17 mol%) formed along with 7 and 8 in the ra-
tio 93:7 (entry 15).
Under the optimal conditions diazepinone 7 was obtained in the
reaction of 6 with PhSNa (1.08 equiv) in MeCN at rt for 7 h (entry
1),6 and pyrimidinone 8 was prepared by the reaction of 6 with
PhSNa (1.10 equiv) in the presence of 2.22 equiv of PhSH in MeCN
at rt for 73 h (entry 9).7
We also attempted to obtain products of direct nucleophilic sub-
stitution of the chlorine in the reaction of 6 with other nucleophiles.
Transformation of 6 into 7 and/or 8 is kinetically controlled. In
fact, heating a mixture of 6, PhSNa, and PhSH in MeCN for 8 or 29 h
at reflux resulted in mixtures of 7 and 8 in similar ratios (Table 1,
entry 12 vs entry 16). Moreover, reflux of 7, PhSH, and PhSNa
(1.0:1.9:0.1, respectively) in MeCN followed by evaporation of
the solvent and aqueous work-up gave only 7 in 88% yield.
From the results obtained we suggest that the reaction of 6 with
PhSNa and PhSK proceeds via two possible mechanisms. In aprotic
Scheme 3. Reaction of pyrimidine 10 with PhSNa/PhSH.

5058
A. A. Fesenko et al. / Tetrahedron Letters 51 (2010) 5056–5059
References and notes
1. Hesse, M. Ring Enlargement in Organic Chemistry; VCH: Weinheim, 1991.
2. For recent examples, see: (a) Brahma, S.; Ray, J. K. J. Heterocycl. Chem. 2008, 45,
311–317; (b) Manning, J. R.; Davies, H. M. L. J. Am. Chem. Soc. 2008, 130, 8602–
8603; (c) Ferreira, M. d. R. R.; Cecere, G.; Pace, P.; Summa, V. Tetrahedron Lett.
2009, 50, 148–151; (d) Cochi, A.; Burger, B.; Navarro, C.; Pardo, D. G.; Cossy, J.;
Zhao, Y.; Cohen, T. Synlett 2009, 2157–2161; (e) Cho, H.; Iwama, Y.; Sugimoto,
K.; Kwon, E.; Tokuyama, H. Heterocycles 2009, 78, 1183–1190; (f) Tsuritani, T.;
Yamamoto, Y.; Kawasaki, M.; Mase, T. Org. Lett. 2009, 11, 1043–1045; (g)
Honda, T.; Aranishi, E.; Kaneda, K. Org. Lett. 2009, 11, 1857–1859; (h)
Dekeukeleire, S.; D’hooghe, M.; De Kimpe, N. J. Org. Chem. 2009, 74, 1644–
1649; (i) Koya, S.; Yamanoi, K.; Yamasaki, R.; Azumaya, I.; Masu, H.; Saito, S.
Org. Lett. 2009, 11, 5438–5441; (j) Ueda, M.; Kawai, S.; Hayashi, M.; Naito, T.;
Miyata, O. J. Org. Chem. 2010, 75, 914–921; (k) Baktharaman, S.; Afagh, N.;
Vandersteen, A.; Yudin, A. K. Org. Lett. 2010, 12, 240–243.
3. (a) Ashby, J.; Griffiths, D. J. Chem. Soc., Chem. Commun. 1974, 607–608; (b)
Ashby, J.; Griffiths, D. J. Chem. Soc., Perkin Trans. 1 1975, 657–662; (c) Bullock,
E.; Garter, R. A.; Cochrane, R.; Gregory, B.; Shields, D. C. Can. J. Chem. 1977, 55,
895–905; (d) Claremon, D. A.; Rosenthal, S. A. Synthesis 1986, 664–665; (e)
Baldwin, J. J.; McClure, D. E.; Claremon, D. A. U.S. Patent 4,677,102, 1987; Chem.
Abstr. 1988, 109, 54794.
Scheme 4. Reaction of pyrimidine 6withNaCN/HCN orNaCH(COOEt)2/CH2(COOEt)2.
However, reaction of 6 with NaCN and HCN (1.00:1.28:2.75) in
DMSO (rt, 32 h) resulted in a mixture of diazepine 13a and starting
material 6 in a ratio of 41:59 (Scheme 4). Analogously, diazepinone
13b formed as a single product in the reaction of 6 with NaCH(COO-
Et)2/CH2(COOEt)2 (1:1.09:2.23) in MeCN (rt, 33.4 h).
Exclusive formation of the products of pyrimidine ring expan-
sion in the reactions of 6 with NaCN/HCN or NaCH(COOEt)2/
CH2(COOEt)2 versus PhSNa(PhSK)/PhSH could be explained by
the higher basicity of NaCN or NaCH(COOEt)2 compared with
PhSNa or PhSK.10
4. Bordwell, F. G.; Hughes, D. L. J. Org. Chem. 1982, 47, 3224–3232.
5. Shutalev, A. D.; Fesenko, A. A.; Cheshkov, D. A.; Goliguzov, D. V. Tetrahedron
Lett. 2008, 49, 4099–4101.
6. Synthesis of ethyl 4-methyl-2-oxo-7-phenylthio-2,3,6,7-tetrahydro-1H-1,3-diaze-
pin-5-carboxylate (7): To a stirred suspension of NaH (0.036 g, 1.50 mmol) in
MeCN (1 mL) was added a solution of thiophenol (0.162 g, 1.47 mmol) in MeCN
(2 mL) and the resulting white suspension was stirred at rt for 9 min.
Chloromethylpyrimidine 63c (0.318 g, 1.37 mmol) and MeCN (2.4 mL) were
added and the resulting suspension was stirred at room temperature for 7 h.
After the reaction was complete the solvent was removed under vacuum, the oily
residue was triturated with light petrol (4 mL) and H2O (4 mL) under cooling
until crystallization was complete. The solid was filtered, washed with ice-cold
water, light petrol, and dried to give 0.276 g (66%) of a mixture of 7 and 8 in a
ratio of 97:3 (Table 1, entry 1). Crystallization from EtOH afforded pure 7.
Mp 169–170 °C (EtOH). 1H NMR (600.13 MHz, DMSO-d6) d: 8.53 (1H, d,
The structures of 7, 8, and 12 were established unambiguously
from their 1H and 13C NMR spectra. The 1H NMR spectrum of 7 in
DMSO-d6 demonstrated long-range couplings between N(1)H and
one of the 6-H protons (4JN(1)H,6-He = 0.9 Hz) and between 4-CH3
and the other 6-H proton (5J4-CH3,6-Ha = 1.3 Hz). Higher values for
3
2
the vicinal JN(1)H,7-H and geminal J6-He,6-Ha coupling constants
(6.1 and 15.1 Hz, respectively) for diazepine 7 compared with the
corresponding constants for pyrimidines 8 and 12 (3JN(3)H,4-H
=
2
3.4-4.1 Hz, JCH(A),CH(B) = 13.7–13.8 Hz) were observed. In the 13C
NMR spectrum of diazepine 7 we observed the chemical shift of
the N-CH fragment at 61.32 ppm, while for pyrimidines 8 and 12
these occured at 49.75 and 49.85 ppm, respectively. The 2D NMR
spectral data (1H,1H-COSY, 1H,13C-HSQC, 1H,13C-HMBC) also
confirmed unambiguously the structures of diazepinones 7 and 8.
In summary, the reaction of 5-functionalized 4-(X–CH2)-1,2,3,4-
tetrahydropyrimidin-2-ones (X = good leaving group) with
nucleophilic reagents resulted in the products of ring expansion
(2,3,4,5-tetrahydro-1H-1,3-diazepin-2-ones) and/or products of
direct substitution of the leaving group (1,2,3,4-tetrahydropyrimi-
din-2-ones) depending on the reaction conditions. The outcome of
the reaction was determined by the nucleophilicity-basicity of the
reaction media. Diazepinones 7 and 11 formed in the reaction of 6
and 10 with strong nucleophiles PhSNa or PhSK possessing rela-
tively low basicity (pKa = 10.3 in DMSO). However, the reaction
of 6 and 10 with PhSNa or PhSK in the presence of their conjugate
acid (PhSH) gave diazepinones 7 and 11 along with the respective
pyrimidines 8 and 12. An increase in the amount of PhSH led to a
significant increase in pyrimidine formation, while the rate of the
conversion of starting materials into products decreased. In aprotic
solvents, almost pure pyrimidines 8 and 12 were obtained when
more than 2 equiv of PhSH were used. However, the reaction of 6
with more basic nucleophiles, NaCN or NaCH(COOEt)2 (pKa = 12.9
and 15.9, respectively, in DMSO), with or without their conjugate
acids yielded only the diazepinones 13a,b.
3
4
4JN(3)H,N(1)H = 2.0 Hz, N(3)H), 7.98 (1H, ddd, JN(1)H,7-H = 6.1, JN(1)H,N(3)H = 2.0,
4JN(1)H,6-He = 0.9 Hz, N(1)H), 7.40–7.43 (2H, m, C(2)H and C(6)H in Ph), 7.31–7.35
(2H, m, C(3)H and C(5)H in Ph), 7.25–7.29 (1H, m, C(4)H in Ph), 5.00 (1H, ddd,
3J7-H,6-He = 6.2, 3J7-H,N(1)H, = 6.1, 3J7-H,6-Ha = 2.0 Hz, 7-H), 3.99–4.08 (2H, m, OCH2),
2
3
4
3.20 (1H, ddd, J6-He,6-Ha = 15.1, J6-He,7-H = 6.2, J6-He,N(1)H = 0.9 Hz, 6-He), 2.69
(1H, ddq, 2J6-Ha,6-He = 15.1, 3J6-Ha,7-H = 2.0 Hz, 5J6-Ha,4-CH3 = 1.3 Hz, 6-Ha), 2.19 (3H,
d, 5J4-CH3,6-Ha = 1.3 Hz, 4-CH3), 1.14 (3H, t, 3JCH3,CH2 = 7.1 Hz, CH3 in OEt). 13C NMR
(150.91 MHz, DMSO-d6) d: 167.40 (C@O in COOEt), 154.08 (C(2)), 147.29 (C(4)),
133.95 (C(1) in Ph), 131.50 (C(2) and C(6) in Ph), 128.91 (C(3) and C(5) in Ph),
127.00 (C(4) in Ph), 105.12 (C(5)), 61.32 (C(7)), 59.46 (OCH2), 33.87 (C(6)), 20.63
(4-CH3), 14.07 (CH3 in OEt). IR (Nujol)
3104 (br s) ( NH), 1689 (s) ( C@O in COOEt), 1673 (s) (amide-I), 1616 (s) (
1510 (m) ( CC in Ph), 1260 (s), 1094 (s) ( C–O), 732 (s), 688 (s) (d CH in Ph). Anal.
m
, cmÀ1: 3324 (m), 3302 (s), 3235 (br s),
C@C),
m
m
m
m
m
Calcd for C15H18N2O3S: C, 58.80; H, 5.92; N, 9.14. Found: C, 58.47; H, 5.95; N, 9.11.
7. Synthesis of ethyl 6-methyl-2-oxo-4-(phenylthiomethyl)-1,2,3,4-tetrahydropyr-
imidin-5-carboxylate (8): To a stirred suspension of NaH (0.043 g, 1.80 mmol) in
MeCN (2 mL) was added a solution of thiophenol (0.596 g, 5.41 mmol) in MeCN
(3.2 mL) and the resulting suspension was stirred at room temperature for
22 min. Chloromethylpyrimidine 6 (0.380 g, 1.63 mmol) and MeCN (2.6 mL)
were added and the resulting suspension was stirred at room temperature for
72 h 40 min. After the reaction was complete the solvent was removed under
vacuum, the oily residue was triturated with light petrol (5 mL) and H2O (5 mL)
under cooling until crystallization was complete. The solid was filtered, washed
with ice-cold water, light petrol, and dried to give 0.455 g (91%) of a mixture of 8
and 6 in a ratio of 97:3 (Table 1, entry 9). Crystallization from EtOH afforded pure
8. Mp 166–168.5 °C (ethanol). 1H NMR (300.13 MHz, DMSO-d6) d: 9.17 (1H, d,
4JN(1)H,N(3)H = 2.0 Hz, N(1)H), 7.46 (1H, dd, JN(3)H,4-H = 3.6, JN(3)H,N(1)H = 2.0 Hz,
N(3)H), 7.25–7.37 (4H, m, C(2)H, C(3)H, C(5)H and C(6)H in Ph), 7.13–7.20 (1H, m,
C(4)H in Ph), 4.30 (1H, ddd, 3J4-H,CH(A) = 6.5, 3J4-H,N(3)H = 3.6, 3J4-H,CH(B) = 3.6 Hz, 4-
H), 3.99 (2H, q, 3JCH2,CH3 = 7.1 Hz, OCH2), 3.10 (1H, dd, 2JCH(A),CH(B) = 13.9, 3JCH(A),4-H
3
4
2
3
= 6.5 Hz, H(A) in SCH(A)H(B)), 3.01 (1H, dd, JCH(B),CH(A) = 13.9, JCH(B),4-H = 3.6 Hz,
H
(B) in SCH(A)H(B)), 2.08 (3H, s, 6-CH3), 1.11 (3H, t, 3JCH3,CH2 = 7.1 Hz, CH3 in OEt).
13C NMR (75.48 MHz, DMSO-d6) d: 165.07 (C@O in COOEt), 152.31 (C(2)), 149.98
(C(6)), 136.27 (C(1) in Ph), 128.90 (C(3) and C(5) in Ph), 128.28 (C(2) and C(6) in
Ph), 125.68 (C(4) in Ph), 97.36 (C(5)), 59.22 (OCH2), 49.75 (C(4)), 39.83 (SCH2),
We envisage that our findings may be of value for other similar
one-carbon ring expansion reactions.1,2
17.83 (6-CH3), 14.15 (CH3 in OEt). IR (Nujol)
NH), 1705 (sh) ( C@O in COOEt), 1696 (vs) (amide-I), 1637 (s) (
CC in Ph), 1227 (vs), 1090 (vs) ( C–O), 746 (s), 691 (m) (d CH in Ph). Anal. Calcd
m
, cmÀ1: 3204 (br s), 3088 (br s) (
C@C), 1580 (m)
m
m
m
(
m
m
Supplementary data
for C15H18N2O3S: C, 58.80; H, 5.92; N, 9.14. Found: C, 59.12; H, 6.18; N, 9.15.
8. Fesenko, A. A.; Tullberg, M. L.; Shutalev, A. D. Tetrahedron 2009, 65, 2344–2350.
9. Synthesis of 6-methyl-4-(phenylthiomethyl)-5-tosyl-1,2,3,4-tetrahydropyrimidin-
2-one (12): A mixture of 12 and 11 (92:8) (0.366 g, 100%) was prepared
(analogously to 87) from 108 (0.353 g, 0.94 mmol), thiophenol (0.525 g,
4.76 mmol), and NaH (0.028 g, 1.17 mmol) in MeCN (5 mL) (rt, 41 h 26 min).
Supplementary data (experimental procedures for the reactions
of 6 with NaCN/HCN and NaCH(COOEt)2/CH2(COOEt)2, 1H and 13C
NMR spectra of 7, 8 and 12, and 2D NMR spectra of 7 and 8
(1H,1H-COSY, 1H,13C-HSQC, 1H,13C-HMBC) in DMSO-d6) associated
with this article can be found, in the online version, at doi:10.1016/
j.tetlet.2010.07.098.
Crystallization from MeCN afforded pure 12. Mp 221–221.5 °C (dec., MeCN). 1
H
4
NMR (300.13 MHz, DMSO-d6) d: 9.48 (1H, d, JN(1)H,N(3)H = 1.9 Hz, N(1)H), 7.72
3
4
(1H, dd, JN(3)H,4-H = 4.1, JN(3)H,N(1)H = 1.9 Hz, N(3)H), 7.61–7.65 (2H, m, C(2)H
and C(6)H in Ts), 7.30–7.41 (6H, m, C(3)H and C(5)H in Ts, C(2)H, C(3)H, C(5)H

A. A. Fesenko et al. / Tetrahedron Letters 51 (2010) 5056–5059
5059
and C(6)H in Ph), 7.19–7.25 (1H, m, C(4)H in Ph), 4.04 (1H, ddd, 3J4-H,CH(A) = 7.9,
3089 (s), 3058 (m) (
m
NH), 1712 (s) (amide-I), 1646 (s) (
m
C@C), 1595 (m), 1583
3
2
3
3J4-H,N(3)H = 4.1, J4-H,CH(B) = 2.7 Hz, 4-H), 3.16 (1H, dd, JCH(A),CH(B) = 13.8, JCH(A),4-H
(m), 1482 (m) ( CC in Ph and C6H4), 1303 (s) (mas SO2), 1152 (s) (ms SO2), 810 (s)
m
2
3
= 2.7 Hz, H(A) in SCH(A)H(B)), 3.11 (1H, dd, JCH(B),CH(A) = 13.8, JCH(B),4-H = 7.9,
H(B) in SCH(A)H(B)), 2.36 (3H, s, CH3 in Ts), 2.17 (3H, s, 6-CH3). 13C NMR
(75.48 MHz, DMSO-d6) d: 151.91 (C(2)), 148.89 (C(4)), 143.63 (C(4) in 4-
MeC6H4), 139.67 (C(1) in 4-MeC6H4), 135.54 (C(1) in Ph), 129.97 (C(3) and C(5)
in 4-MeC6H4), 129.04 (C(3) and C(5) in Ph), 128.71 (C(2) and C(6) in Ph), 126.26
(C(2) and C(6) in 4-MeC6H4), 125.97 (C(4) in Ph), 105.39 (C(5)), 49.85 (C(4)),
(d CH in C6H4), 737 (s) 690 (s) (d CH in Ph). Anal. Calcd for C19H20N2O3S2: C,
58.74; H, 5.19; N, 7.21. Found: C, 58.87; H, 5.34; N, 7.41.
10. For PhSH, HCN, and CH2(COOEt)2 the equilibrium acidities (pKa) in DMSO are
10.3,4,11 12.9,11 and 15.9,12 respectively.
11. Bordwell, F. G. Acc. Chem. Res. 1988, 21, 456–463.
12. Olmstead, W. N.; Bordwell, F. G. J. Org. Chem. 1980, 45, 3299–3305.
40.39 (SCH2), 21.02 (CH3 in Ts), 16.55 (6-CH3). IR (Nujol) m
, cmÀ1: 3219 (s),