Cationic 1,3-diazadienes in annulation reactions. Synthesis of pyrimidine, thiadiazinedioxide and triazine derivatives

Article abstract of DOI:10.1002/jhet.5570380113

Triazapentadienium iodides 2 prepared from N'-thiocarbamoylformamidines 1 are efficient intermediates in heterocyclic synthesis. They react with ketenes, sulfenes, phenyl isocyanate or isothiocyanate and dimethyl acetylenedicarboxylate affording the corre

Full text of DOI:10.1002/jhet.5570380113

Jan-Feb 2001
Cationic 1,3-Diazadienes in Annulation Reactions. Synthesis of
Pyrimidine, Thiadiazinedioxide and Triazine Derivatives
93
Cyrille Landreau, David Deniaud, Alain Reliquet,
Françoise Reliquet and Jean Claude Meslin*
Laboratoire de Synthèse Organique, UMR CNRS 6513, Faculté des Sciences et des Techniques,
BP 92208, 2, rue de la Houssinière, F44322 Nantes Cedex 03 France.
Received May 11, 2000
Triazapentadienium iodides 2 prepared from N'-thiocarbamoylformamidines 1 are efficient intermediates
in heterocyclic synthesis. They react with ketenes, sulfenes, phenyl isocyanate or isothiocyanate and
dimethyl acetylenedicarboxylate affording the corresponding dihydropyrimidinones 3, thiadiazinedioxides
5, triazinones 6, triazinethiones 7 and pyrimidines 9.
J. Heterocyclic Chem., 38, 93 (2001).
The synthetic value of 1,3-diazadienes in heterocyclic
These types of compounds exhibit important pharma-
cological potential. Recently S-alkylsufanylpyrimidine
and S-alkylsulfanylpyrimidinone derivatives have been
identified as highly specific reverse transcriptase inhibitors
of human immunodeficiency virus type 1 [11,12]. Thioxo
derivatives showed a diverse range of biological properties
such as hyperthyroidism treatment, anticarcinogenic,
cardiovascular and antihypertensive activities [13-14]. To
our knowledge, only few monocyclic thiadiazinedioxides
were previously reported [10,15] even though fused pyrido
derivatives were found to be important in several
pharmacological fields [16].
chemistry has been widely demonstrated [1]. During the
last fifteen years [4 + 2] cycloaddition reactions of acyclic
1,3-diazadienes, especially with ketenes, have been
studied giving rise to various dihydropyrimidines [2-9].
The problems encountered in the preparation of stable
1-substituted-1,3-diazadienes were recently solved by the
use of cationic precursors [10].
We have prepared N'-thiocarbamoylformamidines 1
following Bredereck procedure [17]. Subsequent
alkylation using methyliodide led to S-methyl salts 2 in
high yields (Scheme 1).
We report here the reactivity of triazadienium iodides 2
in [4 + 2] cycloaddition reactions affording methyl-
sulfanyldihydropyrimidinones 3 and thioxotetrahydropy-
rimidinones 4, thiadiazinedioxides 5, triazinones 6,
triazinethiones 7 and pyrimidines 9.
Ketenes were prepared in situ from acid chlorides
(methyl or ethyl malonyl chloride, phenylacetyl chloride)
and reacted with S-methyliodides 2 to give the
corresponding dihydropyrimidinones 3. The [4 + 2]
cycloaddition proceeded smoothly and was followed by
loss of dimethylamine. Addition of triethylamine was
necessary to neutralize the two equivalents of the
hydracids generated in these reactions.
Then the methylsulfanylimine group of compounds 3
was eliminated by treatment with hydrogen sulfide to yield
thioxotetrahydropyrimidinones 4 (Scheme 2).

94
C. Landreau, D. Deniaud, A. Reliquet, F. Reliquet and J. C. Meslin
Vol. 38
operative pathway to afford the heterocyclic products is an
addition reaction followed by an intramolecular Diels-
Alder cyclization.
In summary, we have demonstrated the ability of
triazapentadienium salts 2 to undergo annulation reactions
under rather mild conditions providing an efficient
synthetic method for the preparation of various pyrimidine
derivatives. Moreover reactions with sulfenes afforded
novel 4H-1,2,4-thiazine-1,1-dioxides in satisfactory
yields.
EXPERIMENTAL
All reagents were purchased from Acros Organics and
Aldrich. Elemental analyses were performed by the C.N.R.S.
Analysis Laboratory (Vernaison). Column chromatography
was conducted on silica gel 60 (40-63 µm), available from E.
Merck. Thin layer chromatography was performed on 0.5 mm
x 20 cm x 20 cm E. Merck silica gel plate (60 F-254). Melting
points measured using a Reichert microscope are uncorrected.
Sulfenes prepared from the corresponding sulfonic acid
chlorides (mesyl chloride, ethanesulfonyl chloride,
α-toluenesulfonyl chloride) reacted readily with salts 2,
using the same conditions (vide supra), to afford 2H-1,2,4-
thiadiazine-1,1-dioxides 5 (Scheme 3).
A cyclization reaction took place with compounds 2 in
the presence of phenyl isocyanate or phenyl isothiocyanate
resulting in the formation of triazin-2(1H)-ones 6 and
triazine-2(1H)-thiones 7 respectively in good yields
(Scheme 4).
13
1
The
C and H-nmr spectra were recorded at room
temperature using a BRUKER AC200 at 50 and 200 MHz
respectively. Chemical shifts (δ) are given in ppm downfield
from tetramethylsilane as internal standard. Mass spectra were
determined with a Hewlett Packard 5989 spectrometer.
The ir spectra were obtained using a BRUKER Vector22
spectrometer.
General Procedure for the Reaction of Thiourea with Amide
Dimethyl Acetals.
N,N-Dimethyl formamide dimethyl acetal (for 1a, 13 mmoles)
or N,N-dimethyl acetamide dimethyl acetal (for 1b, 13 mmoles)
was added to a suspension of thiourea (10 mmoles) in methanol
(for 1a, 10 ml) or methylene chloride (for 1b, 10 ml). The
mixture was heated under reflux for 4 hours. The solvent was
removed and the residue was crystallized from methanol (for 1a)
or diethyl ether (for 1b).
2-Amino-4-dimethylamino-1,3-thiazabuta-1,3-diene (1a).
This compound was obtained in 70% yield, mp 165° [17].
2-Amino-4-dimethylamino-1,3-thiazapenta-1,3-diene (1b).
This compound was obtained in 76% yield, mp 128-130°; ir
-1
1
(potassium bromide): ν max 3278, 3123, 1583, 1366 cm ; H
nmr (hexadeuteriodimethylsulfoxide): δ 2.17 (s, 3H, CH ), 2.93
3
13
(s, 6H, N(CH ) ), 7.66 and 8.05 (2s, 2H, 2NH); C nmr
3 2
(hexadeuteriodimethylsulfoxide): δ 16.5 (CH ), 37.9 (N(CH ) ),
3
3 2
The reaction of salts 2 with dimethyl acetylene-
dicarboxylate afforded 2-methylsulfanylpyrimidines 9.
Starting from 2b, we have isolated a rather unstable
intermediate compound 8 identified as a linear adduct
between the unsubstituted imine group of the diazadiene
and the triple bond of the acetylenic reagent. A ring
closure of intermediate 8 followed by the loss of dimethyl-
amine provided pyrimidine 9b on heating at 110° for
18 hours (Scheme 5).
+
+
159.0 (CCH ), 194.0 (CS); ms: m/z 145 (M ), 129 (M - NH ),
3
2
+
112 (M - SH).
Anal. Calcd. for C H N S: C, 41.35; H, 7.63; N, 28.94.
5
11 3
Found: C, 41.05; H, 7.72; N, 29.16.
General Procedure for Addition of Methyl Iodide on
Thiazadienes 1.
A suspension of thiazadiene 1 (5 mmoles) in methyl iodide
(4 ml) and tetrahydrofuran (4 ml) was stirred for 18 hours at room
temperature. The mixture was evaporated under reduced
pressure. After addition of diethyl ether (40 ml), compounds 2
were precipitated and collected by filtration.
Although most of our compounds were expected to be
generated by a classical Diels-Alder cycloaddition, the
later result indicated obviously that in this case the

Jan-Feb 2001
Cationic 1,3-Diazadienes in Annulation Reactions
95
1,1-Dimethyl-4-methylsulfanyl-1,3,5-triazapentadienium
Anal. Calcd. for C H N O S: C, 44.85; H, 4.70; N, 13.08.
8 10 2 3
Iodide (2a).
Found: C, 45.17; H, 4.50; N, 13.35.
This compound was prepared from 1a in 98% yield, mp 148°;
5-Ethoxycarbonyl-6-methyl-2-methylsulfanylpyrimidin-4(3H)-
one (3d).
-1
1
ir (potassium bromide): ν max 3232, 3070, 1624, 1521 cm ; H
nmr (hexadeuteriodimethylsulfoxide): δ 2.55 (s, 3H, SCH ), 3.11
3
This compound was prepared from 2b and ethyl malonyl
and 3.27 (2s, 6H, N(CH ) ), 8.39 (s, 1H, CH), 9.53 (s, 2H, NH );
3 2
2
chloride in 84% yield, mp 149° (from diethyl ether); ir (potassium
13
C nmr (hexadeuteriodimethylsulfoxide): δ 14.4 (SCH ), 35.9
3
-1 1
bromide): ν max 1734, 1635 cm ; H nmr (deuteriochloroform): δ
and 41.9 (N(CH ) ), 158.7 (CH), 178.2 (CS).
3 2
1.42 (t, 3H, J = 7.2 Hz, CH CH ), 2.57 and 2.58 (2s, 6H, SCH and
2
3
3
Anal. Calcd. for C H IN S: C, 21.99; H, 4.43; N, 15.38.
5
12
3
13
CH ), 4.43 (q, 2H, J = 7.2 Hz, CH CH ), (NH, exchange); C nmr
3
2
3
Found: C, 21.71; H, 4.60; N, 15.55.
(deuteriochloroform): δ 13.6 (SCH ), 14.2 (CH CH ), 24.2
3
2
3
1,1,2-Trimethyl-4-methylsulfanyl-1,3,5-triazapentadienium
Iodide (2b).
(CCH ), 61.9 (CH CH ), 110.0 (CCO), 165.1 and 167.1 (CCH ,
3
2
3
3
+
+
SCN and 2CO); ms: m/z 228 (M ), 182 (M - C H OH), 126.
2
5
Anal. Calcd. for C H N O S: C, 47.36; H, 5.30; N, 12.27.
Found: C, 47.51; H, 5.03; N, 12.42.
This compound was prepared from 1b in 95% yield, mp 180°; ir
(potassium bromide): ν max 3258, 3108, 1629, 1569 cm ; H nmr
9
12 2 3
-1 1
(hexadeuteriodimethylsulfoxide): δ 2.29 (s, 3H, CH ), 2.41 (s, 3H,
3
6-Methyl-2-methylsulfanyl-5-phenylpyrimidin-4(3H)-one (3e).
13
SCH ), 3.13 and 3.23 (2s, 6H, N(CH ) ), 9.01 (s, 2H, NH );
C
3
3 2
2
This compound was prepared from 2b and phenylacetyl
nmr (hexadeuteriodimethylsulfoxide): δ 14.3 (SCH ), 18.5 (CH ),
3
3
39.2 and 39.8 (N(CH ) ), 166.4 (CCH ), 172.0 (CS).
chloride in 97% yield, mp 196° (from diethyl ether); ir
3 2
3
-1
1
Anal. Calcd. for C H IN S: C, 25.10; H, 4.91; N, 14.63.
(potassium bromide): ν max 1646 cm ; H nmr (deuterio-
chloroform): δ 2.20 (s, 3H, CH ), 2.55 (s, 3H, SCH ), 7.25-7.47
6
14
3
Found: C, 24.88; H, 5.04; N, 14.61.
3
3
13
(m, 5H, C H ), 10.27 (broad s, 1H, NH); C nmr (hexadeuterio-
6
5
General Procedure for the Reaction Between Triazapentadienum
Iodides 2 and Acyl Chlorides or Sulfonyl Chlorides.
dimethylsulfoxide): δ 12.7 (SCH ), 22.4 (CCH ), 120.2
3
3
(CC H ), 127.2, 128.0 and 130.3 (5CHar), 134.3 (Car), 148.0
6
5
To a solution of iodide 2 (2 mmoles) in dry methylene chloride
(10 ml), acyl chloride (for 3, 2.4 mmoles) or sulfonyl chloride
(for 5, 2.4 mmoles) was added under a nitrogen atmosphere. The
mixture was stirred for 4 hours at room temperature, cooled to 0°
then triethylamine (4.8 mmoles) was added. The reaction mixture
was stirred overnight. The solvent was removed and the residue
was purified by flash chromatography (silica gel, methylene
chloride/ethyl acetate 9/1). Products 3 and 5 were crystallized
from appropriate solvents.
+
(CCH ), 159.6 and 162.2 (SCN and CO); ms: m/z 232 (M ).
3
Anal. Calcd. for C H N OS: C, 62.05; H, 5.21; N, 12.06.
12 12
2
Found: C, 61.96; H, 5.18; N, 12.01.
3-Methylsulfanyl-4H-1,2,4-thiadiazine-1,1-dioxide (5a).
This compound was prepared from 2a and methanesulfonyl
chloride in 46% yield, mp 144° (from methylene chloride); ir
-1
1
(potassium bromide): ν max 1646, 1570, 1258, 1119 cm ; H
nmr (hexadeuteriodimethylsulfoxide): δ 2.42 (s, 3H, SCH ), 6.26
3
5-Methoxycarbonyl-2-methylsulfanylpyrimidin-4(3H)-one (3a).
(d, 1H, J = 8.6 Hz, SO CH), 7.01 (d, 1H, J = 8.6 Hz, NCH), 11.71
(broad s, 1H, NH); C nmr (hexadeuteriodimethylsulfoxide): δ
2
13
This compound was prepared from 2a and methyl malonyl
13.8 (SCH ), 103.5 (SO CH), 132.6 (NCH), 160.9 (SCN); ms:
3
2
chloride in 82% yield, mp 205° (from diethyl ether); ir
+
+
m/z 178 (M ), 114 (M - SO ), 81, 74.
2
-1
1
(potassium bromide): ν max 1741, 1651 cm ; H nmr (deuterio-
chloroform): δ 2.60 (s, 3H, SCH ), 3.97 (s, 3H, OCH ), 8.75
Anal. Calcd. for C H N O S : C, 26.96; H, 3.39; N, 15.72.
4
6 2 2 2
3
3
Found: C, 30.21; H, 3.51; N, 15.55.
13
(s, 1H, CH), (NH, exchange); C nmr (deuteriochloroform): δ
13.0 (SCH ), 51.6 (OCH ), 111.5 (CCO), 158.0 (NCH), 159.0,
164.1 and 168.1 (SCN and 2CO); ms: m/z 200 (M ), 168
6-Methyl-3-methylsulfanyl-4H-1,2,4-thiadiazine-1,1-dioxide
(5b).
3
3
+
+
(M -CH OH), 112.
3
This compound was prepared from 2a and ethanesulfonyl
chloride in 86% yield, mp 221° (from diethyl ether); ir
(potassium bromide): ν max 1660, 1574, 1515, 1279, 1132
Anal. Calcd. for C H N O S: C, 41.99; H, 4.03; N, 13.99.
7
8 2 3
Found: C, 42.23; H, 3.97; N, 14.27.
5-Ethoxycarbonyl-2-methylsulfanylpyrimidin-4(3H)-one (3b).
-1 1
cm ; H nmr (hexadeuteriodimethylsulfoxide): δ 1.96 (d, 3H,
J = 1.2 Hz, CH ), 2.41 (s, 3H, SCH ), 6.84 (q, 1H, J = 1.2 Hz,
3
3
This compound was prepared from 2a and ethyl malonyl
chloride in 63% yield, mp 133° (from diethyl ether) [18].
13
CH), 11.69 (broad s, 1H, NH); C nmr (hexadeuterio-
dimethylsulfoxide): δ 10.9 (CH ), 13.0 (SCH ), 112.6
(CCH ), 128.5 (NCH), 159.5 (SCN); ms: m/z 192 (M ), 128
3
3
5-Methoxycarbonyl-6-methyl-2-methylsulfanylpyrimidin-
4(3H)-one (3c).
+
3
+
(M - SO ), 95, 54.
2
Anal. Calcd. for C H N O S : C, 31.24; H, 4.19; N, 14.57.
This compound was prepared from 2b and methyl malonyl
5
8 2 2 2
Found: C, 31.27; H, 4.40; N, 14.68.
chloride in 84% yield, mp 179° (from diethyl ether); ir
-1
1
(potassium bromide): ν max 1734, 1635 cm ; H nmr (deuterio-
chloroform): δ 2.57 and 2.58 (2s, 6H, CH and SCH ), 3.97
3-Methylsulfanyl-6-phenyl-4H-1,2,4-thiadiazine-1,1-dioxide
(5c).
3
3
13
(s, 3H, OCH ), 12.34 (broad s, 1H, NH); C nmr (deuterio-
3
This compound was prepared from 2a and α-toluenesulfonyl
chloride in 77% yield, mp 149° (from diethyl ether); ir
(potassium bromide): ν max 1639, 1569, 1506, 1258, 1143, 1118
chloroform): δ 13.6 (SCH ), 24.2 (CH ), 52.6 (OCH ), 110.2
3
3
3
(CCO), 164.6, 166.8, 167.2 and 167.4 (CCH , SCN and 2CO);
3
+
+
ms: m/z 214 (M ), 182 (M - CH OH), 126.
3

96
C. Landreau, D. Deniaud, A. Reliquet, F. Reliquet and J. C. Meslin
Vol. 38
-1
1
5-Methoxycarbonyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-4-one
cm ; H nmr (deuteriochloroform): δ 2.50 (s, 3H, SCH ), 6.66
3
(4a).
(d, 1H, J = 5.8 Hz, CH), 7.33-7.54 (m, 5H, C H ), 9.43 (d, 1H,
6
5
13
J = 5.8 Hz, NH); C nmr (hexadeuteriodimethylsulfoxide): δ
13.1 (SCH ), 117.6 (CC H ), 127.6, 128.4, 128.6, 129.3 and
This compound was obtained from 3a in 72% yield, mp 181°
(from ethyl acetate); ir (potassium bromide): ν max 1717, 1616,
1549, 1458, 1216, 1165 cm
dimethylsulfoxide): δ 3.70 (s, 3H, OCH ), 7.96 (s, 1H, CH); 10.77
(broad s, 2H, 2NH); C nmr (hexadeuteriodimethylsulfoxide): δ
3
6 5
+
130.1 (5CHar, Car and NCH), 159.4 (SCN); ms: m/z 254 (M ),
190 (M - SO ), 157, 117, 90.
-1
1
;
H nmr (hexadeuterio-
+
2
3
13
Anal. Calcd. for C H N O S : C, 47.23; H, 3.96; N, 11.01.
10 10
2 2 2
51.7 (OCH ), 106.8 (CCO), 147.6 (CH), 157.1 (CCO), 162.8
(NCO), 176.5 (CS); ms: m/z 186 (M ), 170, 139, 69.
3
Found: C, 47.02; H, 4.13; N, 11.27.
+
5-Methyl-3-methylsulfanyl-4H-1,2,4-thiadiazine-1,1-dioxide
(5d).
Anal. Calcd. for C H N O S: C, 38.71; H, 3.25; N, 15.05.
Found: C, 39.98; H, 3.35; N, 15.28.
6
6 2 3
This compound was prepared from 2b and methanesulfonyl
chloride in 69% yield, mp 223-225° (from diethyl ether/methyl-
ene chloride 1/1); ir (potassium bromide): ν max 1653, 1581,
5-Ethoxycarbonyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-4-one
(4b).
This compound was obtained from 3b in 77% yield, mp 244°
(from ethyl acetate) [19].
-1
1
1120 cm ; H nmr (hexadeuteriodimethylsulfoxide): δ 1.98
(s, 3H, CH ), 2.43 (s, 3H, SCH ), 6.18 (s, 1H, CH), 11.77 (broad
3
3
13
s, 1H, NH); C nmr (hexadeuteriodimethylsulfoxide): δ 13.0
(SCH ), 18.5 (CH ), 100.9 (CH), 142.7 (CCH ), 159.2 (SCN);
ms: m/z 192 (M ), 128 (M - SO ), 95, 54.
5-Methoxycarbonyl-6-methyl-2-thioxo-1,2,3,4-tetrahydro-
pyrimidin-4-one (4c).
3
3
3
+
+
2
This compound was obtained from 3c in 90% yield, mp 232°
Anal. Calcd. for C H N O S : C, 31.24; H, 4.19; N, 14.57.
5
8 2 2 2
(from diethyl ether/methylene chloride 1/1); ir (potassium
Found: C, 31.18; H, 4.32; N, 14.46.
-1
1
bromide): ν max 1726, 1628, 1559, 1164 cm ; H nmr
5,6-Dimethyl-3-methylsulfanyl-4H-1,2,4-thiadiazine-1,1-
dioxide (5e).
(hexadeuteriodimethylsulfoxide): δ 2.50 (s, 3H, CH ), 3.73
3
13
(s, 3H, OCH ), 12.61 (broad s, 2H, 2NH);
C nmr
3
(hexadeuteriodimethylsulfoxide): δ 17.2 (CH ), 52.1 (OCH ),
3
3
This compound was prepared from 2b and ethanesulfonyl
108.9 (CCO), 154.9 (CCH ), 157.9 (CCO), 164.4 (NCO), 175.4
3
chloride in 39% yield, mp 206° (from diethyl ether); ir
+
+
(CS); ms: m/z 200 (M ), 169 (M - CH O), 168.
-1
1
3
(potassium bromide): ν max 1661, 1579, 1509, 1142 cm ; H
Anal. Calcd. for C H N O S: C, 41.99; H, 4.03; N, 13.99.
7
8 2 3
nmr (deuteriochloroform): δ 2.06 and 2.11 (2s, 6H, NCCH and
3
Found: C, 42.37; H, 4.27; N, 14.11.
13
SCCH ), 2.49 (s, 3H, SCH ), 9.14 (broad s, 1H, NH); C nmr
3
3
(hexadeuteriodimethylsulfoxide): δ 8.6 (SCCH ), 13.0 (SCH ),
5-Ethoxycarbonyl-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrim-
3
3
15.5 (NCCH ), 108.2 (SCCH ), 137.2 (NCCH ), 158.9 (SCN);
idin-4-one (4d).
3
3
3
+
+
ms: m/z 206 (M ), 142 (M - SO ), 109, 68.
2
This compound was obtained from 3d in 97% yield, mp 211°
(from 50/50 diethyl ether/methylene chloride); ir (potassium
Anal. Calcd. for C H N O S : C, 34.94; H, 4.89; N, 13.58.
6
10 2 2 2
Found: C, 34.65; H, 4.71; N, 13.24.
-1
1
bromide): ν max 1717, 1653, 1558, 1165 cm ; H nmr
(hexadeuteriodimethylsulfoxide): δ 1.23 (t, 3H, J = 7.2 Hz,
CH CH ), 2.20 (s, 3H, CH ), 4.20 (q, 2H, J = 7.2 Hz, CH CH ),
5-Methyl-3-methylsulfanyl-6-phenyl-4H-1,2,4-thiadiazine-1,1-
dioxide (5f).
2
3
3
2
3
13
12.56 (broad s, 2H, 2NH); C nmr (deuteriochloroform): δ 14.0
This compound was prepared from 2b and α-toluenesulfonyl
(CH CH ), 17.1 (CH ), 60.9 (CH CH ), 109.3 (CCO), 154.3
2
3
3
2
3
chloride in 66% yield, mp >300° (from methylene chloride); ir
(CCH ), 157.9 (CCO), 163.8 (NCO), 175.5 (CS); ms: m/z 214
3
-1
(potassium bromide): ν max 1653, 1582, 1509, 1274, 1131 cm ;
+
+
(M ), 169 (M - C H O), 142.
2
5
1
H nmr (hexadeuteriodimethylsulfoxide): δ 1.88 (s, 3H, CH ),
3
Anal. Calcd. for C H N O S: C, 44.85; H, 4.70; N, 13.08.
Found: C, 45.12; H, 4.88; N, 13.33.
8
10 2 3
2.47 (s, 3H, SCH ), 7.37-7.42 (m, 5H, C H ), 11.82 (broad s, 1H,
3
6 5
13
NH); C nmr (hexadeuteriodimethylsulfoxide): δ 13.1 (SCH ),
3
6-Methyl-5-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-4-one
16.8 (CH ), 114.6 (CC H ), 128.4, 128.6, 129.0 and 131.2
3
6 5
(4e).
(5CHar and Car), 138.9 (CCH ), 159.2 (SCN); ms: m/z 268
3
+
(M+), 204 (M - SO ), 171, 131, 104.
2
This compound was obtained from 3e in 98% yield, mp 289°
(from diethyl ether/methylene chloride 1/1) [20].
Anal. Calcd. for C H N O S : C, 49.23; H, 4.51; N, 10.44.
Found: C, 49.51; H, 4.33; N, 10.70.
11 12
2 2 2
General Procedure for the Reaction Between Triazapentadienium
Iodides 2 and Phenyl Isocyanate or Phenyl Isothiocyanate.
General Procedure for the Reaction Between Methylsulfanyl-
pyrimidinones 3 and Hydrogen Sulfide.
A solution of iodide 2 (2 mmoles) and phenyl isocyanate or
phenyl isothiocyanate (2.2 mmoles) in dry tetrahydrofuran
(10 ml) was stirred at room temperature (for compounds 6) or
heated under reflux (for compounds 7) for 6 hours under a
nitrogen atmosphere. The reaction mixture was cooled to 0° and
triethylamine (4.4 mmoles) was added. The mixture was stirred
for 18 hours at room temperature. The solvent was removed and
Hydrogen sulfide was passed for 4 hours through a solution of
methylsulfanyl-pyrimidinone 3 (2 mmoles) in triethylamine
(7 ml) and pyridine (7 ml). The solvents were removed and the
residue was purified by flash chromatography (silica gel, methyl-
ene chloride/ethyl acetate 1/1). The product was crystallized from
an appropriate solvent.

Jan-Feb 2001
Cationic 1,3-Diazadienes in Annulation Reactions
97
the residue was purified by flash chromatography (silica gel,
methylene chloride/ethyl acetate 9:1). The product was
crystallized from an appropriate solvent.
for 15 minutes at room temperature, cooled to 0° then
triethylamine (4 mmoles) was added. The reaction mixture was
stirred for 18 hours at room temperature. The solvent was
removed and the residue was purified by flash chromatography
(silica gel, methylene chloride/ethyl acetate 4:1). Products 8
and 9 were obtained.
4-Methylsulfanyl-1-phenyl-1,3,5-triazin-2(1H)-one (6a).
This compound was prepared from 2a and phenyl isocyanate
in 55% yield, mp 160° (from diethyl ether); ir (potassium
-1 1
Methyl 3-Methoxycarbonyl-7-dimethylamino-5-methylsulfanyl-
4,6-diazaocta-2,4,6- trienoate (8).
bromide): ν max 1730, 1612, 1457, 1233 cm ; H nmr (deuterio-
chloroform): δ 2.58 (s, 3H, SCH ), 7.35-7.55 (m, 5H, C H ),
3
6 5
13
8.07 (s, 1H, CH); C nmr (deuteriochloroform): δ 14.4 (SCH ),
3
This compound was prepared from 2b and dimethyl
126.2, 129.7 and 129.8 (5CHar), 136.4 (Car), 151.2 (CO), 155.9
acetylenedicarboxylate in 79% yield (yellow oil, Rf methylene
+
+
(CH), 184.4 (SCN); ms: m/z 219 (M ), 204 (M - CH ), 104, 77.
3
1
chloride = 0.2); H nmr (deuteriochloroform): δ 2.17
Anal. Calcd. for C H N OS: C, 54.78; H, 4.14; N, 19.16.
10
9 3
(s, 3H, CH ), 2.40 (s, 3H, SCH ), 2.96 (s, 6H, N(CH ) ), 3.70
3
3
3 2
Found: C, 54.58; H, 4.32; N, 18.87.
and 3.79 (2s, 6H, 2OCH ).
3
6-Methyl-4-methylsulfanyl-1-phenyl-1,3,5-triazin-2(1H)-one
(6b).
4,5-Dimethoxycarbonyl-2-methylsulfanylpyrimidine (9a).
This compound was prepared from 2a and dimethyl
acetylenedicarboxylate in 48% yield, mp 133° (from diethyl
ether) [21].
This compound was prepared from 2b and phenyl isocyanate
in 92% yield, mp 143° (from diethyl ether); ir (potassium
-1
1
bromide): ν max 1705, 1684, 1571, 1479, 1286 cm ; H nmr
(deuteriochloroform): δ 2.14 (s, 3H, CH ), 2.56 (s, 3H, SCH ),
4,5-Dimethoxycarbonyl-6-methyl-2-methylsulfanyl-
pyrimidine (9b).
3
3
13
7.21-7.56 (m, 5H, C H ); C nmr (deuteriochloroform): δ 14.2
6
5
(SCH ), 23.0 (CH ), 127.1, 129.7 and 130.1 (5CHar), 136.3
A solution of 8 (1.2 mmoles) in dry toluene (40 ml) was heated
for 18 hours at 110°. The solvent was removed and the residue
was purified by flash chromatography (silica gel, methylene
chloride/ethyl acetate 4:1) to give a yellow oil in 80% yield
(Rf methylene chloride = 0.7); ir (potassium bromide): ν max
3
3
(Car), 152.8 (CCH ), 166.3 (CO), 183.3 (SCN); ms: m/z 233
3
+
+
(M ), 218 (M - CH ), 118, 77.
3
Anal. Calcd. for C H N OS: C, 56.63; H, 4.75; N, 18.01.
11 11
3
Found: C, 56.49; H, 4.78; N, 17.72.
-1
1
1739, 1695, 1549, 1234 cm ; H nmr (deuteriochloroform): δ
2.61 and 2.62 (2s, 6H, CH and SCH ), 3.92 and 3.96 (2s, 6H,
4-Methylsulfanyl-1-phenyl-1,3,5-triazin-2(1H)-thione (7a).
3
3
13
This compound was prepared from 2a and phenyl isothio-
2OCH ); C nmr (deuteriochloroform): δ 14.3 (SCH ), 23.3
3
3
(CH ), 53.0 and 53.4 (2OCH ), 119.7 (CCO), 155.4, 165.0, 166.2
cyanate in 80% yield, mp 228° (from diethyl ether); ir (potassium
3
3
-1
1
and 167.7 (CCH , NCCO and 2CO), 174.3 (SCN); ms: m/z 256
bromide): ν max 1583, 1442, 1237 cm ; H nmr (deuterio-
chloroform): δ 2.63 (s, 3H, SCH ), 7.28-7.55 (m, 5H, C H ),
3
+
+
(M ), 224 (M - CH OH), 196, 166, 138.
3
3
6 5
13
8.02 (s, 1H, NCH); C nmr (hexadeuteriodimethylsulfoxide): δ
13.8 (SCH ), 127.4, 129.3 and 129.4 (5CHar), 140.3 (Car), 156.2
(NCH), 177.6 (CS), 181.7 (SCN); ms: m/z 235 (M ), 220 (M -
CH ), 104, 77.
Acknowledgement.
3
+
+
The authors wish to express their gratitude to the French
Ministry of Education and CNRS for financial support.
3
Anal. Calcd. for C H N S : C, 51.04; H, 3.85; N, 17.86.
10
9 3 2
Found: C, 51.12; H, 4.03; N, 18.04.
REFERENCES AND NOTES
6-Methyl-4-methylsulfanyl-1-phenyl-1,3,5-triazin-2(1H)-thione
(7b).
[1] D. L. Boger and S. M. Weinreb, Hetero Diels-Alder
Methodology in Organic Synthesis, Academic Press, New York 1987, p
272.
[2] S. N. Mazumdar, I. Ibnusaud and M. P. Mahajan, Tetrahedron
Lett., 27, 5875 (1986).
[3] P. Luthardt and E. U. Wurthwein, Tetrahedron Lett., 29, 921
(1988).
[4] J. Barluenga, M. Tomas, A. Ballesteros and A. L. Lopez,
Tetrahedron Lett., 30, 4573 (1989).
[5] S. N. Mazumdar and M. P. Mahajan, Tetrahedron, 47, 1473
(1991).
[6] S. N. Mazumdar, S. Mukherjee, A. K. Sharma, D. Sengupta
and M. P. Mahajan, Tetrahedron, 50, 7579 (1994).
[7] A. K. Sharma and M. P. Mahajan, Heterocycles, 40, 787
(1995).
This compound was prepared from 2b and phenyl isothio-
cyanate in 83% yield, mp 136-137° (from diethyl ether); ir
-1
(potassium bromide): ν max 1569, 1558, 1469, 1450, 1260 cm ;
1
H nmr (deuteriochloroform): δ 2.15 (s, 3H, CCH ), 2.61 (s, 3H,
3
13
SCH ), 7.19-7.58 (m, 5H, C H ); C nmr (deuteriochloroform):
3
6 5
δ 14.3 (SCH ), 24.3 (CH ), 126.9, 129.8 and 130.5 (5CHar),
3
3
139.9 (Car), 164.7 (CCH ), 177.5 (CS), 184.0 (SCN); ms: m/z
3
+
+
249 (M ), 234 (M - CH ), 202, 118, 77.
3
Anal. Calcd. for C H N S : C, 52.99; H, 4.45; N, 16.85.
11 11
3 2
Found: C, 52.77; H, 4.16; N, 16.63.
General Procedure for the Reaction Between Triazapentadienum
Iodides 2 and Dimethyl Acetylenedicarboxylate.
[8] P. D. Dey, A. K. Sharma, S. N. Rai and M. P. Mahajan,
Tetrahedron, 51, 7459 (1995).
[9] A. K. Sharma and M. P. Mahajan, Tetrahedron, 53, 13841
(1997).
[10] C. Friot, A. Reliquet, F. Reliquet and J. C. Meslin, Synthesis,
5, 695 (2000).
Dimethyl acetylenedicarboxylate (2 mmoles) was added to a
solution of iodide 2 (2 mmoles) in dry methylene chloride
(10 ml) under a nitrogen atmosphere. The mixture was stirred

98
C. Landreau, D. Deniaud, A. Reliquet, F. Reliquet and J. C. Meslin
Vol. 38
[11] A. Mai, M. Artico, G. Sbardella, S. Massa, A. G. Loi, E.
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(1989) and references therein.
[19] E. R. Garrett and D. J. Weber, J. Pharm. Sci., 59, 1383 (1970).
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[15] S. N. Mazumdar, M. Sharma and M. P. Mahajan, Tetrahedron
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[21] I. Ibnusaud, E. J. P. Malar and N. Sundaram, Tetrahedron
Lett., 31, 7357 (1990).