Decarboxylation in the synthesis of 4-alkyl-, 4-alkenyl- and 4-acylpyrimidines

Article abstract of DOI:10.1002/jhet.5570400204

Decarboxylation of allylic esters of 4-carboxypyrimidines in toluene at 111°C in the presence of a Pd(0) catalyst, gives a mixture of a 4-alkenylpyrimidine and a pyrimidine unsubstituted in the 4-position. If the decarboxylation is carried out in the presence of benzaldehyde, then benzaldehyde is added to the 4-position. Decarboxylation of 4-carboxypyrimidines in the presence of different electrophiles, results in incorporation of the electrophile into the 4-position together with a pyrimidine unsubstituted in the 4-position. Use of microwave irradiation enhances the rate of the decarboxylations.

Full text of DOI:10.1002/jhet.5570400204

Mar-Apr 2003
219
Decarboxylation in the Synthesis of
4-Alkyl-, 4-Alkenyl- and 4-Acylpyrimidines
Gunnar Herstad and Tore Benneche*
Department of Chemistry, University of Oslo, P.O. Box 1033, Blindern, N-0315 Oslo, Norway.
Received August 22, 2002
Decarboxylation of allylic esters of 4-carboxypyrimidines in toluene at 111 °C in the presence of a Pd(0)
catalyst, gives a mixture of a 4-alkenylpyrimidine and a pyrimidine unsubstituted in the 4-position. If the
decarboxylation is carried out in the presence of benzaldehyde, then benzaldehyde is added to the 4-position.
Decarboxylation of 4-carboxypyrimidines in the presence of different electrophiles, results in incorporation of
the electrophile into the 4-position together with a pyrimidine unsubstituted in the 4-position. Use of microwave
irradiation enhances the rate of the decarboxylations.
J. Heterocyclic Chem., 40, 219 (2003).
Pyrimidines with a carbon substituent in the 4-position
200 °C [10]. We have found that allylic esters of 4-carboxy-
5-chloro-2-methylthiopyrimidine can be decarboxylated in
refluxing toluene in the presence of a catalytic amount of
tetrakis(triphenylphosphine)palladium. Without the catalyst
no decarboxylation takes place. Toluene was found to give
better turn-over than a number of other solvents at the same
temperature e.g., anisole, benzonitrile, DMPU and DMF.
In the decarboxylation of the allylic esters of
4-carboxypyrimidines (1, Table 1) some pyrimidine
unsubstituted in the 4-position (3) were always isolated
together with the 4-alkenylated pyrimidine (2). The
have traditionally been prepared by direct synthesis, i.e.,
that the group to be the 4-substituent is already in place
before the condensation of the pyrimidine ring [1]. The
problem with this method is that the intermediate is not
always easy accessible. A more flexible synthetic route is
to use transition metal catalyzed coupling reactions of
4-halopyrimidines with organometallic compounds [2].
Alkylation by decarboxylation of esters is known from
the Carroll reaction, which is a thermal rearrangement of
allylic acetoacetates [3]. This reaction can be performed
under mild conditions using palladium catalysis [4].
Palladium catalysis has also been used in decarboxylative
alkylation of free β-keto acids [5]. To our knowledge
alkylation by decarboxylation of esters or free acids in the
presence of an electrophile is not known in the pyrimidine
chemistry.
1
product distribution is readily estimated from the H NMR
spectrum of the crude product by integration over the
proton in the 6-position. For example, as shown by
methylthio derivatives in Table 1 and Scheme 1, the H-6 in
the allylic ester 1 is observed at lowest field (1a 8.57, 1b
8.57, 1d 8.53), followed by H-6 in compound 3 (3a 8.45)
and at highest field the H-6 in the alkenylated pyrimidine 2
(2a 8.35, 2b 8.34). Similar procedures are applicable to the
products in Table 2 and 3.
Microwave irradiation has been used to enhance the
decarboxylation of organic compounds [6-8].
In this paper we report our results from decarboxylation
of allylic esters of 4-carboxypyrimidines in the presence of
a palladium catalyst (Table 1). The decarboxylations have
also been done in the presence of benzaldehyde (Table 2).
In Table 3 are presented the results from the decarboxyla-
tion of 4-carboxypyrimidines in the presence of an elec-
trophile. Most of the decarboxylations have been carried
out both pure thermally and by microwave-induction in
order to make a comparison between the two methods.
Decarboxylation of allylic esters by a palladium catalyst,
can occur at relatively low temperature (i.e., room tempera-
ture) if a negative charge, which is presumably formed after
the decarboxylation, can be delocalized into a π-system (as
in the Pd-catalyzed Carroll-reaction [4]). In the decarboxyl-
ation of 4-carboxypyrimidines any carbanion that might be
formed cannot be delocalized into a π-system. Thus higher
temperature is needed to get decarboxylation in these
systems. The exact temperature needed depends on the
substituent pattern in each case, e.g., 4-carboxy-5-chloro-2-
methylthiopyrimidine decarboxylates around 160 °C [9]
while 1,3-dimethylorotic acid decarboxylates around

220
G. Herstad and T. Benneche
Vol. 40
The product distribution is dependent on the reaction
ester 1a, 1b or 1d was also performed in the presence of an
excess of benzaldehyde. In all cases a product was
obtained by 1,2 addition of the pyrimidine ring to ben-
zaldehyde (Scheme 1 and entries 1- 4, Table 2).
Alkenylation of the 4-position was also observed, but this
product was always the minor product, except in the
microwave assisted reaction of 1b (entry 4). Regeneration
of Pd(0) by formation of any allylated alcohol like 5
(Scheme 2) was not observed. This is somewhat surprising
since allylation of alkoxides by π-allyl palladium com-
plexes is known [14].
conditions and on the type of allylic ester used. In the case
of the allylic ester 1a (entry 1, Table 1) under thermal con-
ditions, pyrimidine 3a was the main product. While in the
microwave assisted reaction, decarboxylation of the same
ester (entry 2) gave the alkenylated pyrimidine 2a as the
main product. The allylic ester 1b, however, gave the
alkenyllated pyrimdine 2b as the main product both in the
thermal and the microwave assisted reaction (entries 3 and
4). In the sulfone 1c there was again a difference between
the thermal and the microwave assisted reaction (entries 5
and 6). Use of microwave irradiation greatly reduced the
time needed to get complete decarboxylations. The pure
thermal decarboxylations at 111 °C took from 48 to 72 h,
while the microwave assisted decarboxylations were com-
plete in 20 min.
The formation of the products 3a and 3c (Table 1) has also
to be explained. We anticipated that the required proton
could come from the solvent, from water in the solvent or
from the allyl part of the ester. In order to rule out any water
in the solvent, the solvent was dried and distilled. In addition
all the reactions were run under an atmosphere of argon. The
Since regeneration of Pd(0) is necessary for the catalytic
cycle to work, some other mechanism must be operating.
Decomposition of π-allyl palladium complexes or addition
of π-allyl palladium complexes to an alkene followed by a
β-elimination may be ways in which Pd(0) is regenerated.
An intramolecular version of the reaction above is known
from allylic esters of β-keto acids [15]. Also in this report
is the mechanism for the regeneration of the catalytic
species is unclear.
decarboxylation was run in toluene-d to check if proton
8
donation was by the solvent. The result was no incorpora-
tion of deuterium into the 4-position. This left us with the
option that the hydrogen must come from the allyl part of
the ester. 1,4-Elimination from π-allyl palladium complexes
to form conjugated dienes is well known [11]. Indeed the
decarboxylation of the ester 1d (Scheme 1) gave only the
pyrimidine 3a (85 %) together with isoprene [12].
With the esters 1a and 1b, however, there is no possibil-
ity for formation of any conjugated diene. In the case of 1a
formation of allene from the π-allyl palladium complex
would explain the formation of 3a, while in the case of 1b
the formation of methylenecyclopropane would explain
the formation of 3a. In this context it can be mentioned
that methylenecyclopropane can be prepared from
β-methallyl chloride [13]. Decarboxylation of the allylic
Decarboxylation of the 4-carboxypyrimidines 6 at 115
°C in the presence of an electrophile, lead also to incorpo-
ration of the electrophile into the 4-position of the pyrimi-
dine ring together with 3a or 3c (Table 3). The degree of
incorporation depends on the nature of the electrophile
e.g., benzaldehyde being more reactive than benzophe-
none and benzoyl chloride. In the reaction of compounds
1a and 1e with benzaldehyde (entries 1, 2, 9 and 10), the

Mar-Apr 2003
Decarboxylation in the Synthesis of 4-Alkyl-, 4-Alkenyl
221
mL). The mixture was stirred for 24 h at ambient temperature
before the solvent was removed. The residue was dissolved in
microwave assisted reaction gave more of the addition
product 4 than that of the thermal reaction. In most other
cases the use of microwave heating did not alter the prod-
uct ratio to any great extent.
When 1,3-dimethylorotic acid is heated in benzyl bro-
mide at 198 °C,the benzyl group is then incorporated into
the 6-position of the pyrimidine system (10 % yield [16]).
When the free acid 6a was heated in benzyl bromide at 115
°C for 48 h only the decarboxylation product 3a was
observed.
In summary, we have demonstrated that 4-alkenylpyrim-
idines can be prepared through palladium catalyzed decar-
boxylation of allylic esters of 4-carboxypyrimidines; that
4-alkyl or 4-acylpyrimidines can be prepared by decar-
boxylation of 4-carboxypyrimidines in the presence of an
electrophile. In addition we have shown that the reaction
time can be greatly reduced by microwave irradiation.
EtOAc (50 mL), washed with water (2 x 50 mL), NaHCO (aq,
3
sat) (50 mL) and brine (50 mL) before it was dried (MgSO ). The
4
crude product was purified by flash chromatography using silica
gel. Eluent EtOAc - hexane 1:19. The compound was obtained as
-1
1
a yellow oil; (4.68 g, 65%); ir (neat): 1744 cm ; H nmr (300
MHz, CDCl ): δ 2.54 (3H, s, SCH ), 4.87 (2H, dt, O-CH , J = 5.8
3
3
2
and 1.3 Hz), 5.31 (1H, dq, C=CH , J =10.4 and 1.1 Hz), 5.44 (1H,
a
dq, C=CH , J = 17.2 and 1.1 Hz), 5.93 – 6.06 (1H, m, C=CH),
b
13
8.57(1H, s, N=CH); C nmr (75 MHz, CDCl ): δ 14.4 (S-CH ),
3
3
66.8 (O-CH -CH), 119.4 (C=CH ), 123.2 (C5), 130.7 (C=CH-
2
2
CH ), 154.0 (O=C-O), 158.1 (C6), 162.3 (C4), 171.0 (C2); ms:
2
+
+
m/z (EI) 246 (M +2, 37%), 244 (M , 100%), 231 (24), 229 (66),
205 (35), 203 (99), 161 (28), 159 (68), 146 (16), 144 (39), 41 (44).
HRMS (EI) for C H ClN O S requires M, 244.0073. Found:
9
9
2 2
m/z 244.0079.
5-Chloro-4-(2-methyl-2-propenyloxy)-2-methylthiopyrimidine
(1b).
Compound 1b was prepared as 1a above from 4-carboxy-5-
chloro-2-methylthiopyrimidine [9] (3.05 g, 14.9 mmol) and tri-
ethylamine (5.0 mL, 36 mmol) and 3-bromo-2-methylpropene
EXPERIMENTAL
All reactions were conducted under an inert amosphere of
(1.7 mL, 16.3 mmol) in CH Cl (55 mL). The crude product was
2
2
either Ar or N . N,N-Dimethylformamide (DMF) was dried with
purified by flash chromatography using silica gel. Eluent EtOAc
- hexane 1:19. The compound was obtained as a yellow oil; (2.28
2
MgSO before distillation. Toluene was distilled from sodium
4
1
-1
1
and kept over molecular sieves. The H NMR spectra were
recorded at 200 or 300 MHz and the C NMR spectra at 50 or 75
g, 59%); ir (neat): 1746 cm ; H nmr (300 MHz, CDCl ): δ 1.81
3
13
(3H, s, CH ), 2.54 (3H, s, SCH ), 4.79 (2H, s, O-CH ), 5. 00 (1H,
3
3
2
MHz on Bruker Avance DPX instruments. Mass spectra, under
electron impact conditions, were recorded at 70 eV ionizing
energy on a Fision ProSpec instrument. The spectra are presented
as m/z (% rel. int.). IR spectra were recorded on a Nicolet Magna
FT-IR 550 instrument. The microwave experiments were carried
out using a CEM MDS-81D microwave oven at 600 – 400 W for
20 min (600 W 8 min, 500 W 6 min and 400 W 6 min). The melt-
ing points are uncorrected.
m, C=CH , J = 0.7 Hz), 5.10 (1H, m, C=CH , J = 0.7 Hz), 8.57
b
a
13
(1H, s, N=CH); C nmr (75 MHz, CDCl ): δ 14.5 (S-CH ), 19.4
3
3
(C-CH ), 69.6 (O-CH -C), 114.3 (C=CH ), 123.2 (C5), 138.7
3
2
2
(C=C), 154.2 (O=C-O), 158.2 (C6), 162.5 (C4), 171.1 (C2); ms:
+
+
m/z (EI) 260 (M +2, 11%), 258 (M , 26%), 245 (37), 243 (100),
215 (16), 213(36), 162 (25), 160 (70), 146 (15), 144 (32), 55 (58).
HRMS (EI) for C H ClN O S requires M, 258.0230. Found:
10 11
2 2
m/z 258.0230.
5-Chloro-2-methylthio-4-(2-propenyloxy)pyrimidine (1a).
5-Chloro-4-(2-methyl-2-propenyloxy)-2-methylsulfonylpyrimi-
dine (1c).
3-Bromopropene (5.0 mL, 57.2 mmol) was added to a mixture
of 4-carboxy-5-chloro-2-methylthiopyrimidine [9] (6.02 g, 29.4
3-Bromo-2-methylpropene (2.0 mL, 19.2 mmol) was added to
a mixture of 4-carboxy-5-chloro-2-methylsulfonylpyrimidine [9]
mmol) and triethylamine (10.0 mL, 72 mmol) in CH Cl (150
2
2

222
G. Herstad and T. Benneche
Vol. 40
1
[a] Method A: 115 °C 48 h; Method B: 7 anisole, MW, 20 min. [b] From H NMR of the crude product. [c] Compound 3a was isolated in 14% yield.
e
[d] Compound 3a was isolated in 57% yield. Compound 3a was isolated in 29% yield.
(2.00 g, 8.5 mmol) and triethylamine (1.4 mL, 10 mmol) in
CH Cl (55 mL). The mixture was stirred at ambient temperature
for 48 h before the solvent was evaporated off. The crude product
was purified by flash chromatography using silica gel. Eluent
h. Excess thionyl chloride was removed and 3-methyl-2-buten-1-
ol (7.0 mL, 68 mmol) was added dropwise before the mixture
was heated at 80 °C for 3 h. The reaction mixture was dissolved
2
2
in EtOAc (50 mL), washed with water (2 x 50 mL), NaHCO (aq,
3
sat) (50 mL) and brine (50 mL) before it was dried (MgSO ). The
EtOAc - hexane 1:4. The compound was obtained as a yellow oil;
4
-1 1
crude product was purified by flash chromatography using silica
gel. Eluent EtOAc - hexane 1:19. The compound was obtained as
(2.18 g, 89%); ir (neat): 1745 cm ; H nmr (300 MHz, CDCl ): δ
3
1.81(3H, s, CH ), 3.35 (3H, s, SO CH ), 4.82 (2H, s, O-CH ),
3
2
3
2
-1
1
a yellow oil; (3.58 g, 51%); ir (neat):1744 cm ; H nmr (300
5.01(1H, s, C=CH ), 5.09 (1H, t, C=CH , J = 1 Hz), 9.02 (1H, s,
b
a
13
MHz, CDCl ): δ 1.73 (3H, s, CH ), 1.74 (3H, s, CH ), 2.52 (3H,
N=CH); C nmr (75 MHz, CDCl ): δ 19.4 (C-CH ), 39.4 (SO -
3
3
3
3
3
2
s, SCH ), 4.85(2H, d, O-CH , J = 7.4 Hz), 5.39 – 5.44 (1H, tm,
C=CH, J = 7.4 Hz), 8.53 (1H, s, N=CH); C nmr (75 MHz,
CH ), 70.4 (O-CH -C), 115.0 (C=CH ), 131.6 (C5), 138.2
3
2
3
2
2
13
(C=C), 155.5 (O=C-O), 160.1 (C6), 161.2 (C4), 163.4 (C2); ms:
+
+
+
CDCl ): δ 14.4 (S-CH ), 18.0 (C-CH ), 25.6 (C-CH ), 63.3 (O-
m/z (CI, CH ) 293(M +2, 21%), 291 (M , 64%), 55 (100).
3
3
3
3
5
CH -C), 117.2 (C=CH ), 123.1(C5), 140.8 (C=C), 154.6 (O=C-
2
2
5-Chloro-4-(3-methyl-2-butenyloxy)-2-methylthiopyrimidine (1d).
+
O), 157.9 (C6), 162.8 (C4), 171.0 (C2); ms: m/z (EI) 274 (M + 2,
+
4-Carboxy-5-chloro-2-methylthiopyrimidine [9] (5.30 g 25.9
mmol) was heated in thionyl chloride (12 mL) under reflux for 2
11%), 272 (M , 29%), 229 (6), 227 (16), 206 (25), 204 (65), 162
(19), 160 (60), 69 (100), 41 (48).

Mar-Apr 2003
Decarboxylation in the Synthesis of 4-Alkyl-, 4-Alkenyl
223
HRMS (EI) for C H ClN O S requires M, 272.0386. Found:
m/z 272.0375.
The solvent was evaporated off and the crude product purified by
flash chromatography on silica gel.
11 13
2 2
Method B.
General Methods for Decarboxylation of Allylic Esters of 4-
Carboxypyrimidines (Table 1).
A mixture of the pyrimidine 1 (0.5 mmol), Pd(PPh ) (0.025
3 4
mmol) and benzaldehyde (1.0 mL, 10 mmol) in toluene (1.5 mL)
and benzonitril (1.5 mL) in a teflon container (100 mL) was
heated in a CEM MDS-81D microwave oven at 600 – 400 W for
20 min (600 W 8 min, 500 W 6 min and 400 W 6 min). The
solvent was evaporated off and the crude product purified by
flash chromatography on silica gel.
Method A.
A mixture of the pyrimidine 1 (3.0 mmol) and Pd(PPh ) (0.15
3 4
mmol) in toluene (12 mL) under an atmosphere of argon was
heated under reflux for 72 h. The solvent was evaporated off and
the crude product purified by flash chromatography on silica gel.
Method B.
5-Chloro-2-methylthiopyrimidine (3a)[9].
A mixture of the pyrimidine 1 (0.5 mmol) and Pd(PPh )
3 4
1
This compound has H nmr (300 MHz, CDCl ) δ 2.52 (3H, s,
3
(0.025 mmol) in toluene (1.5 mL) and benzonitrile (1.5 mL) in a
teflon container (100 mL) was heated in a CEM MDS-81D
microwave oven at 600 – 400 W for 20 min (600 W 8 min, 500 W
6 min and 400 W 6 min). The solvent was evaporated off and the
crude product purified by flash chromatography on silica gel.
13
S-CH ), 8.45 (2H, s, N=C-H); C nmr (75 MHz, CDCl ) δ 14.4
(SCH ), 126.4 (C5), 155.5 (C4 and C6), 170.7 (C2).
3
3
3
5-Chloro-2-methylsulfonylpyrimidine (3c)[9].
1
This compound has H nmr (300 MHz, CDCl ) δ 3.34 (3H, s,
3
SO CH ), 8.87 (2H, s, N=C-H).
(E)-5-Chloro-2-methylthio-4-(1-propenyl)pyrimidine (2a) [17].
2
3
4-(α-Hydroxybenzyl)-5-chloro-2-methylthiopyrimidine (4a).
This compound was purified using eluent EtOAc - hexane
1
1:49; H nmr (200 MHz, CDCl ): δ 1.98 (3H, dd, CH , J = 1.7
3
3
This compound was purified using eluent EtOAc - hexane 1:9;
and 6.9 Hz), 2.55 (3H, s, S-CH ), 6.75 (1H, m, C=C-H, J = 1.7
1
3
mp 93 - 95 °C; ir (neat): H nmr (200 MHz, CDCl ): δ 2.60 (3H,
3
and 15.2 Hz), 7.34 (1H, dq, C=C-H J = 7.0 and 15.2 Hz), 8.35
s, SCH ), 4.69 (1H,d, HO-C-H, J = 7.9 Hz), 5.89 (1H, d, H-C-
3
+
+
(1H, s, N=C-H); ms: m/z (EI) 202 (M +2, 33%), 200 (M ,
OH, J = 7.9 Hz), 7,27 – 7.35 (5H, m, Ar), 8.37(1H, s, N=CH);
100%), 169 (29), 167 (86), 119 (22), 65 (22).
13
C nmr (75 MHz, CDCl ) δ 14.5 (S-CH ), 71.8 (H-C-OH),
3
3
HRMS (EI) for C H ClN S requires M, 200.0174. Found: m/z
8
9
2
123.8 (C5), 127.4, 128.4, 128.6, 139.7 (Ar), 156.6 (C6), 165.4
200.0177.
+
+
(C4), 170.2 (C2); ms: m/z (EI) 268 (M +2, 34%), 266 (M ,
100%), 217 (6), 215 (22), 162 (11), 160 (28), 77(47).
5-Chloro-4-(2-methyl-1-propenyl)-2-methylthiopyrimidine (2b).
HRMS (EI) for C H ClN OS requires M, 266.0281. Found:
12 11
2
This compound was purified using eluent EtOAc - hexane
m/z 266.0285.
1
1:49; mp 75 - 77 °C; H nmr (300 MHz, CDCl ): δ 2.02 (3H, d,
3
General Methods for Decarboxylation of 4-Carboxypyrimidines
in the Presence of an Electrophile (Table 3).
CH , J = 1.2 Hz), 2.24 (3H, d, CH , J = 1.2 Hz), 2.53 (3H, s,
3
3
S-CH ), 6.48 (1H, m, C=C-H, J = 1.2 Hz), 8.34 (1H, s, N=C-H);
3
13
C nmr (75 MHz, CDCl ): δ 14.6 (S-CH ), 21.1 (=C-CH ), 28.5
3
3
3
Method A.
(=C-CH ), 118.3 (C=CH), 124.4 (C5), 151.4 (HC=C-(CH ) ),
3
3 2
A mixture of the 4-carboxypyrimidine 6 (2.0 mmol) and the
electrophile (5.0 mL) under an atmosphere of argon was heated
under reflux for 48 h. The solvent was evaporated off and the
crude product purified by flash chromatography on silica gel.
+
156.1 (C6), 160.4 (C4), 169.4 (C2); ms: m/z (EI) 216(M +2,
37%), 214 (M , 100%), 201 (13), 199 (38), 183 (16), 181 (54).
+
HRMS (EI) for C H ClN S requires M, 214.0331. Found:
9
11
2
m/z 214.0327.
Method B.
5-Chloro-4-(2-methyl-1-propenyl)-2-methylsulfonylpyrimidine
(2c).
A mixture of the 4-carboxypyrimidine 6 (0.5 mmol) and the
electrophile (1.0 mL) in anisole (2.0 mL) in a teflon container
(100 mL) was heated in a CEM MDS-81D microwave oven at
600 – 400 W for 20 min (600 W 8 min, 500 W 6 min and 400 W
6 min). The solvent was evaporated off and the crude product
purified by flash chromatography on silica gel.
This compound was purified using eluent EtOAc - hexane 3:7;
mp 111 - 117 °C; H nmr (300 MHz, CDCl ): δ 2.08 (3H, d, CH ,
J = 1.2 Hz), 2.33 (3H, d, CH , J = 1.2 Hz), 3.31 (3H, s, S-CH ),
6.63(1H, m, C=C-H, J = 1.2 Hz), 8.68 (1H, s, N=C-H); C nmr
(75 MHz, CDCl ): δ 21.5 (=C-CH ), 29.1 (=C-CH ), 39.3 (SO -
1
3
3
3
3
13
3
3
3
2
CH ), 117.1( C=CH), 131.0 (C5), 156.8 (HC=C-(CH ) ), 157.1
4-(1-Hydroxy-1-phenylethyl)-5-chloro-2-methylthiopyrimidine
(4b).
3
3 2
+
+
(C6), 161.9 (C4), 162.6 (C2); ms: m/z (CI, CH ): 249 (MH +2,
5
+
35%), 247 (MH , 100%), 169 (5), 167 (19).
This compound was purified using eluent EtOAc - hexane 1:9.
+
HRMS (CI) for C H ClN O S(H ) requires M, 247.0302.
9
11
2 2
-1 1
The compound was obtained as a yellow oil; ir (neat): 3416 cm ; H
Found: m/z 247.0302.
nmr (300 MHz, CDCl ): δ 2.00 (3H, s, C-CH ), 2.61 (3H, s, SCH ),
3
3
3
5.62 (1H, s, C-OH), 7.25 – 7.32 (5H, m, Ar), 8.34 (1H, s, N=C-H);
General Methods for Decarboxylation of Allylic Esters of
4-Carboxypyrimidines in the Presence of Benzaldehyde (Table 2).
13
C nmr (75 MHz, CDCl ): δ 14.6 (S-CH ), 25.2 (C-CH ), 75.3
3
3
3
(HO-C-CH ), 123.8 (C5), 126.4, 127.7, 128.2, 143.0 (Ar), 158.3
3
Method A.
+
(C6), 168.1 (C4), 169.3 (C2); ms: m/z (EI) 282 (M +2, 37%), 280
+
A mixture of the pyrimidine 1 (1.0 mmol), Pd(PPh ) (0.05
(M , 100%), 267 (5), 265 (16), 162 (17), 160 (46), 121 (65).
3 4
mmol) and benzaldehyde (1.0 mL, 10 mmol) in toluene (4 mL)
under an atmosphere of argon was heated under reflux for 72 h.
HRMS (EI) for C
m/z 280.0437.
H ClN OS requires M, 280.0437. Found:
13 13 2

224
G. Herstad and T. Benneche
Vol. 40
REFERENCES AND NOTES
4-Benzoyl-5-chloro-2-methylthiopyrimidine (4c).
This compound was purified using eluent EtOAc - hexane 1:9;
-1 1
mp 96 – 104 °C; ir (neat): 1682 cm ; H nmr (300 MHz, CDCl ):
[1] D. J. Brown, The Pyrimidines, Wiley & Sons, New York,
1962, pp 119.
[2] K. Undheim and T. Benneche, Adv. Heterocycl. Chem.,
62, 305 (1995).
[3a] M. F. Carroll, J. Chem. Soc., 704 (1940); [b] N. Ouvrard,
J. Rodriguez and M. Santelli, Tetrahedron Lett., 34, 1149 (1993).
[4] J. Tsuji, Palladium Reagents and Catalysts, Wiley &
Sons, Chichester, 1995, pp 385.
3
δ 2.51(3H, s, SCH ), 7.46 – 7.85(5H, m, Ar), 8,60 (1H, s, N=C-
H); C nmr (75 MHz, CDCl ): δ 14.6 (S-CH ), 122.8 (C5),
128.9, 130.2, 133.9, 134.7 (Ar), 157.5 (C6), 160.8 (C4), 171.0
(C2), 190.2 (C=O); ms: m/z (EI) 266 (M +2, 15%), 264 (M ,
43%), 267 (5), 105 (100), 77 (59), 51 (17).
HRMS (EI) for C H ClN OS requires M, 264.0124. Found:
3
13
3
3
+
+
12
9
2
m/z 264.0123.
[5] T. Tsuda, M. Okada, S. Nishi and T. Saegusa, J. Org.
Chem., 51, 421 (1986).
[6] L. B. Frederiksen, T. H. Grobosch, J. R. Jones, S.-Y. Lu
and C.-C. Zhao, J. Chem. Res. (S), 42 (2000).
[7] C. Kuang, H. Senboku and M. Tokuda, Tetrahedron
Lett., 42, 3893 (2001).
4-(α-Hydroxybenzyl)-5-chloro-2-methylsulfonylpyrimidine
(4d).
This compound was purified using eluent EtOAc - hexane 3:7.
-1
The compound was obtained as a yellow oil; ir (neat): 3462 cm ;
1
H nmr (300 MHz, CDCl ): δ 3.35 (3H, s, SO CH ), 4.60 (1H, d,
3
2
3
HO-C-H, J = 5.0 Hz), 6.08 (1H, d, H-C-OH, J = 5.0 Hz), 7.28 –
7.37 (5H, m, Ar), 8,73(1H, s, N=CH); C nmr (75 MHz,
[8] C. L. Zara, T. Jin and R. J. Giguere, Synth. Commun., 30,
2099 (2000).
13
CDCl ): δ 39.5 (SO -CH ), 72.4 (H-C-OH), 127.4, 128.9, 128.9
[9] Z. Budesinsky and J. Vavrina, Coll. Czech. Chem.
Commun., 37, 1721 (1972).
[10] P. Beak and B. Siegel, J. Am. Chem. Soc., 98, 3601
(1976).
3
2
3
(Ar), 131.7 (C5), 138.5 (Ar), 157.7 (C6), 163.1 (C4), 168.7
+
+
+
(C2);ms: m/z (ESI, Na ) 323 (MNa +2, 50%), 321 (MNa ,
100%), 301 (5), 299 (14), 283 (13), 281(38).
+
+
HRMS (ESI, Na ) for C
H ClN O S(Na ) requires M,
[11] J. Tsuji, Palladium Reagents and Catalysts, Wiley &
Sons, Chichester, 1995, pp 356.
12 11 2 3
321.0071. Found: m/z 321.0056.
1
[12] Isoprene was collected in a cold trap at - 180 °C. The H
4-(α-Hydroxybenzyl)-5-bromo-2-methylthiopyrimidine (4e).
13
and C NMR spectra were in good agreement with literature spec-
13
1
This compound was purified using eluent EtOAc - hexane 1:9;
tra (The Aldrich Library of C and H NMR Spectra, 1993).
[13] R. Köster, S. Arora and P. Binger, Synthesis, 322 (1971).
[14] F. Guibe and Y. S. M’Leux, Tetrahedron Lett., 22, 3591
(1981).
-1
1
mp 107 – 112 °C; ir (neat): 3436 cm ; H nmr (300 MHz,
CDCl ): δ 2.59 (3H, s, SCH ), 5.85 (1H , s, HO-C-H) 7.27 – 7.36
3
3
13
(5H, m, Ar), 8.48 (1H, s, N=CH); C nmr (75 MHz, CDCl ): δ
3
14.5 (S-CH ), 73.2 (H-C-OH), 113.4 (C5), 127.7, 128.4, 128.6,
[15] J. Nokami, T. Mandai, H. Watanabe, H. Ohyama and J.
Tsuji, J. Am. Chem. Soc., 111, 4126 (1989).
[16] M. P. Nakanishi and W. Wu, Tetrahedron Lett., 39, 6271
(1998).
3
139.7 (Ar), 159.1 (C6), 166.6 (C4), 170.9 (C2); ms: m/z (EI) 312
+
+
(M +2, 55%), 310 (M , 61%), 206 (16), 204 (13), 105 (40), 77
(100), 51 (20).
HRMS (EI) for C H BrN OS requires M, 309.9775. Found:
m/z 309.9789.
[17] J. Solberg and K. Undheim, Acta Chem. Scand., B 41,
712 (1987).
12 11
2