Regiospecific bromination of 2-phenyl-3H-pyrimidin-4-ones

Article abstract of DOI:10.1055/s-0028-1083178

Three methods for the regiospecific bromination of 2-phenyl-3H-pyrimidin-4- ones are presented: bromination of the 5-position of the pyrimidine ring, bromination of the 6-benzylic position and simultaneous bromination of both the 5-position of the pyrimid

Full text of DOI:10.1055/s-0028-1083178

3492
PAPER
Regiospecific Bromination of 2-Phenyl-3H-pyrimidin-4-ones
R
egiospecific Brom
i
inatio
l
n
of 2-P
o
henyl-3
H
-pyrimid
Z
in-4-one
s
anatta,* Leonardo Fantinel, Liana da S. Fernandes, Ana D. Wouters, Helio G. Bonacorso, Marcos A. P. Martins
Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria,
97105-900 Santa Maria, RS, Brazil
Fax +55(55)2208031; E-mail: zanatta@base.ufsm.br
Received 11 June 2008; revised 21 July 2008
taining building block approach has been reported.17a,18 In
the present paper, we present three methods for the re-
giospecific bromination of 2-phenyl-3H-pyrimidin-4-
ones: bromination of the 5-position of the pyrimidine ring,
Abstract: Three methods for the regiospecific bromination of 2-
phenyl-3H-pyrimidin-4-ones are presented: bromination of the 5-
position of the pyrimidine ring, bromination of the 6-benzylic posi-
tion and simultaneous bromination of both the 5-position of the py-
rimidine ring and 6-benzylic position. Reactions were carried out bromination of the 6-benzylic position and simultaneous
using simple protocols and the brominated pyrimidines were ob-
bromination of both the 5-position of the pyrimidine ring
tained in good yields.
and the 6-benzylic position.
Key words: enones, bromination, bromopyrimidines, pyrimidin-4-
Scheme 1 outlines the synthetic strategy used for the
ones, 2-phenyl-pyrimidin-4-ones
regiospecific bromination of 2-phenyl-3H-pyrimidin-4-
ones. Compounds 3a–d were synthesized through the
halogen-containing building block approach as previously
The introduction of halogen and halogenated groups into
organic molecules often confers significant and useful
changes in their chemical, physical, and biological prop-
reported.17a,18 Compounds 2c–d are new. Compounds
3a–d were obtained by the cyclocondensation reaction of
compounds 2a–d with benzamidine hydrochloride in the
presence of sodium hydride, in anhydrous THF, according
erties. For example, 5-fluorouracil is a well-known antitu-
mor agent.1 In addition, 5-halosubstituted pyrimidines
to Scheme 1. Compounds of type 3 are important interme-
exhibit analgesic, antiinflamatory,2 agrochemical fungi-
diates in the preparation of compounds with potential
cidal,3 and herbicidal4 activity, as well as acting as modu-
antitumoral and/or antiviral activities.19
lators of voltage-gated ion channels.5 Furthermore,
halogenated pyrimidines have been utilized as intermedi-
ates for a variety of synthetic transformations of related
O
Br
H
compounds of biological interest.6 It has been shown that
5-halouracil derivatives undergo palladium-catalyzed
cross-coupling reactions with vinyl ketones7 and with
alkynes,8 to give 5-alkanyl- and 5-alkynyl-uracil, respec-
tively. Moreover, halopyrimidines may be used in Suzuki
coupling reactions9 and to generate reactive organometal-
lic intermediates by metalation.10 Therefore, new methods
for the convenient synthesis of 5-halopyrimidine deriva-
tives are of current interest in synthetic chemistry.
O
CH2R
N
O
(ii)
(i)
70–85%
R
R
60–97%
CCl3 OMe
N
Ph
CCl3 OMe
Br
1a–f
2a–d
3a–d
O
N
(iii)
Ref. 20
Br
H
(iv)
O
RH2C
N
Ph
51–84%
H
5a–f
N
Bromination of the 5-position of pyrimidines has been
carried out with bromine/acetic anhydride,11 bromine/
water,12 bromine/dimethylformamide,13 N-bromosuccin-
imide,14 and with lithium bromide in the presence of ceric
ammonium nitrate (CAN).15 Bromination of other posi-
tions of the pyrimidinone ring has been carried out with
phosphorus tribromide16 through substitution of the car-
bonyl oxygen by the bromine atom.
O
RH2C
N
4a–f
Ph
Br
H
(v)
N
71–85%
Br
N
Ph
6b–d
R
R = H (a), Me (b), Et (c), n-Pr (d), i-Pr (e), Ph (f)
Scheme 1 Reagents and conditions: (i) 1. Br2, CH2Cl2, 1 h, 25 °C; 2.
py, 1 h, 0 °C; (ii) benzamidine hydrochloride, NaH, THF, 16 h, reflux;
(iii) benzamidine hydrochloride, 1 M NaOH, CH2Cl2, 15 min, r.t.; (iv)
Br2, MeOH, 5 min, r.t.; (v) NBS, MCPBA, CHCl3, 16 h, r.t.
Although many methods for the bromination of the pyri-
midine ring can be found, the corresponding benzylic
halogenation has been less explored because over-bromi-
nation is a major problem.17 Recently, a convenient and
regiospecific method for mono- and di-bromination of the
benzylic position of pyrimidines using the halogen-con-
Compounds 5a–f were prepared through the bromination
of the pyrimidines 4a–f using bromine in methanol. The
synthesis of pyrimidines 4a–f has been recently report-
ed.20 Compounds 5 are intermediates in the synthesis of
the Bromacil© analogue, which is an important herbicide
used for total weed and brush control on non-crop land.21
SYNTHESIS 2008, No. 21, pp 3492–3496
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Advanced online publication: 16.10.2008
DOI: 10.1055/s-0028-1083178; Art ID: M02908SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Regiospecific Bromination of 2-Phenyl-3H-pyrimidin-4-ones
3493
Compounds 6b–d were obtained through the bromination In summary, we have synthesized a number of useful bro-
of pyrimidines 4b–d with two equivalents of N-bromo- minated 2-phenyl-3H-pyrimidin-4-ones through regio-
succinimide (NBS), in chloroform, in the presence of a specific halogenations. It has been demonstrated that it is
catalytic amount of 3-chloroperoxybenzoic acid, under possible to regiospecifically brominate the 5-pyrimidine
conditions which are typical for free-radical reac- ring position and the 6-benzylic position, as well as to si-
tions.17b,22 However, bromination of the 5-ring position, multaneously brominate both positions, using simple pro-
seems to be carried out by aromatic electrophilic substitu- tocols and rendering good yields. The bromopyrimidines
tion. When bromination was carried out with one equiva- obtained are useful intermediates for the synthesis of po-
lent of NBS, a mixture of ring and benzylic brominated tential biologically active compounds through an im-
products was obtained. Alternatively, compounds of type mense variety of nucleophilic and nucleophilic
6 could be obtained through bromination of compounds 3 heteroaromatic substitution reactions and metal-catalyzed
using bromine in methanol (reaction conditions iv, cross-coupling reactions.
Scheme 1). This, however, would take three reaction steps
instead of two. The reaction of compound 4a failed to give
compound 6a through method v. Compounds 6 are impor-
tant chemical intermediates for the preparation of novel
inhibitors of human thymidine phosphorylase (TP).23 The
optimized reaction conditions and yields for the synthesis
of compounds 3 are presented in Table 1; those obtained
from the synthesis of compounds 5 and 6 are presented in
Table 2. All products described in this paper, except 3a,
are new and were fully characterized by GC-MS, 1H and
13C NMR spectroscopy, and elemental analysis.
The synthesis of compounds 1a–f,24 2a, 2b,18 and 4a–f20 were re-
ported by our group. All melting points were determined on a Kofler
Reichert Thermovar or on a MQAPF-301 apparatus and are uncor-
rected. The CHN microanalyses were performed on a Perkin–Elmer
2400 elemental analyzer from the Department of Chemistry of the
Universidade de São Paulo, São Paulo, SP, Brazil. Mass spectra
were recorded using a HP 5973 MSD connected to a HP 6890 GC.
The GC was equipped with a split-splitless injector, auto-sampler,
cross-linked HP-5 capillary column (30 m, 0.32 mm of internal dia-
1
meter), and helium was used as the carrier gas. H and 13C NMR
spectra were acquired on a Bruker DPX200 or DPX400 spectrome-
ter in CDCl3 or DMSO-d6 with TMS as the internal reference.
Table 1 Optimized Reaction Conditions and Yields for the Synthe-
sis of Compounds 3
5-Bromo-1,1,1-trichloro-4-methoxyalk-3-en-2-ones 2c–d;
General Procedure
Methoda
Yield (%)b Product
To a solution of 1,1,1-trichloro-4-methoxyalk-3-en-2-one 1c–d (50
mmol) in CH2Cl2 (30 mL), a solution of Br2 (50 mmol) in CH2Cl2
(20 mL) was added. The mixture was stirred for 1 h at 25 °C, cooled
to 0 °C and pyridine (50 mmol) was added. After 1 h, the reaction
mixture was washed with HCl (15%, 30 mL) and with H2O (2 × 50
mL). The organic phase was dried with MgSO4 and the solvent was
removed yielding the compounds 2c–d. Subsequent purification
was not required for compounds 2c–d. For the synthesis of com-
pounds 2a–b, see Martins et al.18
Entry
Compd
2a
1
2
3
4
A
A
A
A
60
60
97
74
3a
3b
3c
3d
2b
2c
2d
a Method A: PhC(=NH)NH2·HCl, THF, 0 °C then reflux, 16 h.
b Yield after purification.
5-Bromo-1,1,1-trichloro-4-methoxyhex-3-en-2-one (2c)
Yield: 70%; oil.
GC-MS (EI, 70 eV): m/z (%) = 322 (1) [M+], 324 (2) [M + 2], 326
(1) [M + 4], 205 (100), 207 (100), 125 (36), 111 (45), 69 (24).
Table 2 Optimized Reaction Conditions and Yields for the Synthe-
sis of Compounds 5 and 6
1H NMR (400 MHz, CDCl3): d = 1.00 (t, J = 7.4 Hz, 3 H, CH3), 2.04
(quint, J = 7.4 Hz, 2 H, CH2), 3.88 (s, 3 H, OCH3), 5.82 (t, J = 7.4
Hz, 1 H, CH), 6.01 (s, 1 H, H-3).
13C NMR (100 MHz, CDCl3): d = 12.1 (CH3), 28.4 (CH2), 46.8
(CH), 57.0 (OCH3), 90.5 (C-3), 97.4 (C-1), 177.1 (C-4), 179.6 (C-
2).
Entry
Compd
4a
Methoda
Yield (%)b Product
1
2
3
4
5
6
7
8
9
B
B
B
B
B
B
C
C
C
70
69
73
84
51
60
71
85
85
5a
5b
5c
5d
5e
5f
4b
4c
Anal. Calcd for C8H10BrCl3O2: C, 29.62; H, 3.11. Found: C, 30.11;
H, 2.73.
4d
4e
5-Bromo-1,1,1-trichloro-4-methoxyhep-3-en-2-one (2d)
Yield: 85%; oil.
GC-MS (EI, 70 eV): m/z (%) = 336 (1) [M+], 338 (2) [M + 2], 340
(1) [M + 4], 219 (100), 221 (100), 139 (20), 111 (65).
1H NMR (400 MHz, CDCl3): d = 0.95 (t, J = 7.2 Hz, 3 H, CH3), 1.42
(sext, J = 7.2 Hz, 2 H, CH2), 1.96–2.06 (m, 2 H, CH2), 3.88 (s, 3 H,
OCH3), 5.92 (t, J = 7.2 Hz, 1 H, CH), 5.99 (s, 1 H, H-3).
4f
4b
6b
6c
6d
4c
4d
a Method B: Br2, MeOH, r.t., 5 min; Method C: NBS (2 equiv),
CHCl3, MCPBA (15 mol%), r.t., 16 h.
13C NMR (100 MHz, CDCl3): d = 13.3 (CH3), 20.7 (CH2), 36.8
(CH2), 44.9 (CH), 56.9 (OCH3), 90.3 (C-3), 97.4 (C-1), 177.2 (C-4),
179.6 (C-2).
b Yield after purification.
Synthesis 2008, No. 21, 3492–3496 © Thieme Stuttgart · New York

3494
N. Zanatta et al.
PAPER
Anal. Calcd for C9H12BrCl3O2: C, 31.94; H, 3.57. Found: C, 31.64;
H, 3.22.
13C NMR (100 MHz, CDCl3): d = 13.4 (CH3), 21.0 (CH2), 38.7
(CH2), 53.0 (CH), 110.0 (C-5), 127.9, 129.0, 131.4, 132.3 (Ph),
157.3 (C-2), 165.6 (C-4), 167.2 (C-6).
6-Bromoalkyl-2-phenylpyrimidin-4(3H)-ones 3a–d; General
Procedure
GC-MS (EI, 70 eV): m/z (%) = 306 (2) [M+], 308 (2) [M + 2], 266
(52), 264 (52), 227 (100), 104 (47), 77 (20).
To a solution of benzamidine hydrochloride (0.16 g, 1.0 mmol) in
anhydrous THF (10 mL), stirred in an ice-bath, NaH (36.0 mg, 1.5
mmol) was added. To this mixture, a solution of enone 2a–d (1.0
mmol) in anhydrous THF (1.0 mL) was added dropwise through an
addition funnel. After the addition, the cooling bath was removed
and the reaction mixture was allowed to warm to r.t. and then re-
fluxed for 16 h. At the end of the reaction, NaCl was filtered off and
the solvent was removed with a rotary evaporator. Products 3a–d
were purified by recrystallization from MeOH or hexane–CHCl3
(1:3).
Anal. Calcd for C14H15BrN2O: C, 54.74; H, 4.92; N, 9.12. Found: C,
54.71; H, 4.93; N, 9.12.
5-Bromo-2-phenylpyrimidin-4(3H)-ones 5a–f; General Proce-
dure
To a solution of pyrimidinone 4a–f (1.0 mmol) in MeOH (20 mL),
Br2 (2.72 g, 1.7 mmol) was added under vigorous stirring at r.t. for
5 min. Compounds 5a–f precipitated in the reaction vessel after par-
tial evaporation of the solvent in the rotary evaporator. The products
were collected by filtration and purified by recrystallization from
MeOH.
6-(Bromomethyl)-2-phenylpyrimidin-4(3H)-one (3a)
Yield: 60%; mp 132–135 °C (MeOH).
1H NMR (200 MHz, DMSO-d6): d = 4.47 (s, 2 H, CH2), 6.52 (s, 1 H,
H-5), 7.48–7.63 and 8.09–8.14 (2 m, 5 H, Ph).
13C NMR (100 MHz, DMSO-d6): d = 62.2 (CH2), 109.8 (C-5),
127.8, 128.3, 131.6, 131.9 (Ph), 157.5 (C-6), 163.9 (C-2), 167.1 (C-
4).
GC-MS (EI, 70 eV): m/z (%) = 264 (59) [M+], 157 (29), 104 (100),
77 (38), 51 (21).
5-Bromo-6-methyl-2-phenylpyrimidin-4(3H)-one (5a)
Yield: 70%; mp 160–161 °C (MeOH).
1H NMR (200 MHz, DMSO-d6): d = 2.48 (s, 3 H, CH3), 7.50–7.62,
8.06–8.10 (m, 5 H, Ph).
13C NMR (50 MHz, DMSO-d6): d = 24.2 (CH3), 110.0 (C-5), 128.0,
128.7, 131.1, 132.0 (Ph), 155.0 (C-2), 159.2 (C-6), 161.4 (C-4).
GC-MS (EI, 70 eV): m/z (%) = 264 (75) [M+], 266 (75) [M + 2], 185
(7), 130 (23), 104 (100), 77 (71).
Anal. Calcd for C11H9BrN2O: C, 49.84; H, 3.42; N, 10.57. Found:
C, 50.04; H, 3.53; N, 10.78.
Anal. Calcd for C11H9BrN2O: C, 49.84; H, 3.42; N, 10.57. Found:
C, 49.72; H, 3.38; N, 10.35.
6-(1-Bromoethyl)-2-phenylpyrimidin-4(3H)-one (3b)
Yield: 60%; mp 176–177 °C (CHCl3–hexane, 3:1).
5-Bromo-6-ethyl-2-phenylpyrimidin-4(3H)-one (5b)
Yield: 69%; mp 259–260 °C (MeOH).
1H NMR (200 MHz, CDCl3): d = 2.03 (d, J = 7.0 Hz, 3 H, CH3),
4.96 (q, J = 7.0 Hz, 1 H, CH), 6.56 (s, 1 H, H-5), 7.51–7.57 and
8.22–8.27 (2 m, 5 H, Ph).
13C NMR (100 MHz, CDCl3): d = 23.8 (CH3), 47.2 (CH), 109.5 (C-
5), 127.9, 129.0, 131.7, 132.3 (Ph), 157.2 (C-2), 165.5 (C-4), 167.8
(C-6).
1H NMR (400 MHz, DMSO-d6): d = 1.23 (t, J = 7.4 Hz, 3 H, CH3),
2.78 (q, J = 7.4 Hz, 2 H, CH2), 7.52–7.62, 8.11–8.13 (m, 5 H, Ph),
13.15 (br s, 1 H, NH).
13C NMR (100 MHz, DMSO-d6): d = 11.0 (CH3), 29.9 (CH2), 108.9
(C-5), 127.6, 128.3, 131.1, 131.4 (Ph), 154.9 (C-2), 159.1 (C-4),
165.7 (C-6).
GC-MS (EI, 70 eV): m/z (%) = 278 (20) [M+], 280 (20) [M + 2], 199
(100), 104 (64), 97 (40), 77 (24).
GC-MS (EI, 70 eV): m/z (%) = 278 (97) [M+], 280 (97) [M + 2], 251
(13), 249 (13), 199 (17), 171 (21), 104 (100), 77 (49).
Anal. Calcd for C12H11BrN2O: C, 51.66; H, 3.97; N, 10.04. Found:
C, 51.64; H, 3.90; N, 10.37.
Anal. Calcd for C12H11BrN2O: C, 51.63; H, 3.97; N, 10.04. Found:
C, 51.74; H, 4.43; N, 9.99.
6-(1-Bromopropyl)-2-phenylpyrimidin-4(3H)-one (3c)
Yield: 97%; mp 175–176 °C (CHCl3–hexane, 3:1).
5-Bromo-6-propyl-2-phenylpyrimidin-4(3H)-one (5c)
Yield: 73%; mp 228–230 °C (MeOH).
1H NMR (200 MHz, CDCl3): d = 1.06 (t, J = 7.2 Hz, 3 H, CH3), 2.28
(quint, J = 7.2 Hz, 2 H, CH2), 4.69 (t, J = 7.2 Hz, 1 H, CH), 6.52 (s,
1 H, H-5), 7.53–7.56, 8.23–8.27 (m, 5 H, Ph), 13.09 (br s, 1 H, NH).
13C NMR (100 MHz, CDCl3): d = 12.4 (CH3), 30.1 (CH2), 55.0
(CH), 110.4 (C-5), 127.9, 129.0, 131.7, 132.3 (Ph), 157.2 (C-2),
165.6 (C-4), 167.0 (C-6).
1H NMR (200 MHz, CDCl3): d = 1.04 (t, J = 7.2 Hz, 3 H, CH3), 1.82
(sext, J = 7.2 Hz, 2 H, CH2), 2.85 (q, J = 7.2 Hz, 2 H, CH2), 7.49–
7.52, 8.19–8.21 (m, 5 H, Ph).
13C NMR (100 MHz, DMSO-d6): d = 13.5 (CH3), 20.3 (CH2), 38.9
(CH2), 110.1 (C-5), 127.4, 128.4, 131.2, 131.4 (Ph), 154.1 (C-2),
160.2 (C-4), 166.2 (C-6).
GC-MS (EI, 70 eV): m/z (%) = 292 (2) [M+], 294 (2) [M + 2], 266
(30), 264 (30), 213 (100), 186 (31), 104 (51), 77 (24).
GC-MS (EI, 70 eV): m/z (%) = 292 (8) [M+], 294 (8) [M + 2], 266
(100), 264 (100), 213 (9), 104 (67), 77 (36).
Anal. Calcd for C13H13BrN2O: C, 53.26; H, 4.47; N, 9.56. Found: C,
53.00; H, 4.66; N, 9.76.
Anal. Calcd for C13H13BrN2O: C, 53.26; H, 4.47; N, 9.56. Found: C,
53.43; H, 4.06; N, 9.71.
6-(1-Bromobutyl)-2-phenylpyrimidin-4(3H)-one (3d)
Yield: 74%; mp 152–153 °C (CHCl3–hexane, 3:1).
1H NMR (200 MHz, CDCl3): d = 0.98 (t, J = 7.4 Hz, 3 H, CH3), 1.49
(sext, J = 7.4 Hz, 2 H, CH2), 2.22 (q, J = 7.4 Hz, 2 H, CH2), 4.77 (t,
J = 7.4 Hz, 1 H, CH), 6.51 (s, 1 H, H-5), 7.54–7.56, 8.23–8.27 (m,
5 H, Ph), 13.11 (br s, 1 H, NH).
5-Bromo-6-butyl-2-phenylpyrimidin-4(3H)-one (5d)
Yield: 84%; mp 213–215 °C (MeOH).
1H NMR (400 MHz, DMSO-d6): d = 0.93 (t, J = 7.2 Hz, 3 H, CH3),
1.39 (sext, J = 7.2 Hz, 2 H, CH2), 1.68 (quint, J = 7.2 Hz, 2 H, CH2),
2.77 (t, J = 7.2 Hz, 2 H, CH2), 7.52–7.62, 8.10–8.12 (m, 5 H, Ph),
13.16 (br s, 1 H, NH).
Synthesis 2008, No. 21, 3492–3496 © Thieme Stuttgart · New York

PAPER
Regiospecific Bromination of 2-Phenyl-3H-pyrimidin-4-ones
3495
13C NMR (100 MHz, DMSO-d6): d = 13.7 (CH3), 21.8 (CH2), 28.9
(CH2), 36.2 (CH2), 109.9 (C-5), 127.9, 128.6, 131.4, 131.9 (Ph),
155.0 (C-2), 159.3 (C-4), 164.7 (C-6).
1H NMR (400 MHz, DMSO-d6): d = 0.97 (t, J = 7.2 Hz, 3 H, CH3),
2.22–2.35 (m, 2 H, CH2), 5.29 (t, J = 7.2 Hz, 1 H, CH), 7.53–7.64,
8.13–8.15 (m, 5 H, Ph), 13.29 (br s, 1 H, NH).
GC-MS (EI, 70 eV): m/z (%) = 306 (2) [M+], 308 (2) [M + 2], 266
(100), 264 (100), 227 (10), 104 (83), 77 (45).
13C NMR (100 MHz, DMSO-d6): d = 11.6 (CH3), 28.2 (CH2), 53.3
(CH), 109.7 (C-5), 127.3, 128.2, 130.8, 131.6 (Ph), 155.2 (C-2),
158.8 (C-4), 160.8 (C-6).
GC-MS (EI, 70 eV): m/z (%) = 370 (2) [M+], 372 (4) [M + 2], 374
(2) [M + 4], 346 (25), 344 (50), 342 (25), 293 (45), 291 (45), 266
(40), 264 (40), 104 (100), 77 (60).
Anal. Calcd for C14H15BrN2O: C, 54.74; H, 4.92; N, 9.12. Found: C,
55.15; H, 4.65; N, 9.32.
5-Bromo-6-isobutyl-2-phenylpyrimidin-4(3H)-one (5e)
Yield: 51%; mp 236–238 °C (MeOH).
Anal. Calcd for C13H12Br2N2O: C, 41.97; H, 3.25; N, 7.83. Found:
C, 42.36; H, 3.16; N, 7.83.
1H NMR (400 MHz, DMSO-d6): d = 0.97 (d, J = 7.0 Hz, 6 H, 2 ×
CH3), 2.24 (m, 1 H, CH), 2.68 (d, J = 7.0 Hz, 2 H, CH2), 7.53–7.61,
8.09–8.11 (m, 5 H, Ph).
5-Bromo-6-(1-bromobutyl)-2-phenylpyrimidin-4(3H)-one (6d)
Yield: 85%; mp 209–211 °C (CHCl3–MeOH, 3:1).
13C NMR (100 MHz, DMSO-d6): d = 22.3 (2 × CH3), 27.3 (CH),
45.1 (CH2), 110.8 (C-5), 127.9, 128.7, 131.4, 131.9 (Ph), 154.8 (C-
2), 159.3 (C-4), 164.0 (C-6).
GC-MS (EI, 70 eV): m/z (%) = 306 (5) [M+], 308 (5) [M + 2], 266
(100), 264 (100), 227 (8), 104 (84), 77 (48).
1H NMR (200 MHz, DMSO-d6): d = 0.93 (t, J = 7.2 Hz, 3 H, CH3),
1.39 (sext, J = 7.2 Hz, 2 H, CH2), 2.26 (q, J = 7.2 Hz, 2 H, CH2),
5.38 (t, J = 7.2 Hz, 1 H, CH), 7.54–7.64, 8.13–8.16 (m, 5 H, Ph),
13.34 (br s, 1 H, NH).
13C NMR (100 MHz, DMSO-d6): d = 13.8 (CH3), 18.3 (CH2), 37.2
(CH2), 70.7 (CH), 108.6 (C-5), 128.1, 128.6, 131.4, 132.0 (Ph),
155.5 (C-2), 159.4 (C-4), 165.3 (C-6).
Anal. Calcd for C14H15BrN2O: C, 54.74; H, 4.92; N, 9.12. Found: C,
54.52; H, 4.56; N, 9.08.
5-Bromo-6-phenyl-2-phenylpyrimidin-4(3H)-one (5f)
Yield: 60%; mp 305–306 °C (MeOH).
GC-MS (EI, 70 eV): m/z (%) = 340 (1) [M+ – 44], 342 (2), 344 (1),
302 (25), 300 (100), 298 (72), 263 (50), 261 (16), 234 (38), 104
(80), 77 (42).
1H NMR (400 MHz, DMSO-d6): d = 7.51–7.79, 8.14–8.16 (m,
10 H, 2 × Ph), 13.31 (br s, 1 H, NH).
13C NMR (100 MHz, DMSO-d6): d = 109.4 (C-5), 127.8, 127.9,
128.6, 128.9, 129.5, 131.5, 131.9, 138.0 (Ph), 154.9 (C-2), 159.8
(C-6), 161.1 (C-4).
GC-MS (EI, 70 eV): m/z (%) = 326 (68) [M+], 328 (69) [M + 2], 300
(21), 298 (21), 247 (56), 104 (100), 77 (76).
Anal. Calcd for C14H14Br2N2O: C, 43.55; H, 3.65; N, 7.26. Found:
C, 43.85; H, 3.69; N, 7.41.
Acknowledgment
The authors thank the Fundação de Apoio à Pesquisa do Estado do
Rio Grande do Sul (FAPERGS-PRONEX) and Conselho Nacional
de Desenvolvimento Científico e Tecnológico (CNPq - Universal
grant No. 476634/06-7), for financial support and CAPES (L.
Fantinel, A. D. Wouters) and CNPq (L. da S. Fernandes) for the fel-
lowships.
Anal. Calcd for C16H11BrN2O: C, 58.74; H, 3.39; N, 8.56. Found: C,
59.10; H, 3.30; N, 8.54.
5-Bromo-6-(1-bromoalkyl)-2-phenylpyrimidin-4(3H)-ones
6b–d; General Procedure
To a solution of pyrimidinone 4b–d (1.0 mmol) in CHCl3 (20 mL),
NBS (3.56 g, 2.0 mmol) and MCPBA (15 mol%) were added under
stirring and the reaction was continued at r.t. for 16 h. The solvent
was evaporated by rotary evaporator and the solids were washed
with cold H2O to remove succinimide and benzoic acid residues.
Products were dried in a desiccator under phosphorous pentoxide
and then recrystallized (CHCl3–MeOH, 3:1).
References
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5-Bromo-6-(1-bromoethyl)-2-phenylpyrimidin-4(3H)-one (6b)
Yield: 71%; mp 253–255 °C (CHCl3–MeOH, 3:1).
1H NMR (200 MHz, DMSO-d6): d = 1.98 (d, J = 6.8 Hz, 3 H, CH3),
5.54 (q, J = 6.8 Hz, 1 H, CH), 7.52–7.64, 8.14–8.17 (m, 5 H, Ph),
11.06 (br s, 1 H, NH).
13C NMR (100 MHz, DMSO-d6): d = 30.0 (CH3), 67.1 (CH), 109.1
(C-5), 127.7, 128.4, 128.6, 131.6 (Ph), 155.0 (C-2), 159.2 (C-4),
165.8 (C-6).
GC-MS (EI, 70 eV): m/z (%) = 328 (55) [M+ – 28], 330 (100), 332
(55), 314 (70), 212 (35), 268 (19), 266 (38), 264 (19), 252 (22), 250
(44), 248 (22), 170 (45), 168 (45), 90 (70), 63 (60).
Anal. Calcd for C12H10Br2N2O: C, 40.26; H, 2.82; N, 7.82. Found:
C, 40.60; H, 2.52; N, 8.25.
5-Bromo-6-(1-bromopropyl)-2-phenylpyrimidin-4(3H)-one
(6c)
Yield: 85%; mp 234–236 °C (CHCl3–MeOH, 3:1).
Synthesis 2008, No. 21, 3492–3496 © Thieme Stuttgart · New York

3496
N. Zanatta et al.
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Synthesis 2008, No. 21, 3492–3496 © Thieme Stuttgart · New York