5-Cinnamoyl- and 5-(ethoxycarbonyl)-6-styryl derivatives of 4-aryl-3,4-dihydropyrimidin-2(1H)-ones

Article abstract of DOI:10.1135/cccc20071219

Several 5-cinnamoyl- and 5-(ethoxycarbonyl)-6-styryl derivatives of 4-aryl-3,4-dihydropyrimidin-2(1H)-ones were obtained and their physicochemical properties were investigated. The introduction of alkyl substituent in position 1 of dihydropyrimidine ring

Full text of DOI:10.1135/cccc20071219

Derivatives of 4-Aryl-3,4-dihydropyrimidin-2(1H)-ones
1219
5-CINNAMOYL- AND 5-(ETHOXYCARBONYL)-6-STYRYL DERIVATIVES
OF 4-ARYL-3,4-DIHYDROPYRIMIDIN-2(1H)-ONES
b1
Maksim A. KOLOSOVa1,*, Valeriy D. ORLOVa2, Valeriy V. VASHCHENKO
,
b2
b3
Svetlana V. SHISHKINA and Oleg V. SHISHKIN
a
Department of Organic Chemistry, V. N. Karazin Kharkiv National University, Svobody sq. 4,
61077 Kharkiv, Ukraine; e-mail: kolosov@univer.kharkov.ua, orlov@univer.kharkov.ua
State Scientific Institution “Institute for Single Crystals”, National Academy of Sciences
1
2
b
1
of Ukraine, Lenin Ave. 60, 61001 Kharkiv, Ukraine; e-mail: valeravv@isc.kharkov.com,
2
3
sveta@isc.kharkov.com, shishkin@xray.isc.kharkov.com
Received April 12, 2007
Accepted Jun e 25, 2007
Several 5-cin n am oyl- an d 5-(eth oxycarbon yl)-6-styryl derivatives of 4-aryl-3,4-dih ydropyri-
m idin -2(1H)-on es were obtain ed an d th eir ph ysicoch em ical properties were in vestigated.
Th e in troduction of alkyl substituen t in position 1 of dih ydropyrim idin e rin g was sh own to
prom ote th e Claisen –Sch m idt reaction on acetyl group on ly; with out th e alkyl both acetyl
an d 6-m eth yl groups participate in th e reaction .
Keyw ord s: 5-Acetyl-4-aryl-3,4-dih ydropyrim idin -2(1H)-on es; Pyrim idin es; Ben zaldeh ydes;
Ch alcon es; Claisen –Sch m idt reaction s; Cin n am oyl derivatives.
4-Aryl-3,4-dih ydropyrim idin -2(1H)-on es, th e products of th e Bigin elli reac-
tion , still rem ain of great in terest at presen t1. At th e sam e tim e, th eir
5-acetyl an d 5-cin n am oyl derivatives 1 an d 2, wh ich m igh t be suitable
syn th on es for partially h ydrogen ated h eterocycles, received in sufficien t at-
ten tion . For exam ple, syn th esis of com poun d 2a was described by Zigeun er
with co-workers2, but n eith er detailed procedure n or ch aracteristics for th e
substan ce obtain ed were reported.
We tried to obtain com poun d 2a un der stan dard con dition s of th e
3
Claisen –Sch m idt reaction ; h owever, th e startin g dih ydropyrim idin e 1a re-
m ain ed un reacted. A possible explan ation is th e low activity of th e m eth yl
group in th e acetyl substituen t due to th e poten tial tautom erism of com -
poun ds like 1 (Sch em e 1).
SCHEME 1
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© 2007 Institute of Organic Chemistry and Biochemistry
doi:10.1135/cccc20071219

1220
Kolosov, Orlov, Vashchenko, Shishkina, Shishkin:
We also studied th e reaction of cin n am oylacetoacetic ester with urea an d
ben zaldeh yde in eth an ol in th e presen ce of catalytic am oun ts of HCl as an
altern ative way to com poun d 2a (Sch em e 2).
SCHEME 2
However, th e desired com poun d 2a was n ot form ed eith er. In stead, com -
poun d 3 was isolated in 30% yield. Its structure was proved by 1H NMR
spectrum : th ere are two sign als of NH proton s (9.24 an d 7.87 ppm ), th e sig-
n als of vin yl an d arom atic proton s (7.93–7.18 ppm ), th e doublet of
3
C(4)H-proton (5.25 ppm , J = 3.4 Hz) an d th e sign als of eth oxy group pro-
ton s. Obviously, th e rate decom position of startin g cin n am oylacetic ester is
faster th an th at of keton e. Earlier Kappe an d Falson e4 obtain ed com poun d
3 starting from 5-(ethoxycarbonyl)-6-m ethyl-4-phenyl-3,4-dihydropyrim idin-
2-one and benzaldehyde in the presence of TsOH.
Sin ce we h ave failed to obtain 5-cin n am oyl derivatives of 4-aryl-
3,4-dih ydropyrim idin -2(1H)-on es un der classical protocol of th e Claisen –
Sch m idt con den sation , an attem pt was m ade to carry out th is reaction un der
m ore h ard con dition s usin g com poun d 1a an d 4-brom oben zaldeh yde as
startin g reagen ts.
Th e superbasic m edium (DMSO/CsOH)5 provided too severe con dition s
even at room tem perature: con version of startin g dih ydropyrim idin e 1a
reach ed 85% with in 24 h an d resulted in a com plex m ixture (at least 6
com poun ds were detected by HPLC).
Un der m ilder con dition s (h eatin g th e reactan ts with KOH in eth an ol at
45–50 °C for 24 h ) on ly two com poun ds of th e above m ixture were form ed.
We h ave succeeded in isolation of both n ew substan ces (2b an d 4) from th e
reaction m ixture by fraction al crystallisation from eth an ol an d ben zen e, re-
spectively; h owever, with low yields (Sch em e 3).
Structures of both n ew com poun ds, 2b an d 4, were proved by 1H NMR
an d LC-MS m eth ods (see Experim en tal). It sh ould be n oted th at th e
regioselectivity in teraction of m eth yl groups in com poun d 1c, resultin g in
th e form ation of 2b, was revealed by NOE experim en t: th e suppression of
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Derivatives of 4-Aryl-3,4-dihydropyrimidin-2(1H)-ones
1221
th e on ly m eth yl group sign al of com poun d 2b led to in crease in th e in ten -
sity of th e N(1)H-proton sign al.
SCHEME 3
Th e absen ce of isom eric m on oben zyliden e derivative of 1a on th e 6-Me
group in th e reaction m ixture brin gs on un am biguous eviden ce th at th e first
step is the introduction of the benzylidene fragm ent on the acetyl group.
Accordin g to our h ypoth esis about th e reduced activity of Me in acetyl
group of com poun ds of th e type 1 in th e croton ic con den sation , it m igh t
be en h an ced in N1-alkylated an alogues of 1 (com poun ds 5), wh ere tauto-
m erism is preven ted. Th e required startin g com poun ds (1a–1d ) were ob-
tain ed as described previously6 by con den sation of urea with arom atic alde-
h ydes an d acetoacetic aldeh yde dim eth ylacetal (or acetylaceton e) (see
Experim en tal). Com poun ds 5 were syn th esized by th e treatm en t of 1 with
iodom eth an e or brom oeth an e in h eterogen eous system (con cen trated
aqueous KOH solution –MeCN)6 (Sch em e 4).
SCHEME 4
As it was expected, com poun ds 5a–5e, in con trast to th eir N1-un sub-
stituted an alogues 1, reacted readily with arom atic aldeh ydes in eth an ol in
th e presen ce of KOH, form in g correspon din g cin n am oyl derivatives 6a–6j
(Sch em e 5).
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1222
Kolosov, Orlov, Vashchenko, Shishkina, Shishkin:
SCHEME 5
Th e structure of com poun ds obtain ed was proved by 1H NMR spectro-
scopy. Th us, in con trast to spectra of com poun ds 5a–5e, th e sign al of acetyl
proton s disappeared in th e case of com poun ds 6a–6j, but two doublets of
vin yl proton s n ear 6.86–7.36 ppm (α-H) an d 7.52–7.15 ppm (β-H) appeared.
Th e couplin g con stan ts for th ese products (15.6–16.0 Hz) con firm trans-
con figuration of th e cin n am oyl group. Th e structure of com poun d 6f was
also supported by X-ray an alysis (Fig. 1).
O1W
O2
C15
C7
C5
C13
C4
C16
N1
C12
C11
C3
C2
C6
C8
C14
C17
C1
C9
O1
C10
O3
C18
C19
C23
C22
C20
C21
FIG. 1
Structure of com poun d 6f
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Derivatives of 4-Aryl-3,4-dihydropyrimidin-2(1H)-ones
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Th e tetrah ydropyrim idin e rin g adopts som ewh at asym m etric boat con -
form ation (th e puckerin g param eters are S = 0.48, Θ = 65.3°, Ψ = 9.7°)7. Th e
deviation s of N(1) an d C(2) atom s from th e plan e of rem ain in g atom s of
th e rin g are 0.17 an d 0.40 Å, respectively.
Th e ph en yl group at th e C(2) atom h as a pseudoaxial orien tation
(C(18)–C(2)–C(3)–C(4) torsion an gle is –93.3(5)°) an d is rotated relative to
th e C(3)–C(2) bon d (C(3)–C(2)–C(18)–C(19) torsion an gle is 28.5(6)°). Th is
orien tation of th e ph en yl group leads to th e appearan ce of th e sh orten ed
in tram olecular con tacts H(19)···C(3) 2.66 Å an d H(19)···C(4) 2.82 Å (th e
sum of th e correspon din g van der Waals radii is 2.87 Å)8.
Th e C(5)=O(2) carbon yl group of th e substituen t at th e C(3) atom is
coplan ar with respect to th e C(3)=C(4) en docyclic double bon d
(C(4)–C(3)–C(5)–O(2) torsion an gle is –3.9(7)°) in spite of steric strain in
th is fragm en t (sh orten ed in tram olecular con tacts H(2)···C(6) 2.47 (2.87) Å,
H(2)···H(6) 1.92 (2.34) Å, H(6)···C(2) 2.47 (2.87) Å). On e can assum e th at
th is orien tation of th e carbon yl group is stabilized by th e in tram olecular
h ydrogen bon d C(15)–H(15c)···O(2) (H···O 1.98 Å, C–H···O 136°). Th e
C(6)=C(7) double bon d h as a s-cis-con form ation relative to th e carbon yl
group (O(2)–C(5)–C(6)–C(7) torsion an gle is –1.6(7)°) an d th e ben zen e rin g
h as an tiperiplan ar orien tation relative to th e C(5)–C(6) bon d
(C(5)–C(6)–C(7)–C(8) torsion an gle is –179.4(4)°). Th e repulsion between
th e C(6), H(6) an d C(9), H(9) atom s (th e sh orten ed con tacts H(6)···C(9)
2.78 (2.87) Å, H(6)···H(9) 2.27 (2.34) Å, H(9)···C(6) 2.79 (2.87) Å) leads to an
in crease in th e C(6)–C(7)–C(8) bon d an gle to 127.9(5)° an d a sligh t ben zen e
rin g rotation relative to th e C(6)–C(7) bon d (C(6)–C(7)–C(8)–C(9) torsion
an gle is 9.5(7)°). Th e m eth oxy group lies in th e plan e of th e ben zen e rin g
(C(14)–O(3)–C(11)–C(12) torsion an gle is 0.1(7)°) in spite of th e sh orten ed
in tram olecular con tacts (H(12)···C(14) 2.46 (2.87) Å, H(12)···H(14b) 2.22
(2.34) Å, H(12)···H(14c) 2.28 (2.34) Å, H(14b)···C(12) 2.68 (2.87) Å,
H(14c)···C(12) 2.72 (2.87) Å).
Th e eth yl substituen t at th e N(1) atom is situated perpen dicularly to th e
plan e of th e dih ydro rin g (C(4)–N(1)–C(16)–C(17) torsion an gle is –79.3(7)°),
perh aps as a result of repulsion between th e eth yl group atom s, th e m eth yl
substituen t at C(4) an d th e C(1)=O(1) carbon yl group (th e sh orten ed con-
tacts H(15a)···C(16) 2.81 (2.87) Å, H(15a)···C(17) 2.84 (2.87) Å, H(15a)···H(17b)
2.13 (2.34) Å, H(15b)···C(16) 2.74 (2.87) Å, H(15b)···H(16a) 2.14 (2.34) Å,
H(16a)···C(15) 2.56 (2.87) Å, H(16b)···O(1) 2.25 (2.46) Å, H(17b)···C(15)
2.82 (2.87) Å).
Molecules of 6f in th e crystal are bon ded with each oth er an d with water
m olecules by in term olecular h ydrogen bon ds O(1w)–H(1ow)···O(2)′ (x, y, z)
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1224
Kolosov, Orlov, Vashchenko, Shishkina, Shishkin:
H···O′ 1.56 Å, O–H···O′ 170°; O(1w)–H(2ow)···O(1)′ (x, y – 1, z) H···O′ 1.98 Å,
O–H···O′ 155°; N(2)–H(2a)···O(1)′ (–x, 1 – y, 1 – z) H···O′ 2.11 Å, N–H···O′ 177°.
Th e form ation of h ydrogen bon ds leads to an in crease in th e C(1)–O(1)
bon d len gth (1.244(5) Å) as com pared with its m ean value 1.210 Å 9.
Com poun d 6f was sh own to be readily acylated with acetic an h ydride to
give N3-acetyl derivative 7 (Sch em e 5).
1H NMR spectrum of com poun d 7 does n ot con tain th e N3-H-proton sig-
n al, th e C(4)-H-proton sign al appears as sin glet (6.50 ppm , cf. th e doublet
at 5.34 ppm in com poun d 6f) an d th e sin glet of acetyl group (2.24 ppm ) is
observed.
In con clusion , we h ave exam in ed th e Claisen –Sch m idt reaction of
5-acetyl-4-aryl-3,4-dih ydropyrim idin -2(1H)-on es an d a n um ber of th eir
aryliden e derivatives, wh ich are prom isin g reagen ts for furth er con struction
of various h eterocycles.
EXPERIMENTAL
Startin g arom atic aldeh ydes, urea, alkyl h alides, acetic an h ydride an d dicarbon yl com poun d
derivatives were com m ercially available. Cin n am oylacetoacetic ester was prepared as de-
scribed in literature10. Colum n ch rom atograph y was perform ed usin g Al2O3 (60–100 µm )
with EtOAc–h exan e m ixtures as eluen ts. Th e purity of com poun ds, m on itorin g of th e reac-
tion course an d fraction selection in preparative colum n ch rom atograph y were perform ed
by TLC (Silufol UV-254 plates usin g m ixture of EtOAc–h exan e (1:1) as eluen t) or by HPLC
an alysis on a m icrocolum n ch rom atograph Milich rom 5 equipped with th e reverse ph ase
Silasorb 600 C18 colum n (aceton itrile–water m ixtures were used as eluen ts). Meltin g poin ts
were determ in ed usin g a Kofler apparatus. 1H NMR spectra were recorded in DMSO-d6 at
200 MHz usin g a Varian Mercury VX-200 spectrom eter with Si(CH3)4 as in tern al stan dard.
Ch em ical sh ifts are reported in ppm (δ-scale), couplin g con stan ts (3J) in Hz. IR spectra
(waven um bers in cm –1) were m easured usin g a Specord 75IR spectrom eter in KBr pellets (for
com poun d 5j as a th in layer). LC-MS spectra were obtain ed usin g an Agillen t 1100 in stru-
m en t.
X-ray diffraction study. Yellow sin gle crystals of 6f are triclin ic. At 293 K a = 9.189(2), b =
10.568(3), c = 11.773(4) Å, α = 65.00(2)°, β = 80.98(2)°, γ = 85.89(2)°, V = 1023.3(5) Å3, Mr =
394.46, Z = 2, space group P1, dcalc = 1.280 g/cm 3, µ(MoKα) = 0.088 m m –1, F(000) = 420. In -
ten sity of 3646 reflection s (3418 in depen den t, Rin t = 0.066) were m easured usin g autom atic
four-circle Siem en s P3/PC diffractom eter (graph ite-m on och rom atized MoKα radiation , θ/2θ
scan in g, 2θm ax = 50°). Th e structure was solved by direct m eth od usin g th e SHELXTL pack-
age10. Position s of h ydrogen atom s were located from electron den sity differen ce m aps an d
refin ed by th e “ridin g” m odel with Uiso = nUeq of n on -h ydrogen atom bon ded to a given
h ydrogen atom (n = 1.5 for m eth yl group an d n = 1.2 for oth er h ydrogen atom s). Full-
m atrix least-squares refin em en t again st F2 in an isotropic approxim ation usin g 3297 reflec-
tion s con verged to R1 = 0.065 (for 1246 reflection s with F > 4σ(F)), wR2 = 0.145, S = 0.894.
CCDC 638682 con tain s th e supplem en tary crystallograph ic data for th is paper. Th ese data
can be obtain ed free of ch arge via www.ccdc.cam .ac.uk/con ts/retrievin g.h tm l (or from
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Derivatives of 4-Aryl-3,4-dihydropyrimidin-2(1H)-ones
1225
th e Cam bridge Crystallograph ic Data Cen tre, 12, Un ion Road, Cam bridge, CB2 1EZ, UK; fax:
+44 1223 336033; or deposit@ccdc.cam .ac.uk).
Com poun ds 1b–1d an d 5a–5e were obtain ed sim ilarly as described in literature6. Spectral
data for com poun ds 1a, 1c, 1d an d 5a, 5c–5e agree well with reported values6.
5-Acetyl-6-m eth yl-4-ph en yl-3,4-dih ydropyrim idin -2(1H)-on e (1a)
A solution of urea (8.94 g, 0.149 m ol), ben zaldeh yde (15.75 g, 0.149 m ol) an d acetylaceton e
(14.9 g, 0.149 m ol) in DMF (12 m l) was refluxed for 1 h . Eth an ol (30 m l) was added an d th e
m ixture was refluxed for an oth er 10 m in . After coolin g, th e precipitate was filtered off an d
wash ed with eth an ol. Com poun d 1a (17.5 g, 51%) was obtain ed. M.p. 242–244 °C. For
C
13H14N2O2 (230.3) calculated: 12.17% N; foun d: 12.01% N.
5-Acetyl-4-(4-m eth oxyph en yl)-3,4-dih ydropyrim idin -2(1H)-on e (1b)
Yield 22%. M.p. 250–252 °C. For C13H14N2O3 (246.3) calculated: 11.38% N; foun d: 11.60% N.
IR: 1589 (C=C), 1669 (C=O). 1H NMR: 9.33 bd, 3J = 6.0, 1 H (NH-1); 7.64 bd, 3J = 3.0, 1 H
(NH-3); 7.48 d, 3J = 6.0, 1 H (H-6); 7.11 d, 3J = 8.4, 2 H (ArH); 6.83 d, 3J = 8.4, 2 H (ArH);
5.11 d, 3J = 3.0, 1 H (H-4); 3.68 s, 3 H (OCH3); 2.12 s, 3 H (COCH3).
5-[(2E)-3-(4-Brom oph en yl)prop-2-en oyl]-6-m eth yl-4-ph en yl-3,4-dih ydropyrim idin -
2(1H)-one (2b) and
6-[(1E)-2-(4-Brom oph en yl)eth -1-en yl]-5-[(2E)-3-(4-brom oph en yl)prop-2-en oyl]-4-ph en yl-
3,4-dih ydropyrim idin -2(1H)-on e (4)
A solution of com poun d 1a (2 g, 8.7 m m ol), 4-brom oben zaldeh yde (1.61 g, 8.7 m m ol) an d
KOH (0.12 g, 2.1 m m ol) in eth an ol (40 m l) was stirred at 60 °C for 24 h . After coolin g, th e
precipitate was filtered off an d, after crystallization from eth an ol (40 m l), com poun d 2b
(0.18 g, 5%) was obtain ed. Th e m oth er liquor was evaporated to dryn ess an d th e residue was
recrystallized from ben zen e givin g 0.24 g (5%) of com poun d 4.
Compound (2b). M.p. 224–225 °C. For C20H17BrN2O2 (397.3) calculated: 7.05% N; foun d:
6.87% N. IR: 1578 (C=C), 1695 (C=O). LC-MS, m/z (rel.%): 397 (90), 399 (100) [M+]. 1H NMR:
9.25 bs, 1 H (NH-1); 7.80 bd, 3J = 3.4, 1 H (NH-3); 7.15–7.65 m , 11 H (Ar + vin yl); 5.45 d, 3J =
3.4, 1 H (H-4); 2.27 s, 3 H (CH3).
Compound (4). M.p. 246–248 °C. For C27H20Br2N2O2 (564.3) calculated: 4.96% N; foun d:
4.80% N. IR: 1578 (C=C), 1615 (C=O), 1709 (C=O). LC-MS, m/z (rel.%): 565 (100) [M+], 566
(50) [M+], 563 (30), 568 (15). 1H NMR: 9.31 bs, 1 H (NH-1); 8.01 bd, 3J = 3.2, 1 H (NH-3);
7.15–7.65 m , 17 H (Ar + vin yl); 5.52 d, 3J = 3.2, 1 H (H-4).
Eth yl 2-Oxo-4-ph en yl-6-styryl-1,2,3,4-tetrah ydropyrim idin e-5-carboxylate (3)
A solution of urea (0.23 g, 3.8 m m ol), ben zaldeh yde (0.39 m l, 3.8 m m ol), eth yl 2-acetyl-
3-oxo-5-ph en ylpen t-4-en oate (1 g, 3.8 m m ol) an d 3 drops of con cen trated HCl in EtOH (2 m l)
was refluxed for 1.5 h . After coolin g, th e precipitate of com poun d 3 was filtered off, th e
m oth er liquor was refluxed for an oth er 2 h an d th e precipitate form ed was filtered off. Total
yield 0.40 g (30%) of com poun d 3. M.p. 253–255 °C. For C21H20N2O3 (348.4) calculated:
8.04% N; foun d: 7.85% N. IR: 1602 (C=C), 1702 (C=O). 1H NMR: 9.24 bs, 1 H (NH-1); 7.93 d,
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Kolosov, Orlov, Vashchenko, Shishkina, Shishkin:
3J = 16.8, 1 H (vin yl); 7.87 bd, 3J = 3.4, 1 H (NH-3); 7.18–7.58 m , 11 H (Ar + vin yl); 5.25 d,
3J = 3.4, 1 H (H-4); 4.06 q, 3J = 7.0, 2 H (CH2); 1.14 t, 3J = 7.0, 3 H (CH3CH2).
5-Acetyl-1-eth yl-4-(4-m eth oxyph en yl)-3,4-dih ydropyrim idin -2(1H)-on e (5b)
Yield 80%. M.p. 123–124 °C. For C15H18N2O3 (274.3) calculated: 10.21% N; foun d: 9.97% N.
IR: 1642 (C=C), 1684 (C=O). 1H NMR: 7.76 s, 1 H (H-6); 7.73 bd, 3J = 3.2, 1 H (NH-3); 7.11 d,
3J = 8.4, 2 H (Ar); 6.84 d, 3J = 8.4, 2 H (Ar); 5.13 d, 3J = 3.2, 1 H (H-4); 3.4–3.7 m , 2 H (CH2);
3.70 s, 3 H (OCH3); 2.16 s, 3 H (COCH3); 1.15 t, 3J = 7.2, 3 H (CH2CH3).
Com poun ds 6a–6j. Gen eral Procedure
A solution of 5d (2.5 g, 9.7 m m ol), 4-m eth oxyben zaldeh yde (1.53 m l, 12.6 m m ol) an d po-
tassium h ydroxide (25% aqueous solution , 1.5 m l) in EtOH (11 m l) was stirred at am bien t
tem perature for 3.5 h . Th e precipitate was filtered off an d wash ed 3 tim es with EtOH (5 m l).
Com poun d 6f (2.29 g, 63%) was obtain ed. Com poun ds 6a–6e an d 6g–6j were syn th esized
sim ilarly.
1-Ethyl-5-[(2E)-3-(4-methoxyphenyl)prop-2-enoyl]-4-phenyl-3,4-dihydropyrimidin-2(1H)-one
(6a). Yield 24%. M.p. 218–220 °C. For C22H22N2O3 (362.4) calculated: 7.73% N; foun d:
7.93% N. IR: 1569 (C=C), 1689 (C=O). 1H NMR: 8.18 s, 1 H (H-6); 7.88 bd, 3J = 2.8, 1 H (NH-3);
7.69 d, 3J = 9.0, 2 H (Ar); 7.52 d, 3J = 16.0, 1 H (β-vinyl); 7.36 d, 3J = 16.0, 1 H (α-vinyl);
7.13–7.36 m , 5 H (Ph ); 6.96 d, 3J = 9.0, 2 H (Ar); 5.34 d, 3J = 2.8, 1 H (H-4); 3.78 s, 3 H
(OCH3); 3.5–3.9 m , 2 H (NCH2); 1.20 t, 3J = 7.0, 3 H (CH3CH2).
1-Ethyl-5-[(2E)-3-(4-bromophenyl)prop-2-enoyl]-4-phenyl-3,4-dihydropyrimidin-2(1H)-one (6b).
Yield 87%. M.p. 193–195 °C. For C21H19BrN2O2 (411.3) calculated: 6.81% N; foun d: 7.02% N.
IR: 1582 (C=C), 1635 (C=O), 1682 (C=O). 1H NMR: 8.23 s, 1 H (H-6); 7.91 bd, 3J = 3, 1 H
(NH-3); 7.1–7.8 m , 11 H (Ar + vin yl); 5.34 d, 3J = 3.0, 1 H (H-4); 3.4–3.8 m , 2 H (NCH2);
1.20 t, 3J = 7.0, 3 H (CH3CH2).
1-Ethyl-4-(4-methoxyphenyl)-5-[(2E)-3-(4-methoxyphenyl)prop-2-enoyl]-3,4-dihydropyrimidin-
2(1H)-one (6c). Yield 85%. M.p. 117–118 °C. For C23H24N2O4 (392.5) calculated: 7.14% N;
foun d: 7.30% N. IR: 1569 (C=C), 1602 (C=C), 1635 (C=O), 1682 (C=O). 1H NMR: 8.15 s, 1 H
(H-6); 7.81 bd, 3J = 3.0, 1 H (NH-3); 7.70 d, 3J = 8.4, 2 H (Ar); 7.52 d, 3J = 15.6, 1 H (β-vin yl);
7.36 d, 3J = 15.6, 1 H (α-vin yl); 7.16 d, 3J = 8.4, 2 H (Ar); 6.96 d, 3J = 8.4, 2 H (Ar); 6.85 d, 3J =
8.4, 2 H (Ar); 5.29 d, 3J = 3.0, 1 H (H-4); 3.4–3.8 m , 2 H (NCH2); 3.78 s, 3 H (OCH3); 3.69 s,
3 H (OCH3); 1.20 t, 3J = 7.0, 3 H (CH3CH2).
1,6-Dimethyl-5-[(2E)-3-(4-methoxyphenyl)prop-2-enoyl]-4-phenyl-3,4-dihydropyrimidin-
2(1H)-one (6d ). Yield 24%. M.p. 183–185 °C. For C22H22N2O3 (362.4) calculated: 7.73% N;
foun d: 7.99% N. IR: 1611 (C=C), 1694 (C=O). 1H NMR: 7.98 bd, 3J = 3.4, 1 H (NH-3); 7.60 d,
3J = 9.0, 2 H (Ar); 7.35 d, 3J = 16.0, 1 H (β-vin yl); 7.15–7.35 m , 5 H (Ph ); 7.03 d, 3J = 16.0, 1 H
(α-vin yl); 6.93 d, 3J = 9.0, 2 H (Ar); 5.35 d, 3J = 3.4, 1 H (H-4); 3.76 s, 3 H (OCH3); 3.1 s, 3 H
(NCH3); 2.34 s, 3 H (CH3-6).
5-Cinnamoyl-1-ethyl-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one (6e). Yield 43%. M.p.
139–141 °C. For C22H22N2O2 (346.4) calculated: 8.09% N; foun d: 8.14% N. IR: 1575 (C=C),
1689 (C=O). 1H NMR: 7.96 bd, 3J = 3.4, 1 H (NH-3); 7.60–7.70 m , 2 H (Ar); 7.15–7.45 m , 10 H
(vin yl + Ar); 5.33 d, 3J = 3.4, 1 H (H-4); 3.7–3.9 m , 1 H (NCH2); 3.5–3.7 m , 1 H (NCH2); 2.38 s,
3 H (CH3-6); 1.08 t, 3J = 7.0, 3 H (CH3CH2).
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Derivatives of 4-Aryl-3,4-dihydropyrimidin-2(1H)-ones
1227
1-Ethyl-5-[(2E)-3-(4-methoxyphenyl)prop-2-enoyl]-6-methyl-4-phenyl-3,4-dihydropyrimidin-
2(1H)-one (6f). Yield 63%. M.p. 150–152 °C. For C23H24N2O3 (376.5) calculated: 7.44% N;
foun d: 7.62% N. IR: 1597 (C=C), 1678 (C=O). MS (EI), m/z (%): 376 (M, 100). 1H NMR: 7.90 bd,
3J = 3.4, 1 H (NH-3); 7.61 d, 3J = 9.0, 2 H (Ar); 7.33 d, 3J = 16.0, 1 H (β-vin yl); 7.13–7.36 m ,
5 H (Ph ); 7.05 d, 3J = 16.0, 1 H (α-vin yl); 6.91 d, 3J = 9.0, 2 H (Ar); 5.31 d, 3J = 3.4, 1 H
(H-4); 3.77 s, 3 H (OCH3); 3.7–3.9 m , 1 H (NCH2); 3.5–3.7 m , 1 H (NCH2); 2.35 s, 3 H
(CH3-6); 1.08 t, 3J = 7.0, 3 H (CH3CH2).
5-{(2E)-3-[4-(N,N-Dimethylamino)phenyl]prop-2-enoyl}-1-ethyl-6-methyl-4-phenyl-3,4-dihydro-
pyrimidin-2(1H)-one (6g). Yield 55%. M.p. 210–212 °C. For C24H27N3O2 (389.5) calculated:
10.79% N; foun d: 11.01% N. IR: 1590 (C=C), 1695 (C=O). 1H NMR: 7.80 bd, 3J = 3.4, 1 H
(NH-3); 7.46 d, 3J = 8.0, 2 H (Ar); 7.15–7.37 m , 6 H (Ph + β-vin yl); 6.86 d, 3J = 16.0, 1 H
(α-vin yl); 6.67 d, 3J = 8.0, 2 H (Ar); 5.27 d, 3J = 3.4, 1 H (H-4); 3.7–3.9 m , 1 H (NCH2);
3.45–3.65 m , 1 H (NCH2); 2.96 s, 6 H (N(CH3)2); 2.32 s, 3 H (CH3-6); 1.08 t, 3J = 7.0, 3 H
(CH3CH2).
5-[(2E)-3-(4-Bromophenyl)prop-2-enoyl]-1-ethyl-6-methyl-4-phenyl-3,4-dihydropyrimidin-
2(1H)-one (6h ). Yield 45%. M.p. 158–160 °C. For C22H21BrN2O2 (425.3) calculated: 6.59% N;
foun d: 6.80% N. IR: 1562 (C=C), 1582 (C=C), 1635 (C=O), 1689 (C=O). 1H NMR: 7.91 bd, 3J =
3.4, 1 H (NH-3); 7.54–7.66 m , 4 H (Ar + vin yl); 7.15–7.4 m , 7 H (Ar + vin yl); 5.34 d, 3J = 3.4,
1 H (H-4); 3.5–4.0 m , 2 H (NCH2); 2.37 s, 3 H (CH3-6); 1.07 t, 3J = 7.0, 3 H (CH3CH2).
5-Cinnamoyl-1-ethyl-6-methyl-4-(4-methoxyphenyl)-3,4-dihydropyrimidin-2(1H)-one (6i). Yield
90%. M.p. 121–122 °C. For C23H24N2O3 (376.5) calculated: 7.44% N; foun d: 7.56% N. IR:
1562 (C=C), 1602 (C=C), 1642 (C=O), 1715 (C=O). 1H NMR: 7.87 bd, 3J = 3.4, 1 H (NH-3);
7.60–7.70 m , 2 H (Ar); 7.1–7.45 m , 7 H (vin yl + Ar); 6.85 d, 3J = 8.4, 2 H (Ar); 5.29 d, 3J =
3.4, 1 H (H-4); 3.4–3.9 m , 2 H (NCH2); 3.67 s, 3 H (OCH3); 2.37 s, 3 H (CH3-6); 1.09 t, 3J = 7.0,
3 H (CH3CH2).
1-Ethyl-5-[(2E)-3-(4-methoxyphenyl)prop-2-enoyl]-4-(4-methoxyphenyl)-6-methyl-3,4-dihydro-
pyrimidin-2(1H)-one (6j). Yield 19%. Oil, purified by colum n ch rom atograph y (150 g of Al2O3
(60–100 µm ), eluted with octan e–eth yl acetate 2:1, 500 m l; 1:2, 500 m l; EtOAc, 500 m l). IR:
1569 (C=C), 1689 (C=O). 1H NMR: 7.82 bd, 3J = 3.4, 1 H (NH-3); 7.60 d, 3J = 9.0, 2 H (Ar);
7.34 d, 3J = 16.0, 1 H (β-vin yl); 7.15 d, 3J = 8.0, 2 H (Ar); 7.02 d, 3J = 16.0, 1 H (α-vin yl);
6.93 d, 3J = 9.0, 2 H (Ar); 6.84 d, 3J = 9.0, 2 H (Ar); 5.27 d, 3J = 3.4, 1 H (H-4); 3.77 s, 3 H
(OCH3); 3.68 s, 3 H (OCH3); 3.7–3.9 m , 1 H (NCH2); 3.5–3.7 m , 1 H (NCH2); 2.35 s, 3 H
(CH3-6); 1.08 t, 3J = 7.0, 3 H (CH3CH2).
3-Acetyl-1-eth yl-5-[(2E)-3-(4-m eth oxyph en yl)prop-2-en oyl]-6-m eth yl-4-ph en yl-3,4-dih ydro-
pyrim idin -2(1H)-on e (7)
A solution of 6f (0.4 g, 1.0 m m ol) in Ac2O (3 m l) was refluxed for 3 h . After coolin g, water
(20 m l) was added an d th e precipitate form ed was crystallized from MeOH to give 0.23 g
(52%) of com poun d 7. M.p. 125 °C. For C25H26N2O4 (418.5) calculated: 6.69% N; foun d:
7.05% N. IR: 1509 (C=C), 1702 (C=O). 1H NMR: 7.65 d, 3J = 9.0, 2 H (Ar); 7.50 d, 3J = 16.0,
1 H (β-vin yl); 7.12–7.38 m , 5 H (Ph ); 7.07 d, 3J = 16.0, 1 H (α-vin yl); 6.97 d, 3J = 9.0, 2 H (Ar);
6.50 s, 1 H (H-4); 3.78 s, 3 H (OCH3); 3.74–4.04 m , 1 H (NCH2); 3.38–3.66 m , 1 H (NCH2);
2.42 s, 3 H (COCH3); 2.37 s, 3 H (CH3-6); 1.0 t, 3J = 7.0, 3 H (CH3CH2).
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1228
Kolosov, Orlov, Vashchenko, Shishkina, Shishkin:
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