Alkylation and acylation of 1-(4-phenylaminophenyl)-dihydropyrimidine-2,4-(1H,3H)-diones

Article abstract of DOI:10.1023/A:1020694006778

The C- and N-substituted derivatives of 1-(4-phenylaminophenyl)dihydropyrimidine-2,4-(1H,3H)-diones have been obtained by alkylation and acylation. The secondary amino group takes part in the acylation. The secondary amino group takes part in the acylation reaction, before the amide group of the heterocycle.

Full text of DOI:10.1023/A:1020694006778

Chemistry of Heterocyclic Compounds, Vol. 38, No. 7, 2002
ALKYLATION AND ACYLATION
OF 1-(4-PHENYLAMINOPHENYL)-
DIHYDROPYRIMIDINE-2,4-(1H,3H)-DIONES
K. Rutkauskas and Z.-I. Beresnevicius
The C- and N-substituted derivatives of 1-(4-phenylaminophenyl)dihydropyrimidine-2,4-(1H,3H)-diones
have been obtained by alkylation and acylation. The secondary amino group takes part in the acylation
reaction, before the amide group of the heterocycle.
Keywords: pyrimidinediones, alkylation, acylation.
The presence of a heterocyclic and two aromatic rings and also a secondary amino group in
1-(4-phenylaminophenyl)dihydropyrimidine-2,4-(1H,3H)-dione (1) makes it an interesting subject for
electrophilic substitution reactions. It was shown by us in [1] that the course of the bromination reaction also
depends on the methyl groups in positions 5 or 6 of the heterocycle.
In continuation of the study [2] of the alkylation of pyrimidinedione derivatives, we have carried out the
alkylation and acylation of compounds 1 in the present work.
N(3)-Alkylation occurs on reacting compound 1 with dimethyl sulfate in the presence of an equivalent
of NaOH or KOH at room temperature, and products 2 are formed in yields up to 90%. Alkylation with methyl
iodide occurs with far more difficulty and with lower yields of reaction products.
The absorption band of the amide group at 3228 cm-1, which is well evident in the spectra of compounds
1
1, was absent from the IR spectra of compounds 2. In the H NMR spectra the protons of the methyl group at
N(3) appeared as singlets at 3.10-3.28 ppm. The singlet of the proton of the unsubstituted amide group of the
heterocycle of the initial compounds 1 was detected in the range 7.6-7.8 ppm.
Alkylation of the aromatic part of compounds 1 was carried out with alcohols using acids as
solvent. Reaction with isopropyl alcohol and with cyclohexanol occurs readily in sulfuric and orthophosphoric
acids and leads to the formation of the alkyl derivatives 3 and 4 in good yield. In the case of alkylation with
tertiary butyl alcohol, reaction was continued for 40 h in orthophosphoric acid. In sulfuric acid resinification
occurred and the yield did not exceed 30%. The best results of alkylation with tert-butyl alcohol were
achieved on carrying out the reaction in trifluoroacetic acid. The tert-butyl derivatives 5 were isolated in
77-88% yield.
The dialkyl derivative 6a was obtained by the alkylation of N(3)-methyldihydropyrimidinedione 2a with
tert-butyl alcohol in trifluoroacetic acid and by the action of dimethyl sulfate or methyl iodide in the presence of
KOH on the 4-tert-butyl derivative 5a.
__________________________________________________________________________________________
Kaunas
Technological
University,
Kaunas
LT-3028,
Lithuania;
e-mail:
zigmuntas.beresnevicius@ctf.ktu.lt. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7,
pp. 955-960, July, 2002. Original article submitted February 11, 2002.
846
0009-3122/02/3807-0846$27.00©2002 Plenum Publishing Corporation

R3
N
COR4
NH
N
NH
N
R2
R1
R2
R1
N
O
O
COR4
R2
R1
O
O
N
NH
NH
O
O
1a–c
3a–c – 5a–c
9, 10a,b
R3
R3
N
COR4
NH
NH
N
R2
R1
R2
R1
N
O
O
R2
R1
N
O
O
O
NH
N Me
N Me
O
2a–c
7a–c, 8a–c, 11
6a,c
2a-8a, 9, 10a, 11 R1 = R2 = H; 3b-5b, 7b, 8b, 10b R1 = Me, R2 = H; 2c-8c R1 = H, R2 = Me;
3a-c R3 = Me2CH; 4a-c R3 = C6H11; 5a-c 6a,c, 11 R3 = Me3C; 7a-c, 8a-c R3 = H;
7a-c, 10a,b, 11 R4 = Me; 8a-c, 9 R4 = Ph
There were two overlapping quartets of phenylene protons in the 1H NMR spectra of compounds 3 and
5 at 6.9-7.2 ppm and signals for the methyl or cyclohexyl fragments appeared at high field.
The secondary aromatic amino group proved to be the more reactive in the acylation of compounds 1.
Compounds 7 and 8 were formed on reaction of an equivalent amount of acetyl chloride on compound 1 in
pyridine solution. On acylation with acetic anhydride substitution takes place at the N(3) of the heterocycle and
diacyl derivatives 9 and 10a,b are formed. The singlet of the secondary amino group at 8 ppm was absent from
1
the H NMR spectra of compounds 7 and 8, but a singlet was observed at 10 ppm for the amide group. In the
monoacetylated derivatives 7 there was a singlet for the protons of the acetyl group at 1.9 ppm. The presence of
a benzoyl group in compounds 8 was confirmed by the integral curve corresponding to 14 protons at 6-7 ppm.
1
The signal for the proton of the amide group of the heterocycle was absent from the H NMR spectra of the
diacyl derivatives 9 and 10.
The N-acetyl derivative 11 was formed on boiling 1-[4-(tert-butylphenylamino)phenyl]-
dihydropyrimidine-2,4-(1H,3H)-dione (4a) with an equivalent quantity of acetyl chloride in pyridine for 4 h.
847

EXPERIMENTAL
1
The IR spectra were taken on a UR 20 instrument (KBr disks). The H NMR spectra were obtained on
Bruker AW 80 (80 MHz), Tesla BS-487 (80 MHz), and Jeol FX 100 (100 MHz) instruments, internal standard
was HMDS. A check on the progress of reactions and the purity of the compounds obtained was effected by
TLC on Silufol UV 254 plates.
3-Methyl-1-(4-phenylaminophenyl)dihydropyrimidine-2,4-(1H,3H)-dione (2a). Dimethyl sulfate
(23 ml, 24 mmol) was added to a boiling mixture of dihydrouracil 1a (14.05 g, 50 mmol), 10% NaOH (100 ml),
and 1,4-dioxane (200 ml). The reaction mixture was left for 28 h at room temperature, diluted with water
(100 ml), and acidified with HCl to an acid reaction with Congo Red. Yield 8.2 g (55.6%); mp 203-204°C
(2-propanol). 1H NMR spectrum (CF3COOH), δ, ppm, J (Hz): 2.75 (2H, t, J = 6, CH2CO); 2.97 (3H, s, NCH3);
3.60 (2H, t, J = 6, NCH2); 6.93-7.50 (9H, m, ArH). Found, %: C 69.7; H 5.8; N 13.6. C17H17N3O2.
Calculated, %: C 69.2; H 5.8; N 14.9.
3,5-Dimethyl-1-(4-phenylaminophenyl)dihydropyrimidine-2,4-(1H,3H)-dione (2b) was obtained
from 5-methyldihydrouracil 1b (14.76 g, 50 mmol), 10% NaOH (50 ml), 1,4-dioxane (150 ml), and dimethyl
1
sulfate (15 ml, 210 mmol) in a similar manner to 2a. Yield 10.5 g (75%); mp 155-156°C (ethanol). H NMR
spectrum (CDCl3), δ, ppm: 1.07 (3H, d, 5-CH3); 2.00-3.11 (2H, m, CH2); 3.18 (3H, s, N-CH3); 3.40-4.00 (1H, m,
CH); 5.60-6.00 (1H, m, 1NH); 6.63-7.37 (9H, ArH). Found, %: C 69.9; H 6.7; N 13.9. C18H19N3O2.
Calculated, %: C 70.3; H 6.3; N 13.6.
3,6-Dimethyl-1-(4-phenylaminophenyl)dihydropyrimidine-2,4-(1H,3H)-dione (2c) was obtained
from 6-methyldihydrouracil 1c (14.76 g, 50 mmol), 10% NaOH (50 ml), 1,4-dioxane (150 ml), and dimethyl
sulfate (15 ml, 210 mmol) analogously to compound 2a. Yield 10.5 g (75%); mp 155-156°C (ethanol). 1H NMR
spectrum (CDCl3), δ, ppm: 1.07 (3H, d, 6-CH3); 2.00-3.11 (2H, m, CH2CO); 3.18 (3H, s, N-CH3); 3.40-4.00
(1H, m, CH); 5.60-6.00 (1H, m, 1NH); 6.63-7.37 (9H, m, ArH). Found, %: C 69.9; H 6.2; N 13.6. C18H19N3O2.
Calculated, %: C 70.3; H 6.3; N 13.6.
1-[4-(4-Isopropylphenylamino)phenyl]dihydropyrimidine-2,4-(1H,3H)-dione (3a). 2-Propanol
(2 ml) was added with stirring to a solution of pyrimidinedione 1a (7.0 g, 12.5 mmol) in 80% sulfuric acid
(50 ml) at 80°C, and heating was continued for 24 h. The reaction mixture was poured into cold water (200 ml).
1
The precipitated solid was filtered off. Yield 2.7 g (32.5%); mp 250-251°C (ethanol). H NMR spectrum
(CF3COOH), δ, ppm, J (Hz): 0.5-1.0 (6H, m, 2CH3); 2.68 (2H, t, J = 6, CH2CO); 3.68 (2H, t, J = 6, CH2N); 7.06
(4H, d, J = 8, ArH); 7.21 (4H, d, J = 4, ArH); 9.37 (1H, s, 1NH). Found, %: C 70.6; H 6.4; N 12.8. C17H21N3O2.
Calculated, %: C 70.6; H 6.6; N 13.0.
1-[4-(4-Isopropylphenylamino)phenyl]-5-methyldihydropyrimidine-2,4-(1H,3H)-dione (3b). 2-Propanol
(2.5 ml) was poured with stirring into a solution of 5-methyldihydrouracil 1b (1.52 g, 5 mmol) in 80% sulfuric
acid (80 ml), and the mixture was heated at 80°C for 30 h. The reaction mixture was cooled, poured into water
(100 ml), and neutralized with ammonia. The solid was filtered off, and crystallized from a mixture of
chloroform–hexane, 1:5. Yield 0.89 g (51%); mp 179-180°C (ethanol). 1H NMR spectrum (CDCl3+CF3COOH),
δ, ppm, J (Hz): 0.82 (3H, d, J = 6, CH3); 1.10-1.40 (6H, m, 2CH3); 2.82-3.20 (1H, m, CH); 3.80-4.00 (2H, m,
CH2); 7.21-7.60 (9H, m, ArH); 9.38 (1H, s, NH). Found, %: N 12.71. C20H23N3O2. Calculated, %: N 12.46.
1-[4-(4-Isopropylphenylamino)phenyl]-6-methyldihydropyrimidine-2,4-(1H,3H)-dione (3c).
2-Propanol (2 ml) was added to a solution of 6-methyldihydrouracil 1c (1.52 g, 5 mmol) in 80% sulfuric acid
(80 ml) with stirring and heating to 80°C. The product was isolated analogously to compound 1b. Yield 1.38 g
(81%); mp 160-161°C (ethanol). 1H NMR spectrum (CDCl3), δ, ppm, J (Hz): 0.96 (3H, d, J = 7, CH3); 1.34-1.75
(6H, m, 2CH3); 2.37-3.01 (3H, m, CH2, CH); 5.82-6.10 (1H, m, 1NH); 6.75-7.50 (8H, m, ArH). Found, %:
N 12.52. C20H23N3O2. Calculated, %: N 12.46.
848

1-[4-(4-Cyclohexylphenylamino)phenyl]dihydropyrimidine-2,4-(1H,3H)-dione (4a). Cyclohexanol
(15 ml) was added to a solution of dihydrouracil 1a (14.2 g, 50 mmol) in 80% orthophosphoric acid (100 ml)
with stirring and heating to 80°C and the mixture heated for 50 h. The reaction mixture was poured into water
1
(200 ml). Yield 3.6 g (19.8%); mp 148.5-149.5°C (ethanol). H NMR spectrum (CDCl3), δ, ppm, J (Hz):
1.20-1.94 (14H, m, cyclohexyl, CH3); 2.75 (2H, t, J = 6, CH2CO); 3.75 (2H, t, J = 6, NCH2); 5.10-6.80 (1H, m,
1NH); 6.75-7.25 (8H, m, ArH); 8.0 (1H, br. s, 1NH). Found, %: C 73.01; H 7.1; N 11.8. C22H25N3O2.
Calculated, %: C 72.8; H 6.9; N 11.6.
1-[4-(4-Cyclohexylphenylamino)phenyl]-5-methyldihydropyrimidine-2,4-(1H,3H)-dione (4b).
Cyclohexanol (3 ml) was added to a solution of 5-methyldihydrouracil 1b (1.42 g, 5 mmol) in 80% sulfuric acid
(80 ml) with stirring and the mixture was heated for 30 h at 80°C. The product was isolated analogously to
1
compound 4a. Yield 0.8 g (42.44%); mp 114-115.6°C (ethanol). H NMR spectrum (CDCl3), δ, ppm: 1.1-2.1
(14H, m, cyclohexyl, CH3); 2.80 (1H, s, CH); 3.10-3.90 (2H, m, CH2); 6.80-7.30 (9H, ArH, 1NH); 9.70 (1H, s,
1NH). Found, %: N 11.35. C23H27N3O2. Calculated, %: N 11.14.
1-[4-(4-Cyclohexylphenylamino)phenyl]-6-methyldihydropyrimidine-2,4-(1H,3H)-dione (4c).
Cyclohexanol (3 ml) was added with stirring to a solution of 6-methyldihydrouracil 1c (1.42 g, 5 mmol) in 80%
sulfuric acid (80 ml). The product was isolated analogously to compound 4a. Yield 0.8 g (42.44%);
1
mp 160-161°C (ethanol). H NMR spectrum (CDCl3), δ, ppm: 1.20-1.94 (14H, cyclohexyl, CH3); 2.52-3.145
(2H, m, AB portion of ABX system, CH2); 3.675-4.125 (1H, m, CH); 7.00-7.70 (8H, two overlapping quartets,
ArH); 7.90 (1H, s, 1NH). Found, %: N 11.31. C23H27N3O2. Calculated, %: N 11.14.
tert
A solution of
1-[4-(4- -Butylphenylamino)phenyl]dihydropyrimidine-2,4-(1H,3H)-dione (5a).
dihydrouracil 1a (2.82 g, 10 mmol), tert-butyl alcohol (10 ml, 100 mmol), and trifluoroacetic acid (14 ml) was
boiled for 3 h. The reaction mixture was poured into cold water (100 ml). Yield 2.9 g (87.7%); mp 190-191.5°C
(ethanol). 1H NMR spectrum (DMSO-d6), δ, ppm, J (Hz): 1.22 (9H, s, 3CH3); 2.65 (2H, t, J = 6, CH2CO); 3.70
(2H, t, J = 6, NCH2); 6.88-7.15 (8H, m, ArH); 7.80 (1H, s, NH); 9.86 (1H, s, NHCO). Found, %: N 13.02.
C19H22N3O2. Calculated, %: N 12.95.
tert
1-[4-(4- -Butylphenylamino)phenyl]-5-methyldihydropyrimidine-2,4-(1H,3H)-dione (5b).
A
solution of 5-methyldihydrouracil 1b (2.95 g, 10 mmol) in tert-butyl alcohol (10 ml, 100 mmol) and
trifluoroacetic acid (14 ml) was boiled for 3 h. The product was isolated analogously to compound 5a.
Yield 2.71 g (78.88%); mp 213-214°C (ethanol). 1H NMR spectrum (acetic acid-d4), δ, ppm, J (Hz): 1.17 (3H, d,
J = 6.4, CH3); 1.29 (9H, s, 3CH3); 2.72-3.12 (1H, m, CH); 3.52-3.80 (2H, m, CH2, AB portion of ABX system);
6.80-7.30 (8H, two overlapping quartets, ArH); 9.00 (1H, s, NH). Found, %: N 12.31. C20H24N3O2.
Calculated, %: N 12.42.
tert
1-[4-(4- -Butylphenylamino)phenyl]-6-methyldihydropyrimidine-2,4-(1H,3H)-dione (5c).
A
solution of 6-methyldihydrouracil 1c (2.95 g, 10 mmol) in tert-butyl alcohol (10 ml, 100 mmol) and
trifluoroacetic acid (14 ml) was boiled for 3 h. The product was isolated analogously to compound 5a. Yield
2.64 g (78.1%); mp 226-227°C (ethanol). 1H NMR spectrum (acetone-d6), δ, ppm, J (Hz): 1.30 (3H, d, J = 6.4,
CH3); 2.50-3.30 (2H, m, CH2); 3.90-4.20 (1H, br. s, NH); 7.00-7.50 (8H, m, ArH). Found, %: N 12.30.
C20H24N3O2. Calculated, %: N 12.42.
tert
Dimethyl
1-[4-(4- -Butylphenylamino)phenyl]-3-methyldihydropyrimidine-2,4-(1H,3H)-dione (6a).
sulfate (2.6 ml, 8 mmol) was added to a mixture of compound 5a (1.6 g, 5.7 mmol), 10% NaOH (10 ml), and
1,4-dioxane (20 ml) at the boiling point. The mixture was boiled for 3 h and left for 28 h at room temperature.
The liquid fraction was distilled off on a rotary evaporator. The oily mass was diluted with water (~1:3), and the
1
crystals obtained were filtered off. Yield 1.1 g (55%); mp 68.5-70°C (chloroform–hexane, 1:3). H NMR
spectrum (acetone-d6), δ, ppm, J (Hz): 1.26 (9H, s, 3CH3); 2.86 (2H, t, J = 8, COCH2); 3.06 (3H, s, N-CH3);
3.78 (2H, t, J = 8, N-CH2); 4.75-5.50 (1H, br. s, 1NH); 6.80-7.50 (8H, m, ArH). Found, %: N 11.85.
C21H25N3O2. Calculated, %: N 11.96.
849

tert
1-[4-(4- -Butylphenylamino)phenyl]-3,6-dimethyldihydropyrimidine-2,4-(1H,3H)-dione
(6c).
Dimethyl sulfate (2.6 ml, 8 mmol) was added to a mixture of compound 5c (1.69 g, 5 mmol), 10% NaOH
(10 ml), and 1,4-dioxane (20 ml) at the boiling point. The mixture was boiled for 3 h, left for 28 h at room
temperature, then diluted with water. The solution was acidified with HCl to an acid reaction to Congo Red.
1
Yield 1.65 g (87.1%); mp 118-119°C (chloroform–hexane, 1:3). H NMR spectrum (acetone-D6), δ, ppm,
J, (Hz): 1.13 (3H, d, J = 6.6, CH3); 1.27 (9H, s, 3CH3); νa 2.54, νb 3.13, JAX = -3.9, JBX = 6.1, J = 16.5 or νa 3.76,
νb 2.75 ppm, JAX = 48.0, JBX = 58.4, J = 16.5 (2H, AB portion of ABX system); 3.09 (3H, s, N-CH3); 3.80-4.10
(1H, br. s, 1H); 6.90-7.50 (9H, m, ArH). Found, %: N 11.63. C22H27N3O2. Calculated, %: N 11.55.
3-[N-Acetyl-(4-phenylaminophenyl)]dihydropyrimidine-2,4-(1H,3H)-dione (7a). Acetyl chloride
(1.96 g, 25 mmol) was added to a mixture of dihydrouracil 1a (2.82 g, 10 mmol) in pyridine (25 ml) at the
boiling point and the mixture was boiled for 6 h. The reaction mixture was left at room temperature for 12 h and
then filtered. The filtrate was diluted with water (~1 : 3). The precipitated solid was filtered off, washed with
1
water, and with 2-propanol. Yield 0.9 g (27.8%); mp 248-249°C (ethanol). H NMR spectrum (CF3COOH),
δ, ppm: 1.94 (3H, s, COCH3); 2.55-2.90 (2H, m, CH2CO); 3.50-3.80 (2H, m, NCH2); 6.90-7.50 (9H, m, ArH);
9.15 (1H, s, 1NH). Found, %: N 13.50. C18H17N3O2. Calculated, %: N 13.67.
1-[N-Acetyl-(4-phenylaminophenyl)]-5-methyldihydropyrimidine-2,4-(1H,3H)-dione (7b) was
obtained from 5-methyldihydrouracil 1b (5.9 g, 20 mmol), acetyl chloride (5.3 g, 75 mmol), and pyridine
1
(25 ml) analogously to compound 7a. Yield 5.8 g (84.7%); mp 178-179°C (2-propanol). H NMR spectrum
(DMSO-d6), δ, ppm, J (Hz): 1.04 (3H, d, J = 8, 5-CH3); 1.68 (3H, s, NCH3); 2.57-3.00 (1H, m, CH); 3.50-3.75
(2H, m, NCH2); 7.32 (9H, ArH); 10.40 (1H, s, 1NH). Found, %: N 10.65. C24H21N3O2. Calculated, %: N 10.95.
1-[N-Benzoyl-(4-phenylaminophenyl)]dihydropyrimidine-2,4-(1H,3H)-dione (8a) was obtained
from dihydrouracil 1a (14 g, 50 mmol) and benzoyl chloride (7.8 g, 70 mmol) in pyridine (25 ml) analogously to
1
compound 7a. Yield 11.2 g (58.4%); mp 256-257°C (methyl ethyl ketone). H NMR spectrum (CF3COOH),
δ, ppm: 2.65 (2H, t, CH2CO); 3.67 (2H, t, NCH2); 6.87-8.00 (14H, m, ArH); 9.12 (1H, s, 1NH). Found, %:
N 10.81. C23H19N3O3. Calculated, %: N 10.90.
1-[N-Benzoyl-(4-phenylaminophenyl)]-5-methyldihydropyrimidine-2,4-(1H,3H)-dione (8b) was
obtained from 5-methyldihydrouracil 1b (14 g, 50 mmol) and benzoyl chloride (7.8 g, 70 mmol) in pyridine
1
(25 ml) analogously to compound 7a. Yield 10.6 g (50.5%); mp 216-217°C (2-propanol). H NMR spectrum
(CF3COOH), δ, ppm, J (Hz): 0.95 (3H, two d, J = 8, J = 3); 2.50-2.75 (1H, m, CH); 3.30-3.70 (2H, m, CH2);
6.25-7.75 (14H, m, ArH). Found, %: N 10.61. C24H21N3O3. Calculated, %: N 10.52.
1-[N-Benzoyl-(4-phenylaminophenyl)]-6-methyldihydropyrimidine-2,4-(1H,3H)-dione (8c) was
obtained from 6-methyldihydrouracil 1c (7.4 g, 25 mmol) and benzoyl chloride (11.25 g, 100 mmol)
1
analogously to compound 8a. Yield 5.9 g (60%); mp 207-208°C (toluene). H NMR spectrum (CF3COOH),
δ, ppm, J (Hz): 0.87 (3H, d, J = 3, CH3); 2.37-2.88 (2H, AB portion of ABX system, J = 18, J = 8.6); 3.60-4.00
(1H, m, CH); 6.25-7.50 (14H, m, ArH); 9.12 (1H, s, 1NH). Found, %: N 10.35. C24H21N3O3. Calculated, %:
N 10.52.
3-Benzoyl-[N-benzoyl-(4-phenylaminophenyl)]dihydropyrimidine-2,4-(1H,3H)-dione (9). A
mixture of dihydrouracil 1a (2.8 g, 10 mmol) and benzoyl chloride (11.54 ml, 100 mmol) in pyridine (25 ml)
was boiled for 24 h. The reaction mixture was cooled, and poured into cold water (150 ml). The precipitated
oily mass was separated and washed with water. The mass crystallized on standing. Yield 2.5 g (51.0%);
1
mp 205-206.5°C (a 2-propanol–water mixture). H NMR spectrum (DMSO-d6), δ, ppm, J (Hz): 2.42 (2H, t,
J = 6, COCH2); 3.40 (2H, t, J = 6, NCH2); 6.50-7.20 (19H, m, ArH). Found, %: C 73.61; N 8.71. C30H23N3O4.
Calculated, %: C 73.50; N 8.58.
3-Acetyl-1-[N-acetyl-(4-phenylaminophenyl)]dihydropyrimidine-2,4-(1H,3H)-dione (10a). A
mixture of dihydrouracil 1a (5.06 g, 20 mmol), acetic anhydride (23 ml), and potassium acetate (5 g, 50 mmol)
was heated at 60°C for 6 h. After heating the mixture was stored for 24 h, and poured into cold water (150 ml).
1
Yield 3 g (41%); mp 117-118°C (a mixture of chloroform–hexane, 1:5). H NMR spectrum (acetic acid-d4),
850

δ, ppm, J (Hz): 2.087 (3H, s, COCH3); 2.14 (3H, s, COCH3); 2.85 (2H, t, J = 7, COCH2); 3.87 (2H, t, J = 6.6,
NCH2); 7.40 (8H, m, ArH). Found, %: C 65.81; H 5.14; N 11.26. C20H19N3O4. Calculated, %: C 65.74; H 5.24;
N 11.50.
3-Acetyl-1-[N-acetyl-(4-phenylaminophenyl)]-5-methyldihydropyrimidine-2,4-(1H,3H)-dione (10b)
was obtained from 5-methyldihydrouracil 1b (2.95 g, 10 mmol), potassium acetate (4 g, 40 mmol), and acetic
anhydride (20 ml) analogously to compound 10a. Yield 1.8 g (47.6%); mp 172-173.5°C (chloroform–hexane).
1H NMR spectrum (acetic acid-d4), δ, ppm: 1.32 (3H, d, J = 10 Hz); 2.00 (3H, s, CH3); 2.09 (3H, s, CH3);
2.72-3.01 (1H, m, CH); 6.8-7.4 (8H, m, ArH). Found, %: H 5.63; N 11.35. C21H21N3O4. Calculated, %: H 5.55;
N 11.08.
tert
Acetyl
1-[4-(N-Acetyl-4- -butylphenylamino)phenyl]dihydropyrimidine-2,4-(1H,3H)-dione (11).
chloride (1.96 g, 25 mmol) was added at the boiling point to a mixture of compound 5a (1.67 g, 5 mmol) and
pyridine (13 ml), and the mixture boiled for 4 h. The reaction mixture was left at room temperature for 12 h and
filtered. The filtrate was diluted with water (~1:3), and the solid filtered off. Yield 0.8 g (47.47%);
1
mp 110-111°C (ethanol–water). H NMR spectrum (acetic acid-d4), δ, ppm, J (Hz): 2.51 (2H, t, J = 9.7,
COCH2); 2.61 (3H, s, COCH3); 3.52 (3H, s, NCH3); 3.82 (2H, t, J = 7.5, NCH2); 7.00-7.50 (9H, m, ArH).
Found, %: C 67.76; N 12.53. C19H19N3O3. Calculated, %: C 67.64; N 12.46.
REFERENCES
1.
2.
K. Rutkauskas and Z.-I. Beresnevichyus, Chemija, 1, 65 (1997).
K. Kantminiene, Z. Beresnevicius, G. Mikulskiene, J. Kilberg, and J. Braddefalk, J. Chem. Res.
(Synop.), 1, 16 (1999).
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