Quinazolines. 2*. unsymmetric 1,3-dialkyl-6-chlorosulfonyl- quinazoline-2,4-diones in nucleo- philic substitution reactions

Article abstract of DOI:10.1007/s10593-010-0458-5

The corresponding 6-chlorosulfonylquinazoline-2,4-diones were synthesized by the reactions of 1-methylquinazoline-2,4-dione and its 3-alkyl-substituted derivatives with chlorosulfonic acid. Treatment of the products with nucleophilic agents (water or ammo

Full text of DOI:10.1007/s10593-010-0458-5

Chemistry of Heterocyclic Compounds, Vol. 45, No. 12, 2009
QUINAZOLINES. 2*. UNSYMMETRIC
1,3-DIALKYL-6-CHLOROSULFONYL-
QUINAZOLINE-2,4-DIONES IN NUCLEO-
PHILIC SUBSTITUTION REACTIONS
R. Sh. Kuryazov1, N. S. Mukhamedov1*, and Kh. M. Shakhidoyatov1
The corresponding 6-chlorosulfonylquinazoline-2,4-diones were synthesized by the reactions of
1-methylquinazoline-2,4-dione and its 3-alkyl-substituted derivatives with chlorosulfonic acid.
Treatment of the products with nucleophilic agents (water or ammonia, aliphatic and cyclic amines)
gave 2,4-dioxoquinazolin-6-sulfonic acids or their amides.
Keywords: amides of 2,4-dioxoquinazoline-6-sulfonic acid, 2,4-dioxoquinaxoline-6-sulfonic acids,
unsymmetrical 1,3-dialkylquinazoline-2,4-diones, 6-chlorosulfonylquinazoline-2,4-diones, nucleophilic
and electrophilic substitution.
High biological activity and the wide spectrum of activity of derivatives of quinazoline [2-7] has
resulted in a considerable interest in them. Recently we carried out the chlorosulfonation of symmetrical
1,3-dialkylquinazoline-2,4-diones and studied some chemical conversions of the 6-chlorosulfonyl derivatives
produced [1]. In a continuation of our study on the electrophilic substitution of this series of compounds we
have studied the chlorosulfonation of unsymmetrical 1-methylquinazoline-2,4-dione (1) and its 3-alkyl-
substituted derivatives 2a,b and also the behavior of the 6-chlorosulfonyl derivatives 3a-c obtained with respect
to nucleophilic reagents.
The starting compound was not successfully obtained by direct alkylation of quinazoline-2,4-dione
because of the formation of a complex mixture of products, so it was made by cyclization of N-methyl-
anthranilic acid (4) with sodium cyanate in basic media. Unsymmetrical 3-alkyl-1-methylquinazoline-
2,4-diones 2a,b were synthesized by subsequent alkylation of compound 1 with alkyl iodides in conditions of
phase-transfer catalysis [8].
We have shown that, like the symmetrical 1,3-dialkylquinazoline-2,4-diones [1], their unsymmetrical
analogs 1 and 2a,b reacted with chlorosulfonic acid to give the corresponding 6-chlorosulfonyl derivatives 3a-c.
The intermediate 2,4-dioxoquinazoline-6-sulfonic acids 5a-c were not isolated, despite variation in the
composition of the reagents and the conditions of the reaction.
_______
* For Communication 1 see [1].
** To whom correspondence should be addressed, e-mail: nasirxon@rambler.ru.
1Acad. S. Yu. Yunusov Institute of Vegetable the Chemistry of Plant Substances, Academy of Sciences of the
Republic of Uzbekistan, Tashkent 100170, Republic of Uzbekistan.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, 1870-1877, December, 2009.
Original article received October 17, 2008. Revised version received March 17, 2009.
1508
0009-3122/09/4512-1508©2009 Springer Science+Business Media, Inc.

O
O
R
RI
N
NHMe
COOH
NH
NaNCO
NaOH
NaOH,
Bu4NBr
N
O
N
O
Me
2a,b
4
Me
1
ClSO3H
ClSO3H
O
O
N
R1
R1
O
HO S
O
O
O
H2O
ClSO3H
R
R1
O
HN
R
Cl S
O
N
R
N S
O
N
R1
O
N
O
N
O
N
5a–c
Me
3a–c
Me
Me
6a–c, 7a–f, 8a–f
2 a R = n-Pr, b R = n-Bu; 3, 5 a R = H, b R = n-Pr, c R = n-Bu; 6a–c R1 = H, a R = H,
b R = n-Pr, c R = n-Bu; 7, 8 a, d R = H, b, e R = n-Pr, c, f R = n-Bu; 7a–c R1 = Et,
d–f R1 = n-Bu; 8 a–c R1 + R1=(CH2)5, d–f R1 + R1=(CH2)2O(CH2)2
The sulfonic acids 5a-c were synthesized in high yields (Table 1) by hydrolysis of the corresponding
6-sulfonyl chlorides 3a-c. It was established that the rate of hydrolysis depended on the substituent R. For
example, if it was sufficient for conversion of the sulfonyl chloride 3a (R =H) into the sulfonic acid 5a to heat
the reaction mixture for 2 h, hydrolysis of compounds 3b,c (b R = n-Pr, c R = n-Bu) required 4 and 6 h
respectively.
The sulfonic acids 5a-c were easily converted into the corresponding chlorosulfonyl derivatives 3a-c in
almost quantitative yields by treatment with chlorosulfonic acid.
The reactions of compounds 3a-c with ammonia, aliphatic and cyclic amines occurred readily and did
not depend on the substituent R. Treatment of the sulfonyl chlorides 3a-c with a concentrated aqueous solution
of ammonia led to the corresponding 6-sulfamidoquinazoline-2,4-diones 6a-c. On reaction of compounds 3a-c
with aliphatic amines in the presence of triethylamine at room temperature N,N-dialkylamides of 2,4-dioxo-
6-sulfonic acids 7a-f were formed and with piperidine and morpholine the N-piperidino- and N-morpholino-
substituted amides 8a-f of the same acids respectively were formed.
The compositions and structures of compounds 3, 5-8 were confirmed by IR and 1H NMR spectroscopy,
mass spectrometry, and the results of elemental analysis.
In the IR spectra of compounds 3, 5-8 there are bands characteristic of absorptions of asymmetric and
symmetric vibrations of the SO2 group in the 1100-1400 cm-1 region. In the case of the sulfonic acids 5a-c there
are also bands for the absorption of the stretching of the S-O group (600-700 cm-1 (Table 2).
In the mass spectra of the quinazolinediones 3, 5-8 there are peaks of the molecular ions and fragments
which completely confirm the proposed structure. Independent of the nature of the substituent R and the
character of the amide substituent, these spectra show a uniform fragmentation with rupture of the SO2-N(R1)2
bond and the formation of fragments A [M+-N(R1)2] and B [N(R1)2].
It should be noted that in the case of compounds 6a-c and 8a-c the molecular ion M+ is the maximum
peak, whereas in the compounds 7a-f and 8d-f it is the peak for fragment A. In the case of fragmentation the
sulfonic chloride 3a with no substituent at position 3, rupture of the S-Cl bond occurs whereas in the alkylated
derivatives 3b,c the 3-R substituent is lost.
1509

+
O
R1
R1
O
S
R
N
N
O
O
N
Me
B
A
6–8
TABLE 1. Physicochemical Characteristics of the Compounds
Synthesized, 3, 5-8
Com-
pound
Empirical
formula
Found, %
Calculated, %
mp °C (solvent
for recrystallization)
——————
Yield, %
3a
3b
3c
5a
5b
5c
6a
6b
6c
7a
7b
7c
7d
7e
7f
C9H7ClN2O4S
C12H13ClN2O4S
C13H15ClN2O4S
C9H8N2O5S
208-210
(heptane)
86*
88*
94*
96
88
85
41
76
86
89
94
83
89
90
86
90
70
87
80
91
98
9.87
10.20
136-138
(hexane)
9.15
8.84
128-130
(benzene)
8.26
8.47
314-316
(water)
11.25
10.93
C12H14N2O5S
C13H16N2O5S
C9H9N3O4S
220-222
(water)
9.12
9.39
113–115
(water)
9.22
8.97
338-340
(ethanol)
16.21
16.47
C12H15N3O4S
C13H17N3O4S
C13H17N3O4S
C16H23N3O4S
C17H25N3O4S
C17H25N3O4S
C20H31N3O4S
C21H33N3O4S
C14H17N3O4S
C17H23N3O4S
C18H25N3O4S
C13H15N3O5S
C16H21N3O5S
C17H23N3O5S
264-266
(aqueous ethanol)
13.85
14.14
212-214
(aqueous ethanol)
13.11
13.50
304-306
(methanol)
13.69
13.50
200-202
(methanol)
12.21
11.89
162-164
(aqueous methanol)
11.68
11.44
186-188
(ethanol)
11.09
11.44
202-204
(aqueous methanol)
10.58
10.26
180-182
(aqueous ethanol)
10.23
9.92
8a
8b
8c
8d
8e
8f
320-322
(ethanol
12.77
13.00
224-226
(aqueous methanol)
11.81
11.50
204-206
(aqueous methanol)
10.83
11.08
334-336
(benzene)
13.20
12.92
194-196
(ethanol)
11.68
11.44
170-172
(aqueous methanol)
10.74
11.02
_______
* Yield by method A.
1510

TABLE 2. Spectral Characteristics of Compounds 3, 5-8
IR spectrum, ν, cm–1
SO2(as), SO2(s), C–S
Mass spectrum,
Compound
m/z (Irel, %)
S–O, NH2
—
3a
1370, 1180, 710
274 [M]+ (82)
(for 35Cl)
3b
3c
5a
5b
5c
6a
6b
6c
7a
7b
7c
7d
7e
7f
1365, 1170, 720
1375, 1175, 725
1233, 1063, 744
1245, 1026, 733
1247, 1026, 728
1338, 1164, 756
1345, 1164, 749
1365, 1168, 752
1366, 1175, 744
1358, 1161, 748
1338, 1161, 751
1341, 1166, 752
1340, 1160, 749
1339, 1160, 750
1342, 1166, 749
1342, 1165, 747
1342, 1166, 749
1345, 1153, 743
1348, 1165, 748
1348, 1164, 748
—
—
316 [M]+ (72)
330 [M]+ (78)
256 [M]+ (45)
298 [M]+ (47)
312 [M]+ (44)
255 [M]+ (100)
297 [M]+ (100)
311 [M]+ (100)
311 [M]+ (13)
353 [M]+ (15)
367 [M]+ (20)
367 [M]+ (18)
409 [M]+ (19)
423 [M]+ (22)
323 [M]+ (100)
365 [M]+ (100)
379 [M]+ (100)
325 [M]+ (7)
650
670
675
3565
3370
3360
—
—
—
—
—
—
8a
8b
8c
8d
8e
8f
—
—
—
—
—
367 [M]+ (10)
381 [M]+ (9)
—
1
In the H NMR spectra of compounds 3, 5-8 (Table 3) there are characteristic signals of the protons of
the quinazoline unit: the H-5 doublet at 8.13-8.34 (3J = 2.2-2.3 Hz), a doublet of doublets for H-7 at 7.92-8.04
4
(3J = 8.6-9.0 and J = 2.2-2.3 Hz) and also a doublet for H-8 at 7.32-7.62 ppm (3J = 8.6-9.0 Hz).The signal of
the protons of the alkyl substituents R and R1 appear at relatively strong field (0.46-3.57 ppm) and the proton of
the NH group at weak field (11.66-11.83 ppm).
EXPERIMENTAL
IR spectra of Nujol mulls were recorded on a Perkin-Elmer 2000 Fourier spectrometer, 1H NMR spectra
of CD3COOD solutions with TMS as internal standard on Unity 400+ (400 MHz) machine. Mass spectra were
recorded on a Kratos MS-30 machine with direct insertion into the ion source (energy of ionization 70eV). The
course of reactions and purity of the compounds synthesized were monitored by TLC on Silufol UV-254 strips
with a 10:1 benzene-acetone eluant, and development with 1 g KMnO4 in 4ml H2SO4 and 96 ml H2O.
1-Methylquinqzoline-2,4-dione (1). Sodium cyanate (0.91 g, 14 mmol) in water (18 ml) was added to a
solution of N-methylanthranilic acid (4) (1.51 g, 10 mmol) and acetic acid (0.1 ml) in water (53 ml) with
stirring. The temperature of the reaction mixture reached 40°C and NaOH (11.68 g, 292 mmol) was added in
portions, the reaction temperature reaching 75°C. Stirring was continued without cooling for 4 h, after which
the crystals were filtered off and dissolved in boiling water (30 ml). The solution was carefully acidified with
~50% H2SO4 to pH 1-2. The precipitated crystals were filtered off, washed with water and recrystallized from
50% MeCOOH to give compound 1 (1.47 g, 84%); mp 276-278°C (mp 277-279°C [9]).
3-Alkyl-1-methylqunazoline-2,4-diones 2a,b. An alkyl iodide (15 mmol) was added to a mixture of
compound 1 (1.76 g, 10 mmol), a solution of NaOH (2 g, 50 mmol) in water (20 ml), tetrabutylammonium
bromide (1.28, 4 mmol) and benzene (40 ml). The reaction mixture was heated to 60°C and held at this
1511

TABLE 3. 1H NMR Spectra of Compounds 3, 5-8
Com-
pound
1H NMR spectrum, δ, ppm (J, Hz)
1
2
3a
3b
11.86 (1H, s, NH); 8.26 (1H, d, J5,7 = 2.2, H-5);
7.95 (1H, dd, J7,5 = 2.2, J7,8 = 8.6, H-7); 7.40 (1H, d, J8,7 = 8.6, H-8); 3.44 (3H, s, 1-CH3)
8.29 (1H, d, J5,7 = 2.2, H-5); 7.96 (1H, dd, J7,5 = 2.2, J7,8 = 8.6, H-7);
7.35 (1H, d, J8,7 = 8.6, H-8); 3.95 (2H, t, J = 7.2, 3-CH2CH2CH3); 3.51 (3H, s, 1-CH3);
1.64 (2H, m, 3-CH2CH2CH3); 0.87 (3H, t, J = 7.2, 3-CH2CH2CH3)
3c
8.25 (1H, d, J5,7 = 2.2, H-5); 7.92 (1H, dd, J7,5 = 2.2, J7,8 = 8.6, H-7);
7.40 (1H, d, J8,7 = 8.6, H-8); 3.90-3.96 (2H, m, 3-CH2C3H7); 3.50 (3H, s, 1-CH3);
1.55 (2H, m, 3-CH2CH2C2H5); 1.31 (2H, m, 3-C2H4CH2CH3); 0.90 (3H, m, 3-C3H6CH3)
5a
5b
11.67 (1H, s, NH); 8.19 (1H, d, J5,7 = 2.2, H-5); 7.95 (1H, dd, J7,5 = 2.2, J7,8 = 8.9, H-7);
7.31 (1H, d, J8,7 = 8.9, H-8); 3.35 (3H, s, 1-CH3)
8.21 (1H, d, J5,7 = 2.2, H-5); 7.96 (1H, dd, J7,5 = 2.2, J7,8 = 8.9, H-7);
7.32 (1H, d, J8,7 = 8.9, H-8); 3.97 (2H, t, J = 7.2, 3-CH2CH2CH3); 3.37 (3H, s, 1-CH3);
1.69 (2H, m, 3-CH2CH2CH3); 0.89 (3H, t, J = 7.2, 3-CH2CH2CH3)
5c
8.20 (1H, d, J5,7 = 2.2, H-5); 7.95 (1H, dd, J7,5 = 2.2, J7,8 = 8.9, H-7);
7.32 (1H, d, J8,7 = 8.9, H-8); 3.91–3.97 (2H, m, 3-CH2C3H7); 3.37 (3H, s, 1-CH3);
1.57 (2H, m, 3-CH2CH2C2H5); 1.32 (2H, m, 3-C2H4CH2CH3); 0.91 (3H, m, 3-C3H6CH3)
6a
6b
11.66 (1H, br. s, NH); 8.34 (1H, d, J5,7 = 2.2, H-5);
8.04 (1H, dd, J7,5 = 2.2, J7,8 = 8.9, H-7); 7.54 (1H, d, J8,7 = 8.9, H-8); 3.41 (3H, s, 1-CH3)
8.32 (1H, d, J5,7 = 2.2, H-5); 8.03 (1H, dd, J7,5 = 2.2, J7,8 = 8.9, H-7);
7.55 (1H, d, J8,7 = 8.9, H-8); 3.96 (2H, t, J = 7.2, 3-CH2CH2CH3); 3.42 (3H, s, 1-CH3);
1.70 (2H, m, 3-CH2CH2CH3); 0.90 (3H, t, J = 7.2, 3-CH2CH2CH3)
6c
7a
7b
8.31 (1H, d, J5,7 = 2.2, H-5); 8.01 (1H, dd, J7,5 = 2.2, J7,8 = 8.9, H-7);
7.53 (1H, d, J8,7 = 8.9, H-8); 3.90-3.97 (2H, m, 3-CH2C3H7); 3.41 (3H, s, 1-CH3);
1.58 (2H, m, 3-CH2CH2C2H5); 1.31 (2H, m, 3-C2H4CH2CH3); 0.90 (3H, m, 3-C3H6CH3)
11.79 (1H, s, NH); 8.19 (1H, d, J5,7 = 2.3, H-5); 8.02 (1H, dd, J7,5 = 2.3, J7,8 = 8.9, H-7);
7.54 (1H, d, J8,7 = 8.9, H-8); 3.41 (3H, s, 1-CH3); 2.45 (4H, q, J = 6.9, N(CH2CH3)2);
1.00 (6H, t, J = 7.2, N(CH2CH3)2
8.27 (1H, d, J5,7 = 2.3, H-5); 8.02 (1H, dd, J7,5 = 2.3, J7,8 = 8.9, H-7);
7.55 (1H, d, J8,7 = 8.9, H-8); 3.86 (2H, t, J = 3.6, 3-CH2C2H5); 3.48 (3H, s, 1-CH3);
2.45 (4H, m, N(CH2)2); 1.56 (2H, m, 3-CH2CH2CH3);
1.02 0.84 (3H, t, J = 7.1, 3-C2H4CH3); 1.01 (6H, t, J = 7.3, N(CH2CH3)2)
7c
8.27 (1H, d, J5,7 = 2.3, H-5); 8.02 (1H, dd, J7,5 = 2.3, J7,8 = 8.9, H-7);
7.55 (1H, d, J8,7 = 8.9, H-8); 3.87-3.91 (2H, m, 3-CH2C3H7); 3.48 (3H, s, 1-CH3);
2.44 (4H, q, J = 7.3, N(CH2)2); 1.51-1.54 (2H, m, 3-CH2CH2C2H5);
1.29 (2H, m, 3-C2H4CH2CH3); 1.02 (6H, t, J = 7.3, N(CH2CH3)2);
7d
7e
11.8 (1H, s, NH); 8.18 (1H, d, J5,7 = 2.3, H-5); 8.03 (1H, dd, J7,5 = 2.3, J7,8 = 9.0, H-7);
7.54 (1H, d, J8,7=9.0, H-8); 3.41 (3H, s, 1-CH3); 3.01 (4H, m, N(CH2)2);
1.32-1.44 (4H, m, N(СН2СН2)2); 0.95-1.24 (4H, m, N(С2Н4CH2)2);
0.78-0.84 (6H, m, N(С3Н6CH3)2)
8.26 (1H, d, J5,7 = 2.3, H-5); 8.02 (1H, dd, J7,5 = 2.3, J7,8 = 8.9, H-7);
7.55 (1H, d, J8,7 = 8.9, H-8); 3.88 (2H, t, J = 7.3, 3-CH2C2H5); 3.49 (3H, s, 1-CH3);
3.02-3.22 (4H, m, N(CH2)2); 1.56 (2H, m, 3-CH2CH2CH3);
1.50-1.65 (4H, m, N(СН2СН2)2); 1.35-1.45 (4H, m, N(С2Н4CH2)2);
1.23 (3H, t, J = 7.1, 3-C2H4CH3); 0.75-0.85 (6H, m, N(С3Н6CH3)2)
7f
8.28 (1H, d, J5,7 = 2.3, H-5); 8.02 (1H, dd, J7,5 = 2.3, J7,8 = 8.9, H-7);
7.55 (1H, d, J8,7 = 8.9, H-8); 3.85-3.95 (2H, m, 3-CH2C3H7); 3.49 (3H, s, 1-CH3);
3.01-3.10 (4H, m, N(CH2)2); 1.50–1.60 (2H, m, 3-CH2CH2C2H5);
1.36-1.46 (4H, m, N(СН2СН2)2); 1.31 (2H, m, 3-C2H4CH2CH3);
1.16-1.28 (4H, m, N(С2Н4CH2)2); 0.90 (3H, m, 3-C3H6CH3);
0.76-0.86 (6H, m, N(С3Н6CH3)2)
8a
8b
11.83 (1H, s, NH); 8.13 (1H, d, J5,7 = 2.3, H-5); 7.96 (1H, dd, J7,5 = 2.3, J7,8 = 8.7, H-7);
7.57 (1H, d, J8,7 = 8.7, H-8); 3.59 (4H, t, J = 6.5, N(CH2)2); 3.42 (3H, s, 1-CH3);
2.83 (4H, t, J = 6.9, N(СН2СН2)2); 2.45 (2H, m, N(С2Н4)2CH2)
8.20 (1H, d, J5,7 = 2.3, H-5); 7.97 (1H, dd, J7,5 = 2.3, J7,8 = 8.9, H-7);
7.59 (1H, d, J8,7 = 8.9, H-8); 3.85 (2H, t, J = 7.2, 3-CH2C2H5); 3.49 (3H, s, 1-CH3);
2.86 (4H, t, J = 6.5, N(CH2)2); 2.45 (4H, t, J = 6.9, N(СН2СН2)2);
1.62 (2H, m, 3-CH2CH2CH3); 1.52 (2H, m, N(С2Н4)2CH2);
0.85 (3H, t, J = 7.2, 3-C2H4CH3)
1512

TABLE 3 (continued)
1
2
8c
8.21 (1H, d, J5,7 = 2.3, H-5); 7.95 (1H, dd, J7,5 = 2.3, J7,8 = 8.7, H-7);
7.58 (1H, d, J8,7 = 8.7, H-8); 3.90 (2H, t, J = 7.3, 3-CH2C3H7); 3.49 (3H, s, 1-CH3);
2.95 (4H, t, J = 6.5, N(CH2)2); 1.57 (2H, m, 3-CH2CH2C2H5);
1.44 (4H, dt, J = 6.9, N(СН2СН2)2); 1.31 (2H, m, 3-C2H4CH2CH3);
1.25 (2H, m, N(С2Н4)2CH2); 0.93 (3H, t, J = 7.1, 3-C3H6CH3)
8d
8e
11.83 (1H, s, NH); 8.14 (1H, d, J5,7 = 2.2, H-5); 7.97 (1H, dd, J7,5 = 2.2, J7,8 = 8.8, H-7);
7.6 (1H, d, J8,7 = 8.8, H-8); 3.58 (4H, t, J = 6.0, N(CH2)2); 3.42 (3H, s, 1-CH3);
2.82 (4H, t, J = 8.0, O(CH2)2)
8.22 (1H, d, J5,7 = 2.2, H-5); 7.97 (1H, dd, J7,5 = 2.2, J7,8 = 8.8, H-7);
7.62 (1H, d, J8,7 = 8.8, H-8); 3.87 (2H, t, J = 7.2, 3-CH2C2H5);
3.58 (4H, t, J = 6.0, N(CH2)2); 3.50 (3H, s, 1-CH3); 2.82 (4H, t, J = 8.0, O(CH2)2);
1.55 (2H, q, J = 5.7, 3-CH2CH2CH3); 0.85 (3H, t, J = 7.2, 3-C2H4CH3)
8f
8.20 (1H, d, J5,7 = 2.2, H-5); 7.96 (1H, dd, J7,5 = 2.2, J7,8 = 8.8, H-7);
7.61 (1H, d, J8,7 = 8.8, H-8); 3.88 (2H, t, J = 7.3, 3-CH2C3H7);
3.58 (4H, t, J = 6.0, N(CH2)2); 3.49 (3H, s, 1-CH3); 2.84 (4H, t, J = 8.0, O(CH2)2);
1.52 (2H, m, 3-CH2CH2C2H5); 1.26 (2H, m, 3-C2H4CH2CH3);
0.85 (3H, t, J = 7.1, 3-C3H6CH3)
temperature for 6 h. After cooling, the organic layer was separated, washed with water until neutral and dried
over Na2SO4. The benzene was evaporated and the residue was recrystallized. Product 2a (1.98g 91%); mp
90-92°C (91-93° [9]) was obtained from n-propyl iodide, and compound 2b (1.9 g, 82%); mp 70-72°C (71-73°
[9]) from n-butyl iodide.
6-Chlorosulfonyl-1-methylquinazoline-2,4-dione (3a) and 3-Alkyl-6-chlorosulfonyl-1-methylquin-
azolin-2,4-diones 3b,c. Method A. Compounds 1 or 2a,b (10 mmol) were added in portions to chlorosulfonic
acid (5.83 g, 50 mmol) at 5-10°C with stirring at such a rate that the solution temperature did not exceed 15°C.
The reaction mixture was then heated to 50-60°C, kept at this temperature for 6 h and then poured over broken
ice. The precipitate of 3 was filtered off, washed with water, and crystallized.
Compounds 3a-c were also obtained from the sulfoacids 5a-c by method B (see below).
1-Methyl-2,4-dioxoquinazoline-6-sulfoacid (5a) and 3-Alkyl-1-methyl-2,4-dioxoquinazolinesulfo-
acids 5b,c. A mixture of compound 3 (10 mmol) and water (20 ml) was boiled for 2 h, the solvent was partially
removed, the precipitate of product 5 was filtered off and recrystallized from water.
The sulfoacids 5a-c were treated with chlorosulfonic acid by method B to give compounds 3a-c.
Method B. Sulfoacids 5 (10 mmol) were added in portions to chlorosulfonic acid (2.33 g, 20 mmol),
cooled to 0°C, at such a rate that the temperature did not exceed 10°C. The mixture was heated to 50-60°C, kept
at this temperature for 2 h and poured onto broken ice. The precipitate of compound 3 was filtered off, washed
with water, and recrystallized. The yields of compounds 3a-c were close to quantitative. Samples of compounds
3a-c, obtained by methods A and B were identical (there was no depression of the melting point with mixed
probes).
1-Methyl-6-sulfamidoquinazoline-2,4-dione (6a) and 3-Alkyl-1-methyl-6-sulfamidoquinazoline-
2,4-diones 6b,c. A mixture of compound 3 (10 mmol) and concentrated ammonia solution (100 ml) was heated
with stirring on a boiling water bath for 6 h then kept at room temperature for 16 h. The precipitate of
compound 6 was filtered off and recrystallized.
N,N-Diethyl- and N,N-Dibutylamides of 1-Methyl-2,4-dioxoquinazoline-6-sulfoacids 7a,d and
3-Alkyl-1-methyl-2,4-dioxoquinazoline-6-sulfoacids 7b,c,e,f. Diethyl- or dibutylamine (10 mmol) and
triethylamine (1.01 g, 10 mmol) in acetone (15 ml) was added dropwise to a solution of compound 3 (10 mmol)
in acetone (30 ml). The reaction mixture was stirred at room temperature for 2 h, the acetone was then
evaporated, and water (100 ml) was added to the residue. The precipitate of compound 7 was filtered off and
recrystallized.
1513

N-Piperidides and N-Morpholides of 1-Methyl-2,4-dioxoquinazoline-6-sulfoacids 8a,d and
3-Alkyl-1-methyl2,4-dioxoquinazoline-6-sulfoacids 8b,c,e,f were synthesized analogously to the dialkyl-
amides 7a-f using piperidine (10 mmol) or morpholine (10 mmol) in place of the dialkylamines.
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