Synthesis of new 3,4-di-and 1,2,3,4-tetrahydroquinazolin-4-one derivatives and X-ray diffraction study of crystal solvates of 3-methylsulfonylamino-2-(2- methylsulfonylaminophenyl)-1,2,3,4-tetrahydroquinazolin-4-one

Article abstract of DOI:10.1007/s11172-006-0404-y

The reactions of hydrazide, mesyl hydrazide, succinyl hydrazide, and maleyl hydrazide of anthranilic acid with carbonyl compounds were studied, and new di-and tetrahydroquinazolin-4-one derivatives were prepared. The structure of one reaction product, viz., 3-methylsulfonylamino-2-(2- methylsulfonylaminophenyl)-1,2,3,4-tetrahydroquinazolin-4-one, was established by X-ray diffraction study of two crystal solvates of this compound. The characteristic features of the crystal packings of these solvates are discussed. Springer Science+Business Media, Inc. 2006.

Full text of DOI:10.1007/s11172-006-0404-y

Russian Chemical Bulletin, International Edition, Vol. 55, No. 7, pp. 1229—1238, July, 2006
1229
Synthesis of new 3,4ꢀdiꢀ and 1,2,3,4ꢀtetrahydroquinazolinꢀ4ꢀone
derivatives and Xꢀray diffraction study of crystal solvates of
3ꢀmethylsulfonylaminoꢀ2ꢀ(2ꢀmethylsulfonylaminophenyl)ꢀ
1,2,3,4ꢀtetrahydroquinazolinꢀ4ꢀone
b
L. Yu. Ukhina and L. G. Kuz´mina
ꢀ
aInstitute of Physical and Organic Chemistry, Rostov State University,
194/2 prosp. Stachki, 344090 RostovꢀonꢀDon, Russian Federation.
Fax: +7 (863) 243 4667. Eꢀmail: may@ipoc.rsu.ru
bN. S. Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences,
31 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (495) 953 1279. Eꢀmail: kuzmina@igic.ras.ru
The reactions of hydrazide, mesyl hydrazide, succinyl hydrazide, and maleyl hydrazide of
anthranilic acid with carbonyl compounds were studied, and new diꢀ and tetrahydroquinazolinꢀ
4ꢀone derivatives were prepared. The structure of one reaction product, viz., 3ꢀmethylꢀ
sulfonylaminoꢀ2ꢀ(2ꢀmethylsulfonylaminophenyl)ꢀ1,2,3,4ꢀtetrahydroquinazolinꢀ4ꢀone, was
established by Xꢀray diffraction study of two crystal solvates of this compound. The characterꢀ
istic features of the crystal packings of these solvates are discussed.
Key words: anthranilic acid hydrazide, anthranilic acid mesyl hydrazide, succinic anꢀ
hydride, maleic anhydride, carbonyl compounds, diꢀ and tetrahydroquinazolinꢀ4ꢀone derivaꢀ
tives, supramolecular architecture.
First representatives of 1,2,3,4ꢀtetrahydroquinazolinꢀ
4ꢀones were synthesized by condensation of oꢀaminoꢀ
benzanilides with formaldehyde in 1904.1 More recently,
it has appeared that many such compounds are physiꢀ
ologically active. Nowadays, there are abundant data on
these compounds (see, for example, Refs 2—4 and referꢀ
ences therein).
We synthesized new substituted 1,2,3,4ꢀtetrahydroꢀ
quinazolinꢀ4ꢀones with the use of anthranilic acid mesyl
hydrazide 1, which we have prepared for the first time. It
was found that compound 1 smoothly reacts with aldeꢀ
hydes 2 on heating in PrOH to form 1,2,3,4ꢀtetraꢀ
hydroquinazolinꢀ4ꢀones 3 and is transformed into
3ꢀmethylsulfonylaminoꢀ3,4ꢀdihydroquinazolinꢀ4ꢀone (4)
on refluxing with formic acid (Scheme 1).
Under the same conditions, the reaction of anthraꢀ
nilic acid hydrazide 5 with furfural produced quinazoꢀ
linone 6. Refluxing of hydrazide 5 with formic acid
afforded 3ꢀaminoꢀ3,4ꢀdihydroquinazolinꢀ4ꢀone (7)
(Scheme 2).
Cyclic ketones can be condensed with anthranilamides
and their analogs to form spirocyclic structures.4—6 The
simplest method giving rise to the target products in high
yields is based on heating of the reactants under solventꢀ
free conditions without catalysts.7
We found that refluxing of hydrazide 1 with cycloꢀ
pentanone or cyclohexanone in ethylene glycol afforded
3ꢀmethylsulfonylaminoꢀ2ꢀspirocyclopentaneꢀ1,2,3,4ꢀ
tetrahydroquinazolinꢀ4ꢀone (8) and 3ꢀmethylsulfonylꢀ
aminoꢀ2ꢀspirocyclohexaneꢀ1,2,3,4ꢀtetrahydroquinazolinꢀ
4ꢀone (9), respectively. Spiro derivatives 10 and 11 were
prepared from hydrazide 5 and the same cyclic ketones
under solventꢀfree conditions (Scheme 3).
Refluxing of hydrazide 1 with acetylacetone gave
2ꢀmethylꢀ3ꢀmethylsulfonylaminoꢀ3,4ꢀdihydroquinazoꢀ
linꢀ4ꢀone (12) presumably via elimination of acetone from
intermediate tetrahydro derivative A (Scheme 4).
It is known8 that anthranilhydrazide 5 is acylated with
cyclic dicarboxylic acid anhydrides at the hydrazine
nitrogen atom. Heating of this reaction product with sucꢀ
cinic anhydride in acetic anhydride followed by hydrolyꢀ
sis afforded 3ꢀ(3ꢀcarboxypropanoylamino)ꢀ2ꢀmethylꢀ
quinazolinꢀ4ꢀone.8
We used acylation products of anthranilhydrazide 5
with succinic and maleic anhydrides in reactions with
aldehydes to synthesize 1,2,3,4ꢀtetrahydroquinazolinꢀ4ꢀ
one derivatives 13 and 14, respectively. The reactions
were carried out without isolation of intermediate acylaꢀ
tion products B and C. Analogous reactions can be perꢀ
formed with cyclic ketones, as was exemplified by comꢀ
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1183—1191, July, 2006.
1066ꢀ5285/06/5507ꢀ1229 © 2006 Springer Science+Business Media, Inc.

1230
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 7, July, 2006
Ukhin and Kuz´mina
Scheme 1
Scheme 3
Scheme 4
Scheme 2
pound 15. The reaction of anthranilhydrazide 5, succinic
anhydride, and acetylacetone produced 3ꢀ(3ꢀcarboxyꢀ
propanoylamino)ꢀ2ꢀmethylquinazolinꢀ4ꢀone (16) deꢀ
scribed earlier.8*
* The positions of the signals in the 1H NMR spectrum of the
compound synthesized in the study8 are virtually identical to our
data. However, the melting point of this compound is ~100 °C
lower than that determined in the present study, which is apparꢀ
ently a technical error.

3,4ꢀDiꢀ and 1,2,3,4ꢀtetrahydroquinazolinꢀ4ꢀones
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 7, July, 2006
1231
Scheme 5
The structure of compound 3i was established by
Xꢀray diffraction. Crystals were grown from solutions in
nitromethane and acetonitrile as 1 : 1 crystal solvates
3i•MeNO2 and 3i•MeCN. These crystal solvates were
studied by Xꢀray diffraction (Fig. 1, Table 1). The correꢀ
sponding bond lengths and bond angles in the basic molꢀ
ecules of the crystals of 3i•MeNO2 and 3i•MeCN are
identical within experimental error.
The dihedral angle between the mean plane of the sixꢀ
membered heterocycle and the plane of the benzene ring
C(2)...C(7) is 87° and 83° in 3i•MeNO2 and 3i•MeCN,
respectively.
It should be noted that the conformational parameters
of the basic molecules of the crystal solvates have similar
values. The dihedral angles between different fragments
of the molecule in the crystals of 3i•MeNO2 are very
similar to those in 3i•MeCN (Fig. 2).
In molecules 3i•MeNO2 and 3i•MeCN, the N(1)
atom has a nearly planarꢀtrigonal bond configuration. The
sum of the bond angles at the N(1) atom (~355—356°) is
close to the ideal value of 360° characteristic of the plaꢀ
narꢀtrigonal bond configuration. The geometry of the
bonds at the N(2) atom is pyramidal (the sum of the bond
angles is ~342—343°). There is no conjugation between
the lone electron pair of the N(1) atom and the correꢀ
sponding aromatic system. The S(1)—N(1)—C(3)—C(4)
torsion angle is 94.7(2) and 99.5(3)° in the basic molꢀ
ecules of 3i•MeNO2 and 3i•MeCN, respectively, which
is evidence for the nearly perpendicular mutual orientaꢀ
tion of the bond systems of the nitrogen atoms and the
aromatic fragment. The dihedral angle between the plane
through the S(1),C(3),H(1) atoms and the plane of the
benzene ring C(2)…C(7) (~59° in 3i•MeNO2 and ~57° in
3i•MeCN) indicates that the orientation of the lone pair
of this atom is unfavorable for its conjugation with the
benzene ring.
Such a detailed similarity of the conformational paꢀ
rameters of the molecule in the crystal solvates under
consideration is indicative of the similarity of their crystal
environment. This is unusual taking into account the
difference in the nature of the solvate molecules and
the fact that 3i•MeNO2 and 3i•MeCN crystallize in difꢀ
ferent space groups. It is well known that nitromethane
is not involved in weak interactions, i.e., it generally
has no effect on the supramolecular architecture beꢀ
cause it is located in the cavities of the crystal structure.
Unlike nitromethane, acetonitrile can form hydrogen
bonds. Taking into account the presence of three "active"
protons in molecule 3i, hydrogen bonding between the
basic molecule and the acetonitrile molecule would be
expected to occur in crystal solvate 3i•MeCN. However,
the present study demonstrated that in neither crystal
structure are the solvate molecules involved in weak
ineractions with the basic molecules; instead the solꢀ
vate molecules are located in the cavities of the crystal
packing.
The heterocycle of the tricyclic system adopts a twistꢀ
boat conformation. The C(8)—C(9)—C(14)—N(3) fragꢀ
ment is planar, and the C(1) and N(4) atoms deviate from
this plane in the same direction, the deviations being
different. In 3i•MeNO2, the deviations of the C(1) and
N(4) atoms are 0.592 and 0.184 Å, respectively; in
3i•MeCN, 0.538 and 0.133 Å.
In the crystal packing of 3i•MeNO2, the molecules
are linked to each other to form infinite ribbons through
hydrogen bonds involving all "active" protons (Fig. 3).
The basic molecules in the crystal structure of
3i•MeCN form analogous ribbons.

1232
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 7, July, 2006
Ukhin and Kuz´mina
Table 1. Selected bond lengths (d/Å) and bond angles (ω/deg) in
crystal solvates 3i•MeNO2 and 3i•MeCN
C(5)
a
C(4)
C(6)
Parameter
3i•MeNO2
3i•MeCN
C(3)
C(7)
H(2)
N(2)
O(4)
Bond
d/Å
H(1)
C(15)
O(2)
S(1)—O(2)
S(1)—O(3)
S(2)—O(4)
S(2)—O(5)
S(1)—N(1)
S(2)—N(2)
S(1)—C(15)
S(2)—C(16)
N(1)—C(3)
N(2)—N(4)
N(3)—C(14)
N(4)—C(1)
C(1)—N(3)
C(1)—C(2)
C(2)—C(3)
C(3)—C(4)
C(4)—C(5)
C(5)—C(6)
C(6)—C(7)
C(7)—C(2)
C(8)—O(1)
C(9)—C(8)
C(14)—C(9)
Bond angle
O(2)—S(1)—O(3)
O(2)—S(1)—N(1)
O(2)—S(1)—C(15)
O(3)—S(1)—N(1)
O(3)—S(1)—C(15)
O(4)—S(2)—O(3)
O(4)—S(2)—N(2)
O(4)—S(2)—C(16)
O(5)—S(2)—N(2)
O(5)—S(2)—C(16)
N(1)—S(1)—C(15)
N(2)—S(2)—C(16)
S(1)—N(1)—C(3)
S(2)—N(2)—N(4)
1.435(1)
1.436(1)
1.434(1)
1.430(1)
1.616(1)
1.652(1)
1.756(2)
1.756(2)
1.439(2)
1.405(2)
1.380(2)
1.473(2)
1.453(2)
1.522(2)
1.394(2)
1.391(2)
1.385(2)
1.392(2)
1.389(2)
1.398(2)
1.232(2)
1.467(2)
1.403(2)
1.439(2)
1.440(2)
1.437(2)
1.433(2)
1.619(2)
1.653(2)
1.762(3)
1.762(3)
1.439(3)
1.403(3)
1.383(3)
1.476(3)
1.462(3)
1.525(3)
1.400(3)
1.403(4)
1.386(4)
1.393(4)
1.387(4)
1.399(3)
1.234(3)
1.478(3)
1.404(4)
C(2)
S(2)
O(1)
N(1)
H(3)
N(4)
S(1)
C(1)
N(3)
O(5)
C(9)
C(8)
C(10)
C(16)
O(3)
C(14)
C(13)
C(11)
C(12)
C(1´)
O(1´)
N(1´)
O(2´)
b
C(2´)
C(1´)
N(1´)
O(4)
O(5)
C(16)
O(2)
S(1)
ω/deg
S(2)
118.0(1)
106.4(1)
108.7(1)
107.9(1)
107.8(1)
119.5(1)
103.4(1)
109.2(1)
107.0(1)
108.9(1)
107.7(1)
108.4(1)
120.8(1)
117.3(1)
118.6(1)
106.3(1)
108.2(1)
107.9(1)
107.5(1)
119.3(1)
103.3(1)
109.4(1)
107.2(1)
108.8(1)
107.9(1)
108.2(1)
121.6(2)
117.4(2)
N(1)
C(3)
N(2)
C(1)
C(15)
O(3)
N(4)
C(8)
C(2)
O(1)
C(4)
C(5)
N(3)
C(14)
C(9)
C(10)
C(7)
C(6)
C(13)
C(11)
C(12)
Fig. 1. Structures of the structural units of compound 3i in
crystal solvates 3i•MeNO2 (a) and 3i•MeCN (b). The same
atomic numbering scheme is used for molecule 3i in both crystal
solvates.
of 3i•MeNO2 and the N(2A)—H(2A)...O(1D) and
N(2D)—H(2D)...O(1A) fragments in the crystals of
3i•MeCN. The parameters of these interactions in
3i•MeNO2 are as follows: N...O, 2.851(2) Å; H...O,
1.96(3) Å; N—H...O, 176(1)°. The corresponding paramꢀ
eters in 3i•MeCN are 2.833(3) Å, 2.00(4) Å, and 172(2)°.
The geometric parameters correspond to mediumꢀstrength
hydrogen bonds.
The remaining "active" proton at the N(3) atom in the
aboveꢀconsidered ribbon associate is located in the vicinꢀ
ity of the O(3) atom of the basic molecule. The N(3)...O(3)
and H(3)...O(3) distances are 2.963(2) and 2.38(4) Å,
respectively, in molecule 3i•MeNO2 and 3.001(4) and
2.38(7) Å in molecule 3i•MeCN. The angle at the
In both crystals, the infinite chains are formed
through centrosymmetric pairs of hydrogen bonds resultꢀ
ing in the closure of sixꢀmembered rings. One pair of
hydrogen bonds exists in the N(1B)—H(1B)...O(2D) and
N(1D)—H(1D)...O(2B) fragments in both crystals (see
Fig. 3). In 3i•MeNO2, the N...O distance is 2.872(2) Å,
the H...O distance is 2.13(3) Å, and the angle at the
H atom is 170(1)°. In 3i•MeCN, the corresponding paꢀ
rameters are 2.842(3) Å, 2.01(4) Å, and 168(2)°. Another
pair of hydrogen bonds links the N(2B)—H(2B)...O(1C)
and N(2C)—H(2C)...O(1B) fragments in the crystals

3,4ꢀDiꢀ and 1,2,3,4ꢀtetrahydroquinazolinꢀ4ꢀones
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 7, July, 2006
1233
except for 3f, were measured on a Varian UNITYꢀ300 specꢀ
trometer. The spectrum of 3f was recorded on a Bruker DRX500
spectrometer. The spectroscopic characteristics of the resulting
compounds are given in Tables 2 and 3. The mass spectra were
obtained on a Finnigan mar. INCOS 50 GLCꢀmass spectromꢀ
eter using a direct inlet system. Attempts to prepare anthranilic
acid mesyl hydrazide according to a standard procedure9 with
the use of mesyl chloride and pyridine failed. Only a bisꢀ
mesylated product was isolated from the reaction mixture when
the reagents were taken in a ratio of 1 : 1.
Anthranilic acid mesyl hydrazide (1). Mesyl chloride (3 mL,
0.04 mol) was added with stirring to a suspension of anthranilic
acid hydrazide (6 g, 0.04 mol) in MeCN (40 mL), which was
distilled over P2O5, and the reaction mixture was heated to
boiling. The mixture rapidly became viscous and then again
became liquid after 5—10 min. The reaction mixture was reꢀ
fluxed for 20 min and filtered in the hot state. The filtrate was
cooled on ice. The crystalline precipitate that formed was filꢀ
tered off, washed with cold MeCN, and dried. A colorless comꢀ
pound with m.p. of 174—177 °C was obtained. The yield was
2.6 g (29%). The filtrate was concentrated and an additional
amount of compound 1 (1.2 g) was obtained. The total yield
was 3.8 g (42%). Found (%): C, 41.65; H, 5.11; N, 18.20.
C8H11N3O3S. Calculated (%): C, 41.91; H, 4.84; N, 18.33.
3ꢀMethylsulfonylaminoꢀ2ꢀ(3ꢀnitrophenyl)ꢀ1,2,3,4ꢀtetraꢀ
hydroquinazolinꢀ4ꢀone (3a). A mixture of hydrazide 1 (0.23 g,
1 mmol) and mꢀnitrobenzaldehyde (0.15 g, 1 mmol) was reꢀ
fluxed in PrOH (5 mL) for 1 h, cooled using rubbing with a rod,
and kept on ice. The precipitate that formed was filtered off,
washed with cold PrOH and petroleum ether, and dried. Yelꢀ
lowish crystals of compound 3a with m.p. of 207—210 °C were
obtained. The yield was 0.3 g (83%). M+ 362. Found (%):
C, 49.79; H, 4.12; N, 15.11. C15H14N4O5S. Calculated (%):
C, 49.72; H, 3.89; N, 15.46.
O(4)
C(16)
S(2)
N(2)
O(1)
O(5)
C(5)
C(6)
C(7)
C(2)
N(4)
C(8)
C(10)
C(4)
C(3)
C(9)
C(14)
N(1)
C(1)
N(3)
C(13)
C(11)
S(1)
O(2)
O(3)
C(15)
C(12)
Fig. 2. Superposition of the planes of basic molecules 3i passꢀ
ing through the atoms of the benzene ring C(9)—C(14) and
the nearest substituents, C(8) and N(3), in crystal solvates
3i•MeNO2 and 3i•MeCN.
hydrogen atom (134(3)° and 135(4)° in 3i•MeNO2 and
3i•MeCN, respectively) most likely characterizes a forced
contact, which efficiently shields the proton, thus hinderꢀ
ing its involvement in hydrogen bonding with the acetoꢀ
nitrile solvate molecule in crystal solvate 3i•MeCN.
Therefore, the ribbon packing of the basic molecules,
which we revealed in the crystals belonging to different
space groups and containing solvate molecules of differꢀ
ent nature, is the prevailing motif in the supramolecular
architecture of the compound under study.
Experimental
3ꢀMethylsulfonylaminoꢀ2ꢀ(4ꢀnitrophenyl)ꢀ1,2,3,4ꢀtetraꢀ
hydroquinazolinꢀ4ꢀone (3b) was prepared analogously to 3a from
hydrazide 1 (0.46 g, 2 mmol) and pꢀnitrobenzaldehyde (0.33 g,
2 mmol) in PriOH (10 mL). Compound 3b was recrystallized
The IR spectra were recorded on a Specord IRꢀ75 instruꢀ
ment in Nujol mulls. The 1H NMR spectra of all compounds,
0
b
O(3C)
O(4A)
S(2A)
a
N(3C)
S(1C)
C(1C)
O(2C)
N(1C)
O(3D)
O(4B)
N(2A)
N(4A)
N(3D)
O(5A)
O(1A)
N(4C)
N(2C)
S(1D)
C(1D)
S(2B)
O(1C)
O(1B)
O(2D)
O(5B)
O(5C)
N(1A)
S(1A)
O(2A)
C(1A)
N(3A)
N(1D)
S(2C)
N(2B)
N(4B)
N(4D)
N(2D)
O(1D)
O(5D)
S(2D)
N(1B)
O(4C)
O(3A)
C(1B)
O(2B)
S(1B)
N(3B)
O(4D)
c
O(3B)
Fig. 3. Fragment of the crystal packing of 3i•MeNO2. The hydrogen atoms are omitted.

1234
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 7, July, 2006
Ukhin and Kuz´mina
Table 2. Spectroscopic characteristics of compounds 1, 3a—m, and 4
Comꢀ
pound
IR, ν/cm–1
1H NMR (DMCOꢀd6), δ (J/Hz)
1
3507, 3400, 3300, 3220 (NH);
1647 (CO); 1621, 1594,
1521 (arom.); 1340, 1154 (SO2)
3360, 3147 (NH); 1661 (CO);
1614, 1581, 1500, 1487 (arom.);
1527, 1341 (NO2); 1354,
2.95 (s, 3 H, Me); 6.37 (s, 2 H, NH2); 6.47 (m, 1 H, C(4)H); 6.69 (d, 1 H,
C(3)H, J = 8.2); 7.12 (m, 1 H, C(5)H); 7.55 (d, 1 H, C(6)H, J = 7.9);
9.25, 10.35 (both s, 1 H each, NH)
2.98 (s, 3 H, Me); 6.11 (d, 1 H, C(2)H, J = 3.2); 6.69 (m, 2 H, СНarom);
7.23 (m, 1 H, СHarom); 7.50—7.80 (m, 4 H, NH, CHarom); 8.13 (br.dd, 1 H,
C(5)H); 8.25 (s, 1 H, C(2´)H); 10.33 (s, 1 H, NH)
3а
1167 (SO2)
3b
3407, 3153 (NH); 1660 (CO);
1607, 1500 (arom.); 1521,
1341 (NO2); 1354, 1160 (SO2)
3540, 3380, 3167 (OH, NH);
1700, 1661 (CO); 1614, 1607,
2.98 (s, 3 H, Me); 6.10 (d, 1 H, C(2)H, J = 3.2); 6.68 (m, 2 H, СНarom);
7.23 (m, 1 H, СHarom); 7.50—7.80 (m, 4 H, NH, CHarom); 8.15 (d, 2 H, C(3´)H,
C(5´)H, J = 8.6); 10.28 (s, 1 H, NH)
0.86 (t, 3 H, Me, J = 7.3); 1.42 (m, 2 H, CH2); 2.99 (s, 3 H, Me);
3.34 (m 2 H, CH2); 4.02 (t, 1 H, OH, J = 5.2); 6.22 (d, 1 H, C(2)H, J = 2.8);
3c*
1514 (arom.); 1507, 1335 (NO2); 6.82 (m, 2 H, CHarom); 7.01 (d, 1 H, CHarom, J = 9.0); 7.20 (m, 2 H,
1340, 1167 (SO2)
NH, CHarom); 7.75 (dd, 1 H, CHarom, 3J = 7.8, 4J = 1.25); 7.84 (s, 1 H,
C(6´)H); 8.00 (dd, 1 H, C(5)H, 3J = 9.0, 4J = 2.8); 10.36 (s, 1 H, NH);
11.54 (s, 1 H, OH)
3d
3340, 3326, 3127 (NH);
1654 (CO); 1614, 1500,
1480 (arom.); 1334, 1327,
1160 (SO2)
2.93 (s, 3 H, Me); 5.86 (d, 1 H, C(2)H, J = 3.1); 6.28 (m, 2 H,
С(3´)Н, C(4´)H); 6.69 (m, 2 H, C(7)H, C(8)H); 7.23 (m, 1 H, С(6)H);
7.44 (br.d, 1 H, C(5´)H); 7.55 (d, 1 H, NH, J = 3.1); 7.68 (d, 1 H, C(5)H,
J = 7.8); 10.02 (s, 1 H, NH)
3e
3366, 3133, 3100 (NH);
1660, 1647 sh. (CO); 1614,
1500, 1487 (arom.); 1334,
1154 (SO2)
2.94 (s, 3 H, Me); 6.12 (d, 1 H, C(2)H, J = 3.2); 6.65—6.80 (m, 2 H, СНarom);
6.90 (m, 1 H, СHarom); 7.07 (d, 1 H, C(3´)H, J = 3.3); 7.27 (m, 2 H, CHarom);
7.63 (d, 1 H, NH, J = 3.2); 7.68 (d, 1 H, C(5)H, J = 7.8); 10.09 (s, 1 H, NH)
3f**
3g
3393, 3387, 3233 (NH);
1661 (CO); 1614,
1567 (arom.); 1321, 1154 (SO2)
2.96 (s, 3 H, Me); 6.22 (br.d, C(2)H); 6.70 (m, 2 H, СHarom); 6.97 (m, 1 H,
CHarom); 7.17 (m, 1 H, CHarom); 7.30 (br.d, CHarom); 7.56 (m, 1 H, СНarom);
7.69 (d, 1 H, CHarom, J = 8.0);7.70 (br.d, 1 H, NH); 7.75 (d, 1 H, CHarom,
J = 8.00); 7.93 (d, 1 H, CHarom, J = 8.0); 10.05 (s, 1 H, NH); 11.05 (s, 1 H, NH)
2.95 (s, 3 H, Me); 6.19 (d, 1 H, C(2)H, J = 2.1); 6.65 (m, 3 H, СHarom);
6.84 (d, 1 H, C(8)H, J = 8.0); 6.90 (d, 1 H, CHarom, J = 7.4); 6.94 (br.d, 1 H,
NH); 7.05 (m, 1 H, C(7)H); 7.15 (m, 1 H, С(6)Н); 7.68 (d, 1 H, C(5)H, J = 7.7);
9.83 (s, 1 H, OH); 10.04 (s, 1 H, NH)
3460, 3400, 3347, 3213,
3167 (OH, NH); 1661,
1647 (CO); 1621, 1614,
1601, 1501 (arom.); 1154,
1327, 1167, 1354 (SO2)
3h
3i
3500 (OH); 3414, 3113 (NH);
1640 (CO); 1607, 1507,
1500 (arom.); 1327, 1141 (SO2)
3380, 3293, 3140 (NH);
1714, 1641 (CO); 1614,
1467 (arom.); 1341, 1321,
1167, 1154 (SO2)
2.93 (s, 3 H, Me); 3.74 (s, 3 H, OMe); 5.84 (d, 1 H, CH, J = 2.0);
6.50—6.80 (m, 4 H, СHarom); 6.88 (s, 1 H, C(2´)H); 7.18 (m, 1 H, CHarom);
7.37 (br.d, 1 H, NH); 7.66 (d, 1 H, C(5)H); 8.71 (s, 1 H, OH); 9.95 (s, 1 H, NH)
2.97 (s, 3 H, Me); 2.98 (s, 3 H, Me); 6.38 (d, 1 H, CH, J = 2.6); 6.60 (d, 1 H,
C(8)H, J = 8.0); 6.71 (m, 1 H, C(7)H); 6.82 (d br, 1 H, NH);
7.05—7.40 (m, 4 H, CHarom); 7.45 (d, 1 H, C(3´)H, J = 7.85); 7.75 (d, 1 H, C(5)H,
J = 7.75); 9.30, 9.98 (both s, 1 H each, NH)
3j
3380, 3220 (NH); 1674 (CO);
1621, 1607, 1527, 1487 (arom.);
1334, 1161 (SO2)
2.99 (s, 3 H, Me); 6.12 (d, 1 H, CH, J = 3.4); 6.72 (m, 2 H, CHarom);
3
7.00—7.60 (m, 6 H, NH, 5 CHarom); 7.75 (dd, 1 H, С(5)H, J = 7.8, 4J = 1.25);
9.85, 12.27 (both s, 1 H each, NH)
3k
3l
3366, 3193 (NH); 1687 (CO);
1607, 1594, 1560, 1494 (arom.);
1334, 1321, 1167, 1154 (SO2)
3387, 3300 (NH); 3113 (≡CH);
3127 (C≡C); 1647 sh,
1634 (CO); 1614, 1500, 1487,
1474 (arom.); 1354, 1327,
1170, 1160 (SO2)
3.01 (s, 3 H, Me); 6.35 (d, 1 H, C(2)H, J = 3.8); 6.70 (m, 2 H, CHarom);
7.20, 7.57 (both m, 1 H each, CHarom); 7.69 (d, 1 H, NH, J = 3.8);
7.75, 7.88 (both m, 2 H each, CHarom); 8.00 (s, 1 H, CHarom); 10.25 (s, 1 H, NH)
2.96 (s, 3 H, Me); 3.30 (br.t, 1 H, ≡CH); 4.84, 4.86 (both d, 2 H, CH2,
J = 2.2); 6.15 (d, 1 H, C(2)H, J = 2.9); 6.66 (m, 2 H, CHarom); 6.97 (br.d, 1 H,
NH); 7.10—7.25 (m, 4 H, CHarom); 7.71 (d, 1 H, CHarom, J = 7.9);
10.30 (s, 1 H, NH)
(to be continued)

3,4ꢀDiꢀ and 1,2,3,4ꢀtetrahydroquinazolinꢀ4ꢀones
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 7, July, 2006
1235
Table 2 (continued)
Comꢀ
pound
IR, ν/cm–1
1H NMR (DMCOꢀd6), δ (J/Hz)
3m
3333, 3306, 3067 (NH);
3287 (≡CH); 2127 (C≡C);
1660 (CO); 1621, 1614,
1534, 1514, 1487, 1480,
1474 (arom.); 1334, 1154,
1147 (SO2)
2.94 (s, 3 H, Me); 3.16 (t, 1 H, ≡CH, J = 2.4); 3.73 (s, 3 H, OMe);
4.66 (d, 2 H, CH2, J = 2.4); 5.88 (d, 1 H, C(2)H, J = 2.1); 6.65 (m, 2 H, CHarom);
6.80 (dd, 1 H, СHarom, 3J = 8.3, 4J = 1.8); 6.89 (d, 1 H, CHarom, J = 8.1);
6.95 (br.d, 1 H, NH); 7.20 (m, 1 H, CHarom); 7.45 (с, 1 H, C(2´)H);
7.66 (dd, 1 H, C(5)H, 3J = 7.8, 4J = 1.2); 10.07 (s, 1 H, NH)
4
3033 (NH); 1700 (CO);
1614, 1567, 1480 (arom.);
1347, 1165 (SO2)
3.14 (s, 3 H, Me); 7.56 (m, 1 H, C(7)H); 7.70 (d, 1 H, C(8)H, J = 7.9);
7.84 (m, 1 H, C(6)H); 8.15 (s, 1 H, C(2)H); 8.21 (dd, 1 H, C(5)H, 3J = 8.0,
4J = 1.25); 11.33 (s, 1 H, NH)
* The 1 : 1 solvate with PrOH.
** The spectrum was recorded on a Bruker DRX 500 spectrometer.
Table 3. Spectroscopic characteristics of compounds 6—16
Comꢀ
pound
IR, ν/cm–1
1H NMR (DMCOꢀd6), δ (J/Hz)
6
3340 (NH); 1634 (CO);
1607 (CH=N); 1500,
1487 (arom.)
6.18 (d, 1 Н, С(3´)Н, J = 3.3); 6.24 (d, 1 H, CH, J = 3.4);
6.26, 6.53 (both m, 1 H each, C(4´)H); 6.72 (m, 1 H, C(7)H); 6.78 (d, 1 H, C(8)H,
J = 8.0); 6.84 (d, 1 H, C(3´)H, J = 3.3); 7.24 (m, 1 H, C(6)H); 7.44 (d, 1 H,
C(5´)H, J = 1.7); 7.63 (d, 1 H, NH, J = 3.4); 7.68 (d, 1 H, C(5´)H, J = 1.7);
7.71 (dd, C(5)H, 3J = 7.9, 4J = 1.4)
7
8
9
3287, 3153 (NH); 1687 (CO);
1634, 1607, 1594, 1567 (arom.)
5.73 (s, 2 H, NH2); 7.50 (m, 1 H, C(7)H); 7.63 (d, 1 H, C(8)H, J = 7.9);
7.74 (m, 1 H, C(6)H); 8.17 (dd, 1 H, C(5)H, 3J = 8.0, 4J = 1.0);
8.23 (s, 1 H, C(2)H)
1.40—2.00 (m, 7 H, CH2); 2.66 (m, 1 H, CH2); 2.91 (s, 3 H, Me); 6.65 (m,
1 H, C(7)H); 6.73 (d, 1 H, C(8)H, J = 8.1); 7.06 (s, 1 H, NH); 7.23 (m, 1 H,
C(6)H); 7.66 (dd, 1 H, C(5)H, 3J = 7.8, 4J = 1.3); 9.44 (s, 1 H, NH)
1.00—2.20 (m, 10 H, CH2); 2.90 (s, 3 H, Me); 6.65 (m, 1 H, C(7)H); 6.79 (s, 1 H,
NH); 6.90 (d, 1 H, C(8)H, J = 8.0); 7.24 (m, 1 H, C(6)H); 7.65 (dd, 1 H, C(5)H,
3J = 7.9, 4J = 1.3); 9.38 (s, 1 H, NH)
3380, 3153 (NH); 1660 (CO);
1620, 1520, 1487 (arom.);
1340, 1160 (SO2)
3387, 3193, 3167 (NH);
1660 (CO); 1614, 1514,
1487 (arom.); 1330, 1160 (SO2)
10
11
3267 (NH); 1640, 1634 (CO, C=N); 1.50—2.60 ( m, 16 H, CH2); 6.61 (m, 1 H, C(7)H); 6.67 (d, 1 H, C(8)H, J = 8.0);
1614, 1580, 1514, 1487 (arom.)
3320 (NH); 1640 sh,
6.75 (s, 1 H, NH); 7.13 (m, 1 H, C(6)H); 7.59 (d, 1 H, C(5)H, J = 7.0)
1.00—2.50 (m, 20 H, CH2); 6.51 (s, 1 H, NH); 6.61 (m, 1 H, C(7)H);
6.87 (d, 1 H, C(8)H, J = 8.0); 7.16 (m, 1 H, C(6)H); 7.57 (dd, 1 H, C(5)H,
3J = 7.8, 4J = 1.4)
1620 (CO, C=N); 1607, 1580,
1514, 1487 (arom.)
12
3167 (NH); 1660 (CO); 1607,
1600, 1567, 1475 (arom.);
1354, 1167 (SO2)
2.61, 3.18 (both s, 3 H each, Me); 7.47 (m, 1 H, C(7)H); 7.60 (d, 1 H, C(8)H,
J = 8.0); 7.77 (m, 1 H, C(6)H); 8.12 (dd, 1 H, C(5)H, 3J = 7.9, 4J = 1.1);
10.95 (s, 1 H, NH)
13a
3313, 3260 (OH, NH); 1707,
1687, 1634 (CO); 1607 (arom.)
2.40 (m, 4 H, CH2); 5.90 (d, 1 H, C(2)H, J = 2.0); 6.35 (m, 2 H, C(3´)H,
C(4´)H); 6.72 (m, 2 H, CHarom); 7.23 (m, 1 H, CHarom); 7.29 (d, 1 H, C(5´)H,
J = 1.7); 7.51 (br.d, 1 H, NH); 7.65 (d, C(5)H, J = 7.0); 10.08 (s, 1 H, NH);
11.92 (s, 1 H, OH)
13b
14
3319, 3260, 3033 (OH, NH);
1734, 1714, 1667 (CO); 1614,
1540, 1500, 1487 (arom.)
3320, 3193, 3020 (OH, NH);
1700, 1687, 1640 (CO); 1614,
1527, 1507, 1487 (arom.)
2.30 (m, 4 H, CH2); 6.00 (br.d, 1 H, C(2)H); 6.70 (m, 2 H, CHarom);
7.10 (m, 3 H, CHarom); 7.23 (m, 1 H, CHarom); 7.49 (m, 2 H, NH, CHarom);
7.66 (br.dd, C(5)H); 9.77 (s, 1 H, NH); 11.90 (s, 1 H, OH)
5.98 (d, 1 H, C(2)H, J = 2.6); 6.20—6.40 (m, 4 H, C(3´)H, C(4´)H, CHolef);
6.72 (m, 2 H, CHarom); 7.25 (m, 1 H, CHarom); 7.44 (d, 1 H, NH, J = 2.6);
3
7.50 (m, 1 H, C(5´)H); 7.68 (dd, 1 H, C(5)H, J = 7.8, 4J = 1.5);
10.87 (s, 1 H, NH); 13.33 (s, 1 H, OH).
15
16
3326, 3253 (OH, NH);
1707, 1674 (CO); 1634,
1620, 1607, 1580 (arom.)
3333 (NH); 1714, 1660 (CO);
1607, 1567, 1520, 1480 (arom.)
1.40—2.30 (m, 8 H, CH2); 2.45 (m, 4 H, CH2); 6.88 (m, 2 H, C(7)H, C(8)H);
6.85 (s, 1 H, NH); 7.19 (m, 1 H, C(6)H); 7.60 (dd, 1 H, C(5)H, 3J = 7.8,
4J = 1.2); 9.72 (s, 1 H, NH); 11.91 (s, 1 H, OH)
2.40 (s, 3 H, Me); 2.58 (m, 4 H, CH2); 7.44 (m, 1 H, C(7)H); 7.57 (d, 1 H, C(8)H,
J = 8.1); 7.72 (m, 1 H, C(6)H); 8.11 (d, 1 H, C(5)H, J = 7.9); 10.97 (s, 1 H, NH);
12.03 (s, 1 H, OH)

1236
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 7, July, 2006
Ukhin and Kuz´mina
from EtOH (75 mL). Lemonꢀyellow crystals with m.p. of
241—249 °C were obtained. The yield was 0.55 g (75%).
Found (%): C, 49.83; H, 4.16; N, 15.32. C15H14N4O5S. Calcuꢀ
lated (%): C, 49.72; H, 3.89; N, 15.46.
2ꢀ(2ꢀHydroxyꢀ5ꢀnitrophenyl)ꢀ3ꢀmethylsulfonylaminoꢀ
1,2,3,4ꢀtetrahydroquinazolinꢀ4ꢀone (3c) was prepared analoꢀ
gously to 3a. The reaction time was 15 min. Yellowish crystals
containing a PrOH solvate molecule were obtained, the solꢀ
vate molecule being gradually eliminated on heating. M.p.
225—240 °C. The yield was 0.33 g (75%). M+ 378.
2ꢀ(2ꢀFuryl)ꢀ3ꢀmethylsulfonylaminoꢀ1,2,3,4ꢀtetrahydroꢀ
quinazolinꢀ4ꢀone (3d) was prepared analogously to 3a with the
use of furfural (0.2 mL, a 100% excess). Colorless crystals with
m.p. of 215—220 °C were obtained. The yield was 0.25 g (81%).
Found (%): C, 51.13; H, 4.37; N, 13.31. C13H13N3O4S. Calcuꢀ
lated (%): C, 50.81; H, 4.26; N, 13.67.
3ꢀMethylsulfonylaminoꢀ2ꢀ(2ꢀthienyl)ꢀ1,2,3,4ꢀtetrahydroꢀ
quinazolinꢀ4ꢀone (3e) was prepared analogously to 3a from hydrꢀ
azide 1 (0.46 g, 2 mmol) and 2ꢀthiophenecarbaldehyde (0.3 mL,
3.2 mmol) in PriOH (10 mL). Compound 3e was recrystallized
from EtOH (20 mL). Colorless crystals with m.p. of 230—234 °C
were obtained. The yield was 0.45 g (69%). Found (%): C, 47.92;
H, 4.37; N, 12.63. C13H13N3O3S2. Calculated (%): C, 48.28;
H, 4.05; N, 12.99.
2ꢀ(3ꢀIndolyl)ꢀ3ꢀmethylsulfonylaminoꢀ1,2,3,4ꢀtetrahydroꢀ
quinazolinꢀ4ꢀone (3f) was prepared analogously to 3a. The reacꢀ
tion time was 35 min. Colorless crystals with m.p. of 225—228 °C
were obtained. The yield was 0.2 g (56%). The filtrate was parꢀ
tially concentrated and an additional amount (0.07 g) of comꢀ
pound 3f was obtained. The total yield was 0.27 g (76%).
Found (%): C, 57.35; H, 4.72; N, 15.54. C17H16N4O3S. Calcuꢀ
lated (%): C, 57.29; H, 4.53; N, 15.72.
2ꢀ(2ꢀHydroxyphenyl)ꢀ3ꢀmethylsulfonylaminoꢀ1,2,3,4ꢀtetraꢀ
hydroquinazolinꢀ4ꢀone (3g) was prepared analogously to 3a from
hydrazide 1 (1.3 g) and salicylaldehyde (0.7 mL, 0.1 mL excess)
in PrOH (5 mL). After cooling on ice, PriOH (3 mL) was added.
Colorless crystals with m.p. of 237—240 °C were obtained. The
yield was 1.5 g (79%). A compound with m.p. of 232—239 °C
was precipitated from the filtrate with petroleum ether in a yield
of 0.19 g. The IR spectrum of the latter compound was identical
with that of 3g. Found (%): C, 53.82; H, 4.79; N, 12.83.
C15H15N3O4S. Calculated (%): C, 54.05; H, 4.53; N, 12.60.
2ꢀ(4ꢀHydroxyꢀ3ꢀmethoxyphenyl)ꢀ3ꢀmethylsulfonylaminoꢀ
1,2,3,4ꢀtetrahydroquinazolinꢀ4ꢀone (3h) was prepared analoꢀ
gously to 3a by the reaction with vanillin. The reaction mixture
was cooled to room temperature, water (20 mL) was added, and
the mixture was cooled on ice. The precipitate was filtered off,
washed with water, and dried. A colorless compound with m.p.
of 232—238 °C was obtained. The yield was 0.28 g (77%).
M+ 363. Found (%): C, 52.50; H, 5.11; N, 11.34. C16H17N3O5S.
Calculated (%): C, 52.88; H, 4.72; N, 11.56.
Then H2O (30 mL) was added and the mixture was kept on ice
for 1 h. The precipitate was filtered off and dried in vacuo.
A colorless compound with m.p. of 195—200 °C was obtained.
The yield was 0.2 g (56%). Found (%): C, 53.34; H, 4.32;
N, 19.30. C16H15N5O3S. Calculated (%): C, 53.77; H, 4.23;
N, 19.60.
2ꢀ[2ꢀ(Chloroquinolinꢀ3ꢀyl)]ꢀ3ꢀmethylsulfonylaminoꢀ1,2,3,4ꢀ
tetrahydroquinazolinꢀ4ꢀone (3k). A mixture of hydrazide 1
(0.46 g, 2 mmol) and 2ꢀchloroꢀ3ꢀformylquinoline10 (0.38 g,
2 mmol) was refluxed in PrOH (5 mL) for 15 min. The new
crystalline precipitate that formed after dissolution of the startꢀ
ing compounds was filtered off from the hot solution, washed
with PrOH and petroleum ether, and dried. A colorless comꢀ
pound, which decomposes upon heating above 250 °C, was obꢀ
tained. The yield was 0.5 g (62%). Found (%): C, 53.55; H, 3.91;
N, 14.11. C18H15N4ClO3S. Calculated (%): C, 53.67; H, 3.75;
N, 13.91.
2ꢀ(5ꢀChloroꢀ2ꢀpropargyloxyphenyl)ꢀ3ꢀmethylsulfonylaminoꢀ
1,2,3,4ꢀtetrahydroquinazolinꢀ4ꢀone (3l). Propargyl ether of
5ꢀchlorosalicylaldehyde11 (0.39 g, 2 mmol) was added to a boilꢀ
ing solution of hydrazide 1 (0.46 g, 2 mmol) in PrOH (10 mL).
The mixture was refluxed for 30 min. The precipitate that formed
was filtered off in the hot state and washed with PriOH and
petroleum ether. Colorless crystals with m.p. of 213—220 °C
were obtained. The yield was 0.57 g (70%). Found (%): C, 52.94;
H, 4.27; N, 10.41. C18H16N3ClO4S. Calculated (%): C, 53.27;
H, 3.97; N, 10.35.
2ꢀ(3ꢀMethoxyꢀ4ꢀpropargyloxyphenyl)ꢀ3ꢀmethylsulfonylꢀ
aminoꢀ1,2,3,4ꢀtetrahydroquinazolinꢀ4ꢀone (3m). A mixture of
hydrazide 1 (0.46 g, 2 mmol) and propargyl ether of vanillin11
(0.38 g, 2 mmol) was refluxed in PrOH (10 mL) for 30 min and
then cooled to room temperature by gradually adding water with
stirring and rubbing with a rod. Then the mixture was kept on
ice for 3 h. The precipitate that formed was filtered off and
recrystallized from toluene with cooling to room temperature
and rubbing with a rod. A colorless compound with m.p. of
141—142 °C was obtained. The yield was 0.43 g (54%).
Found (%): C, 56.63; H, 5.11; N, 10.24. C19H19N3O5S. Calcuꢀ
lated (%): C, 56.85; H, 4.77; N, 10.47.
3ꢀMethylsulfonylaminoꢀ3,4ꢀdihydroquinazolinꢀ4ꢀone (4).
Hydrazide 1 (0.46 g, 2 mmol) was refluxed in HCOOH (2 mL)
for 1 h and then cooled. An oil that was precipitated with water
crystallized out by rubbing with a rod. The precipitate was filꢀ
tered off and recrystallized from MeOH. A colorless compound
with m.p. of 222—228 °C was obtained. The yield was 0.42 g
(87%). M+ 239. Found (%): C, 45.23; H, 4.13; N, 17.32.
C9H9N3O3S. Calculated (%): C, 45.18; H, 3.79; N, 17.56.
2ꢀ(2ꢀFuryl)ꢀ3ꢀ(2ꢀfurfurylideneamino)ꢀ1,2,3,4ꢀtetrahydroꢀ
quinazolinꢀ4ꢀone (6). A mixture of hydrazide 5 (0.75 g, 5 mmol)
and furfural (1 mL, 12 mmol) was refluxed in PrOH (5 mL) for
1 h and cooled on ice using rubbing with a rod. The precipitate
that formed was filtered off, washed with cold PriOH and petroꢀ
leum ether, and dried. Creamꢀcolor crystals with m.p. of
127—130 °C (from PriOH) were obtained. The yield was 1.27 g
(83%). Found (%): C, 66.72; H, 4.34; N, 13.41. C17H13N3O3.
Calculated (%): C, 66.44; H, 4.26; N, 13.67.
3ꢀMethylsulfonylaminoꢀ2ꢀ(2ꢀmethylsulfonylaminophenyl)ꢀ
1,2,3,4ꢀtetrahydroquinazolinꢀ4ꢀone (3i) was prepared analogously
to 3a by the reaction with oꢀmesylaminobenzaldehyde.9 A colꢀ
orless compound with m.p. of 157 °C was obtained. The yield
was 0.26 g (63%). The structure was established by Xꢀray difꢀ
fraction.
2ꢀ(2ꢀBenzimidazolyl)ꢀ3ꢀmethylsulfonylaminoꢀ1,2,3,4ꢀtetraꢀ
hydroquinazolinꢀ4ꢀone (3j) was prepared analogously to 3a in
PrOH (10 mL). The reaction time was 2 h. The reaction mixture
was filtered off from a small insoluble precipitate and cooled.
3ꢀAminoꢀ3,4ꢀdihydroquinazolinꢀ4ꢀone (7). Hydrazide 5 (1 g,
6.6 mmol) was refluxed in HCOOH (2 mL) for 1 h and cooled.
Then H2O (10 mL) and concentrated NH4OH (6 mL) were
added. The precipitate that formed was filtered off and reꢀ
crystallied from MeOH. A colorless compound with m.p. of

3,4ꢀDiꢀ and 1,2,3,4ꢀtetrahydroquinazolinꢀ4ꢀones
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 7, July, 2006
1237
212—214 °C was obtained. The yield was 0.3 g (28%). Found (%):
C, 63.21; H, 5.41; N, 31.72. C7H7N3O. Calculated (%): C, 63.14;
H, 5.30; N, 31.56.
Nꢀ[2ꢀ(4ꢀFluorophenyl)ꢀ4ꢀoxoꢀ1,2,3,4ꢀtetrahydroquinazolinꢀ
3ꢀyl]succinamic acid (13b). A colorless compound with m.p. of
155—160 °C (from MeCN) was obtained. The yield was 1 g
(56%). Found (%): C, 60.31; H, 4.62; N, 11.54. C18H16N3O4F.
Calculated, (%): C, 60.50; H, 4.51; N, 11.76.
Nꢀ[2ꢀ(2ꢀFuryl)ꢀ4ꢀoxoꢀ1,2,3,4ꢀtetrahydroquinazolinꢀ3ꢀ
yl]maleinamic acid (14). A colorless compound with m.p. of
177—178 °C (from propylene carbonate) was obtained. The yield
was 0.8 g (50%). M+ 327. Found (%): C, 58.41; H, 4.35; N, 12.60.
3ꢀMethylsulfonylaminoꢀ2ꢀspirocyclopentaneꢀ1,2,3,4ꢀtetraꢀ
hydroquinazolinꢀ4ꢀone (8). A mixture of hydrazide 1 (0.46 g,
2 mmol) and cyclopentanone (1 mL) in ethylene glycol (3 mL)
was refluxed for 1.5 h and cooled. Then PriOH (5 mL) was
added and the mixture was kept on ice for 1 h. The precipitate
that formed was filtered off and washed with cold PriOH and
petroleum ether. A colorless compound with m.p. of 283—286 °C
was obtained. The yield was 0.45 g (76%). Found (%): C, 52.69;
H, 5.98; N, 14.00. C13H17N3O3S. Calculated (%): C, 52.87;
H, 5.80; N, 14.23.
3ꢀMethylsulfonylaminoꢀ2ꢀspirocyclohexaneꢀ1,2,3,4ꢀtetraꢀ
hydroquinazolinꢀ4ꢀone (9). A mixture of hydrazide 1 (0.23 g,
1 mmol) and cyclohexanone (1 mL) in glycol (3 mL) was reꢀ
fluxed for 2 h and then cooled. The precipitate that formed was
filtered off and washed with EtOH. A colorless compound with
m.p. of 282—284 °C was obtained. The yield was 0.21 g (68%).
Found (%): C, 54.11; H, 6.51; N, 13.21. C14H19N3O3S. Calcuꢀ
lated (%): C, 54.35; H, 6.19; N, 13.58.
2ꢀSpirocyclopentaneꢀ3ꢀcyclopentylideneaminoꢀ1,2,3,4ꢀtetraꢀ
hydroquinazolinꢀ4ꢀone (10). Hydrazide 5 (0.5 g, 3.3 mmol) was
refluxed in cyclopentanone (3 mL) for 1 h, the reaction mixture
was cooled, and petroleum ether (10 mL) was added to the
precipitate that formed. Then the precipitate was filtered off and
washed with petroleum ether. A colorless compound with m.p.
of 155—166 °C (from isooctane) was obtained. The yield was 0.9 g
(96%). Found (%): C, 72.60; H, 7.68; N, 14.52. C17H21N3O.
Calculated (%): C, 72.31; H, 7.50; N, 14.88.
2ꢀSpirocyclohexaneꢀ3ꢀcyclohexylideneaminoꢀ1,2,3,4ꢀtetraꢀ
hydroquinazolinꢀ4ꢀone (11) was prepared analogously to comꢀ
pound 10 in cyclohexanone (3 mL). A colorless compound with
m.p. of 228—230 °C was obtained. The yield was 0.85 g (82.5%).
Found (%): C, 73.16; H, 8.24; N, 13.51. C19H25N3O. Calcuꢀ
lated (%): C, 73.28; H, 8.09; N, 13.49.
C
16H13N3O5. Calculated (%): C, 58.72; H, 4.00; N, 12.84.
Table 4. Crystallographic parameters and details of Xꢀray difꢀ
fraction study of crystal solvates 3i•MeNO2 and 3i•MeCN
Parameter
3i•MeNO2
3i•MeCN
Molecular formula
C17H21N5O7S2
471.51
C18H21N5O5S2
451.52
Molecular weight
/kg kmol–1
Crystal system
Space group
a/Å
b/Å
c/Å
α/deg
β/deg
Monoclinic
P21/c
9.3609(5)
22.979(1)
9.8990(6)
—
96.083(2)
—
2117.3(2)
4
Triclinic
–
P1
9.4160(4)
9.8709(3)
12.3807(4)
72.796(2)
73.176(2)
84.917(2)
1052.18(6)
2
γ/deg
V/Å3
Z
ρ
calc/g cm–1
1.479
1.425
F(000)
984
0.302
472
0.294
µ(MoꢀKα)/mm–1
Crystal dimensions/mm
T/K
0.28×0.12×0.10 0.18×0.08×0.02
120.0(2)
120.0(2)
Radiation (λ/Å)
MoꢀKα
MoꢀKα
(0.71073)
ω
(0.71073)
ω
2ꢀMethylꢀ3ꢀmethylsulfonylaminoꢀ3,4ꢀdihydroquinazolinꢀ4ꢀ
one (12). Hydrazide 1 (1 g, 4.3 mmol) was refluxed in acetylꢀ
acetone (4 mL) for 30 min, PriOH (4 mL) was added, and the
mixture was cooled on ice using rubbing with a rod. The precipiꢀ
tate that formed was filtered off and washed with PriOH and
petroleum ether. A colorless compound with m.p. of 195—197 °C
(from PriOH) was obtained. The yield was 0.7 g (63%). M+ 253.
Found (%): C, 47.20; H, 4.53; N, 16.41. C10H11N3O3S. Calcuꢀ
lated (%): C, 47.42; H, 4.38; N, 16.59.
Scanning mode
Scan range, θ/deg
Ranges of indices
of measured reflections
1.77—28.00
–12 ≤ h ≤ 12
–29 ≤ k ≤ 30
–8 ≤ l ≤ 13
15029
1.79—29.82
–12 ≤ h ≤ 10
–13 ≤ k ≤ 11
–17 ≤ l ≤ 16
7818
Number of measured
reflections
Number of independent
reflections
5096
5279
Synthesis of compounds 13 and 14 (general procedure). Hydrꢀ
azide 5 (0.75 g, 5 mmol) and succinic (in the case of 13a,b) or
maleic (in the case of 14) anhydride (0.5 g, 5 mmol) were trituꢀ
rated in a mortar and placed in a roundꢀbottom flask. Then
MeCN (5 mL), which was distilled over P2O5 before use, was
added, and the reaction mixture was refluxed for 5 min. Furfural
(in the case of 13a and 14) or pꢀfluorobenzaldehyde (in the case
of 13b) (0.6 mL) was added. The reaction mixture was refluxed
for 30 min (in the case of 13a,b) or 15 min (in the case of 14) and
cooled on ice. The precipitate that formed was filtered off,
washed with cold MeCN and petroleum ether, and dried.
Nꢀ[2ꢀ(2ꢀFuryl)ꢀ4ꢀoxoꢀ1,2,3,4ꢀtetrahydroquinazolinꢀ3ꢀ
yl]succinamic acid (13a). A colorless compound with m.p. of
154—156 °C was obtained. The yield was 1 g (61%). M+ 329.
Found (%): C, 58.11; H, 4.78; N, 12.50. C16H15N3O5. Calcuꢀ
lated (%): C, 58.36; H, 4.59; N, 12.76.
(Rint
)
(0.0277)
4309
(0.0221)
4163
Number of reflections
with I >2σ(I )
Variables in refinement
R factors
based on reflections
with I > 2σ(I )
R1
365
344
0.0401
0.1008
0.0533
0.1365
wR2
based on all reflections
R1
0.0491
0.1048
1.055
0.0740
0.1471
1.005
wR2
Goodnessꢀofꢀfit on F 2
Residual electron density
(min/max)/e Å3
–0.426/0.437
–0.518/0.370

1238
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 7, July, 2006
Ukhin and Kuz´mina
Nꢀ(4ꢀOxoꢀ2ꢀspirocyclopentaneꢀ1,2,3,4ꢀtetrahydroquinazoꢀ
linꢀ3ꢀyl)succinamic acid (15) was prepared analogously to 13
from hydrazide 5 (1.5 g), succinic anhydride (1 g), and cycloꢀ
pentanone (2 mL) in MeCN (5 mL). A colorless compound
with m.p. of 191—193 °C (from MeOH) was obtained. The yield
was 2.4 g (75%). Found (%): C, 60.44; H, 6.35; N, 13.42.
and other experimental data were deposited with the Cambridge
Crystallographic Data Center.*
References
1. S. Gabriel and J. Colman, Ber., 1904, 37, 3643.
2. C. Parkanyi, H. L. Yuan, B. H. E. Strömberg, and
A. Evenzahav, J. Heterocycl. Chem., 1992, 29, 749.
3. P. K. Mohanta and K. Kim, Heterocycles, 2002, 57, 1471.
4. H. Böhme and H. Böing, Arch. Pharm., 1960, 293, 1011.
5. R. H. Klemm, J. Wang, and L. Hawkins, J. Heterocycl. Chem.,
1995, 32, 1039.
6. R. H. Klemm, T. J. R. Weakley, R. D. Gilbertson, and
YangꢀHeonꢀSong, J. Heterocycl. Chem., 1998, 35, 1269.
7. J. Lessel, Arch. Pharm. (Weinheim), 1994, 327, 571.
8. L. A. Shemchuk, Zh. Org. Khim., 1998, 34, 568 [Russ. J. Org.
Chem., 1998, 34 (Engl. Transl.)].
9. L. Yu. Ukhin and L. G. Kuz´mina, Izv. Akad. Nauk, Ser.
Khim., 2004, 2165 [Russ. Chem. Bull., Int. Ed., 2004,
53, 2262].
10. D. MethꢀCohn, B. Narine, and B. Tarnowski, Tetrahedron
Lett., 1997, 33, 3111.
C
16H19N3O4. Calculated (%): C, 60.56; H, 6.04; N, 13.24.
Nꢀ(2ꢀMethylꢀ4ꢀoxoꢀ3,4ꢀdihydroquinazolinꢀ3ꢀyl)succinamic
acid (16) was prepared analogously to 15 with the use of
acetylacetone (2 mL). After refluxing for 1 h, the solution was
cooled and kept on ice for 3 h. The precipitate that formed was
filtered off, washed with cold MeCN, diethyl ether, and petroꢀ
leum ether, and dried. Colorless crystals with m.p. of 203—205 °C
were obtained. The yield was 0.65 g (24%). M+ 275. Found (%):
C, 56.38; H, 5.13; N, 15.10. C13H13N3O4. Calculated (%):
C, 56.73; H, 4.76; N, 15.27.
Xꢀray diffraction study of crystal solvates 3i•MeNO2 and
3i•MeCN. Single crystals of crystal solvates 3i•MeNO2 and
3i•MeCN were coated with a perfluorinated oil and mounted
on a Bruker SMARTꢀCCD diffractometer under a stream of
cold nitrogen. The experimental Xꢀray data sets were collected
from single crystals (MoꢀKα radiation) using the ωꢀscanning
technique. The crystallographic parameters and characteristics
of Xꢀray diffraction study are given in Table 4.
11. L. Yu. Ukhin, K. Yu. Suponitskii, and V. G. Kartsev, Khim.
Prirod. Soedin., 2003, 395 [Chem. Nat. Compd., 2003 (Engl.
Transl.)].
12. SAINT. Version 6.02A, Bruker AXS Inc., Madison (Wisconꢀ
sin, USA), 2001.
The experimental reflections were processed using the Bruker
SAINT software.12
Both structures were solved by direct methods and refined
by the fullꢀmatrix leastꢀsquares method against F 2 with anisoꢀ
tropic displacement parameters for all nonhydrogen atoms. The
positions of the hydrogen atoms, including the hydrogen atoms
of the methyl groups of the nitromethane solvate molecule in
3i•MeNO2 and the acetonitrile solvate molecule in 3i•MeCN,
were revealed in difference Fourier maps and refined isoꢀ
tropically.
13. SHELXTLꢀPlus, Release 5.10, Bruker AXS Inc., Madison
(Wisconsin, USA), 1997.
Received April 25, 2005;
in revised form November 25, 2005
* CCDC, 12 Union Road, Cambridge CB21EZ, UK (fax:
(+44)1223ꢀ336ꢀ033; eꢀmail: deposit@ccdc.cam.ac). The data
can also be obtained from the authors.
All calculations were carried out with the use of the
SHELXTLꢀPlus program package.13 The atomic coordinates