Glycolurils in α-ureido-and α-aminoalkylation reactions 1. α-Ureidoalkylation of sulfamides with N-(hydroxymethyl)glycolurils

Article abstract of DOI:10.1007/s11172-007-0358-8

α-Ureidoalkylation of sulfamides with 2-hydroxymethyl-, 2,6-and 2,8-bis(hydroxymethyl)-, and 2,4,6,8-tetrakis(hydroxymethyl)glycolurils gave novel bi-, tri-, and tetracyclic fused systems combining the glycoluril and sulfamide fragments.

Full text of DOI:10.1007/s11172-007-0358-8

Russian Chemical Bulletin, International Edition, Vol. 56, No. 11, pp. 2272—2276, November, 2007
2272
Glycolurils in αꢀureidoꢀ and αꢀaminoalkylation reactions
1. αꢀUreidoalkylation of sulfamides with Nꢀ(hydroxymethyl)glycolurils
G. A. Gazieva,ꢀ A. N. Kravchenko, N. S. Trunova, and N. N. Makhova
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. Eꢀmail: gaz@server.ioc.ac.ru
αꢀUreidoalkylation of sulfamides with 2ꢀhydroxymethylꢀ, 2,6ꢀ and 2,8ꢀbis(hydroxyꢀ
methyl)ꢀ, and 2,4,6,8ꢀtetrakis(hydroxymethyl)glycolurils gave novel biꢀ, triꢀ, and tetracyclic
fused systems combining the glycoluril and sulfamide fragments.
Key words: αꢀureidoalkylation, Nꢀ(hydroxymethyl)glycolurils, Nꢀ(arylsulfonylaminoꢀ
methyl)glycolurils, 9,11ꢀdialkylꢀ8,12ꢀdioxoꢀ4ꢀthiaꢀ1,3,5,7,9,11ꢀhexaazatricyclo[5.5.1.010,13]triꢀ
decane 4,4ꢀdioxides, 3,5,11,13ꢀtetramethylꢀ8,16ꢀdioxoꢀ4,12ꢀdithiaꢀ1,3,5,7,9,11,13,15ꢀoctaazaꢀ
tetracyclo[7.7.2.0.7,17015,18]octadecane 4,4,12,12ꢀtetraoxide.
Earlier, we have studied in detail αꢀureidoalkylation
2ꢀones 3—5 and 1,3ꢀdialkylꢀ4ꢀguanidinoiminoimidꢀ
azolidinꢀ2ꢀones 6.3,4
Out of Nꢀ(hydroxymethyl)glycolurils, only 2,4,6,8ꢀtetꢀ
rakis(hydroxymethyl)glycolurils have been used hitherto
as ureidoalkylating reagents (in the synthesis of cucurꢀ
biturils).7,8
Because glycolurils belong to a novel class of neuroꢀ
tropic compounds9—11 and exhibit other types of bioꢀ
logical activity,12,13 it was of practical interest to deꢀ
sign a molecule combining the glycoluril fragment and
other pharmacophore (e.g., sulfamide14) groups. The
fundamental possibility of the synthesis of such comꢀ
pounds has been demonstrated earlier with single exꢀ
amples.15 Here we studied αꢀureidoalkylation with variꢀ
ous 2ꢀhydroxymethylꢀ, 2,6ꢀ and 2,8ꢀbis(hydroxymethyl)ꢀ,
and 2,4,6,8ꢀtetrakis(hydroxymethyl)glycolurils 7 of sulꢀ
fonamides 8, sulfamide, and N,N´ꢀdialkylsulfamides 9
with the aim of obtaining novel biꢀ, triꢀ, and tetracyclic
fused systems combining the glycoluril and sulfamide
fragments.
of ureas1,2 and their analogs (thiosemicarbazide and
aminoguanidine3,4) with 4,5ꢀdihydroxyimidazolidinꢀ2ꢀ
ones. Based on the results obtained, we have developed
general methods for the targeted synthesis of various
Nꢀsubstituted glycolurils (2,4,6,8ꢀtetraazabicyclo[3.3.0]ꢀ
octaneꢀ3,7ꢀdiones) 1 (including hydroxy(carboxy)alkylꢀ
ated ones)1,5,6 and 3ꢀthioxoperhydroimidazo[4,5ꢀe]ꢀ
[1,2,4]triazinꢀ6ꢀones 2.3,4 In addition, we have discovꢀ
ered novel reactions leading to 4,5ꢀbis(3ꢀalkylureidoꢀ,
thiosemicarbazidoꢀ, and 3ꢀaminoguanidino)imidazolidinꢀ
Conditions for the synthesis of bicyclic compounds
10a—h (Scheme 1) were optimized with a reaction of
2ꢀhydroxymethylꢀ4,6,8ꢀtrimethylglycoluril (7a) with
benzenesulfonamide (8a) in boiling methanol in the presꢀ
ence of HCl as an example, by analogy with acidꢀcataꢀ
lyzed αꢀureidoalkylation with 4,5ꢀdihydroxyimidazolidinꢀ
2ꢀones conducted in either water or lower alcohols.
Methanol was used as a solvent because the starting
sulfamides are soluble in methanol better than in water.
1
The course of the reaction was monitored by H NMR
spectroscopy regarding disappearance of the signals for
the OH protons in the starting glycoluril 7a. The optiꢀ
mized reaction time was 1 h. αꢀUreidoalkylation of
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2195—2199, November, 2007.
1066ꢀ5285/07/5611ꢀ2272 © 2007 Springer Science+Business Media, Inc.

αꢀUreidoalkylation of sulfamides
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 11, November, 2007 2273
Scheme 1
Scheme 2
Comꢀ
R1
R2
R3
R4
pound
7: R1 = Me (e), Et (f); 9: R2 = H (a), Me (b), Pr (c);
7a
7b
7c
7d
10a
10b
10c
10d
10e
10f
10g
10h
Me
Me
Me
Et
Me
Me
Me
Me
Me
Me
Et
Me
Me
CH2OH
CH2OH
Me
Me
Me
Me
Me
Et
Me
Et
Me
Me
Et
—
—
—
—
Ph
11: R1 = Me, R2 = H (a); R1 = R2 = Me (b); R1 = Me, R2 = Pr (c);
R
1 = Et, R2 = H (d)
The 1H NMR spectra of compounds 11a—d show douꢀ
blets of doublets at δ 4.26—4.80 due to the diastereotopic
CH2 protons of the eightꢀmembered ring and doublets of
doublets at δ 5.16—5.35 for the CH—CH protons. The
IR spectra exhibit characteristic intense absorption bands
due to the SO2 (1144—1167 and 1320—1361 cm–1) and
C=O groups (1699—1728 cm–1); for compounds 11a,d,
the bands for the NH groups were also observed
(3239—3346 cm–1). The mass spectrum of the tricyclic
compound 11a contains a sufficiently intense molecular
ion peak. These peaks are absent for compounds 11b,c:
their mass spectra show peaks of the fragmentation ions
[M+ – 64] produced by elimination of an SO2 molecule
(Table 3).
4ꢀMeC6H4
Ph
4ꢀMeC6H4
Ph
4ꢀMeC6H4
Ph
4ꢀMeC6H4
Et
CH2NHSO2R4
CH2NHSO2R4
CH2NHSO2R4
CH2NHSO2R4
Me
Me
Et
Et
Et
8: R4 = Ph (a), 4ꢀMeC6H4 (b)
sulfonamides 8a,b with 2ꢀhydroxymethylꢀ (7a,b) and
2,6ꢀbis(hydroxymethyl)glycolurils (7c,d) under the optiꢀ
mized conditions gave 2ꢀ(arylsulfonylaminomethyl)ꢀ and
2,6ꢀbis(arylsulfonylaminomethyl)glycolurils 10a—h in
27—50% yields (Table 1).
The 1H NMR spectra of the compounds obtained show
characteristic triplets for the NH protons of the sulfamide
fragments at δ 8.51—8.65 (Table 2). The signals for the
CH—CH protons appear at δ 4.65—5.17 as two doublets
(10a—d) or a singlet (10e—h). The diastereotopic proꢀ
tons of the NCH2 groups resonate at δ 4.09—4.27 and
4.63—4.71. The 13C NMR spectra contain characteristic
signals for the NCH2 groups at δ 51—52; the signals for
the CH—CH and CO groups appear at δ 65—69 and
156—159, respectively. The IR spectra show intense abꢀ
sorption bands due to SO2 (1320—1328 cm–1), C=O
(1688—1712 cm–1), and NH groups (3184—3272 cm–1
and bands assignable to the framework vibrations of the
bicycles (1496—1508 cm–1).5
A similar approach was used to obtain 9,11ꢀdiꢀ
alkylꢀ8,12ꢀdioxoꢀ4ꢀthiaꢀ1,3,5,7,9,11ꢀhexaazatriꢀ
cyclo[5.5.1.010,13]tridecane 4,4ꢀdioxides 11a—d by conꢀ
densation of sulfamides 9a—c with 2,8ꢀbis(hydroxyꢀ
methyl)glycolurils 7e,f. The reactions were carried out in
MeOH (for sulfamides 9a,c) or PriOH (for sulfamide 9b)
(Scheme 2).
2,4,6,8ꢀTetrakis(hydroxymethyl)glycoluril (7g) is
soluble in water better than in MeOH; for this reason, we
carried out its condensation with N,N´ꢀdimethylsulfamide
1
(9b) in water at pH 1 (HCl) (Scheme 3). The H NMR
spectrum of the compound obtained shows a singlet at
δ 2.85, a doublet of doublets at δ 4.81, and a singlet at
δ 5.44 with an integral intensity ratio of 6 : 4 : 1.
This corresponds to the structure of tetracyclic comꢀ
pound 12: 3,5,11,13ꢀtetramethylꢀ8,16ꢀdioxoꢀ4,12ꢀdithiaꢀ
1,3,5,7,9,11,13,15ꢀoctaazatetracyclo[7.7.2.0.7,17015,18]ꢀ
octadecane 4,4,12,12ꢀtetraoxide. The mass spectrum conꢀ
tains a peak of the ion [M+ – 64] (due to eliminaꢀ
tion of SO2).
)
Compounds 10h and 11a were tested for antimicrobial
and fungicidal activities, respectively*. The test for
* The fungicidal activity was studied at the AllꢀRussia Research
Institute for chemical plant protectors under the supervision of
V. A. Abelentsev. The antimicrobial activity was studied at the
NaturalꢀScience Institute of the Perm State University under
the supervision of G. A. Aleksandrova.

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Russ.Chem.Bull., Int.Ed., Vol. 56, No. 11, November, 2007
Gazieva et al.
Table 1. Yields, melting points, and elemental analysis data for compounds 10a—h, 11a—d,
and 12
Comꢀ
pound
Yield
(%)
M.p.
/°С
Found
Calculated
Molecular
formula
(%)
C
H
N
S
10a
10b
10c
10d
10e
10f
48—50
30—35
43—47
30—34
20—25
27—31
44—48
40—45
58—60
43—45
24—27
47—49
51—55
176—178 47.62 5.39
47.58 5.42
174—176 49.05 5.78
49.03 5.76
210—212 48.98 5.79
49.03 5.76
174—176 50.41 6.05
50.38 6.08
233—235 47.21 4.79
47.23 4.76
238—240 49.20 5.28
49.24 5.26
237—239 49.27 5.26
49.24 5.26
197—199 51.03 5.76
51.05 5.71
237—239 32.93 4.99
(decomp.) 33.10 4.86
271—272 37.61 5.76
(decomp.) 37.73 5.70
265—267 44.87 7.03
(decomp.) 44.91 7.00
229—231 37.72 5.67
37.73 5.70
19.84
19.82
19.03
19.06
19.11
19.06
18.37
18.36
16.49
16.52
15.69
15.66
15.64
15.66
14.89
14.88
29.10
28.95
26.45
26.40
22.47
22.44
26.43
26.40
25.32
25.55
9.01
9.07
8.67
8.73
8.65
8.73
8.35
8.40
12.57
12.61
11.91
11.95
11.92
11.95
11.33
11.36
10.87
11.04
9.93
C14H19N5O4S
C15H21N5O4S
C15H21N5O4S
C16H23N5O4S
C20H24N6O6S2
C22H28N6O6S2
C22H28N6O6S2
C24H32N6O6S2
C8H14N6O4S
C10H18N6O4S
C14H26N6O4S
C10H18N6O4S
C12H22N8O6S2
10g
10h
11a
11b
11c
11d
12
10.07
8.48
8.56
9.96
10.07
14.87
14.63
>300
32.75 4.95
(decomp.) 32.87 5.06
antimicrobial activity revealed that compound 10h has
no bacteriostatic effect on Staphylococcus aureus and
Esherichia coli. Compound 11a was tested for fungiꢀ
cidal activity against pathogens causing root rot and
molding of agricultural seeds: Botrytis cinerea, Fusarium
oxysporum, Helminthosporium sativum, and Fusarium
graminearum. The fungicide thiram was used as a referꢀ
ence. According to the results of the tests (see below),
compound 11a exhibits a slight fungicidal activity. Bioꢀ
logical testing of the compounds obtained will be conꢀ
tinued.
Scheme 3
Comꢀ
pound
Growth suppression (%) of the fungi
Botrytis Fusarium
cinerea oxysporum
Helminthospoꢀ
rium sativum graminearum
Fusarium
11a
9
36
33
22
Thiram
100
100
100
100
In conclusion, we have studied for the first time
αꢀureidoalkylation of sulfamides with monoꢀ, bisꢀ, and
tetrakisꢀNꢀ(hydroxymethyl)glycolurils and obtained
novel Nꢀmonoꢀ and Nꢀbis(arylsulfonylaminomethyl)ꢀ
glycolurils: 9,11ꢀdialkylꢀ8,12ꢀdioxoꢀ4ꢀthiaꢀ1,3,5,7,9,11ꢀ
hexaazatricyclo[5.5.1.010,13]tridecane 4,4ꢀdioxides and
3,5,11,13ꢀtetramethylꢀ8,16ꢀdioxoꢀ4,12ꢀdithiaꢀ
1,3,5,7,9,11,13,15ꢀoctaazatetracyclo[7.7.2.0.7,17015,18]ꢀ
octadecane 4,4,12,12ꢀtetraoxide.

αꢀUreidoalkylation of sulfamides
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 11, November, 2007 2275
Table 2. IR and 1H and 13C NMR spectra of compounds 10a—h (DMSOꢀd6)
Comꢀ
pound
IR,
ν/cm–1
NMR, δ (J/Hz)
1H
13C
10a
—
2.73, 2.79, 2.81 (all s, 3 H each, NMe); 4.22, 4.65
(both dd, 1 H each, NCH2, J = 6.2); 4.82, 5.12
(both d, 1 H each, CH, J = 7.8); 7.54—7.64 (m, 3 H,
H(3)—H(5) (Ph)); 7.79 (d, 2 H, H(2), H(6) (Ph));
8.56 (t, 1 H, NH, J = 5.9)
2.37 (s, 3 H, Me (Ts)); 2.71, 2.78, 2.80 (all s, 3 H each,
NMe); 4.23, 4.65 (both dd, 1 H each, NCH2, J = 6.2);
4.76, 5.09 (both d, 1 H each, CH, J = 7.8); 7.39, 7.70
(both d, 2 H each, Ts, J = 7.8); 8.56 (t, 1 H, NH, J = 5.9)
1.01 (t, 3 H, Me (Et), J = 7.0); 2.76, 2.80 (both s,
3 H each, NMe); 3.03—3.26 (m, 2 H, NCH2 (Et));
4.23, 4.66 (both d, 1 H each, NCH2, J = 5.5); 4.92, 5.12
(both d, 1 H each, CH, J = 8.6); 7.52—7.63 (m, 3 H,
H(3)—H(5) (Ph)); 7.79 (d, 2 H, H(2), H(6) (Ph),
J = 6.7); 8.63 (t, 1 H, NH, J = 5.8)
—
—
10b
10c
—
3184, 1696,
1508, 1328
13.26 (Me (Et)); 29.80, 30.33 (2 MeN);
37.07 (CH2 (Et)); 51.04 (CH2); 67.62,
69.53 (2 CH); 126.29 (C(4) (Ph)); 129.27
(C(3), C(5) (Ph)); 132.64 (C(2), C(6) (Ph));
140.98 (C(1) (Ph)); 156.96, 158.73 (2 CO)
10d
3188, 1700,
1500, 1320
1.03 (t, 3 H, Me (Et), J = 6.7); 2.39 (s, 3 H, Me (Ts));
2.80, 2.82 (both s, 3 H each, NMe); 3.07—3.29 (m, 2 H,
NCH2 (Et)); 4.19—4.27, 4.63—4.71 (both m, 1 H each,
NCH2); 4.97, 5.17 (both d, 1 H each, СHСH, J = 8.5);
7.39 (d, 2 H, Ts, J = 8.0); 7.69 (d, 2 H, Ts, J = 8.6);
8.51 (t, 1 H, NH, J = 8.5)
13.16 (Me (Et)); 20.97 (Me (Ts)); 29.78,
30.29 (2 MeN); 36.97 (CH2 (Et)); 50.96
(CH2); 67.53, 69.46 (2 CH); 126.33
(C(4) (Ts)); 129.43 (C(3), C(5) (Ts));
138.13 (C(2), C(6) (Ts)); 142.84 (C(1)
(Ts)); 156.89, 158.65 (2 CO)
10e
10f
3264, 3220,
1712, 1688,
1504, 1328
2.68 (s, 6 H, 2 NMe); 4.22 (d, 2 H, NCH2, J = 14.7);
4.70 (m, 4 H, NCH2 + CHCH); 7.58—7.68 (m, 6 H,
Ph); 7.78 (d, 4 H, Ph, J = 7.3); 8.62 (br.s, 2 H, 2 NH)
29.07 (2 MeN); 51.06 (2 CH2); 66.75 (2 CH);
126.31 (C(4) (Ph)); 129.16 (C(3), C(5) (Ph));
132.61 (C(2), C(6) (Ph)); 141.01 (C(1) (Ph));
156.83 (2 CO)
3272, 3180,
1708, 1692,
1504, 1328
2.43 (s, 6 H, 2 Me (Ts)); 2.67 (s, 6 H, 2 NMe); 4.19
(d, 2 H, NCH2, J = 11.1); 4.65 (m, 4 H, NCH2 +
+ CHCH); 7.40, 7.64 (both d, 4 H, Ts, J = 6.6);
8.56 (m, 2 H, 2 NH)
0.97 (t, 6 H, 2 Me (Et), J = 6.7); 3.02—3.29 (m, 4 H,
2 NCH2 (Et)); 4.12, 4.66 (both dd, 2 H, NCH2, J = 5.8);
4.98 (s, 2 H, СHСH); 7.61 (m, 6 H, Ph); 7.78 (d, 4 H,
Ph, J = 6.1); 8.65 (t, 1 H, NH, J = 5.8)
0.97 (t, 6 H, 2 Me (Et), J = 6.7); 2.39 (s, 6 H, 2 Me
(Ts)); 3.01—3.26 (m, 4 H, 2 NCH2 (Et)); 4.09, 4.65
(both dd, 2 H, NCH2, J = 5.5); 4.94 (s, 2 H, СHСH);
7.39, 7.66 (both d, 4 H each, Ts, J = 8.2); 8.57 (t, 1 H,
NH, J = 5.5)
20.97 (Me (Ts)); 29.33 (2 MeN); 52.19
(2 CH2); 65.94 (2 CH); 126.14 (C(4) (Ts));
129.57 (C(3), C(5) (Ts)); 137.96 (C(2), C(6)
(Ts)); 142.34 (C(1) (Ts)); 156.43 (2 CO)
13.41 (2 Me (Et)); 36.76 (2 CH2 (Et)); 51.81
(2 CH2); 65.64 (2 CH); 126.18 (C(4) (Ph));
129.22 (C(3), C(5) (Ph)); 132.62 (C(2), C(6)
(Ph)); 140.82 (C(1) (Ph)); 156.86 (2 CO)
13.14 (2 Me (Et)); 21.01 (2 Me (Ts)); 36.74
(2 CH2 (Et)); 51.08 (2 CH2); 65.38 (2 CH);
126.26 (C(4) (Ts)); 129.67 (C(3), C(5) (Ts));
138.07 (C(2), C(6) (Ts)); 143.00 (C(1) (Ts));
156.85 (2 CO)
10g
10h
3252, 3192,
1688, 1496,
1324
3212, 1688,
1496, 1328
was refluxed for 1 h and concentrated in a rotary evaporator.
The residue was diluted with water (4 mL) and left for ~14 h.
The white precipitate that formed was filtered off, washed with
hot water, and crystallized from methanol—water (1 : 2).
Synthesis of glycolurils 10e—h (general procedure). Apꢀ
propriate 4,8ꢀdialkylꢀ2,6ꢀbis(hydroxymethyl)glycoluril 7c,d
(0.0025 mol) and arenesulfonamide 8a,b (0.005 mol) were disꢀ
solved in methanol (7 mL) and three drops of conc. HCl were
added. The mixture was refluxed for 1 h and concentrated in a
rotary evaporator to an oily residue, which was crystallized from
water—methanol (1 : 2).
Synthesis of compounds 11a—d (general procedure). Apꢀ
propriate 4,6ꢀdialkylꢀ2,8ꢀbis(hydroxymethyl)glycoluril 7e—f
(0.01 mol) and sulfamide 9a—c (0.01 mol) were dissolved in
methanol (5 mL) (for 11a,c,d) or propanꢀ2ꢀol (5 mL) (for 11b).
Two drops of conc. HCl were added and the mixture was reꢀ
Experimental
IR spectra were recorded on a Specord M82 instrument
(KBr pellets). NMR spectra were recorded on Bruker AMꢀ250
(250.13 MHz (1H)) and Bruker AMꢀ300 spectrometers
(300.13 (1H) and 75.5 MHz (13C)) in DMSOꢀd6. Chemical
shifts are given on the δ scale with reference to Me4Si as the
internal standard. Mass spectra were recorded on a Kratos MSꢀ30
spectrometer (70 eV). Melting points were determined on
a GALLENKAMP instrument (Sanyo). 2ꢀHydroxymethylꢀ,
2,6ꢀ and 2,8ꢀbis(hydroxymethyl)ꢀ, and 2,4,6,8ꢀtetrakis(hydroxyꢀ
methyl)glycolurils 7a—g were prepared as described earlier.16
Synthesis of glycolurils 10a—d (general procedure). Appropriꢀ
ate 4,6,8ꢀtrialkylꢀ2ꢀ(hydroxymethyl)glycoluril 7a,b (0.005 mol)
and arenesulfonamide 8a,b (0.005 mol) were dissolved in methaꢀ
nol (5 mL) and two drops of conc. HCl were added. The mixture

2276
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 11, November, 2007
Gazieva et al.
1
Table 3. IR, H NMR (DMSOꢀd6), and mass spectra of compounds 11a—d and 12
Comꢀ
pound
IR,
ν/cm–1
1H NMR,
δ (J/Hz)
MS,
m/z (Irel (%))
11a
11b
11c
3346, 3239, 1718, 2.86 (s, 6 H, 2 NMe); 4.28 (dd, 2 H, NCH2, J = 9.5);
1699, 1516, 1331, 4.82 (dd, 2 H, NCH2, J = 3.6); 5.16 (dd, 2 H, CHCH,
290 [M]+ (37), 210 (62),
183 (54), 170 (100), 141 (29),
126 (72), 98 (44), 80 (81)
254 [M – SO2]+ (9), 239 (8),
183 (26), 167 (9), 154 (9),
139 (100), 126 (73), 98 (72)
345 [M – C2H5]+ (2), 310
[M – SO2]+ (4), 253 (10),
224 (8), 183 (7), 163 (18),
151 (22), 64 (5)
1167
1723, 1710, 1320, 2.88, 2.92 (both s, 6 H each, 4 NMe); 4.76 (dd, 4 H,
1155 2 NCH2, J = 14.5); 5.23 (dd, 2 H, СHСH, J = 9.1)
J = 8.0); 7.60 (d, 2 H, NH, J = 6.6)
1728, 1712, 1509, 0.91 (t, 6 H, 2 Me (Pr), J = 7.5); 1.58—1.72 (m, 4 H,
1361, 1158
2 CH2 (Pr)); 2.89 (s, 6 H, 2 NMe); 2.97—3.13,
3.22—3.37 (both m, 2 H, NCH2 (Pr)); 4.80 (dd, 4 H,
2 NCH2, J = 15.3); 5.17 (dd, 2 H, СHСH, J = 9.9)
11d
12
3300, 1720, 1700, 1.07 (t, 6 H, 2 Me (Et), J = 7.0); 3.10—3.43 (m, 4 H,
—
1488, 1340, 1144
2 NCH2 (Et)); 4.26, 4.72 (both d, 2 H, NCH2, J = 15.3);
5.16, 5.35 (both d, 1 H each, СH, J = 8.6);
7.57 (br.s, 2 H, 2 NH)
1730, 1355, 1160
2.85 (s, 12 H, 4 NMe); 4.81 (dd, 8 H, 4 CH2, J = 15.1);
5.44 (s, 2 H, СHСH)
374 [M – SO2]+ (2), 251 (15),
196 (11), 138 (20), 124 (23), 64 (21)
fluxed with stirring for 1 h. On cooling to ~20 °C, the colorless
precipitate that formed was filtered off and crystallized from
methanol (11a,c,d) or methanol—propanꢀ2ꢀol (1 : 3) (11b).
Compound 12. 2,4,6,8ꢀTetrakis(hydroxymethyl)glycoluril 7g
(2.62 g, 0.01 mol) and sulfamide 9b (2.48 g, 0.02 mol) were
dissolved in water (5 mL). The mixture was acidified with two
drops of conc. HCl (pH 1) and stirred at 80—90 °C for 2 h. On
cooling to ~20 °C, the white precipitate that formed was filtered
off and recrystallized from DMSO.
6. A. N. Kravchenko and I. E. Chikunov, Usp. Khim., 2006, 75,
217 [Russ. Chem. Rev., 2006, 75, 191 (Engl. Transl.)].
7. O. A. Geras´ko, D. G. Samsonenko, and V. P. Fedin, Usp.
Khim., 2002, 71, 840 [Russ. Chem. Rev., 2002, 71, 741 (Engl.
Transl.)].
8. W. Sliwa, G. Matusiak, and J. Peszke, Heterocycles, 2004,
63, 419.
9. M. D. Mashkovskii, Lekarstvennye sredstva [Drugs], Novaya
Volna, Moscow, 2000, 1, 86 (in Russian).
The yields and physicochemical characteristics of comꢀ
pounds 10—12 are given in Tables 1—3.
10. S. S. Novikov, Izv. Akad. Nauk SSSR, Ser. Khim., 1979,
2261 [Bull. Acad. Sci. USSR, Div. Chem. Sci., 1979, 28, 2247
(Engl. Transl.)].
11. Yu. B. Vikharev, L. V. Anikina, I. E. Chikunov, A. S. Sigachev,
A. N. Kravchenko, Yu. V. Shklyaev, and N. N. Makhova,
Vopr. Biol. Med. Farm. Khim., 2006, 3, 12 (in Russian).
12. A. A. Bakibaev, R. R. Akhmedzhanov, A. Yu. Yagovkin,
T. P. Novozheeva, V. D. Filimonov, and A. S. Saratikov,
Khim.ꢀFarm. Zh., 1993, 27, 6, 29 [Pharm. Chem. J., 1993, 27,
6, 401 (Engl. Transl.)].
This work was financially supported by the Division of
Chemistry and Materials Science of the Russian Acadꢀ
emy of Sciences (Program OKhꢀ10).
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Received May 29, 2007;
in revised form July 5, 2007