Interaction of barbituric acids with o-dialkylaminobenzaldehydes

Article abstract of DOI:10.1070/MC2006v016n01ABEH002216

Barbituric or 2-thiobarbituric acids interact with o- dialkylaminobenzaldehydes to give 5-o-dialkylaminobenzylidene derivatives, which cyclise into 2,4,6-trioxoperhydropyrimidine-5-spiro-3′-(1′, 2′,3′,4′-tetrahydroquinolines) under mild conditions; the me

Full text of DOI:10.1070/MC2006v016n01ABEH002216

Mendeleev Commun., 2006, 16(1), 52–54
Interaction of barbituric acids with o-dialkylaminobenzaldehydes
Konstantin A. Krasnov,a Viktor G. Kartsevb and Victor N. Khrustalev*c
a I. I. Mechnikov State Medical Academy, 195067 St. Petersburg, Russian Federation
b InterBioScreen Ltd., 142432 Chernogolovka, Moscow Region, Russian Federation
c A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow, Russian Federation.
Fax: +7 495 135 5085; e-mail: vkh@xray.ineos.ac.ru
DOI: 10.1070/MC2006v016n01ABEH002216
Barbituric or 2-thiobarbituric acids interact with o-dialkylaminobenzaldehydes to give 5-o-dialkylaminobenzylidene derivatives,
which cyclise into 2,4,6-trioxoperhydropyrimidine-5-spiro-3'-(1',2',3',4'-tetrahydroquinolines) under mild conditions; the mechanism
of the key stage of a tert-amino effect reaction is disclosed on the basis of the XRD analysis of 1,3-dimethyl-5-(2-dimethylamino-
4-nitrobenzylidene)barbituric acid.
The chemistry of barbituric acids attracts permanent attention
because barbiturates and related pyrimidine derivatives are of
importance for biology and medicine. Here, we report a simple
approach to a new group of 5,5-spirobarbituric acids.
of 5-arylidenebarbiturate 3a in acetic acid afforded spirocyclic
system 4a in a high yield.§ Similarly, the condensation of 1,3-di-
methylbarbituric acid 1b with aldehyde 2a gave Knövenagel
product 3b,¶ which was isomerised into spirobarbiturate 4b††
(Scheme 1).
The rearrangement of 5-arylidenebarbiturates 3a,b into spiro-
cyclic system derivatives 4a,b can be classified as the tert-amino
effect.4 This approach has been generally employed to the syn-
thesis of annelated quinoline derivatives, but no spirocyclic
systems have been afforded in this way.4 Only at a recent time,
tert-amino effect reactions (T-reactions) were applied to the
preparation of spirocyclic systems containing barbituric acid,
cyclohexane-1,3-dione or a Meldrum’s acid moiety.5–9
Although it is believed1–3 that the interaction of barbituric
acid 1a and related compounds with aromatic aldehydes has
been explored in detail, no data on the condensation of acid
1a with ortho-dialkylamino benzaldehydes, such as 2-dimethyl-
amino-4-nitrobenzaldehyde 2a,† have been reported. A careful
treatment of acid 1a with aldehyde 2a in aqueous ethanol
resulted in a typical Knövenagel product, 5-(2-dimethylamino-
4-nitrobenzylidene)barbituric acid 3a.‡ Furthermore, short heating
†
The 1H and 13C NMR spectra were recorded on a Bruker AM spectro-
Typically, the rearrangement of o-vinyl-substituted N,N-di-
alkylanilines into the corresponding heterocycles required severe
conditions.10,11 In contrast to non-spirocyclic analogues, com-
pounds 4a,b were obtained under surprisingly mild conditions.
Kinetic measurements identified that compound 3b isomerised
meter at 500 and 125 MHz, respectively. Reagents 1a–e were purchased
from commercial suppliers. Aldehydes 2a-e were synthesised by fol-
lowing procedures.
2-Dimethylamino-4-nitrobenzaldehyde 2a. Aqueous dimethylamine
33% (35 ml, 0.25 mol) was added to a solution of 2-chloro-4-nitrobenz-
aldehyde (18.5 g, 0.1 mol) in DMF (50 ml), and the reaction mixture
was stirred under reflux at 50 °C for 2 h. The mixture was diluted with
water (100 ml), the precipitate was washed with water and recrystallised
from aqueous EtOH to give 2a. Yield 90%, yellow crystals, mp 132–
133 °C. 1H NMR ([2H6]DMSO) d: 3.08 (s, 6H, NMe2), 6.93 (d, 1H,
ArH, J 8.6 Hz), 8.14 (d, 1H, ArH, J 8.6 Hz), 8.49 (s, 1H, ArH), 9.97 (s,
1H, CHO). Found (%): C, 55.45; H, 5.62; N, 14.18. Calc. for C9H10N2O3
(%): C, 55.67; H, 5.19; N, 14.43.
2-Dimethylamino-4-methylbenzaldehyde 2b. N,N-Dimethyl-4-methyl-
aniline (13.5 g, 0.1 mol) was added to a solution of POCl3 (23.1 g,
0.15 mol) in DMF (50 ml) and the reaction mixture was heated for 5 h
at 95 °C. After cooling, the solution was poured into water (200 ml),
neutralised with NH4OH and extracted with Et2O (2×50 ml). The com-
bined organics were washed with aqueous AcOH (10%) and water, dried
with Na2SO4 and concentrated in vacuo. Yield 60%, colourless oil.
1H NMR (CDCl3) d: 2.31 (s, 3H, ArMe), 2.87 (s, 6H, NMe2), 6.96
(d, 1H, ArH, J 8.9 Hz), 7.26 (d, 1H, ArH, J 8.9 Hz), 7.56 (s, 1H, ArH),
10.25 (s, 1H, CHO). Found (%): C, 73.14; H, 8.21; N, 8.40. Calc. for
C10H13NO (%): C, 73.59; H, 8.03; N, 8.58.
‡
5-(2-Dimethylamino-4-nitrobenzylidene)barbituric acid 3a. A solu-
tion of 2a (1.94 g, 10 mmol) in 25 ml EtOH was added to a solution of
1a (1.28 g, 10 mmol) in 50 ml of H2O–EtOH (1:1) at 60 °C, and the
reaction mixture was stirred for 5 min. The precipitate was separated,
washed with aqueous EtOH and air dried. Yield 94%, red crystals,
1
mp 290 °C (decomp.). H NMR ([2H6]DMSO) d: 3.06 (s, 6H, NMe2),
7.07 (d, 1H, ArH, J 7.0 Hz), 8.12 (d, 1H, ArH, J 7.0 Hz), 8.15 (s, 1H,
ArH), 8.64 (s, 1H, =CH), 11.21 (s, 1H, NH), 11.31 (s, 1H, NH). 13C NMR
([2H6]DMSO) d: 43.73 (2Me), 115.45 (CH), 117.57 (C=CH), 120.71
(CH), 126.46 (CH), 128.80 (CCH=), 137.27 (CNO2), 150.24 [C(2)O],
151.21 (CNMe2), 157.91 (CH=), 163.28, 161.52 [C(4)O, C(6)O]. Found
(%): C, 51.11; H, 4.13; N, 18.25. Calc. for C13H12N4O5 (%): C, 51.32;
H, 3.98; N, 18.41.
§
2,4,6-Trioxoperhydropyrimidine-5-spiro-3'-(1'-methyl-6'-nitro-1',2',3',4'-
tetrahydroquinoline) 4a. A suspension of 3a (0.3 g, 1 mmol) in AcOH
(20 ml) was heated for 2–3 min until complete dissolution. After cooling,
the mixture was diluted with water (30 ml), the precipitate was washed with
water and air dried. Yield 84%, yellow crystals, mp > 316 °C (decomp.).
1H NMR ([2H6]DMSO) d: 3.12 (s, 3H, NMe), 3.18 (s, 2H, CH2), 3.68
(s, 2H, NCH2), 6.64 (d, 1H, ArH, J 9.5 Hz), 7.87 (s, 1H, ArH), 7.93 (d,
1H, ArH, J 9.5 Hz), 11.17 (s, 2H, 2NH). 13C NMR ([2H6]DMSO) d:
33.07 (Me), 38.51 (CH2N), 46.90 (CCO), 53.78 (CH2N), 109.27 (CH),
119.45 [C(5)], 123.83 (CH), 123.98 (CH), 135.60 (CNO2), 150.19 [C(2)O],
150.31 (CNMe2), 170.60 [C(4)O + C(6)O]. MS, m/z (%): 304 (100) [M]+,
287 (61), 274 (11), 257 (13), 188 (22), 171 (10), 160 (11), 143 (19), 131
(24). Found (%): C, 51.20; H, 4.03; N, 18.29. Calc. for C13H12N4O5 (%):
C, 51.32; H, 3.98; N, 18.41.
2-Dimethylamino-4,5-dimethylbenzaldehyde 2c was obtained similarly
by formylation of N,N-dimethyl-4,5-dimethylaniline. Yield 36%, colour-
1
less oil. H NMR (CDCl3) d: 2.29 (s, 3H, ArMe), 2.32 (s, 3H, ArMe),
2.85 (s, 6H, NMe2), 7.32 (s, 1H, ArH), 7.49 (s, 1H, ArH), 10.28 (s, 1H,
CHO). Found (%): C, 74.16; H, 8.81; N, 8.03. Calc. for C11H15NO (%):
C, 74.54; H, 8.53; N, 7.90.
2-Diethylamino-4-nitrobenzaldehyde 2d. A mixture of 2-chloro-4-nitro-
benzaldehyde (18.5 g, 0.1 mol), diethylamine (8.0 g, 0.11 mol) and K2CO3
(15.2 g, 1.1 mol) in DMF (45 ml) was stirred for 3 h at 80–90 °C. The
reaction mixture was diluted with water (150 ml), the precipitate was
washed with water and recrystallised from aqueous EtOH to give 2d.
Yield 82%, yellow crystals, mp 68–69 °C. 1H NMR (CDCl3) d: 1.22
(t, 6H, 2Me, J 7.2 Hz), 3.43 [q, 4H, N(CH2)2, J 7.2 Hz], 7.01 (d, 1H,
ArH, J 8.4 Hz), 8.20 (d, 1H, ArH, J 8.4 Hz), 8.58 (s, 1H, ArH), 10.01
(s, 1H, CHO). Found (%): C, 59.11; H, 6.56; N, 12.33. Calc. for
C11H14N2O3 (%): C, 59.45; H, 6.35; N, 12.60.
¶
1,3-Dimethyl-5-(2-dimethylamino-4-nitrobenzylidene)barbituric acid
3b was obtained from 1b and 2a. Yield 91%, red crystals, mp 233–
1
234 °C. H NMR (CDCl3) d: 3.03 (s, 6H, NMe2), 3.37 (s, 3H, NMe),
3.42 (s, 3H, NMe), 6.94 (d, 1H, ArH, J 9.2 Hz), 8.17 (dd, 1H, ArH,
J1 9.5 Hz, J2 2.5 Hz), 8.44 (s, 1H, =CH), 8.70 (d, 1H, =CH, J 2.5 Hz).
Found (%): C, 54.07; H, 4.94; N, 16.70. Calc. for C15H16N4O5 (%):
C, 54.22; H, 4.85; N, 16.86.
2-(N-methyl-N-benzylamino)-4-nitrobenzaldehyde 2e was obtained
†† 1,3-Dimethyl-2,4,6-trioxoperhydropyrimidine-5-spiro-3'-(1'-methyl-
6'-nitro-1',2',3',4'-tetrahydroquinoline) 4b obtained from 3b. Yield 85%,
yellow crystals, mp 244–245 °C. 1H NMR (CDCl3) d: 3.12 (s, 3H,
NpiperidMe), 3.24 (s, 3H, NMe), 3.29 (s, 2H, CH2Ar), 3.30 (s, 3H, NMe),
3.69 (s, 2H, CH2N), 6.64 (d, 1H, ArH, J 9.5 Hz), 7.91 (d, 1H, ArH,
J 2.3 Hz), 8.07 (dd, 1H, ArH, J1 9.5 Hz, J2 2.3 Hz). Found (%): C, 54.13;
H, 4.91; N, 16.75. Calc. for C15H16N4O5 (%): C, 54.22; H, 4.85; N, 16.86.
similarly, using N-methyl-N-benzylamine. Yield 73%, yellow crystals,
1
mp 135–136 °C. H NMR (CDCl3) d: 3.04 (s, 3H, NMe), 4.63 (s, 2H,
NCH2), 6.97 (d, 1H, ArH, J 8.9 Hz), 7.15–7.36 (m, 5H, Ph), 8.19 (d, 1H,
ArH, J 8.9 Hz), 8.62 (s, 1H, ArH), 10.05 (s, 1H, CHO). Found (%): C,
66.17; H, 5.00; N, 10.03. Calc. for C11H14N2O3 (%): C, 66.66; H, 5.22;
N, 10.36.
52 Mendeleev Commun. 2006

Mendeleev Commun., 2006, 16(1), 52–54
O(7)
O(8)
O
N
N(14)
R
aqueous EtOH
50 °C, 5 min
N
O
C(7)
C(2)
C(14)
C(15)
O
N
R
O
C(6)
O(2)
N(3)
O(6)
C(5)
C(9)
C(13)
C(12)
NO2
N(1)
C(10)
1a,b
2a
NO2
C(4)
C(8)
NO2
C(11)
N(11)
O(4)
O
O
C(17)
R
R
AcOH
N
N
N
C(16)
118 °C, 2 min
N
O
N
R
O
O
N
R
O
Figure 1 Molecular structure of 3b.
atoms is 2.95 Å, and that for two carbon atoms is 3.50 Å. The
(N)C–H···C=C contact, as well as the spatial orientation of the
methyl group, presumes the presence of very strong C–H···π(C=C)
intramolecular interaction in the crystal, which cannot be ex-
plained solely by packing effects. Note that there are no steric
hindrances for the free rotation of the dimethylamino group
around the N–Caryl bond in the crystal. Moreover, due to the
C–H···π(C=C) intramolecular interaction, the nitrogen atom N(11)
of this group adopts a slightly pyramidalised configuration (the
sum of the bond angles at the nitrogen atom is 356.5°), and the
carbon atom C(17) deviates from the benzene plane by 0.732 Å
[meanwhile, the deviation of another methyl carbon atom C(16)
from the same plane is only 0.096 Å]. The interactions of this
type are well known.12–16 In the case of compound 3b, the
involvement of the methyl group into the C–H···π(C=C) inter-
action is attributed to the strong polarization of the C(5)=C(9)
bond. Note that the respective double bond exhibits rather strong
Lewis acidity: in particular, 1,3-dimethyl-5-arylidenebarbiturates
react with amines and other nucleophiles forming stable zwitter-
ionic adducts.17
3a,b
4a,b
a R = H
b R = Me
Scheme 1
into 4b at the rate constants k = 2.3×10–5 s–1 at 60 °C, 1.6×10–4 s–1
at 80 °C, and 1.2×10–3 s–1 at 100 °C; the activation energy of the
process can be estimated as Ea = 24.5 0.5 kcal mol–1.‡‡
All reactions of these types are two-step processes, first involv-
ing hydrogen detachment from the a position of the t-amino
function followed by the cyclization of the dipolar intermediate.4
Hydrogen transfer should be considered as the key stage of the
tert-amino effect; however, the mechanism of this stage is still
unclear. To get an insight into this mechanism, the structure
of 5-arylidenebarbiturate 3b was studied by X-ray diffraction
analysis.§§
NO2
NO2
O
O
N
N
O
The strong intramolecular C–H···π(C=C) interaction in 5-aryli-
denebarbiturate 3b may be considered as a contributory factor
for the subsequent hydrogen migration that proceeds via transi-
tion state 5 to give intermediate 6. On the other hand, the
N
N
3b
4b
O
H
H
N
N
O
O
H
H
R2
R3
5
6
O
N
R1
X
Scheme 2
N
O
Note that the hydrogen atom H(17A) of one of the two
methyl groups of the dimethylamino substituent in compound
3b is located at a distance of 2.34(2) Å from the vinylic carbon
atom C(9) [the C(17)...C(9) distance is 2.867(3) Å, the C(17)–
H(17A)···C(9) angle is 113(2)°] (Figure 1). For comparison,
the sum of van der Waals radii for carbon and hydrogen
R4
N
O
R1
R5
1a X = O, R1 = H
1b X = O, R1 = Me
1c X = O, R1 = Ph
1d X = S, R1 = Me
1e X = S, R1 = Ph
2b R2 = R3 = R5 = Me, R4 = H
2c R2 = R3 = R4 = R5 = Me
2d R2 = R3 = Et, R4 = H, R5 = NO2
2e R2 = Me, R3 = CH2Ph, R4 = H, R5 = NO2
‡‡ Kinetic measurements. Compound 3b (10 mg, 0.03 mmol) was dis-
solved in [2H6]DMSO (0.6 ml) in an NMR tube and thermostated at the
1
given temperatures for the reaction time. At known intervals, H NMR
spectra were recorded. Concentrations of starting compound 3b and
product 4b were calculated as average values of integrals of aromatic
CH signals. The maximum integration error is 2%.
60 °C, 10–15 min aqueous EtOH
R5
§§ Crystal data for 3b: C15H16N4O5, M = 332.32, triclinic, space group
P1, at T = 120 K: a = 8.208(5), b = 8.741(5) and c = 11.540(7) Å, a =
= 102.827(11)°, b = 102.443(11)°, g = 104.090(10)°, V = 750.5(8) Å3,
Z = 2, dcalc = 1.470 g cm–3, R1 = 0.0484 for 2210 independent reflections
with I > 2s(I), wR2 = 0.1218 for all 3254 independent reflections.
6944 reflections were measured on a Bruker SMART 1000 CCD
diffractometer [l(MoKα)-radiation, graphite monochromator, j and w scan
mode, qmax = 27°]. The structure was determined by direct methods and
by full-matrix least squares refinement with anisotropic thermal parameters
for non-hydrogen atoms. The hydrogen atoms were objectively localised
in the difference Fourier syntheses and refined isotropically.
R4
O
R1
N
N
R2
R6
N
X
O
R1
4c X = O, R1 = R4 = R6 = H, R2 = R5 = Me
4d X = O, R1 = R2 = R5 = Me, R4 = R6 = H
4e X = O, R1 = Ph, R2 = R5 = Me, R4 = R6 = H
4f X = S, R1 = R2 = R5 = Me, R4 = R6 = H
4g X = S, R1 = Ph, R2 = R5 = Me, R4 = R6 = H
4h X = O, R1 = R2 = R4 = R5 = Me, R6 = H
4i X = O, R1 = R4 = H, R2 = Et, R5 = NO2, R6 = Me
4j X = O, R1 = R4 = H, R2 = Me, R5 = NO2, R6 = Ph
Atomic coordinates, bond lengths, bond angles and thermal param-
eters have been deposited at the Cambridge Crystallographic Data Centre
(CCDC). These data can be obtained free of charge via www.ccdc.cam.uk/
conts/retrieving.html (or from the CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK; fax: +44 1223 336 033; or deposit@ccdc.cam.ac.uk).
Any request to the CCDC for data should quote the full literature citation
and CCDC reference number 278524. For details, see ‘Notice to Authors’,
Mendeleev Commun., Issue 1, 2006.
Scheme 3
Mendeleev Commun. 2006 53

Mendeleev Commun., 2006, 16(1), 52–54
cyclization of compound 3b and its analogues is favoured by
adducts with barbituric acids. It seems evident that the con-
siderably higher affinity of 5-arylidenebarbiturates derived from
aldehydes 2b–e towards cyclization is due to an increase in the
electron density at the alkylamino group and to the stabilization
of cationic segment in the zwitter-ionic intermediate.
In conclusion, the study of T-reactions of barbituric acid deri-
vatives clarified the mechanism of hydrogen migration in the
tert-amino effect and enabled a simple method for the prepara-
tion of new heterocyclic systems containing the pyrimidine-5-
spiro-3'-quinoline skeleton.
the stabilization of zwitter-ionic system 6 through the effective
delocalization of the negative charge over the atoms of the
β-dicarbonyl pentad. Taking all these aspects into consideration,
the mechanism of hydrogen migration in 5-arylidenebarbiturate
3b may be described as the intramolecular uptake of a hydrid
ion by a Lewis acceptor.
A high rate of the tert-amino effect cyclization was proved by
the examination of the reactivity of 2-dimethylamino-4-methyl-
benzaldehyde 2b† in these reactions. The condensation of acid
1a with aldehyde 2b afforded spirocyclic derivative 4c¶¶ without
stopping at the Knövenagel stage, even at a room temperature.
The formation of the Knövenagel intermediate manifests itself
only by appearance of a deep red colour of the reaction mixture.
Kinetic measurements showed that the rate of this two-step pro-
cess was limited by the first stage. We have restricted ourselves
by estimation that the rate of the rearrangement of 5-(2-dimethyl-
amino-4-methylbenzylidene)barbiturate at 20 °C in DMSO is
three orders of magnitude (or more) higher than that in the case
of its 4-nitro analogue 3a.
1,3-Dimethylbarbituric 1b and 1,3-diphenylbarbituric 1c acids,
as well as their 2-thio analogues 1d,e, interact with aldehyde 2b
to afford spirocyclic products 4d–g.¶¶ 2-Dimethylamino-4,5-di-
methylbenzaldehyde 2c† was found to react similarly to its
analogue 2b: the condensation of 2c with acid 1a yielded spiro-
cyclic product 4h.¶¶ The interaction of 2-diethylamino-4-nitro
2d or 2-benzylmethylamino-4-nitro 2e benzaldehydes† with acid
1a proceeds to give 5-spirobarbiturates 4i,j.¶¶
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2
3
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¶¶ General procedure. An ethanolic solution of aldehyde 2b–e (10 mmol)
was added to a stirred solution of barbituric or 2-thiobarbituric acid
derivative 1a–e (10 mmol) in aqueous EtOH (70%) at 60–70 °C, and
the mixture was heated at 60 °C for 10–15 min. Then the mixture was
cooled and the precipitate was purified by crystallization from EtOH.
2,4,6-Trioxoperhydropyrimidine-5-spiro-3'-(1',6'-dimethyl-1',2',3',4'-
tetrahydroquinoline) 4c. Yield 91%, colourless crystals, mp 286–287 °C.
1H NMR ([2H6]DMSO) d: 2.21 (s, 3H, ArMe), 2.87 (s, 3H, NMe), 3.05 (s,
2H, ArCH2), 3.35 (s, 2H, NCH2), 6.50 (d, 1H, ArH, J 7.3 Hz), 6.80 (s,
1H, ArH), 6.81 (d, 1H, ArH, J 7.3 Hz), 11.12 (s, 2H, 2NH). 13C NMR
([2H6]DMSO) d: 19.97 (MeAr), 31.06 (NMe), 38.67 (CH2Ar), 50.09
(CCO), 56.38 (NCH2), 111.47 (CH), 121.52 (C), 125.41 (C), 126.81
(CH), 128.58 (CH), 143.47 (CaromN), 171.13 [C(4)O, C(6)O], 150.36
[C(2)O]. MS, m/z (%): 273 (100) [M]+, 258 (43), 201 (25), 186 (14).
Found (%): C, 61.41; H, 5.66; N, 15.29. Calc. for C14H15N3O3 (%): C,
61.53; H, 5.53; N, 15.38.
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Chem., 1984, 115, 375.
Received: 14th July 2005; Com. 05/2549
1,3-Diphenyl-2-thioxo-4,6-dioxoperhydropyrimidine-5-spiro-3'-(1',6'-
1,3-Dimethyl-2,4,6-trioxoperhydropyrimidine-5-spiro-3'-(1',6'-dimethyl-
dimethyl-1',2',3',4'-tetrahydroquinoline) 4g. Yield 84%, colourless crys-
tals, mp 241–242 °C. H NMR (CDCl3) d: 2.25 (s, 3H, ArMe), 3.05 (s,
1
1',2',3',4'-tetrahydroquinoline) 4d. Yield 79%, colourless crystals, mp 151–
1
152 °C. H NMR (CDCl3) d: 6.92 (d, 1H, ArH, J 7.3 Hz), 6.85 (s, 1H,
3H, NMe), 3.46 (s, 2H, ArCH2), 3.74 (s, 2H, NCH2), 6.60 (d, 1H, ArH,
J 7.2 Hz), 6.91 (d, 1H, ArH, J 7.2 Hz), 6.96 (s, 1H, ArH), 7.16 (m, 4H,
2Ph), 7.41–7.48 (m, 6H, 2Ph). Found (%): C, 70.45; H, 5.48; N, 9.33;
S, 7.14. Calc. for C26H23N3O2S (%): C, 70.72; H, 5.25; N, 9.52; S, 7.26.
1,3-Dimethyl-2,4,6-trioxoperhydropyrimidine-5-spiro-3'-(1',5',6'-tri-
methyl-1',2',3',4'-tetrahydroquinoline) 4h. Yield 76%, colourless crys-
tals, mp 143–144 °C. 1H NMR ([2H6]DMSO) d: 2.08 (s, 3H, ArMe),
2.12 (s, 3H, ArMe), 2.85 (s, 3H, NMe), 3.10 (s, 2H, CCH2), 3.34 (s, 2H,
NCH2), 6.40 (s, 1H, ArH), 6.72 (s, 1H, ArH), 11.06 (s, 2H, 2NH).
13C NMR ([2H6]DMSO) d: 18.55 (MeAr), 19.84 (MeAr), 32.21 (MeNAr),
38.87 (CH2Ar), 50.32 (CCO), 56.90 (CH2N), 112.13 (CH), 118.68 (C),
126.51 (C), 130.79 (CH), 135.92 (C), 143.15 (CaromN), 150.44 [C(2)O],
170.94 [C(4)O, C(6)O]. Found (%): C, 64.91; H, 6.86; N, 13.22. Calc.
for C17H21N3O3 (%): C, 64.74; H, 6.71; N, 13.32.
2,4,6-Trioxoperhydropyrimidine-5-spiro-3'-(1'-ethyl-2'-methyl-6'-nitro-
1',2',3',4'-tetrahydroquinoline) 4i. Yield 70%, yellow crystals, mp 244–
245 °C. 1H NMR ([2H6]DMSO) d: 1.02 (d, 3H, CHMe, J 6.6 Hz), 1.11 (t,
3H, CH2Me, J 7.5 Hz), 2.88 and 3.49 (AB-d, 2H, ArCH2, J 17.5 Hz), 3.33
and 3.60 (AB-m, 2H, NCH2), 4.01 (q, 1H, NCH, J 6.6 Hz), 6.68 (d, 1H,
ArH, J 9.3 Hz), 7.89 (d, 1H, ArH, J 9.3 Hz), 7.94 (s, 1H, ArH), 11.08 (s,
1H, NH), 11.25 (s, 1H, NH). Found (%): C, 54.57; H, 4.97; N, 16.79.
Calc. for C15H16N4O5 (%): C, 54.22; H, 4.85; N, 16.86.
ArH), 6.59 (d, 1H, ArH, J 7.3 Hz), 3.40 (s, 2H, NCH2), 3.30 (s, 6H,
2NMe), 3.22 (s, 2H, ArCH2), 2.92 (s, 3H, NMe), 2.25 (s, 3H, ArMe).
13C NMR (CDCl3) d: 169.53 [C(4)O, C(6)O], 151.36 [C(2)O], 142.74
(CaromN), 128.98 (CH), 127.84 (CH), 127.32 (C), 120.52 (C), 112.04
(CH), 58.11 (CH2N) 50.95 (CCO), 39.47 (CH2Ar), 32.82 (MeNAr),
29.05 (2MeN), 20.36 (MeAr). Found (%): C, 63.59; H, 6.54; N, 13.80.
Calc. for C16H19N3O3 (%): C, 63.77; H, 6.36; N, 13.94.
1,3-Diphenyl-2,4,6-trioxoperhydropyrimidine-5-spiro-3'-(1',6'-dimethyl-
1',2',3',4'-tetrahydroquinoline) 4e. Yield 82%, colourless crystals,
1
mp 253–254 C. H NMR (CDCl3) d: 2.22 (s, 3H, ArMe), 2.97 (s, 3H,
NMe), 3.29 (s, 2H, ArCH2), 3.73 (s, 2H, NCH2), 6.53 (d, 1H, ArH,
J 8.0 Hz), 6.80 (d, 1H, ArH, J 8.0 Hz), 6.89 (s, 1H, ArH), 7.29–7.47 (m,
10H, 2Ph). 13C NMR (CDCl3) d: 20.32 (MeAr), 32.36 (MeN), 39.53
(CH2Ar), 52.37 (CCO), 58.23 (CH2N), 112.14 (CH), 120.26 (C), 127.56
(CH), 127.90 (CH), 128.20 (C), 128.28 (4CH), 129.02 (2CH), 129.30
(4CH), 134.37 (2C), 142.64 (CaromN), 150.63 [C(2)O], 168.94 [C(4)O,
C(6)O]. Found (%): C, 72.98; H, 5.73; N, 9.56. Calc. for C26H23N3O3
(%): C, 73.40; H, 5.45; N, 9.88.
1,3-Dimethyl-2-thioxo-4,6-dioxoperhydropyrimidine-5-spiro-3'-(1',6'-
dimethyl-1',2',3',4'-tetrahydroquinoline) 4f. Yield 75%, colourless crystals,
1
mp 192–193 °C. H NMR (CDCl3) d: 2.26 (s, 3H, ArMe), 2.92 (s, 3H,
ArNMe), 3.29 (s, 2H, ArCH2), 3.42 (s, 2H, NCH2), 3.66 (s, 6H, 2NMe),
6.62 (d, 1H, ArH, J 8.2 Hz), 6.89 (s, 1H, ArH), 6.93 (d, 1H, ArH,
J 8.2 Hz). 13C NMR (CDCl3) d: 20.39 (MeAr), 32.22 (MeNAr), 35.95
(2MeN), 39.50 (CH2Ar), 52.11 (CCO), 57.74 (CH2N), 112.14 (CH),
120.42 (C), 127.50 (C), 127.88 (CH), 129.07 (CH), 142.68 (CaromN),
168.04 (2CO), 180.60 (CS). Found (%): C, 54.27; H, 4.99; N, 16.84; S,
10.06. Calc. for C16H19N3O2S (%): C, 54.22; H, 4.85; N, 16.86; S, 10.10.
2,4,6-Trioxoperhydropyrimidine-5-spiro-3'-(1'-methyl-2'-phenyl-6'-nitro-
1',2',3',4'-tetrahydroquinoline) 4j. Yield 87%, yellow crystals, mp 224–
1
225 °C. H NMR ([2H6]DMSO) d: 2.90 (s, 3H, NMe), 3.36 and 3.13
(AB-d, 2H, NCH2, J 17.5 Hz), 5.13 (s, 1H, NCH), 6.65 (m, 1H, ArH),
7.01 (m, 2H, Ph), 7.24 (m, 3H, Ph), 7.92 (d, 1H, ArH, J 5.0 Hz), 8.04
(m, 1H, ArH), 11.12 (s, 2H, 2NH). Found (%): C, 59.88; H, 4.30; N,
14.79. Calc. for C19H16N4O5 (%): C, 60.00; H, 4.24; N, 14.73.
54 Mendeleev Commun. 2006