Facile synthesis of 5, 6, 7, 8-tetrahydropyrimido [4, 5-b]-quinoline derivatives

Article abstract of DOI:10.3390/11110890

2-Amino-4-phenyl-5,6,7,8-tetrahydroquinoline-3-carbonitrile (3) was synthesized by treating cyclohexanone (1) with 2-benzylidenemalononitrile (2) in the presence of ammonium acetate. The reactivity of compound 3 towards dimethylformamide dimethyl acetal (

Full text of DOI:10.3390/11110890

Molecules 2006, 11, 890-903
molecules
ISSN 1420-3049
http://www.mdpi.org
Full Paper
Facile Synthesis of 5, 6, 7, 8-Tetrahydropyrimido [4, 5-b]-
quinoline Derivatives
Yehya Mahmoud Elkholy * and Mohamed Abdelhamed Morsy
Chemistry Department, Faculty of Science, Helwan University, Helwan, Cairo, Egypt
* Author to whom correspondence should be addressed; e-mail: Y_elkholy@ yahoo.com
Received: 18 October 2006; in revised form: 7 November 2006 / Accepted: 7 November 2006 /
Published: 17 November 2006
Abstract: 2–Amino–4-phenyl–5,6,7,8–tetrahydroquinoline–3–carbonitrile (3) was
synthesized by treating cyclohexanone (1) with 2–benzylidenemalononitrile (2) in the
presence of ammonium acetate. The reactivity of compound
3
towards
dimethylformamide dimethyl acetal (DMF-DMA), carbon disulfide, urea, thiourea,
formamide, formic acid, acetyl chloride and isothiocyanate were studied. In addition, the
antimicrobial activity of some selected derivatives is reported.
Keywords: Tetrahydroquinoline; pyrimidine; thioureide; pyrimidoquinoline; X-ray
crystal structure.
Introduction
Pyrimidoquinolines are important compounds because of their biological properties, which are
known to depend mainly on the nature and position of substituents, and include antimalarial [1],
anticancer [2], antimicrobial [3, 4], and anti-inflammatory activities [5, 6]. Recently there has also been
considerable interest in the synthesis and chemistry of tetrahydroquinolines and their fused derivatives
[7-11]. Our aim in the work presented herein was to synthesize pyrimido[4,5-b]quinolines using
tetrahydroqinolinecarbonitriles as building blocks. Such a synthesis of condensed azines is of
biological interest due to the formal isoelectronic relationship that exists between the pyrimidine ring
and tetrahydroquinoline [12-23].

Molecules 2006, 11
891
Results and Discussion
Treatment of cyclohexanone (1) with the α,β-unsaturated nitrile derivative 2 in the presence of
ammonium acetate afforded the tetrahydroquinoline derivative 3. The structure of 3 was
unambiguously confirmed by X-ray crystallography (cf. Figure 1 and Table 1). On the other hand,
compounds 4a,b could be obtained upon reaction of 1 with 2 in absolute ethanol in the presence of p-
chloroaniline or p-hydroxyaniline (Scheme 1).
Scheme 1.
Ph
H
- +
CN
N
CN
CN
CH3COONH4
+
..
C
Ph
EtOH /
O
N
H2
2
1
NH2
X
CN
CN
Ph
Ph
H
CN
NH
N
H
Ph
H
CN
NH2
N
X
Ph
H
Ph
CN
CN
(O)
-H2
NH2
N
H
4a,x=Cl
4b,x=OH
NH2
N
3
Figure 1. ORTEP diagram of compound 3.

Molecules 2006, 11
892
Table 1. Crystal data and structure refinement for compound 3.
Empirical formula
Formula weight
C16H15N3
249.317
Temperature
289 K
Wavelength
0.71073A
Crystal system, space group
Unit cell dimensions
Monoclinic, P21/c
a = 12.7076 (11)Å
b = 5.8985 (5)Å
c = 18.227 (2)Å
α = 90.00°
β = 101.395 (3)°
1339 3(2) A3
Volume
Z, Calculated density
Absorption coefficient
F(000)
4, 1.237 Mg/m3
0.08 mm-1
236
Crystal size
1.00 x 0.22 x 0.16 mm
Kappa CCD
Diffract meter
Θ Rang (0)
2.910—19.211 °
Limiting indices -11<=h<=11, -5<=k<=5, -16<=l<=16
Reflections collected / unique
2106 / 1242 [R(int) = 0.044]
None
Absorption correction
Refinement method
Full-matrix least-squares on F2
1242 / 0 / 172
Data / restraints / parameters
Goodness-of-fit on F2
2.291
Final R indices [I>3sigma(I)]
R indices (all data)
R1 = 0.055, wR2 = 0.103
R1 = 0.1261, wR2 = 0.117
0.047(2)
Extinction coefficient
Largest diff. peak and hole
0.37 and -0.30 e. Å3
Compound 3 reacted with DMF-DMA in dioxane to afford compound 5, whose structure was also
unambiguously confirmed by X-ray crystallography (Figure 2 and Table 2). When compound 5 was
refluxed with hydrazine hydrate in absolute ethanol it yielded the corresponding 3–amino–4(3H)
imino–5-phenyl–6,7,8,9–tetrahydropyrimido[4, 5-b]quinoline (7) through the intermediate 6 (Scheme
2).
Scheme 2.
Ph
CN
.
DMF-DMA
dry dioxane
NH2NH2 H2O
3
EtOH
N
N=CHN(Me)2
5
Ph
NH
N
N
C
Ph
N
N-NH2
NHNH2
CH
N
N
7
6

Molecules 2006, 11
893
Figure 2. ORTEP diagram of Compound 5.
Table 2. Crystallographic and experimental data of compound 5.
Empirical formula
Formula weight
C19H20N4
304.359
Temperature
298 K
Wavelength
0.71073A
Crystal system, space group
Unit cell dimensions
Monoclinic, P21/c
a = 7.3256 (4)Å
b = 11.4319 (6)Å
c = 20.2817 (11)Å
α = 90.00°
β = 98.810 (3) °
Volume
1678.5 (2)Å3
Z, Calculated density
4, 1.493 Mg/m3
Absorption coefficient
F(000)
0.10 mm-1
236
Crystal size
1.00 x 0.22 x 0.16 mm
Kappa CCD
Diffract meter
Θ Rang (0)
2.910—26.733 °
Limiting indices -9<=h<=9, -13<=k<=14, -25<=l<=24
Reflections collected / unique
5914 / 4177 [R(int) = 0.048]
None
Absorption correction
Refinement method
Full-matrix least-squares on F2
1395 / 0 / 208
Data / restraints / parameters
Goodness-of-fit on F2
2.768
Final R indices [I>3sigma(I)]
R indices (all data)
R1 = 0.093, wR2 = 0.223
R1 = 0.381, wR2 = 0.218
0.030(2)
Extinction coefficient
Largest diff. peak and hole
0.68 and -0.67 e. Å3
Compound 3 reacted with thiourea or urea in an ethanol/sodium ethoxide mixture for 6 h to afford
the 4–amino–10–phenyl–6, 7, 8, 9–tetrahydropyrimido[4,5-b]quinoline–2(1H)–thione/one derivatives
9a and 9b (Scheme 3). The reaction products 9 were formed via the intermediate 8 by loss of an
ammonia molecule, followed by an intramolecular addition to the cyano function to give the final
isolated products 9a,b.

Molecules 2006, 11
894
The target ring system 12 was synthesized by reaction of 3 with carbon disulfide through the
intermediates 10 and 11, whose subsequent rearrangement leads to the fused pyrimidinedithione 12.
Scheme 3.
X
C
N
C
Ph
Ph
N
C
CS2
NH2
H2N
C2H5OH
C2H5ONa
3
..
-
S
NH2
pyridine
C=X
C=S
N
N
N
N
H
H
8
10
Ph
NH2
Ph
S
Ph
NH
N
NH
S
N
N
H
X
N
N
H
S
N
N
H
S
11
12
9a, X=S
9b, X=O
Compound 3 reacted with formic acid to yield 13, which was treated with alkaline hydrogen
peroxide to give the corresponding cyclized pyrimidoquinoline derivative 15 via the intermediate 14.
The reaction proceeds by initial hydration of the nitrile group to give a carboxamide, which then
undergoes cyclization in the alkaline medium. The structures of both 13 and 15 were confirmed by
elemental and spectral analyses. Meanwhile, acylation of 3 with acid chloride gave 2–methyl–5–
phenyl–6,7,8,9–tetrahydropyrimido[4,5-b]quinolin–4–(3H)one (18) through the intermediates 16 and
17 (Scheme 4).
Scheme 4.
Ph
NH2
N
N
N
19
HCONH2
3
HCOOH
CH3COCl
Ph
Ph
O
Ph
H2O2
CN
C-NH2
CN
CHO
CHO
O
N
N
H
N
N
H
N
NH-C-CH3
16
14
13
- H2O
Ph
O
Ph
O
NH2
..
O
NH
N
NH-C-CH3
N
N
15
17
- H2O
Ph
N
O
NH
N
CH3
18

Molecules 2006, 11
895
In addition, compound 3 was refluxed with excess formamide to afford 4–amino–5-phenyl–
6,7,8,9–tetrahydropyrimido[4,5-b]quinoline (19) (Scheme 4). The structure of the reaction product was
established based on its elemental analysis and spectra data. Both isocyanates and isothiocyanates
reacted with 3 to give initially the corresponding substituted ureido or thioureido derivatives 20a,b,
which readily cyclized to give the corresponding fused heterocyclic systems 21a,b (Scheme 5). The
same reaction products 21a,b could be obtained in a one step reaction through prolonged heating of 3
with phenylisocyanate or phenyl isothiocyanate in DMF containing a catalytic amount of TEA.
Finally, compound 3 reacted with benzoylisothiocyanate to yield 22, which then cyclized into 23
which undergoes a Dimroth rearrangement to give 24 (Scheme 5).
Scheme 5.
Ph
Ph
Ph
CN
CN
NHCOPh
C
CN
PhCONCS
NHPh
N
H
N
22
S
N
NH2
N
NH-C
X
3
20a,b
PhNCX
DMF,TEA
10 h
Ph
NH2
DMF, TEA
/ 6 h
COPh
N
N
N
H
S
Ph
NH2
23
Ph
NH
N-Ph
N-Ph
N
N
X
N
N
H
X
Ph
NHCOPh
N
21a X=S
21b X=O
N
N
H
S
24
Biological Activity
Screening of antimicrobial activity was performed at the Microbiology Lab of the National
Research Center. Representative derivatives 3, 4a, 4b, 7, 9a, 12, 13, 15, 18, 20, 22 and 24 were
selected and tested for their antimicrobial activity against three yeasts (Candida albicans, Aspergillus
niger and Saccharomyces cervisiae) and two bacteria (Staphylococcus aureus and Esherichia coli )
using the modified agar diffusion cylinder method [24]. The results are given in Table 3.
Table 3. The antimicrobial activity of select derivatives at 1000 ppm concentration.
Species tested
S. cerevisiae S. aureus Gram (+ve )
Compd.
C. albicans A. niger
E. coli Gram (- ve )
3
-
+
-
+
+
-
4a
4b
7
-
++
++
++
-
++
-
+
+
+
-
+
-
-
++
-
9a
+++
+
-

Molecules 2006, 11
896
Table 3. Cont.
Species tested
S. cerevisiae S. aureus Gram (+ve )
Compd.
C. albicans A. niger
E. coli Gram (- ve )
12
13
++
-
-
+
+++
-
+
-
-
+
+
-
15
+
++
++
+
+
+
-
18
-
+
-
20a
22
++
++
++
+
+
+
+
+
++
++
-
24
+
-
+++: Strong activity, ++: Moderate activity, +: Weak activity, - : No activity
Conclusions
The varied biological activities of tetrahydropyrimidoquinoline derivatives prompted us to
synthesize some new compounds and study their antimicrobial activities. The antifungal activity
assays showed that compounds 12, 20a, 22 and 24 display moderate activity against C. albicans, while
compound 9a shows strong activity against A. niger and compound 13 shows strong activity against S.
cerevisiae. The bactericidal activity studies revealed that compounds 4a and 7 show moderate
activities against S. aureus.
Experimental
General
All melting points are uncorrected. Elemental analyses were carried out in the Microanalytical
Center, Cairo University, Giza, Egypt. IR spectra (KBr) were recorded on Pye Unicam SP 1200
Spectrophotometer. 1H-NMR spectra were recorded in CDCl3 or DMSO- d6 on a 90 MHz Varian NMR
Spectrometer using TMS as an internal standard and chemical shifts are expressed as δ ppm units. The
mass spectra were determined with HP model MS-5988 at electron energy 70 eV. The homogeneity of
all compounds synthesized was checked by TLC on 2.0cm x 6.0cm aluminum sheets recoated with
silica gel 60 containing a fluorescent indicator, to a thickness of 0.25. Characterization data of the
various compounds prepared are given in Tables 4 and 5.
X-ray crystallography [25]
X-ray quality crystals of the title compounds 3 and 5 were obtained by slow crystallization from
dimethyl sulfoxide. Experimental data is summarized in Tables 1 and 2. The data were collected with
the maXus computer programs on a Bruker Nonius instrument [26-30].

Molecules 2006, 11
897
2–Amino–4–phenyl–5,6,7,8–tetrahydroquinoline–3–carbonitrile (3).
A solution of cyclohexanone (1, 0.01 mol) in absolute ethanol (30 mL) containing excess
ammonium acetate and the arylidene derivative 2 (0.01 mol) was heated under reflux for 3-5 h. The
solid material which separated during heating was collected by filtration and recrystallized from
ethanol to yield the tetrahydroquinoline derivative 3.
2–Amino–3–cyano–1,4–diphenyl–1,4,5,6,7,8–hexahydroquinoline derivatives 4a,b.
A solution of 2 (0.01 mol) and absolute ethanol (100 mL) was placed in a conical flask,
cyclohexanone (1, 0.01 mol) and p-chloroaniline or p-hydroxylaniline (0.01 mol) were added and the
reaction mixture was refluxed for 10-12 h. and then left to cool to room temperature overnight. The
solids obtained were recrystallized from ethanol to give the title compounds 4a,b.
2–Dimethylaminomethelenimino–3–cyano–4–phenyl–5,6,7,8–tetrahydroquinoline (5)
A solution of 3 (0.005 mol) in dry dioxane (20 mL) and DMF-DMA (0.005 mol) was refluxed for
4 hr. and the reaction mixture was then cooled to room temperature and poured into ice/cold water to
complete precipitation. The solid was filtered off and recrystallized from ethanol to give compound 5.
3–Amino–4–(3H)imino–5–phenyl–6,7,8,9–tetrahydropyrimido[4,5–b]quinoline (7).
A mixture of 5 (0.005 mol) and hydrazine hydrate (0.005 mol) in absolute ethanol (30 mL) was
refluxed for 4 hr. and the reaction mixture was left at room temperature overnight and then poured into
ice/cold water to complete precipitation. The product was filtered off and recrystallized from dry
benzene to give compound 7.
4–Amino–5–phenyl–6,7,8,9–tetrahydropyrimido[4,5–b]quinoline–2(1H)–thione/one derivatives 9a,b.
A mixture of 3 (0.005 mol) and thiourea (0.005 mol) or urea (0.005 mol) in absolute ethanol (20
mL) containing sodium ethoxide (0.005 mol) was refluxed for 6 hr. The reaction mixture was left to
cool to room temperature, then poured into ice cold water (50 mL) and neutralized with dilute
hydrochloric acid; the separated material was filtered off and recrystallized from ethanol to give
compounds 9a,b.
5–Phenyl–1,3,6,7,8,9–hexahydropyrimido[4,5–b]quinolin–2,4–dithione (12).
To a solution of 3 (0.005 mol) in dry pyridine (30 mL) carbon disulphide (0.005 mol) was added
and the reaction mixture was refluxed on a water bath for 6 hr., then left to cool to room temperature,
poured into cold water and neutralized with diluted hydrochloric acid to complete precipitation. The
solid obtained was filtered off, washed with water, dried well and recrystallized from methanol to give
compound 12.

Molecules 2006, 11
898
2–Formylamino–3–cyano–4–phenyl–5,6,7,8–tetrahydroquinoline (13).
An equimolar amount of 3 (0.005 mol) and formic acid (0.005 mol) in absolute ethanol (30 mL)
was refluxed for 2 hr. The reaction mixture was then concentrated and left to cool overnight to room
temperature for complete precipitation. The precipitated solid was filtered off, dried well and
recrystallized from aqueous ethanol to give compound 13.
5–Phenyl–6,7,8,9–tetrahydropyrimido[4,5–b]quinolin–4(3H)–one (15).
A solution of 13 (0.002 mol) in potassium carbonate (10 %, 10 mL) and hydrogen peroxide (30 %,
5 mL) was refluxed for 1 hr. The reaction mixture was left to cool at room temperature for complete
precipitation. The precipitated solid was collected by filtration and recrystallized from aqueous ethanol
to give compound 15.
2–Methyl–5–phenyl–6,7,8,9–tetrahydropyrimido[4,5–b]quinolin –4–(3H)one (18).
Acetyl chloride (0.005 mol) was added to a solution of 3 (0.005 mol) in dry pyridine (30 mL) and
the mixture was refluxed on a water bath for 3 hr., then left to cool to room temperature and poured
into ice cold water and neutralized by diluted hydrochloric acid for complete precipitation. The
separated material was collected by filtration, washed with water, dried well and recrystallized from
acetic acid to yield compound 18.
4–Amino–5–phenyl–6,7,8,9–tetrahydropyrimido[4,5–b]quinoline (19).
Compound 3 (0.005 mol) and an excess of formamide was placed in a conical flask and the
reaction mixture was refluxed for 4 hr., then left to cool for complete precipitation. The separated solid
product was filtered and recrystallized from ethanol to give compound 19.
2–(Phenylthioureido)–4–phenyl–5,6,7,8–tetrahydroquinoline–3–carbonitrile (20a,b).
A mixture of 3 (0.005 mol) and phenylisothiocyanate (0.005 mol) or phenylisocyanate (0.005 mol)
in dimethylformamide containing a catalytic amount of triethylamine (4 drops) was refluxed for 6 hr.
and then left to cool to room temperature. The reaction mixture was poured into cold water for
complete precipitation, then filtered off washed with water dried well and recrystallized from aqueous
methanol to give compounds 20a,b
4–Amino–5–phenyl–6,7,8,9–tetrahydropyrimido[4,5–b]quinoline2–(3H) thione/one
derivatives
(21a,b).
Method A: A few drops of triethylamine were added to a solution of 20a,b (0.005 mol) in
dimethylformamide and the reaction mixture was refluxed for 6 hr., then left to cool. The product was
filtered off, washed with water, dried well and recrystallized from ethanol to give compounds 21a,b .

Molecules 2006, 11
899
Method B: An equimolar mixture of 3 (0.005 mol) and phenylisocyanate (0.005 mol) or phenyl–
isothiocyanate (0.005 mol) in dimethylformamide (30 mL) in the presence of a few drops of
triethylamine (4 drops) was refluxed for 10 hr. The reaction mixture was left to cool and poured into
cold water for complete precipitation. The separated solid was filtered off, washed with water, dried
well and recrystallized from ethanol to give compounds 21a, b.
2–(Phenylthioureido)–4–phenyl–5,6,7,8–tetrahydroquinoline–3–carbonitrile (22).
A mixture of 3 (0.005 mol) and benzoylisothiocyanate (0.005 mol) in dimethylformamide (30 mL)
containing a catalytic amount of triethylamine (4 drops) was refluxed for 6 hr. and left to cool to room
temperature. The reaction mixture was poured into cold water for complete precipitation, and then
filtered off, washed with water dried well and recrystallized from aqueous methanol to give compound
22.
3–Benzoylamino–5–phenyl–6,7,8,9–tetrahydropyrimido[4,5–b]quinolin–2–(1H)thione (24).
Method A: To a solution of 22 (0.005 mol) in dimethylformamide was added few drops of
triethylamine. The reaction mixture was refluxed 6 hr., then left to cool, the solids filtered off, washed
with water, dried well and recrystallized from ethanol to give compound 24.
Method B: An equimolar mixture of 3 (0.005 mol) and benzoylisothiocyanate (0.005 mol) was
refluxed for 10 hr. in dimethylformamide (30 mL) containing four drops of triethylamine. The reaction
mixture was left to cool and poured into cold water for complete precipitation. The separated solid was
filtered off, washed with water, dried well and recrystallized from ethanol to give compound 24.
Table 4. Physical properties and elemental analyses of the new compounds.
Formula
(mw)
Analysis % Calcd. (Found)
Compd. M.P.°C
C
H
N
S
Cl
C16H15N3
(249.326)
C22H20N3Cl
361.87
77.08
(77.02)
73.02
(73.00)
76.94
(76.89)
74.98
(74.89)
70.33
(70.24)
66.21
(66.07)
69.85
(69.74)
6.06
16.86
(16.86)
11.61
(11.49)
12.24
(12.15)
18.14
(18.20)
24.12
(24.04)
18.17
(18.07)
19.17
(19.11)
–
–
3
4a
4b
5
240
270
260
184
210
290
213
(6.01)
5.57
–
–
9.8
(5.46)
6.16
(9.74)
–
C22H21N3O
(343.43)
(6.04)
6.62
C19H20N4
(304.373)
C17H17N5
(291.323)
C17H16N4S
(308.413)
C17H16N4O
(292.342)
(6.56)
5.55
–
–
–
–
7
(5.47)
5.22
10.4
(10.34)
–
9a
9b
(5.09)
5.51
(5.43)

Molecules 2006, 11
900
Table 4. Cont.
Analysis % Calcd. (Found)
Formula
(mw)
Compd. M.P.°C
S
Cl
C
H
N
C17H15N3S2
(325.464)
C17H15N3O
(277.332)
C17H15N3O
(277.332)
C18H17N3O
(291.364)
C17H16N4
62.74
4.64
12.91
19.70
(19.79)
–
–
12
13
207~209
195~196
187~188
187~188
205
(62.79)
73.63
(4.62)
5.45
(12.94)
15.15
–
–
–
–
–
–
(73.74)
73.63
(5.40)
5.45
(15.21)
15.15
–
–
–
15
18
(73.83)
74.21
(5.14)
5.88
(15.27)
14.42
(74.03)
73.89
(5.73)
5.83
(14.27)
20.27
19
20a
20b
21a
21b
22
(276.343)
C23H20N4S
(384.51)
(73.84)
71.84
(5.78)
5.24
(20.18)
14.57
8.34
(8.29)
–
172
(72.01)
74.98
(5.29)
5.47
(14.59)
15.21
C23H20N4O
(368.444)
C23H20N4S
(384.51)
160
(74.67)
71.84
(5.63)
5.24
(15.04)
14.57
8.34
(8.29)
–
218
(72.00)
74.98
(5.29)
5.47
(14.52)
15.21
C23H20N4O
(368.444)
C24H20N4OS
(412.527)
C24H20N4OS
412.527
–
–
–
190
(74.71)
69.88
(5.67)
4.88
(15.11)
13.58
7.77
174
(69.74)
69.88
(4.73)
4.88
(13.42)
13.58
(7.71)
7.77
24
225
(69.79)
(4.81)
(13.52)
(7.71)
Table 5. IR, 1H-NMR, and MS of the new compounds.
Compd. IR (cm-1)
1H-NMR (δ, ppm) and/or MS
3
3420-3305 (NH2), 2212 (CN), 1645
1.6-2.8 (m, 8H, 4CH2); 5.3(s, 2H, NH2); 7.2-7.6
(m, 5H, Ar-H).
MS: m/e = 249 (M+, 100%).
(C=N).
4a
4b
3424-3345 (NH2), 2211 (CN), 1650
(C=N).
1.6-2.8 (m, 8H, 4CH2); 4.8 (s, 1H, quinoline H-4),
5.8 (s, 2H, NH2), 7.2-7.4 (m, 9H, Ar-H).
MS: m/e = 361 (M+, 18%), 362 (M+1, 6%).
1.6-2.8 (m, 8H, 4CH2); 4.8 (s, 1H, quinoline H-4);
5.3 (s, 2H, NH2); 7.2-7.6 (m, 9H, Ar-H); 9.2 (s,
1H, OH).
3421 (OH), 3306 (NH2), 2215 (CN),
1622 (C=N).
MS: m/e = 343 (M+, 75 %).
5
7
2216 (CN), 1623 (C=N).
1.6-2.8 (m, 8H, 4CH2); 3.2 (s, 6H, 2CH3); 7.2-7.4
(m, 5H, Ar-H); 8.4 (s, 1H, vinyl H).
MS: m/e =304 (M+, 100%).
3421-3360 (NH2), 3148 (NH), 1645
(C=N).
1.6-2.8 (m, 8H, 4CH2); 5.4 (s, 2H, NH2); 7.2-7.4
(m, 5H, Ar-H); 7.50 (s, 1H, pyrimidine H); 8.01
(s, 1H, NH).
MS: m/e = 291 (M+, 15%).

Molecules 2006, 11
901
Table 5. Cont.
1H-NMR (δ, ppm) and/or MS
Compd. IR (cm-1)
9a
3408-3320 (NH2), 3226 (NH), 1337
(C=S).
1.6-2.8 (m, 8H, 4CH2); 5.4 (s, 2H, NH2); 7.1-7.5
(m, 5H, Ar-H); 8.2 (s, 1H, NH).
MS: m/e = 308 (M+, 15 %).
9b
12
3421 (NH2), 3426 (NH), 1717 (C=O), MS: m/e = 292 (M+, 50%).
1646 (C=N).
3426 (NH), 1643 (C=N), 1344 (C=S). 1.62-2.88 (m, 8H, 4CH2); 5.8 (s, 1H
exchangeable, NH); 7.12- 7.64 (m, 5H, Ar-H);
9.08 (bs, 1H, exchangeable, NH).
MS: m/e = 325 (M+, 10%).
13
15
18
3228 (NH), 2211 (CN), 1692 (C=O),
1581 (C=N).
MS: m/e = 277 (M+, 30%).
3146 (NH), 1707 (C=O), 1645 (C=N). 1.34-1.98 (m, 8H, 4CH2); 7.13-7.35 (m, 5H, Ar-
H); 7.50 (s, 1H, pyrimidine H); 8.01 (s, 1H, NH).
3146 (NH), 1707 (C=O), 1645 (C=N). 0.9 (s, 3H, CH3); 1.34-1.96 (m, 8H, 4CH2); 7.14-
7.30 (m, 5H, Ar-H); 8.01 (s, 1H, NH).
MS: m/e = 291 (M+, 15%).
19
3319-3322 (NH2), 1661 (C=N).
1.35-2.68 (m, 8H, 4CH2); 5.4 (s, 2H, NH2); 4.8 (s,
1H, pyrimidine H); 7.13-7.46 (m, 5H, Ar-H).
MS: m/e = 276 (M+, 55 %).
20a
20b
21a
21b
22
3148 (NH), 3059 (NH), 2211(CN),
645 (C=N), 1346 (C=S).
MS: m/e = 384 (M+, 10%).
3179 (NH), 3149 (NH), 2228 (CN),
1707 (C=O), 1631 (C=N).
3421 – 3307 (NH2), 1645 (C=N), 1346 MS: m/e = 384 (M+, 10%).
(C=S).
MS: m/e = 368(M+, 40%).
3419-3303 (NH2), 1645 (C=N), 1707
(C=O).
MS: m/e = 368 (M+, 40%).
MS: m/e = 412 (M+, 10%).
MS: m/e = 412 (M+, 10%).
3148 (NH), 3059 (NH), 2211 (CN),
1677 (C=O), 1645(C=N), 1346 (C=S).
3182 (NH), 3120 (NH), 1672 (C=O),
1605 (C=N), 1363 (C=S ) .
24
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Sample Availability: Available from the authors.
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