New synthetic approach to 4-N-arylaminoazuleno[2,1-d]pyrimides

Article abstract of DOI:10.1080/00397910802654807

1-Cyano-2-N,N-dimethylformamidinylazulenes as new synthons directed to heterocycle-fused azulenes were obtained by the condensation of 2-amino-1-cyanoazulenes and N,N-dimethylformamide dimethyl acetal (DMFDMA). 1-Cyano-2-N,N-dimethylformamidinylazulene (2

Full text of DOI:10.1080/00397910802654807

Synthetic Communications1, 39: 2329–2338, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802654807
New Synthetic Approach to
4-N-Arylaminoazuleno[2,1-d]pyrimides
Dao-Lin Wang,1 Zheng Gu,1 Jiao Xu,2 Shan Han,1
and Kimiaki Imafuku3
1College of Chemistry and Chemical Engineering, Liaoning Key
Laboratory of Apple Chemistry, Bohai University, Jinzhou, China
2Heilongjiang University of Chinese Medicine, Jiamusi Institute,
Cosmetology Department, Jiamusi, China
3Department of Chemistry, Faculty of Science, Kumamoto University,
Kurokami, Kumamoto, Japan
Abstract: 1-Cyano-2-N,N-dimethylformamidinylazulenes as new synthons
directed to heterocycle-fused azulenes were obtained by the condensation of
2-amino-1-cyanoazulenes and N,N-dimethylformamide dimethyl acetal
(DMFDMA). 1-Cyano-2-N,N-dimethylformamidinylazulene (2a) and 1-bromo-
3-cyano-2-N,N-dimethylformamidinylazulene (2b) reacted with anilines (3a–h)
to give 4-N-arylaminoazuleno-[2,1-d]pyrimidines in moderate yields. This reac-
tion provides a new procedure for synthesis of pyrimidine-fused azulenes.
Keywords: Azulene, azuleno[2,1-d]pyrimidines, DMFDMA, synthesis
INTRODUCTION
Heterocycle-fused azulenes with a variety of chemical properties and
physiological activities have been obtained by several synthetic
methods.[1–4] In a previous article, we reported that 1-acetyl-2-(bromo-
methyl)azulene reacted with anilines or thioacetamide to give
2-aryl-3methylazuleno[1,2-c]pyrroles[5] or azuleno-[1,2-c]thiophenes[6]
Received September 12, 2008.
Address correspondence to Dao-Lin Wang, College of Chemistry and
Chemical Engineering, Liaoning Key Laboratory of Apple Chemistry, Bohai
University, Jinzhou 121001, China. E-mail: wangdaolin@sina.com
2329

2330
D.-L. Wang et al.
respectively. Of these, pyrimidine-fused azulenes were prepared using
different types of starting materials as follows. 2-amino-1-formylazulene
reacted with guanidine to convert to 2-aminoazuleno[2,1-d]pyrimidine.[7]
The reaction of 2-acetylimino-2H-cyclohepta[b]furan derivatives with active
methylene compounds afforded the azuleno[2,1-d]pyrimidine derivatives.[8]
In connection with our studies on the synthetic utilities of
heterocycle-fused azulenes, this article describes a new synthetic method
of 4-N-arylaminoazuleno-[2,1-d]pyrimidines by the reactions of 1-cyano-
2-N,N-dimethylformamidinyl azulenes with anilines.
RESULTS AND DISCUSSION
Synthesis of 1-Cyano-2-N,N-dimethylformamidinylazulenes
2-Amino-1-cyanoazulene (1a)[9] and 2-amino-3-bromo-1-cyanoazulene
(1b), which was obtained by bromination of 1a with N-bromosuccini-
mide, were treated with 3 molar equivalents of N,N-dimethylformamide
dimethyl acetal (DMFDMA) for 8 h under reflux in toluene to afford
1-cyano-2-N,N-dimethylformamidinylazulenes (2a, 2b) in 78 and 73%
yields respectively (Scheme 1). Because intermediates (2) have two reac-
tive functional groups, cyano and N,N-dimethylformamidinyl groups,
at neighboring positions, they seem to be useful building blocks for
heterocycle-fused azulenes.
Reactions of New Building Blocks (2a, 2b) with Anilines
A solution of 1-cyano-2-N,N-dimethylformamidinylazulene (2a) and
aniline (3a) in benzene was stirred for 12 h at 80ꢀC to give 4-N-phenyl-
aminoazuleno[2,1-d]pyrimidine (4a) in 38%. The formula of 4a was deter-
mined to be C18H13N3 from the elemental and spectral data.
To optimize the conditions, we studied the effects of molar ratio,
temperature, reaction time, and solvent. In a typical experiment, a mixture
Scheme 1. Synthesis of 1-cyano-2-N,N-dimethylformamidinazulenes.

4-N-Arylaminoazuleno[2,1-d]pyrimides
2331
Scheme 2. Synthesis of 4-N-phenylaminoazulen[2,1-d]pyrimidine.
of 1-cyano-2-N,N-dimethylformamidinylazulene (2a) and aniline (3a)
was monitored by high-performance liquid chromatography (HPLC)
(Scheme 2), and the results are summarized in Table 1. Good results were
obtained in the reactions using 2 molar equivalents of aniline in toluene as
the solvent at 80ꢀC.
The reactions with methyl, methoxy, chloro, fluoro, and nitro group
substitued anilines (3b–g), 1-naphthylamine (3h), and 2-naphthylamine
(3i) were carried out to give the corresponding 4-N-arylaminoazu-
leno[2,1-d]pyrimidines (4a–i). In a similar manner, 9-bromo-substituted
4-N-arylaminoazuleno[2,1-d] pyrimidines (4j–m) were obtained in the
reactions of 1-bromo-3-cyano-2-N,N-dimethylformamidinylazulene (2b)
and anilines (3b, 3g, 3j, 3k) (Scheme 3). These results are summarized
in Table 2.
It was found that 1-cyano-2-N,N-dimethylformamidinylazulenes
were useful starting materials for syntheses of 4-N-arylaminoazu-
leno[2,1-d]pyrimidines. Furthermore, the intermediates are expected to
be building blocks for other heterocycle-fused azulene derivatives, and
their reactions are now in progress.
EXPERIMENTAL
All melting points were determined with a Yanaco MP JP-3 apparatus
and are uncorrected. The infrared (IR) spectra were measured on a Jasco
Scheme 3. Synthesis of 4-N-arylaminoazuleno[2,1-d]pyrimidines.

2332
D.-L. Wang et al.
Table 1. Optimization of reaction conditions and results
Entry
Molar ratio
Solvent
Temp (ꢀC)
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
10
1:1.5
1:1.5
1:1.5
1:2
1:2
1:2
1:2
1:2
1:2
1:2
Benzene
Toluene
Toluene
Toluene
CH2Cl2
CHCl3
25
80
110
80
40
60
75
80
24
12
8
10
24
12
12
8
22
40
39
49
30
41
26
31
29
43
CCl4
CH2ClCH2Cl
EtOH
AcOH
75
80
8
8
A-102 IR spectrophotometer. The NMR spectra were recorded with a
1
Jeol JNM-EX 300 spectrometer (400 MHz for H). Elemental analysis
was carried out using a Heraus CHN rapid analyzer.
Preparation of 2-Amino-1-bromo-3-cyanoazulene (1b) by
Bromination of 2-Amino-1-cyanoazulene (1a) with N-Bromosuccinimide
N-bromosuccinimide (106 mg, 0.6 mmol) was added to a solution of
2-amino-1-cyanoazulene (1a)[9] (0.5 mmol) in benzene (20 mL). After
stirring for 1 h at rt, cold water (20 mL) was added to the mixture. The
Table 2. Synthesis of 4-N-arylaminoazuleno[2,1-d]pyrimidines
Entry Azulene (2) R1
Aniline (3) R2
Time (h) Product 4 Yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
H
H
H
H
H
H
H
H
H
Br
Br
Br
Br
a
b
c
d
e
f
C6H5
4-MeC6H4
4-FC6H4
4-NO2C6H4
3,4-(Me)2C6H3
3,5-(Me)2C6H3
3-F-4-ClC6H3
1-Naphthyl
2-Naphthyl
4-MeC6H4
10
10
11
16
10
10
12
14
12
8
a
b
c
d
e
f
49
51
29
35
34
29
52
26
30
32
40
30
18
g
h
i
g
h
i
b
j
j
4-MeOC6H4
3-F-4-ClC6H3
2,4,6-(Me)3C6H2
8
12
10
k
l
g
k
m

4-N-Arylaminoazuleno[2,1-d]pyrimides
2333
combined organic layer and extracts were washed with water and dried
over sodium sulfate. The evaporation residue was chromatographed on
a silica-gel column with benzene as an eluent to afford 2-amino-1-
bromo-3-cyanoazulenes (1b); yield 110 mg (89%), mp 192–193ꢀC; IR
(KBr): n 3042, 2951, 2921, 2820, 2209 cmꢁ1
;
1H NMR (CDCl3,
400 MHz) d (ppm): 5.29 (s, 2H, NH2), 7.41–7.49 (m, 3H, 5, 6, 7-H),
7.99 (d, 1H, J ¼ 10.0 Hz, 4-H), 8.08 (d, 1H, J ¼ 9.2 Hz,
8-H). MS: m=z 247 (Mþ). Anal. calcd. for C11H7BrN2: C, 53.47; H,
2.86; N, 11.34. Found: C, 53.36; H, 3.06; N, 11.43%.
1-Cyano-2-N,N-dimethylformamidinylazulenes (2)
General Procedure
A mixture of 2-amino-1-cyanoazulenes (1) (10 mmol) and DMFDMA
(2.52 g, 20 mmol) in toluene (100 mL) was heated under reflux for 8 h.
The reaction mixture was cooled with ice and extracted with EtOAc.
The organic layer was washed with saturated brine and dried over anhy-
drous sodium sulfate. After filtration, the filtrate was concentrated. The
residue was purified by silica-gel column chromatography with benzene
as eluent to obtain 1-cyano-2-N,N-dimethylform-amidinylazulenes (2).
1-Cyano-2-N,N-dimethylformamidinylazulene (2a)
Brown-yellow needles; yield 78%; mp 105–107ꢀC; IR (KBr): n 3042, 2951,
2921, 2820, 2205 cmꢁ1; 1H NMR (CDCl3, 400 MHz) d (ppm): 3.15 (s, 3H,
NCH3), 3.19 (s, 3H, NCH3), 6.86 (s, 1H, 3-H), 7.36 (dd, 1H, J ¼ 9.6,
10.4 Hz, 5-H), 7.36 (dd, 1H, J ¼ 9.2, 9.6 Hz, 7-H), 7.45 (dd, 1H, J ¼ 9.6,
9.6 Hz, 6-H), 8.03 (d, 1H, J ¼ 10.0 Hz, 4-H), 8.16 (s, 1H, -N¼CH-), 8.23
(d, 1H, J ¼ 9.2 Hz, 8-H). MS: m=z 223 (Mþ). Anal. calcd. for C14H13N3:
C, 75.31; H, 5.87; N, 18.82. Found: C, 75.26; H, 6.06; N, 18.73%.
1-Cyano-3-bromo-2-N,N-dimethylformamidinylazulene (2b)
Bluish dark needles; yield 73%; mp 126–128ꢀC; IR (KBr): n 3045, 2956,
1
2927, 2810, 2207 cmꢁ1; H NMR (CDCl3, 400 MHz) d (ppm): 3.19 (s,
3H, NCH3), 3.24 (s, 3H, NCH3), 7.43 (dd, 1H, J ¼ 9.6, 10.4 Hz, 5-H),
7.45 (dd, 1H, J ¼ 9.2, 9.6 Hz, 7-H), 7.52 (dd, 1H, J ¼ 9.6, 9.6 Hz, 6-H),
8.18 (d, 1H, J ¼ 9.6 Hz, 4-H), 8.20 (d, 1H, J ¼ 9.6 Hz, 8-H), 8.36 (s, 1H,
-N¼CH-). MS: m=z 302 (Mþ). Anal. calcd. for C14H12BrN3: C, 55.65;
H, 4.00; N, 13.91. Found: C, 55.78; H, 4.06; N, 13.75%.

2334
D.-L. Wang et al.
Reactions of 1-Cyano-2-N,N-dimethylformamidinylazulene
(2) with Anilines
General Procedure
Anilines (3) (1.0 mmol) were added to a solution of 1-cyano-2-N,N-
dimethylformamidinylazulenes (2) (0.5 mmol) in toluene (20 mL). The
mixture was heated at 80ꢀC for 8–16 h (tracked with thin-layer chroma-
tography, TLC). After cooling, cold water (50 mL) was added to the mix-
ture. Then the mixture was extracted in ethyl acetate (2 ꢂ 20 mL), and the
organic layer was washed with water and a solution of saturated aqueous
NaHCO3, dried over sodium sulfate, and evaporated in vacuum to afford
4-N-arylaminoazuleno[2,1-d]pyrimidines (4a–m). They were purified by
chromatography on a silica-gel column with benzene as eluent.
4-N-(4-Phenyl)aminoazulen[2,1-d]pyrimidine (4a)
Brown needle crystals; yield 49%; mp 69–70ꢀC; IR (KBr): n 3426, 3228,
2961, 2928, 1612, 1564, 1388 cmꢁ1 1H NMR (CDCl3, 400 MHz) d
;
(ppm): 7.28–7.30 (m, 3H, 30, 40, 50-H), 7.41 (dd, 1H, J ¼ 9.6, 9.6 Hz,
6-H), 7.46 (dd, 1H, J ¼ 9.6, 9.6 Hz, 8-H), 7.48 (s, 1H, 10-H), 7.61 (dd,
1H, J ¼ 9.6, 10.0 Hz, 7-H), 7.72–7.75 (m, 3H, 5, 20, 60-H), 8.01 (d, 1H,
J ¼ 10.0 Hz, 9-H), 8.28 (br s, 1H, NH), 8.92 (s, 1H, 2-H). MS: m=z 271
(Mþ). Anal. calcd. for C18H13N3: C, 79.68; H, 4.83; N, 15.49. Found:
C, 79.70; H, 4.74; N, 15.65%.
4-N-(4-Methylphenyl)aminoazulen[2,1-d]pyrimidine (4b)
Brown needle crystals; yield 51%; mp 174–176ꢀC; IR (KBr): n 3455, 3224,
1
2959, 2926, 1598, 1561, 1384, 813 cmꢁ1; H NMR (CDCl3, 400 MHz) d
(ppm): 2.31 (s, 3H, CH3), 7.24 (d, 2H, 30, 50-H, J ¼ 8.4 Hz), 7.27 (dd,
1H, J ¼ 9.6, 9.6 Hz, 6-H), 7.37 (dd, 1H, J ¼ 9.6, 9.6 Hz, 8-H), 7.42 (s,
1H, 10-H), 7.49–7.52 (m, 2H, 5,7-H), 7.55 (d, 2H, J ¼ 8.4 Hz, 20, 60-H),
8.25 (d, 1H, J ¼ 10.8 Hz, 9-H), 8.39 (br s, 1H, NH), 8.85 (s, 1H, 2-H).
MS: m=z 285 (Mþ). Anal. calcd. for C19H15N3: C, 79.97; H, 5.30; N,
14.73. Found: C, 79.82; H, 5.44; N, 14.65%.
4-N-(4-Fluorophenyl)aminoazulen[2,1-d]pyrimidine (4c)
Brown needle crystals; yield 29%; mp 141–143ꢀC; IR (KBr): n 3442, 3293,
1
2955, 2929, 1617, 1560, 1508, 836 cmꢁ1; H NMR (CDCl3, 400 MHz) d

4-N-Arylaminoazuleno[2,1-d]pyrimides
2335
(ppm): 7.11–7.15 (d, 2H, 30, 50-H), 7.35 (dd, 1H, J ¼ 9.6, 9.6 Hz, 6-H), 7.42
(dd, 1H, J ¼ 9.6, 9.6 Hz, 8-H ), 7.43 (s, 1H, 10-H), 7.51–7.55 (m, 2H, 5, 7-H),
7.60–7.62 (m, 2H, 20, 60-H), 8.28 (d, 1H, J ¼ 10.8 Hz, 9-H), 8.36 (br s, 1H,
NH), 8.87 (s, 1H, 2-H). MS: m=z 289 (Mþ). Anal. calcd. for C18H12FN3:
C, 74.73; H, 4.18; N, 14.53. Found: C, 74.65; H, 4.24; N, 14.45%.
4-N-(4-Nitrophenyl)aminoazulen[2,1-d]pyrimidine (4d)
Brown needle crystals; yield of 35%; mp 205–208ꢀC; IR (KBr): n 3278,
1
2957, 2921, 1618, 1569, 1506, 849 cmꢁ1; H NMR (CDCl3, 400 MHz) d
(ppm): 7.31–7.39 (m, 2H, 6, 8-H), 7.48 (s, 1H, 10-H), 7.52–7.60 (m, 2H,
5, 7-H), 7.88 (d, 2H, J ¼ 8.8 Hz, 30, 50-H), 8.30 (d, 2H, J ¼ 8.8 Hz, 20,
60-H), 8.42 (d, 1H, J ¼ 10.8 Hz, 9-H), 8.32 (br s, 1H, NH), 8.97 (s, 1H,
2-H). MS: m=z 316 (Mþ). Anal. calcd. for C18H12N4O2: C, 68.35; H,
3.82; N, 17.71. Found: C, 68.27; H, 3.93; N, 17.68%.
4-N-(3,4-Dimethylphenyl)aminoazulen[2,1-d]pyrimidine (4e)
Brown needle crystals; yield 34%; mp 245–247ꢀC; IR (KBr): n 3430, 3225,
1
2961, 2925, 1596, 1561, 1447, 815 cmꢁ1; H NMR (CDCl3, 400 MHz) d
(ppm): 2.29 (s, 3H, CH3), 2.32 (s, 3H, CH3), 7.21 (s, 1H, 20-H), 7.29
(dd, 1H, J ¼ 9.6, 9.6 Hz, 6-H), 7.37–7.41 (m, 3H, 60, 5, 7-H), 7.42 (s,
1H, 10-H), 7.50–7.53 (m, 1H, 50-H), 7.54 (dd, 1H, J ¼ 9.6, 9.6 Hz, 8-H),
8.26 (d, 1H, J ¼ 10.8 Hz, 9-H), 8.40 (br s, 1H, NH), 8.85 (s, 1H, 2-H).
MS: m=z 299 (Mþ). Anal. calcd. for C20H17N3: C, 80.24; H, 5.72; N,
14.04. Found: C, 80.27; H, 5.54; N, 14.15%.
4-N-(3,5-Dimethylphenyl)aminoazulen[2,1-d]pyrimidine (4f)
Brown needle crystals; yield 29%; mp 203–205ꢀC; IR (KBr): n 3342, 3031,
1
2920, 1609, 1570, 1448, 844, 811 cmꢁ1; H NMR (CDCl3): d 2.11 (s, 3H,
CH3), 2.40 (s, 3H, CH3), 7.01 (s, 1H, 40-H), 7.28–7.35 (m, 3H, 5, 6, 7-H),
7.41 (s, 1H, 10-H), 7.42 (s, 2H, 20, 60-H), 7.52 (dd, 1H, J ¼ 9.6, 9.6 Hz,
8-H), 8.25 (d, 1H, J ¼ 10.8 Hz, 9-H), 8.33 (br s, 1H, NH), 8.83 (s, 1H,
2-H). MS: m=z 299 (Mþ). Anal. calcd. for C20H17N3: C, 80.24; H, 5.72;
N, 14.04. Found: C, 80.43; H, 5.54; N, 14.14%.
4-N-(3-Fluoro-4-chlorolphenyl)aminoazulen[2,1-d]pyrimidine (4g)
Brown needle crystals; yield 52%; mp 169–170ꢀC; IR (KBr): n 3435, 3045,
2968, 2929, 1617, 1571, 1445, 1106 cmꢁ1; 1H NMR (CDCl3): d 7.27–7.33

2336
D.-L. Wang et al.
(m, 3H, 5, 6, 7-H), 7.41 (s, 1H, 10-H), 7.42–7.45 (m, 1H, 60-H), 7.50–7.53
(m, 1H, 50-H), 8.58 (d, 1H, J ¼ 9.6, 9.6 Hz, 8-H), 7.83 (s, 1H, 20-H), 8.27
(d, 1H, J ¼ 10.8 Hz, 9-H), 8.44 (br s, 1H, NH), 8.83 (s, 1H, 2-H). MS: m=z
323 (Mþ). Anal. calcd. for C18H11ClFN3: C, 66.78; H, 3.42; N, 12.98.
Found: C, 66.57; H, 3.54; N, 12.88%.
4-N-(1-Naphthyl)aminoazulen[2,1-d]pyrimidine (4h)
Brown needle crystals; yield 26%; mp 210–212ꢀC; IR (KBr): n 3425, 3050,
1
2926, 1569, 1541, 1384, 775 cmꢁ1; H NMR (CDCl3, 400 MHz) d (ppm):
7.29–7.36 (m, 3H, 5, 6, 7-H), 7.46–7.48 (m, 1H, 8-H), 7.49 (s, 1H, 10-H),
7.51–7.57 (m, 4H, 8, 50, 60, 70-H), 7.54 (d, 1H, J ¼ 9.6, 9.6 Hz, 8-H), 7.79
(d, 1H, J ¼ 8.8 Hz, 40-H), 7.84–7.86 (m, 2H, 50, 80-H), 7.92 (d, 1H,
J ¼ 8.8 Hz, 80-H), 8.09 (d, 1H, J ¼ 6.8 Hz, 20-H), 8.32 (d, 1H, J ¼ 10.8 Hz,
9-H), 8.47 (br s, 1H, NH), 8.87 (s, 1H, 2-H). MS: m=z 321 (Mþ). Anal.
calcd. for C22H15N3: C, 82.22; H, 4.70; N, 13.08. Found: C, 82.27; H,
4.64; N, 13.21%.
4-N-(2-Naphthyl)aminoazulen[2,1-d]pyrimidine (4i)
Brown needle crystals; yield 30%; mp 210–212ꢀC; IR (KBr): n 3425,
3050, 2926, 1569, 1541, 1384, 775 cmꢁ1 1H NMR (CDCl3): d 7.29
;
(d, 1H, J ¼ 9.6 Hz, 5-H), 7.38 (dd, 1H, J ¼ 9.6, 9.6 Hz, 6-H), 7.39 (dd,
1H, J ¼ 9.6, 9.6 Hz, 7-H), 7.41–7.43 (m, 1H, 50-H), 7.44 (s, 1H, 10-H),
7.46–7.48 (m, 2H, 60, 70-H), 7.54 (d, 1H, J ¼ 9.6, 9.6 Hz, 8-H), 7.79 (d,
1H, J¼ 8.8 Hz, 40-H), 7.84–7.86 (m, 2H, 50, 80-H), 7.90 (d, 1H, J¼ 8.8 Hz,
30-H), 8.18 (s, 1H, 10-H), 8.27 (d, 1H, J ¼ 10.8 Hz, 9-H), 8.48 (br s,
1H, NH), 8.88 (s, 1H, 2-H). MS: m=z 321 (Mþ). Anal. calcd. for
C22H15N3: C, 82.22; H, 4.70; N, 13.08. Found: C, 82.31; H, 4.62; N,
13.30%.
9-Bromo-4-N-(4-methylphenyl)aminoazuleno[2,1-d]pyrimidine (4j)
Brown needles crystals; yield 32%; mp 254–256ꢀC; IR (KBr): n 3199,
1
2960, 2928, 1568, 1536, 1326, 925 cmꢁ1; H NMR (CDCl3, 400 MHz) d
(ppm): 2.34 (s, 3H, CH3), 7.09–7.18 (m, 3H, 5, 6, 8-H), 7.23 (d, 2H, 30,
50-H, J ¼ 8.8 Hz), 7.31 (d, 2H, J ¼ 8.8 Hz, 20, 60-H), 7.40–7.43 (m, 2H,
5, 7-H), 8.34 (d, 1H, J ¼ 10.8 Hz, 9-H), 8.38 (br s, 1H, NH), 8.94 (s,
1H, 2-H). MS: m=z 364 (Mþ). Anal. calcd. for C19H14BrN3: C, 62.65;
H, 3.87; N, 11.54. Found: C, 62.67; H, 3.74; N, 11.68%.

4-N-Arylaminoazuleno[2,1-d]pyrimides
2337
9-Bromo-4-N-(4-Methoxyphenyl)aminoazuleno[2,1-d]pyrimidine (4k)
Brown needle crystals; yield 40%; mp 240–242ꢀC; IR (KBr): n 3242, 3068,
2960, 1607, 1567, 1512, 1247, 1033, 730 cmꢁ1 1H NMR (CDCl3,
;
400 MHz) d (ppm): 3.85 (s, 3H, OCH3), 6.98 (d, 2H, 30, 50-H, J¼ 7.6 Hz),
7.40–7.43 (m, 2H, 6, 8-H), 7.52 (d, 2H, J ¼ 7.6 Hz, 20, 60-H), 7.54–7.58
(m, 2H, 5, 7-H), 8.35 (br s, 1H, NH), 8.39 (d, 1H, J ¼ 10.4 Hz, 9-H), 8.94
(s, 1H, 2-H). MS: m=z 380 (Mþ). Anal. calcd. for C19H14BrON3: C,
60.01; H, 3.71; N, 11.05. Found: C, 60.27; H, 3.84; N, 11.23%.
9-Bromo-4-N-(4-fluoro-3-chlorophenyl)aminoazuleno[2,1-d]-
pyrimidine (4l)
Brown needle crystals; yield 30%; mp 255–257ꢀC; IR (KBr): n 3296, 3068,
2918, 2850, 1606, 1572, 1535, 1326, 1170, 795, 736 cmꢁ1 1H NMR
;
(CDCl3, 400 MHz) d (ppm): 7.40–7.46 (m, 2H, 5, 7-H), 7.52–7.55 (m,
1H, 60-H), 7.61 (d, 1H, J ¼ 9.6, 9.6 Hz, 6-H), 7.68 (s, 1H, 20-H), 7.71–
7.74 (m, 1H, 50-H), 7.84 (dd, 1H, J ¼ 9.6, 9.6 Hz, 8-H), 8.33 (br s, 1H,
NH), 8.43 (d, 1H, J ¼ 10.8 Hz, 9-H), 9.05 (s, 1H, 2-H). MS: m=z 402
(Mþ). Anal. calcd. for C18H10BrClFN3: C, 53.69; H, 2.50; N, 10.44.
Found: C, 53.57; H, 2.64; N, 10.58%.
9-Bromo-4-N-(2,4,6-trimethylphenyl)aminoazuleno[2,1-d]-
pyrimidine (4m)
Brown needle crystals; yield 18%; mp > 300ꢀC; IR (KBr): n 3294, 2961,
2918, 1560, 1534, 1436, 1323, 923, 742 cmꢁ1
;
1H NMR (CDCl3,
400 MHz) d (ppm): 2.22 (s, 6H, 2 ꢂ CH3), 2.38 (s, 3H, CH3), 7.01 (s,
2H, 30, 50-H), 7.40–7.46 (m, 3H, 5, 6, 7-H), 7.54 (dd, 1H, J ¼ 9.6,
9.6 Hz, 8-H), 8.39 (br s, 1H, NH), 8.44 (d, 1H, J ¼ 10.8 Hz, 9-H), 8.89
(s, 1H, 2-H). MS: m=z 392 (Mþ). Anal. calcd. for C21H18BrN3: C,
64.29; H, 4.63; N, 10.71. Found: C, 64.37; H, 4.44; N, 10.68%.
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