Studies on cyclization of o-(alka-1,3-diynyl)arenediazonium salts

Article abstract of DOI:10.1007/s11172-008-0228-z

The Richter reaction of o-(alka-1,3-diynyl)arenediazonium salts, obtained by diazotization of diacetylenic derivatives of anilines, leads to 3-alkynyl-4-chloro- or 3-alkynyl-4-bromocinnolines and/or 3-alkynyl-4- hydroxycinnolines (the latter cyclize into furo[3,2-c]-cinnolines under the reaction conditions). 3-Alkynyl-4-chlorocinnolines undergo solvolysis in methanol giving rise to 3-alkynyl-4-methoxycinnolines, the subsequent hydrolysis of which also gives furo[3,2-c]cinnolines. Effects of the nature of substituents in the aromatic ring and of the reaction conditions on the product composition and yields have been established. The reaction course has been studied by spectrophotometry.

Full text of DOI:10.1007/s11172-008-0228-z

Russian Chemical Bulletin, International Edition, Vol. 57, No. 8, pp. 1725—1733, August, 2008
1725
Studies on cyclization of oꢀ(alkaꢀ1,3ꢀdiynyl)arenediazonium salts
O. V. Vinogradova,a V. N. Sorokoumov,a S. F. Vasilevskii,b and I. A. Balovaa
aSt.ꢀPetersburg State University, Department of Chemistry,
26 Universitetskii prosp., 198504 St.ꢀPetersburg, Russian Federation.
Fax: +7 (812) 4284137. Eꢀmail: irinabalova@yandex.ru
bInstitute of Chemical Kinetics and Combustion, Russian Academy of Sciences,
3 ul. Institutskaya, 630090 Novosibirsk, Russian Federation
The Richter reaction of oꢀ(alkaꢀ1,3ꢀdiynyl)arenediazonium salts, obtained by diazotizaꢀ
tion of diacetylenic derivatives of anilines, leads to 3ꢀalkynylꢀ4ꢀchloroꢀ or 3ꢀalkynylꢀ
4ꢀbromocinnolines and/or 3ꢀalkynylꢀ4ꢀhydroxycinnolines (the latter cyclize into furo[3,2ꢀc]ꢀ
cinnolines under the reaction conditions). 3ꢀAlkynylꢀ4ꢀchlorocinnolines undergo solvolysis in
methanol giving rise to 3ꢀalkynylꢀ4ꢀmethoxycinnolines, the subsequent hydrolysis of which
also gives furo[3,2ꢀc]cinnolines. Effects of the nature of substituents in the aromatic ring and of
the reaction conditions on the product composition and yields have been established. The
reaction course has been studied by spectrophotometry.
Key words: diacetylenes, anilines, diazotization, diazonium salts, the Richter cyclization,
cinnolines, furo[3,2ꢀc]cinnolines, spectrophotometry.
Chemistry of cinnolins is an intensively developing
field of organic chemistry since these compounds display
a wide range of biological activity and can be used as
anticancer,1 antifungal,2 and antithrombocentic3 drugs.
Cinnoline derivatives also possess fluorescence4 and are
potential objects for the use in nonlinear optics.5
particular, for the synthesis of polyfused heterocycles,11
we continued our efforts in this field. Earlier, we briefly
reported that the result of diazotization of oꢀ(alkaꢀ
1,3ꢀdiynyl)anilines greatly depends on the reaction
conditions and the nature of substituents in the aromatic
ring.12 In the present work, detailed results on the study
of factors influencing a cyclization course of oꢀ(alkaꢀ
1,3ꢀdiynyl)arenediazonium salts are presented.
The synthesis of cinnoline core was accomplished for
the first time by Richter by diazotization of oꢀaminoꢀ
phenylpropyolic acid and cyclization of the arenediazoꢀ
nium salt thus obtained with the formation of 4ꢀhydroxyꢀ
cinnolineꢀ3ꢀcarboxylic acid.6 Afterwards, it was shown
that the cyclization of oꢀethynylꢀsubstituted arenediazoꢀ
nium salts (the Richter reaction), along with 4ꢀhydroxyꢀ
Results and Discussion
The synthesis of starting diacetylenic arylamines 1a—i
was accomplished in accordance with the procedure sugꢀ
gested in Ref. 10. A diazotization of oꢀ(alkaꢀ1,3ꢀdiynyl)ꢀ
arylamines 1a—i was carried out with the use of proceꢀ
dures A—F (Scheme 1), the experimental data are given
in Table 1. By diazotization of amines 1b and 1d with
sodium nitrite in concentrated hydrochloric acid (proceꢀ
dure A) under conditions used earlier for acetylenic amines
of benzene and pyrazole series,7 the corresponding
3ꢀ(alkꢀ1ꢀynyl)ꢀ4ꢀchlorocinnolines 2b,d were obtained
in 23% and 10% yield, respectively (Table 1, entries 1
and 2). In addition, the products of reductive deaminaꢀ
tion, viz., (alkaꢀ1,3ꢀdiynyl)benzenes 3b,d, were formed
in the reaction. The starting compounds are poorly soluble
in aqueous medium, that leads to an increase in the reacꢀ
tion time and resinification. Therefore, the subsequent
reactions with compounds 1a—d were carried out with
addition of organic solvents or with the use of organic
diazotizing agent, butyl nitrite (Table 1, entries 3—6).
cinnolines, leads to the formation of 4ꢀhalocinnolines.7,8
.
The latter are of special interest for the combinatorial
chemistry since they can be derivatized by substitution of
the halogen atom for various nucleophiles.9
When oꢀ(butaꢀ1,3ꢀdiynyl)aniline was diazotized,
4ꢀchloroꢀ3ꢀethynylcinnoline7 was isolated, however, for
a long time this example remained the only one in the
series of diacetylenic derivatives of arenediazonium salts
due to the poor availability of such starting compounds.
A suggested by us earlier method for the synthesis of
functional derivatives of 1ꢀarylalkaꢀ1,3ꢀdiynes by the
sequence of the “diacetylenic zipper” reaction and
the Sonogashira reaction allow one to obtain alkaꢀ1,3ꢀdiynylꢀ
substituted arylꢀ or hetarylamines in good yields.10 Since
the cyclization of diacetylenic derivatives of arenediazoꢀ
nium salts can serve as a oneꢀstep pathway to 4ꢀhaloꢀ
3ꢀethynylcinnolines, the promising building blocks, in
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1693—1700, August, 2008.
1066ꢀ5285/08/5708ꢀ1725 © 2008 Springer Science+Business Media, Inc.

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Russ.Chem.Bull., Int.Ed., Vol. 57, No. 8, August, 2008
Vinogradova et al.
Scheme 1
A: NaNO , HCl (36%); B: BuONO, HCl (36%); C: NaNO , HCl (36%), THF; D: NaNO , HCl (36%), Et O—hexane; E: BuONO, H SO (conc.),
2
2
2
2
2
4
Et O; F: NaNO (solid), MeOH saturated with HCl.
2
2
The use of BuONO in water (procedure B) or in THF
agreement with a suggestion that the latter can be
obtained by hydrolysis of 4ꢀhalocinnolines in the reaction
course.7 It is known that hydrolysis in the series
of cinnolines proceeds by the SNAr mechanism of
“addition—elimination” and should be promoted by
electronꢀwithdrawing substituents.13 In the case of
2ꢀ(decaꢀ1,3ꢀdiynyl)ꢀ4ꢀnitroaniline (1i) (entry 12), strong
resinification of the reaction mixture was observed, thereꢀ
fore, the cyclization time was decreased to 2 h. This
allowed us to increase the total yield of the products
(entry 13), however, in contrast to experiment 12, a sigꢀ
nificant amount of the reductive deamination product 3i
was isolated resulted from decomposition of unreacted
diazonium salt.
(procedure C) did not lead to considerable increase in the
yield of 4ꢀchlorocinnolines, whereas the formation of
deamination product 3b also occurred. Conducting the
reaction in Et2O—hexane (procedure D) was found to be
the optimum. For diacetylenic derivatives of arenediazoniumꢀ
salts containing donating (Me) or weakly withdrawing
(Br) substituents in orthoꢀ or paraꢀpositions, the target
3ꢀalkynylꢀ4ꢀchlorocinnolines 2 were the only reaction
products in this case (entries 5—10).
When strong withdrawing groups, COOMe (1h) or
NO2 (1i), are present in the molecule of the starting
amines, furo[3,2ꢀc]cinnolines 4h,i were isolated as the
major reaction products in addition to 3ꢀalkynylꢀ4ꢀchloroꢀ
cinnolines 2h,i (entries 11, 12), the formation of which
results from the intramolecular cyclization of correspondꢀ
ing 3ꢀalkynylꢀ4ꢀhydroxycinnolines. These results are in
During the diazotization of amine hydrochloride 1h
with butyl nitrite in the presence of catalytic amount of
conc. sulfuric acid and at lower temperature as –20 °C
Table 1. Results of the Richter reaction of oꢀ(alkaꢀ1,3ꢀdiynyl)arylamines
Entry
Starting
R
X
Y
Procedurea
Product yields (%)
compound
2
3
4
1
2
3
4
5
6
7
8
1b
1d
1b
1d
1а
1b
1c
1eb
1fb
1gb
1h
C8H17
C6H13
C8H17
C6H13
C6H13
C8H17
C10H21
C8H17
C8H17
C8H17
C8H17
C6H13
C6H13
C8H17
C8H17
C8H17
C10H21
C8H17
H
H
H
H
H
H
H
H
H
Br
H
H
H
H
H
H
H
H
H
Br
H
Br
H
H
H
Br
Me
Me
COOMe
NO2
NO2
COOMe
COOMe
Me
A
A
B
C
D
D
D
D
D
D
D
D
2b (23)
2d (10)
2b (24)
2d (12)
2а (36)
2b (54)
2c (34)
2e (27)
2f (28)
2g (33)
2h (15)
2i (3.5)
2i (4.7)
2h (5)
2h (14)
2f (6)
3b (7)
3d (5)
3b (5)
3d (12)
—
—
—
—
—
—
—
—
3i (20)
3h (25)
3h (13)
3f (34)
—
—
—
—
—
—
—
—
—
—
—
4h (27)
4i (12)
4i (47)
—
4h (15)
—
9
10
11
12
13
14
15
16
17
18
1i
1ic
1hb
1hb
1fb
1c
D
E (–20 °С)
D (–20 °С)
D (–20 °С)
F
H
—
—
4c (39)
4h (54)
1hc
COOMe
F
3h (11)
a Conditions are given in Scheme 1. Diazotization was carried out at –5 °C, cyclization at room temperature for 8—16 h.
b
Hydrochlorides of starting amines were used.
c The reaction time was 2 h.

Diacetylenes in the Richter reaction
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 8, August, 2008
1727
D
D
2
2
a
b
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0
1.4
1.2
1
2
5
1
2
3
4
1
1
3
1.0
4
0.8
5
0.6
0.4
0.2
0
250
300
350
400
450
λ/nm
250
300
350
400
450
λ/nm
Fig. 1. Spectrophotometric monitoring of the cyclization of diazonium salt 1h at the beginning of the process (a) and at the end (b):
1, the spectrum of 4ꢀchlorocinnoline; 2, the spectrum of furo[3,2ꢀc]cinnoline; 3—5, the spectra of the reaction mixture after 5 min (3),
3 h 30 min (4), 24 h (5).
(procedure E, entry 14), the formation of furo[3,2ꢀc]ꢀ
cinnoline was not observed. However, chlorocinnoline
2h was isolated in 5% yield only with deaminated comꢀ
pound 3h being the major product. Apparently, lowering
temperature leads to a decrease in the cyclization rate and
the process of deamination becomes a competing one to
the process of the cinnoline formation. This suggestion
was confirmed by subsequent experiments, in which the
Richter reaction for compounds 1f,h was carried out
with the use of procedure C at –20 °C, and in which an
increase in the yield of products 3f,h was also observed
(cf. entries 9, 16 and 11, 15).
An interesting result was obtained when the Richter
reaction was carried out in MeOH. The reaction for
compounds 1c,h was accomplished under anhydrous
conditions, when dry MeOH saturated with HCl was used.
In this case, the formation of 4ꢀchlorocinnolines was
not observed even during diazotization of oꢀ(tetraꢀ
decaꢀ1,3ꢀdiynyl)aniline 1c containing no electronꢀwithꢀ
drawing substituents, rather furo[3,2ꢀc]cinnolines were
the major reaction products (entries 17 and 18). TLC
monitoring of the reaction course in experiment 18
showed formation of the products having much lower Rf
in comparison with the used authentic samples of
4ꢀchlorocinnoline 2h and furo[3,2ꢀc]cinnoline 4h. Howꢀ
ever, treatment of the reaction mixture with alkaline soluꢀ
tion already after 2 h from the beginning of the reaction
led to furo[3,2ꢀc]cinnoline 4h as the major product in
54% yield.
furo[3,2ꢀc]cinnoline, result from the hydrolysis of
4ꢀchlorocinnoline during the reaction course.14 The diazoꢀ
nium salt cyclization rate is significantly higher than the
rate of subsequent hydrolysis of chlorocinnoline.
To clarify processes taking place in MeOH saturated
with HCl, we carried out spectrophotometric study of the
cyclization process of the diazonium salt obtained from
compound 1h (Fig. 1). The UV spectra of 4ꢀchloroꢀ
cinnoline 2h and furo[3,2ꢀc]cinnoline 4h were obtained
preliminary under the same conditions. During the first
three hours, in the spectrum of the reaction mixture
(see Fig. 1, a), no appearance of absorption bands of
furo[3,2ꢀc]cinnoline 4h was observed, while the product
formed had absorption band characteristic of the
spectrum of 4ꢀchlorocinnoline (λ = 268, 322, 363, and
385 nm, cf. spectra 1 and 3). However, after 1 day the
spectrum of the reaction mixture completely corresponded
to the spectrum of furo[3,2ꢀc]cinnoline 4h (see Fig. 1, b,
cf. spectra 2 and 3).
These data confirmed that in MeOH the reaction first
leads to the formation of 4ꢀchlorocinnoline, too, but its
hydrolysis and subsequent cyclization of 4ꢀhydroxyꢀ
cinnoline proceed significantly faster in comparison with
the reaction in diethyl ether.14 The TLC monitoring of
the cyclization also revealed that, in comparison with the
reactions carried out under other conditions, in anhyꢀ
drous methanol saturated with HCl the products formed
have considerably lower Rf values. Detection of more
polar products in the reaction mixture allowed us to
suggest that under these conditions the cinnoline system
of the products is protonated, while the electronꢀwithꢀ
drawing substituent facilitate hydrolysis of 4ꢀchloroꢀ
cinnoline both in the course of the reaction and during
the isolation step.
Spectrophotometric study of the cyclization of the diaꢀ
zonium salt, obtained from amine 1h in Et2O—HCl, conꢀ
firmed that 4ꢀchloroꢀ3ꢀethynylcinnoline was the only
product of the Richter reaction, whereas 4ꢀhydroxyꢀ3ꢀ
ethynylcinnoline and the product of its cyclization,

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Vinogradova et al.
Scheme 2
C8H17
C8H17
OMe
C8H17
Cl
2
Br
Br
Br
F
+
+
N
N
N
N
NH2•HCl
1e
2e (5%)
5e (15%)
C8H17
C8H17
O
2
Br
Br
+
+
N
N
4e (14%)
3e (14%)
Scheme 3
Br
Br
C10H21
i
N
Br
C10H21
N
6 (43%)
–18 °C
Br
N
C10H21
Br
C10H21
NH2
Br
ii
+
1c
N
N
N
7 (37%)
7a (14%)
i. NaNO2 (2 equiv.), Et2O/hexane/HBr; ii. NaNO2 (1.1 equiv.), Et2O/hexane/HBr.
An additional experiment on cyclization of the diazoꢀ
nium salt obtained by diazotization of compound 1e in
MeOH (procedure F) has been conducted, in which
A
1
1.0
0.8
0.6
0.4
0.2
0.0
quenching of the reaction mixture was carried out with
anhydrous Et3N (Scheme 2).
2
In this case, we succeeded in the isolation of
4ꢀchlorocinnoline 2e, in addition, 4ꢀmethoxycinnoline
5e was obtained as one of the major products. It was also
found that in methanol saturated with HCl, 4ꢀchloroꢀ
cinnoline 2e is completely converted into 4ꢀmethoxyꢀ
cinnoline 5e for 30 min. Interestingly that in the UV
spectra of 4ꢀchlorocinnoline 2e and 4ꢀmethoxycinnoline
5e, the absorption band maxima positions coincide,
however, the bands of 4ꢀchlorocinnoline have higher
extinction. When 4ꢀchlorocinnoline 2h was dissolved in
MeOH saturated with HCl, the process of its fast transꢀ
formation was demonstrated spectrophotometrically: in
15 min, a sharp decrease in intensity of the absorption
band maximum at 268 nm was observed, however, there
was no shift of the maximum (Fig. 2). The changes
1
2
3
4
5
3
4
5
250
300
350
400
450
λ/nm
Fig. 2. Spectrophotometric monitoring of the solvolysis
of 4ꢀchlorocinnoline 2h in MeOH, τ/min: 2 (1), 4 (2), 8 (3),
10 (4), 15 (5).

Diacetylenes in the Richter reaction
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 8, August, 2008
1729
Scheme 4
C8H17
Br
O
Br
Cl
2
Me
H
C8
17
Me
Me
C8H17
i
ii
N
Br
N
Br
NH2•HCl
N
N
H
1f
8 (38%)
9 (52%)
iii
i. 1) NaNO2 (solid), HBr; 2) Hexane. ii. MeOH, HCl (36%), 50 °C, 24 h. iii. MeOH, KOH, H2O, 50 °C, 24 h.
observed correspond to the formation of 4ꢀmethoxyꢀ
cinnoline by solvolysis of 4ꢀchlorocinnoline.
diazonium cation. 4ꢀChlorocinnoline 8 was obtained as
the only reaction product, in which the triple bond turned
out to be brominated.
To confirm a position of the Cl atom in the cinnoline
ring, the acidꢀ and baseꢀcatalyzed hydrolyses of comꢀ
pound 8 have been undertaken. It turned out that the
presence of an acid facilitates the hydrolysis, which
results in 4ꢀcinnolinone 9.
On the basis of data obtained, a conclusion has been
drawn that 4ꢀchlorocinnoline is too the product of
the cyclization in MeOH saturated with HCl, which
undergoes fast solvolysis to 4ꢀmethoxycinnoline. Since
water is present in the reaction mixture, formed in the
course of diazotization, 4ꢀmethoxycinnoline hydrolyzes
already in the course of the reaction. This hydrolysis
is irreversible because of the cyclization of 4ꢀhydroxyꢀ
3ꢀalkynylcinnoline into furo[3,2ꢀc]cinnoline.
These data make the possibility of participation of
external nucleophile in the cyclization step questionable,
as well as confirm the possibility of hydrolysis of
4ꢀchlorocinnoline under the reaction conditions.
In conclusion, the Richter reaction of orthoꢀ(alkaꢀ
1,3ꢀdiynyl)arenediazonium salts, obtained by diazotizaꢀ
tion of arylamines, leads to 4ꢀchloroꢀ or bromoꢀ
3ꢀethynylcinnolines. In the absence of strong electronꢀ
withdrawing substituents in the benzene ring, 4ꢀchloroꢀ
3ꢀethynylcinnolines can be obtained in moderate yields.
The presence of electronꢀwithdrawing substituents in the
benzene ring, as well as conducting the reaction in MeOH
saturated with HCl facilitate hydrolysis of 3ꢀ(alkꢀ1ꢀynyl)ꢀ
4ꢀchlorocinnolines in the course of the reaction. The
formed 3ꢀ(alkꢀ1ꢀynyl)ꢀ4ꢀhydroxycinnolines undergo
a spontaneous cyclization giving rise to 2ꢀalkylfuroꢀ
[3,2ꢀc]cinnolines. In MeOH saturated with HCl, the
hydrolysis is preceded by the reaction with the solvent
resulting in the formation of 4ꢀmethoxycinnolines. The
diazotization in hydrobromic acid is accompanied by
the side bromination of the triple bond and benzene ring
of 3ꢀalkynylꢀ4ꢀbromocinnolines.
Earlier, it was shown that diazotization of monoꢀ
acetylenic amines in HBr allows one to considerably
increase the yield of 4ꢀbromocinnolines in the Richter
reaction in comparison with 4ꢀchloro derivatives.7 We
also carried out a research on the diazotization of oꢀ(alkaꢀ
1,3ꢀdiynyl)anilines in the presence of hydrobromic acid.
A mixed solvent Et2O—hexane—HBrconc in the ratio
of 1 : 1 : 6 (Scheme 3) has been used for conducting the
reaction. The diazotization reaction of 1c and subsequent
cyclization were carried out at –18 °C and no deaminaꢀ
tion occurred, but other side processes took place.
A twoꢀfold excess of solid NaNO2 was added in the
first diazotization experiment. It was found that in the
reaction course, the triple bond of the alkynyl substituent
of forming 4ꢀbromocinnoline underwent bromination and
4ꢀbromoꢀ3ꢀ(1,2ꢀdibromododecꢀ1ꢀenyl)cinnoline (6) was
obtained in 43% yield. In the second experiment, the
diazotization was carried out with aq. NaNO2 taken in
10% excess. The target 4ꢀbromoꢀ3ꢀ(dodecꢀ1ꢀynyl)cinꢀ
noline (7) was the major product in this case, the yield
was 37%. However, a side bromination of the benzene
ring occurred in this experiment and 4,6ꢀdibromoꢀ
3ꢀ(dodecꢀ1ꢀynyl)cinnoline (7a) was isolated along with
bromocinnoline 7.
Experimental
Elemental analysis data were obtained on a HewlettꢀPackard
185B instrument. IR spectra were recorded on a SpecordꢀIR 75
instrument in the range of 4000—400 cm–1 and on a URꢀ20
instrument for 2% solutions in CCl4 and for samples in KBr
pellets. 1H NMR (300.13 MHz) and 13C NMR (75.5 MHz)
spectra were recorded on a Bruker AМꢀ300 spectrometer for
solutions in CDCl3, DMSOꢀd6, and DMSOꢀd6 : CCl4 in ratios
1 : 4 and 1 : 10. Assignment of signals was made relatively to the
residual signals of the solvents: (for the 1H/13C spectra in CDCl3
Another experiment was also conducted, in which
amine hydrochloride 1f was taken as the starting comꢀ
pound for the diazotization in HBr (Scheme 4). Despite
of the excess of bromine anions and their high nucleophiꢀ
licity, the ring closure took place with participation
of chlorine anion present as the intimate ion pair with

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Russ.Chem.Bull., Int.Ed., Vol. 57, No. 8, August, 2008
Vinogradova et al.
δ 7.280/77.16, in DMSOꢀd6 δ = 2.50/39.52). Mass spectra were
recorded on a Agilent 68ꢀ90 instrument with ionization energy
of 70 eV, electron impact, and an Agilent 5973 detector. UV
spectra were recorded on a CC 103 spectrophotometer in the
range of 180—500 nm in an 1ꢀcm pathlength cuvette; the range
C(7)H); 8.16—8.20 (m, 1 H, C(5)H); 8.52—8.57 (m, 1 H,
C(8)H). 13C NMR (CDCl3), δ: 14.4 (CH3); 20.3 (C≡CCH2);
22.9, 28.6, 29.0, 31.7 (4 CH2); 76.5, 101.2 (C≡C); 123.5, 124.6,
130.6, 131.5, 132.8, 136.4, 141.2, 149.2 (CAr). MS (EI, 70 eV),
m/z (Irel (%)): 272 [M]+ (2), 257 [M – CH3]+ (4); 244
[M – C2H4]+ (100); 237 [M – Cl]+ (54); 215 [M – C4H9]+ (19).
Found (%): C, 70.44; H, 6.33; N, 12.86. C16H17ClN2. Calculated
(%): C, 70.45; H, 6.28; N, 13.00.
of concentrations 3.6—38•10–5 mol L–1
.
The Richter reaction in the series of alkadiynylamines (general
procedure). The diazotization and cyclization were carried out
in a flask equipped with magnetic stirrer, thermometer, dropping
funnel, and a cooling bath under conditions A—E. When a
diazotizing agent was being added, the temperature of
the reaction was kept in the range of –5—0 °C. After the
diazotization was complete (TLC monitoring), the reaction
mixture was stirred under cooling for 20—30 min; then the
stirring was continued at room temperature for 8—16 h. After
the time was up, the reaction mixture was poured in aqueous
soda and extracted with ethyl acetate (3×15 mL). Combined
organic layers were washed with water until neutral pH of the
reaction medium and died with MgSO4. After the solvent was
removed, the products were isolated by column chromatography
on silica gel 40—60 µm.
1. Procedures A (see Ref. 7) and B. Hydrochloric acid (36%
aq., 3 mL) was added to aromatic amine 1 or its hydrochloride
(2 mmol) at room temperature. When a free amine was used, the
reaction mixture was preliminary stirred at room temperature
for 1 h for the complete formation of the salt. Then, NaNO2
(152 mg, 2.2 mmol) in water (1 mL) (procedure A) or freshly
distilled BuONO (350 mg, 2.2 mmol) (procedure B) was added
dropwise with stirring to the mixture cooled to –10 °C.
2. Procedures C and D. Aromatic amine 1 or its hydrochloride
(2 mmol) was added to a mixture of 36% aq. HCl (3 mL) with
THF (3 mL, procedure C) or diethyl ether (3 mL, procedure D)
at room temperature. After the diazotization was complete in
the case of procedure C, hexane (3 mL) was added to the reaction
mixture.
4ꢀChloroꢀ3ꢀ(decꢀ1ꢀynyl)cinnoline (2b). IR (CCl4), ν/cm–1
:
1
3
2960, 2925, 2850 (Csp —H); 2225 (C≡C). H NMR (CDCl3), δ:
0.92 (t, 3 H, Me, J = 7.5 Hz); 1.32—1.79 (m, 12 H, 6 CH2);
2.62 (t, 3 H, C≡CCH2, J = 7.5 Hz); 7.86—7.90 (m, 2 H, C(6)H,
C(7)H); 8.18—8.22 (m, 1 H, C(5)H); 8.5—8.59 (m, 1 H, C(8)H).
13C NMR (CDCl3), δ: 14.5 (Me); 20.3, 23.1, 28.6, 29.4, 29.5,
29.6, 32.2 (7 CH2); 76.5, 101.2 (C≡C); 123.5, 124.7, 130.7, 131.4,
132.8, 136.4, 141.2, 149.2 (CAr). Found (%): C, 71.75; H 7.11;
N 8.98. C18H21ClN2. Calculated (%): C, 71.73; H, 7.02; N, 9.29.
4ꢀChloroꢀ3ꢀ(dodecꢀ1ꢀynyl)cinnoline (2c). 1H NMR (CDCl3),
δ: 0.87 (t, 3 H, Me, J = 7.5 Hz); 1.19—1.39 (m, 12 H, 6 CH2);
1.50—1.62 (m, 2 H, C≡CCH2CH2CH2); 1.68—1.84 (m, 2 H,
C≡CCH2CH2); 2.63 (t, 2 H, C≡CCH2, J = 7.5 Hz); 7.82—7.91
(m, 2 H, C(6)H, C(7)H); 8.12—8.21 (m, 1 H, C(5)H);
8.51—8.61 (m, 1 H, C(8)H). 13C NMR (CDCl3), δ: 14.5 (Me);
20.3 (C≡CCH2); 23.1, 28.6, 29.3, 29.5, 29.7, 29.9, 30.0, 32.3
(8 CH2); 76.5, 101.2 (C≡C); 123.5, 124.6, 130.7, 131.4, 132.9,
136.4, 141.2, 149.2 (CAr).
6ꢀBromoꢀ4ꢀchloroꢀ3ꢀ(octꢀ1ꢀynyl)cinnoline (2d). IR (CCl4),
ν/cm–1: 2950, 2932, 2860 (Csp —H); 2240 (C≡C); 1548; 1456;
3
1416. 1H NMR (CDCl3), δ: 0.93 (t, 3 H, Me, J = 7.5 Hz);
1.26—1.58 (m, 8 H, 4 CH2); 2.64 (t, 2 H, C≡CCH2, J = 7.5 Hz);
7.91 (dd, 1 H, C(7)H, J = 7.8 Hz, J = 2.4 Hz); 8.35 (d, 1 H,
C(5)H, J = 2.4 Hz); 8.42 (d, 1 H, C(8)H, J = 7.8 Hz). 13C NMR
(CDCl3), δ: 14.5 (Me); 20.3, 22.9, 28.5, 29.0, 31.7 (5 CH2);
76.4, 102.2 (C≡C); 125.7, 125.8 128.4, 132.3, 134.9, 135.2, 141.7,
147.6 (CAr). Found (%): C, 54.86; H, 4.83; N, 7.84. C16H16BrClN2.
Calculated (%): C, 54.64; H, 4.59; N, 7.97.
Procedure E. A mixture of amine hydrochloride (2 mmol)
and diethyl ether (7 mL) was cooled to –5 °C followed by
addition of catalytic amount of H2SO4 and dropwise addition of
freshly distilled BuONO (227 mg, 2.2 mmol).
6ꢀBromoꢀ4ꢀchloroꢀ3ꢀ(decꢀ1ꢀynyl)cinnoline (2e). M.p. 41—43 °C
(hexane—diethyl ether, 1 : 2). UV (MeOH saturated with HCl),
1
λ
max/nm (ε): 267 (5.9•104). H NMR (CDCl3), δ: 0.89 (t, 3 H,
Procedure F. Methanol (15 mL) was saturated with dry HCl
for 1 h. A starting amine hydrochloride 1 (2 mmol) and NaNO2
(152 mg, 2.2 mmol) were added to the solution obtained keeping
the temperature in the range of –5—0 °C. After the diazotizaꢀ
tion was complete, the reaction mixture was stirred at room
temperature, then poured in 10% aq. NaOH, extracted with
EtOAc (3×15 mL), and dried with CaCl2. Alternatively, a
mixture of MeOH with Et3N (1 : 2) was added dropwise to the
reaction mixture cooled on an ice bath until the solution became
basic (pH ~8); the solution obtained was concentrated on rotary
evaporator in vacuo of waterꢀjet aspirator pump, the precipitate
of triethylamine hydrochloride was filtered off. The products
were isolated by chromatography on silica gel 40—60 µm.
The structures of products of reductive deamination 3 were
established by analysis of the NMR spectra, and by TLC analysis
with the use of the corresponding 1ꢀarylalkaꢀ1,3ꢀdiynes, obtained
earlier by the reaction of Pd/Cuꢀcatalyzed crossꢀcoupling, as
the authentic samples.10,15
Me, J = 7.5 Hz); 1.30—1.54 (m, 10 H, 5 CH2); 1.72—1.77 (m,
2 H, C≡CCH2CH2); 2.63 (t, 2 H, C≡CCH2, J = 7.5 Hz); 7.91
(d, 1 H, C(7)H, J = 7.8 Hz); 8.34 (s, 1 H, C(5)H); 8.41 (d, 1 H,
C(8)H, J = 7.8 Hz). 13C NMR (CDCl3), δ: 14.5 (Me); 20.3,
23.1, 28.6, 29.3, 29.5, 29.6, 32.2 (7 CH2); 76.4, 102.2 (C≡C);
125.7, 125.8 128.4, 132.3, 134.9, 135.2, 141.7, 147.6 (CAr).
MS (EI, 70 eV), m/z (Irel (%)): 381 [M + 2]+ (8), 379 [M]+ (17);
344 [M – Cl]+ (98), 342 [M – Cl]+ (100). Found (%): C, 57.04;
H, 5.39; N, 7.27. C18H20BrClN2. Calculated (%): C, 56.94;
H, 5.31; N, 7.38.
4ꢀChloroꢀ3ꢀ(decꢀ1ꢀynyl)ꢀ6ꢀmethylcinnoline (2f). IR (CCl4),
ν/cm–1: 2970, 2940, 2870 (Csp —H); 2250 (C≡C); 1720; 1610; 1480.
3
1H NMR (CDCl3), δ: 0.89 (t, 3 H, Me, J = 7.5 Hz); 1.30—1.33
(m, 8 H, 4 (CH2)); 1.54—1.57 (m, 2 H, C≡CCH2CH2CH2);
1.74 (m, 2 H, C≡CCH2CH2); 2.62 (t, 2 H, C≡CCH2, J = 7.5 Hz);
2.62 (s, 3 H, C(6)Me); 7.66 (d, 1 H, C(7)H, J = 9.2 Hz); 7.89 (s,
1 H, C(5)H); 8.41 (d, 1 H, C(8)H, J = 9.2 Hz). 13C NMR
(CDCl3), δ: 14.5 (CH3); 20.3 (C≡CCH2); 22.8 (C(6)CH3); 23.1,
28.6, 29.4, 29.5, 29.6, 32.2 (6 CH2); 76.6, 100.9 (C≡C); 121.9, 124.8,
130.3, 134.0, 135.7, 141.1, 144.1, 148.28 (CAr). MS (EI, 70 eV), m/z
(Irel (%)): 316 [M + 2]+ (8), 314 [M]+ (23); 287 [M + 2 – C2H5]+
(10), 285 [M – C2H5]+ (13); 279 [M – Cl]+ (100).
4ꢀChloroꢀ3ꢀ(octꢀ1ꢀynyl)cinnoline (2a). IR (CCl4), ν/cm–1
:
1
3
2965, 2925, 2860 (Csp —H); 2230 (C≡C). H NMR (CDCl ), δ:
0.91 (t, 3 H, Me, J = 7.5 Hz); 1.32—1.79 (m, 8 H, 4 CH2);32.63
(t, 3 H, C≡CCH2, J = 7.5 Hz); 7.85—7.91 (m, 2 H, C(6)H,

Diacetylenes in the Richter reaction
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 8, August, 2008
1731
8ꢀBromoꢀ4ꢀchloroꢀ3ꢀ(decꢀ1ꢀynyl)ꢀ6ꢀmethylcinnoline (2g).
5 CH2); 1.80—1.90 (m, 2 H, C(Ar)CH2CH2); 2.95 (t, 2 H,
C(Ar)CH2, J = 7.5 Hz); 7.10 (s, 1 H, C(3)H); 7.84 (dd, 1 H,
C(7)H, J = 9.2 Hz, J = 2.4 Hz); 8.40 (d, 1 H, C(9)H, J = 2.4 Hz);
8.49 (d, 1 H, C(6)H, J = 9.2 Hz). 13C NMR (CDCl3), δ: 14.5
(Me); 23.0, 27.9, 29.1, 29.5, 29.6, 29.6, 32.2 (7 CH2); 103.2,
115.3, 121.9, 126.3, 132.4, 132.6, 141.9, 146.6, 147.7, 164.1 (CAr).
MS (EI, 70 eV), m/z (Irel (%)): 362 [M + 2]+ (55), 360 [М]+
(56); 333 [M + 2 – C2H5]+ (13), 331 [M – C2H5]+ (13); 305
[M + 2 – C4H9]+ (13), 303 [M – C4H9]+ (13), 291 [M + 2 – C5H11]+
M.p. 52—54 °C (hexane—diethyl ether, 1 : 2). IR (CCl4),
ν/cm–1: 2980, 2950, 2875 (Csp —H); 2250 (C≡C); 1625; 1485;
3
1450. 1H NMR (CDCl3), δ: 0.90 (t, 3 H, Me, J = 7.5 Hz);
1.31—1.77 (m, 12 H, 6 CH2); 2.61 (s, 3 H, C(6)Me); 2.64 (t,
2 H, C≡CCH2, J = 7.5 Hz); 7.87 (s, 1 H, C(7)H); 7.99 (s, 1 H,
C(5)H). 13C NMR (CDCl3), δ: 14.5 (Me); 20.3 (C≡CCH2);
20.5 (C(6)CH3); 23.1, 28.6, 29.3, 29.5, 29.6, 32.2 (6 CH2); 76.5,
101.9 (C≡C); 122.0, 126.1, 126.1, 135.3, 137.5, 141.9, 144.4,
144.9 (CAr). MS (EI, 70 eV), m/z (Irel (%)): 396 [M + 4]+ (5), 394
[M + 2]+ (22), 392 [M]+ (17); 359 [M – Cl]+ (100), 357
[M – Cl]+ (100); 317 [M – Cl – C3H6]+ (78), 315 [M – Cl – C3H6]+
(78). Found (%): C, 58.09; H, 5.73; N, 7.15. C19H22BrClN2.
Calculated (%): C, 57.96; H, 5.63; N, 7.11.
+
+
(11), 289 [M – C5H11
] (11); 277 [M + 2ꢀC6H13] (70), 275
[M – C6H13]+ (72); 263 [M + 2 – C7H15]+ (98), 261 [M – C7H15]+
(100). Found (%): C, 59.81; H, 5.71; N, 7.60. C18H21BrN2O.
Calculated (%): C, 59.84; H, 5.86; N, 7.75.
Methyl 2ꢀoctylfuro[3,2ꢀc]cinnolineꢀ8ꢀcarboxylate (4h).
UV (Et2O : HCl (36%) 1 : 1), λmax/nm (ε): 256 (3.6•104), 325
Methyl 4ꢀchloroꢀ3ꢀ(decꢀ1ꢀynyl)cinnolineꢀ6ꢀcarboxylate (2h).
UV (Et2O : HCl (36%) 1 : 1), λmax/nm (ε): 271 (4.2•104), 382
(5.7•103), 411 (2.5•103). IR (CCl4), ν/cm–1: 2970, 2940,
(3.5•103), 389 (3.5•103). IR (CCl4), ν/cm–1: 2970, 2940, 2860
1
3
(Csp —H); 1730 (C=O); 1600; 1450; 1410. H NMR (CDCl ),
2860 (Csp —H); 2250 (C≡C); 1730 (C=O); 1460; 1440; 1430.
δ: 0.90 (t, 3 H, Me, J = 7.5 Hz); 1.31—1.48 (m, 10 H, 5 CH32);
1.86—1.91 (m, 2 H, C(Ar)CH2CH2); 2.98 (t, 2 H, C(Ar)CH2,
J = 7.5 Hz); 4.07 (s, 3 H, OMe); 7.15 (s, 1 H, C(3)H); 8.36 (dd,
1 H, C(7)H, J = 9.2 Hz, J = 2.4 Hz); 8.70 (d, 1 H, C(6)H,
J = 9.2 Hz); 9.01 (d, 1 H, C(9)H, J = 2.4 Hz). 13C NMR
(CDCl3), δ: 14.2 (CH3); 22.7, 27.6, 28.1, 29.2, 2·29.3, 31.9
(7 CH2); 52.9 (OMe); 102.9, 113.3, 122.8, 127.9, 130.7, 131.9,
3
1H NMR (CDCl3), δ: 0.90 (t, 3 H, Me, J = 7.5 Hz); 1.34—1.48
(m, 8 H, 4 CH2); 1.54—1.58 (m, 2 H, C≡CCH2CH2CH2);
1.74—1.79 (m, 2 H, C≡CCH2CH2); 2.66 (t, 2 H, C≡CCH2,
J = 7.5 Hz); 4.06 (s, 3 H, OMe); 8.43 (dd, 1 H, C(7)H, J = 9.2 Hz,
J = 2.4 Hz); 8.63 (d, 1 H, C(8)H, J = 9.2 Hz); 8.91 (d, 1 H,
C(5)H, J = 2.4 Hz). 13C NMR (CDCl3), δ: 14.2 (CH3); 20.0,
22.9, 28.3, 29.1, 29.2, 29.3, 32.0 (7 CH2); 53.1 (OMe); 76.0,
101.9 (C≡C); 123.9, 126.4, 130.5, 130.9, 133.4, 137.1, 141.8,
149.3, (CAr); 165.5 (C=O). MS (EI, 70 eV), m/z (Irel (%)):
360 [M + 2]+ (5), 358 [M]+ (16); 323 [M – Cl]+ (100); 295
[M – Cl – CH3 + H]+ (20); 281 [M – Cl – C2H4]+ (88); 267
[M – Cl – C3H6]+ (59). Found (%): C, 66.97; H, 6.41; N, 7.60.
C20H23ClN2O2. Calculated (%): C, 66.93; H, 6.46; N, 7.81.
4ꢀChloroꢀ6ꢀnitroꢀ3ꢀ(octꢀ1ꢀynyl)cinnoline (2i). IR (CCl4),
143.4, 147.8, 148.2, 163.9 (CAr); 165.9 (C=O). MS (EI, 70 eV),
+
m/z (Irel (%)): 340 [М]+ (22); 269 [M – C5H11
]
(15); 241
+
[M – C7H15
]
(100). Found (%): C, 70.35; H, 7.09; N, 7.94.
C20H24N2O3. Calculated (%): C, 70.56; H, 7.11; N, 8.23.
2ꢀHexylꢀ8ꢀnitrofuro[3,2ꢀc]cinnoline (4i). IR (CCl4),
ν/cm–1: 2970, 2940, 2880 (Csp —H); 1750; 1620; 1600; 1525.
3
1H NMR (CDCl3), δ: 0,93 (t, 3 H, CH3, J = 7.5 Hz); 1.36—1.52
(m, 6 H, 3 CH2); 1.85—2.06 (m, 2 H, C(Ar)CH2CH2); 3.02
(t, 2 H, C(Ar)CH2, J =7.5 Hz); 7.22 (s, 1 H, C(3)H); 8.53 (dd,
1 H, C(7)H, J = 9.2 Hz, J = 2.4 Hz); 8.84 (d, 1 H, C(6)H,
J = 9.2 Hz); 9.21 (d, 1 H, C(9)H, J = 2.4 Hz). 13C NMR
(CDCl3), δ: 14.4 (Me); 22.9, 27.8, 29.2, 29.2, 31.8 (5 CH2);
103.4, 113.8, 117.5, 122.2, 133.1, 143.8, 147.8, 148.4, 148.6,
ν/cm–1: 2975, 2948, 2870 (Csp —H); 2250 (C≡C); 1740; 1630;
3
1570; 1530; 1460; 1440. 1H NMR (CDCl3), δ: 0.92 (t, 3 H, Me,
J = 7.5 Hz); 1.27—1.78 (m, 8 H, 4 CH2); 2.68 (t, 2 H, C≡CCH2,
J = 7.5 Hz); 8.60 (dd, 1 H, C(7)H, J = 9.2 Hz, J = 2.4 Hz); 8.79
(d, 1 H, C(8)H, J = 9.2 Hz); 9.12 (d, 1 H, C(5)H, J = 2.4 Hz).
13C NMR (CDCl3), δ: 14.5 (CH3); 20.4, 23.1, 28.5, 29.0, 31.7
(5 CH2); 76.0, 103.8 (C≡C); 120.4, 123.8, 124.1, 132.8, 137.0,
142.22, 148.4, 148.9 (CAr). MS (EI, 70 eV), m/z (Irel (%)):
319 [M + 2]+ (1), 317 [M]+ (8), 282 [M – Cl]+ (100), 254
[M – Cl – C2H4]+ (62), 236 [M – Cl – NO2]+ (23), 165
[M – Cl – NO2 – C5H11]+ (21), 137 [M – Cl – NO2 – C7H13]+ (39).
2ꢀDecylfuro[3,2ꢀc]cinnoline (4c). M.p. 27—29 °C (CH2Cl2).
165.4 (CAr). MS (EI, 70 eV), m/z (Irel (%)): 299 [М]+ (100);
+
270 [M – C2H5]+ (25); 228 [M – C5H11
]
(91); 182 [M –
C5H11 – NO2]+ (84). Found (%): C, 64.08; H, 5.78; N, 14.10.
C16H17N3O3. Calculated (%): C, 64.20; H, 5.72; N, 14.04.
6ꢀBromoꢀ3ꢀ(decꢀ1ꢀynyl)ꢀ4ꢀmethoxycinnoline (5e). UV
(MeOH saturated with HCl), λmax/nm (ε): 265 (4.5•104).
IR (CCl4), ν/cm–1: 2950, 2900, 2820 (Csp —H); 2200 (C≡C);
3
IR (CCl4), ν/cm–1: 2970, 2940, 2880 (Csp —H); 1750; 1620;
1725; 1650; 1600; 1550. 1H NMR (CDCl3), δ: 0.90 (t, 3 H, Me,
J = 7.5 Hz); 1.30—1.33 (m, 8 H, 4 CH2); 1.49—1.54 (m, 2 H,
C≡CCH2CH2CH2); 1.69—1.75 (m, 2 H, C≡CCH2CH2); 2.61
(t, 2 H, C≡CCH2, J = 7.5 Hz); 4.46 (s, 3 H, OMe); 7.85 (dd,
1 H, C(7)H, J = 9.2 Hz, J = 2.4 Hz); 8.32—8.35 (m, 2 H,
C(3)H, C(8)H). 13C NMR (CDCl3), δ: 14.2 (Me); 20.1, 22.8,
28.3, 29.2, 29.26, 29.32, 32.0 (7 CH2); 61.0 (OMe); 76.3, 100.2
(C≡C); 121.4, 123.6, 125.6, 131.1, 134.4, 137.7, 148.2, 153.5
(CAr). MS (EI, 70 eV), m/z (Irel (%)): 376 [M + 2]+ (8), 374
[M]+ (9); 345 [M + 2 – C2H5]+ (52), 343 [M – C2H5]+
(46); 319 [M + 2 – C4H9]+ (36), 317 [M – C4H9]+ (36);
3
1600; 1525; 1490. 1H NMR (CDCl3), δ: 0.87 (t, 3 H, Me,
J = 7.5 Hz); 1.21—1.99 (m, 14 H, 7 CH2); 1.84 (m, 2 H,
C≡CCH2CH2); 2.93 (t, 2 H, C≡CCH2, J = 7.5 Hz); 7.08 (s, 1 H,
C(3)H); 7.76—7.81 (m, 2 H, C(7)H, C(8)H); 8.19—8.24 (m,
1 H, C(9)H); 8.60—8.63 (m, 1 H, C(6)H). 13C NMR (CDCl3),
δ: 14.50 (Me); 23.07, 27.93, 29.07, 29.53, 29.69, 29.90, 29.95,
30.05, 32.28 (9 CH2); 103.08, 114.42, 119.48, 128.81, 130.57,
131.38, 143.38, 147.25, 150.74, 163.38 (CAr). MS (EI, 70 eV),
+
m/z (Irel (%)): 310 [M]+ (68); 239 [M – C5H11
]
(38); 197
+
+
[M – C8H17
]
(100); 183 [M – C9H21
]
(54). Found (%):
+
+
C, 77.41; H, 8.35; N, 8.79. C20H26N2O. Calculated (%):
C, 77.38; H, 8.44; N, 9.02.
291 [M + 2 – C6H13
[M + 2 – C7H15+
+ (54), 275 [M – C7H15
OMe – C7H15 (23). Found (%): C, 60.85; H, 6.11; N, 7.36.
]
(98), 289 [M – C6H13
] (100); 277
]
]
+ (55), 165 [M – Br –
8ꢀBromoꢀ2ꢀoctylfuro[3,2ꢀc]cinnoline (4e). UV (MeOH saturated
]
with HCl), λmax/nm (ε): 259 (4.0•104). IR (CCl4), ν/cm–1
2990, 2940, 2860 (Csp —H); 1710; 1625; 1600; 1580. H NMR
:
C19H23BrN2O. Calculated (%): C, 60.81; H, 6.18; N, 7.46.
4ꢀBromoꢀ3ꢀ(1,2ꢀdibromododecꢀ1ꢀenyl)cinnoline (6) was
obtained from 1c (1.4 g, 5 mmol) under conditions of procedure
1
3
(CDCl3), δ: 0.89 (t, 3 H, Me, J = 7.5 Hz); 1.30—1.46 (m, 10 H,

1732
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 8, August, 2008
Vinogradova et al.
D (–15÷–18 °C) in conc. HBr with the use of crystalline NaNO2
(m, 1 H, =CBr—CH2); 3.02—3.11 (m, 1 H, =CBr—CH2); 7.74
(d, 1 H, C(7)H, J = 9.2 Hz); 8.01 (s, 1 H, C(5)H); 8.49 (d, 1 H,
C(8)H, J = 9.2 Hz). 13C NMR (CDCl3), δ: 14.6 (CH3); 22.8
(C(Ar)Me); 23.1, 27.3, 29.0, 29.6, 29.8, 32.3, 40.3 (7 CH2);
110.7, 122.4, 125.3, 130.3, 130.4, 133.1, 134.6, 144.2, 149.6,
153.3. MS (EI, 70 eV), m/z (Irel (%)): 476 [M + 4]+ (3), 474
[M + 2]+ (5), 472 [M]+ (2); [M – Cl]+ 441 (4.5), 439 (9), 437
(4.5); [M – Cl – Et – Me]+ 397 (28), 395 (100), 393 (74); 165
[M – Cl – 2 Br – C7H15 – Me]+ (11). Found (%): C, 47.62;
H, 4.91; N, 5.74. C19H23Br2ClN2. Calculated (%): C, 48.08;
H, 4.88; N, 5.90.
(690 mg, 10 mmol). The yield of the product was 43% (1.15 g,
1
2.2 mmol). M.p. 65—67 °C (from EtOAc). H NMR (CDCl3),
δ: 0.90 (t, 3 H, Me, J = 7.5 Hz); 1.26—1.45 (m, 14 H, 7 CH2);
1.80 (m, 2 H, C=CCH2CH2); 2.98 (dt, 2 H, C=CCH2, J = 7.5 Hz,
J = 7.5 Hz); 7.86—8.02 (m, 2 H, C(6)H, C(7)H); 8.22—8.24
(m, 1 H, C(5)H); 8.59—8.62 (m, 1 H, C(8)H). 13C NMR
(CDCl3), δ: 14.54 (Me); 23.11; 27.75, 29.01, 29.75, 29.82, 29.97,
30.02, 32.33 (8 CH2); 40.26 (C=CCH2); 112.23, 126.69, 126.99,
127.36, 130.29, 130.72, 132.18, 133.14, 150.20, 155.39. MS (EI,
70 eV), m/z (Irel (%)): 536 [M + 6]+ (3); 534 [M + 4]+ (7); 532
[M+2]+ (7); 530 [M]+ (3); [M – Br]+ 455 (49), 453 (100), 451
3ꢀ(1,2ꢀDibromodecꢀ1ꢀenyl)ꢀ6ꢀmethylꢀ(1H)ꢀcinnolinꢀ4ꢀone
(9) was obtained by heating of a solution of 4ꢀchlorocinnoline
(18) (230 mg, 0.48 mmol) in a mixture of MeOH (5 mL) and
conc. HCl (3 mL). The reaction was carried out for 1 day at
50 °C. After the reaction was complete (TLC monitoring), the
solvent was partially removed in vacuo of waterꢀjet aspirator
pump, the precipitate of the product was filtered off and purified
by recrystallization from MeOH. The yield of the product was
+
+
(49); 261 [M + 2 – C8H17
]
(15); 259 [M – C8H17
]
(15).
Found (%): C, 45.05; H, 4.62; N, 4.95. C20H25Br3N2. Calculated
(%): C, 45.06; H, 4.73; N, 5.25.
4ꢀBromoꢀ3ꢀ(dodecꢀ1ꢀynyl)cinnoline (7) was obtained from
1c under conditions of procedure D (15 h, –18 °C) in conc. HBr
in 37% yield (690 mg, 1.85 mmol), 4,6ꢀdibromoꢀ3ꢀ(dodecꢀ
1ꢀynyl)cinnoline was isolated along with the major product in
14% yield (316 mg, 0.7 mmol). M.p. 74—76 °C (from EtOAc).
1H NMR (CDCl3), δ: 0.89 (t, 3 H, Me, J = 7.5 Hz); 1.21—1.42
(m, 12 H, 6 CH2); 1.49—1.66 (m, 2 H, C≡CCH2CH2CH2); 1.76
(m, 2 H, C≡CCH2CH2); 2.63 (t, 2 H, C≡CCH2, J = 7.5 Hz);
7.79—7.95 (m, 2 H, C(6)H, C(7)H); 8.09—8.19 (m, 1 H,
C(5)H); 8.51—8.60 (m, 1 H, C(8)H). 13C NMR (CDCl3), δ:
14.50 (Me); 20.25 (C≡CCH2); 23.08, 28.59, 29.36, 29.53, 29.71,
29.94, 29.99, 32.30 (8 CH2); 78.41, 100.43 (C≡C); 126.41,
127.59, 130.72, 131.43, 133.07, 134.38, 143.47, 148.93 (CAr).
52% (114 mg, 0.25 mmol). IR (CCl4), ν/cm–1: 3178 (NH);
1
3
2980, 2922, 2850 (Csp —H); 1568 (C=O); 1488; 1338. H NMR
(DMSOꢀd6), δ: 0.87 (t, 3 H, Me, J = 7.5 Hz); 1.14—1.62 (m, 12 H,
6 CH2); 2.44 (s, 3 H, C(Ar)Me); 2.80 (t, 2 H, C=CCH2, J = 7.5 Hz);
7.59 (d, 1 H, C(8)H, J = 8.3 Hz); 7.68 (d, 1 H, C(7)H, J = 8.3 Hz);
7.88 (s, 1 H, C(5)H); 13.74 (s, 1 H, NH). 13C NMR (DMSOꢀd6),
δ: 14.0 (Me); 20.9 (C(Ar)Me); 22.1, 26.9, 27.7, 28.6, 28.7, 29.0,
31.2 (7 CH2); 110.8, 116.9, 123.1, 123.8, 127.1, 135.5, 135.7,
139.2, 147.1; 166.2 (C=O). MS (EI, 70 eV), m/z (Irel (%)): 377
MS (EI, 70 eV), m/z (Irel (%)): 374 [М + 2]+ (16); 372 [М]+
[M – 79Br]+ (100), 375 [M – 81Br]+ (98); 211 [M – 2Br – C6H13]+
+
+
(16); 293 [M – Br]+ (100); 261 [М + 2 – C8H17
]
(25); 259
(17); 197 [M – 2Br – C7H15
]
(19). Found (%): C, 49.84;
[М – C8H17
]
+ (25); 152 [M – Br – C10H21
]
+ (23). Found (%):
H, 5.86; N, 5.72. C19H24Br2N2O. Calculated (%): C, 50.02;
H, 5.30; N, 6.14.
C, 64.56; H, 6.81; N, 6.80. C20H25BrN2. Calculated (%):
C, 64.34; H, 6.75; N, 7.50.
4,6ꢀDibromoꢀ3ꢀ(dodecꢀ1ꢀynyl)cinnoline (7a). 1H NMR
(CDCl3), δ: 0.88 (t, 3 H, Me, J = 7.5 Hz); 1.21—1.43 (m, 12 H,
6 CH2); 1.48—1.63 (m, 2 H, C≡CCH2CH2CH2); 1.74 (m, 2 H,
C≡CCH2CH2); 2.63 (t, 2 H, C≡CCH2, J = 7.5 Hz); 7.90 (d,
1 H, C(7)H, J = 9.2 Hz); 8.29 (s, 1 H, C(5)H); 8.41 (d, 1 H,
C(8)H, J = 9.2 Hz). 13C NMR (CDCl3), δ: 14.50 (Me); 20.27
(C≡CCH2); 23.07, 28.54, 29.36, 29.52, 29.71, 29.93, 29.98, 32.29
(8 CH2); 78.25, 101.41 (C≡C); 125.77, 127.44, 127.76, 128.59,
132.26, 135.16, 144.00, 147.29 (CAr). MS (EI, 70 eV), m/z
(Irel (%)): 454 [M + 4]+ (7); 452 [M + 2]+ (15); 450 [M]+ (7); 373 [M
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 05ꢀ03ꢀ32504).
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+
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]
]
+
(46); 301 [M – Br – C5H10
]
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+
(25); 287 [M – Br – C6H12
]
(29). Found (%): C, 53.31;
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Hydrochloride 1f (560 mg, 1.8 mmol) was diazotized with a
solution of NaNO2 (137 mg, 2 mmol) in H2O (1 mL) and conc.
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0.7 mmol). Yellow oil. IR (CCl4), ν/cm–1: 2960, 2940, 2870
1
3
(Csp —H); 1640; 1550; 1480. H NMR (CDCl3), δ: 0.91 (t, 3 H,
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Me, J =7 Hz); 1.32—1.51 (m, 10 H, 5 CH2); 1.74—1.84 (m,
2 H, BrC=CBr—CH2CH2); 2.65 (s, 1 H, C(Ar)Me); 2.83—2.92

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Received October 25, 2007;
in revised form February 21, 2008