Reactions of 3-cyanochromones with primary amines: Structures of the products

Article abstract of DOI:10.1007/s11172-010-0127-y

Reactions of 3-cyanochromones with primary aromatic amines in boiling benzene gave mixtures of Z- and E-3-arylamino-2-(2-hydroxyaroyl)acrylonitriles and 2-amino-3-(aryl- iminomethyl)chromones. The latter can easily be obtained in the individual state when

Full text of DOI:10.1007/s11172-010-0127-y

Russian Chemical Bulletin, International Edition, Vol. 59, No. 3, pp. 615—625, March, 2010
615
Reactions of 3ꢀcyanochromones with primary amines:
structures of the products
V. Ya. Sosnovskikh,a V. S. Moshkin,a and M. I. Kodessb
aA. M. Gorky Ural State University,
51 prosp. Lenina, 620083 Ekaterinburg, Russian Federation.
Fax: +7 (343) 261 5978. Eꢀmail: Vyacheslav.Sosnovskikh@usu.ru
bI. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences,
22 ul. S. Kovalevskoi, 620041 Ekaterinburg, Russian Federation.
Reactions of 3ꢀcyanochromones with primary aromatic amines in boiling benzene gave
mixtures of Zꢀ and Eꢀ3ꢀarylaminoꢀ2ꢀ(2ꢀhydroxyaroyl)acrylonitriles and 2ꢀaminoꢀ3ꢀ(arylꢀ
iminomethyl)chromones. The latter can easily be obtained in the individual state when the
reaction is carried out in the presence of triethylamine. In the case of primary aliphatic amines,
the openꢀchain reaction product immediately undergoes cyclization into 3ꢀalkyliminomethylꢀ
2ꢀaminochromones. The structures of the products were examined by 1D and 2D 1H, 13C, and
15N NMR spectroscopy in DMSOꢀd6 and CDCl3.
Key words: 3ꢀcyanochromones, primary amines, recyclization, 2ꢀaminoꢀ3ꢀ(aryliminoꢀ
methyl)chromones, 3ꢀalkyliminomethylꢀ2ꢀaminochromones, 3ꢀarylaminoꢀ2ꢀ(2ꢀhydroxyꢀ
aroyl)acrylonitriles, 1H, 13C, and 15N NMR spectroscopy.
The intensive development of the chemistry of 3ꢀcyꢀ
anochromones was triggered by the discovery of a simple
and convenient route to 3ꢀformylchromones involving the
Vilsmeier—Haack reaction of 2ꢀhydroxyacetophenones
with DMF and POCl3 in 1973 (see Refs 1—3). Treatꢀ
ment of 3ꢀformylchromones with hydroxylamine affords,
through the formation of chromone 3ꢀoximes, 3ꢀcyꢀ
anochromones 1 in good yields.4—6 Recently, chromones
1 have been obtained by the Vilsmeier—Haack reaction7
directly from 2ꢀhydroxyacetophenones and hydroxylamine
and from Oꢀmethylated chromone 3ꢀoximes.8
Introduction of a cyano group into position 3 of
chromones radically changes the reactivity of the pyrone
ring toward nucleophilic reagents and opens up a broad
synthetic scope of this important oxygenꢀcontaining
heterocyclic system. Being essentially gemꢀactivated alkꢀ
enes (simultaneously α,βꢀunsaturated ketones and niꢀ
triles), 3ꢀcyanochromones 1 exhibit a variety of properꢀ
ties and can undergo additional transformations through
opening of the γꢀpyrone ring and heterocyclizations at
the carbonyl or cyano group because of the presence of
a good leaving group (phenolate anion).9 For instance,
when treated with morpholine in aqueous DMF,10 with
nꢀpropylamine in ethanol,11 or with aqueous NaOH,6
chromone 1 easily undergoes recyclization into 2ꢀamiꢀ
noꢀ3ꢀformylchromone 2 and acts as its chemical equiꢀ
valent in reactions with active methylene compounds.9
However, data on reactions of 3ꢀcyanochromones 1 with
primary amines are very scarce. It has been only reportꢀ
ed12 that reactions of 3ꢀcyanochromone and 3ꢀcyanoꢀ6ꢀ
methylchromone with pꢀtoluidine yield equilibrium mixꢀ
tures of an openꢀchain tautomer (amino enone 3) and two
cyclic tautomers 4 and 5 (Scheme 1). It is also known13
that 2ꢀaminoꢀ3ꢀformylchromones 2 react with aniline to
give 2ꢀaminoꢀ3ꢀ(phenyliminomethyl)chromones 4. In the
present work, we endeavored for the first time to deterꢀ
mine the structures of the products obtained by reactions
of 3ꢀcyanochromones 1 with aromatic and aliphatic
amines using 1D and 2D NMR spectroscopy in DMSOꢀd6
and CDCl3.
Results and Discussion
The closely related structural analogs of chromones 4
are 3ꢀaminomethylidenechromaneꢀ2,4ꢀdiones 6, which
exist as mixtures of Eꢀ and Zꢀisomers stabilized by inꢀ
tramolecular hydrogen bonds (IntraHB) between the keꢀ
tone or lactone carbonyl group and the amino group. The
1H NMR spectra of these compounds show two sets of
signals (doublets at δ 12—14 and ~9 with J = 13—14 Hz
for the amino and vinylic protons, respectively14,15). Howꢀ
ever, in contrast to 2ꢀhydroxychromones mainly existing
as 4ꢀhydroxycoumarins 7,16 less acid 2ꢀaminochromones
8 does not tend toward tautomerization into the coumarin
system17 and, because of the pushꢀpull character of the
double bond of the pyrone ring, are thermodynamically
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 602—611, March, 2010.
1066ꢀ5285/10/5903ꢀ0615 © 2010 Springer Science+Business Media, Inc.

616
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 3, March, 2010
Sosnovskikh et al.
Scheme 1
stable (Scheme 2). This casts doubt on the presumed dyꢀ
namic equilibrium between the chromone system 4 and
compounds 3 and 5 (Scheme 1).
In connection with this, we studied again reactions of
chromones 1 with aromatic amines in boiling benzene for
4 h (procedure A)12. The results obtained are summarized
in Table 1 and Scheme 3. It turned out that 3ꢀcyanoꢀ
chromones 1 (R = H (a), Me (b), or Cl (c)) react with
aniline, pꢀtoluidine, and 2,4ꢀxylidine to give mainly mixꢀ
tures of Zꢀ and Eꢀacrylonitriles 3 and chromones 4; only
the reaction of compound 1b with aniline afforded the
Zꢀ and Eꢀisomers of acrylonitrile 3b without an impurity
of product 4b. With 4ꢀmethoxyꢀ and 4ꢀbromoanilines and
2ꢀaminopyridine, chromones 4f,h—j were obtained as the
sole reaction products, while 4ꢀnitroaniline remained inꢀ
ert to compound 1a under these and more drastic condiꢀ
tions. Reactions of aliphatic amines (such as benzylamine,
phenethylamine, and isopropylamine) with chromones
1a,b in boiling benzene proceed through the formation of
acrylonitriles to give chromones 4m—p in good yields
(48—65%). A reduction in the reflux time from 4 h to
5—30 min (procedure B) did not afford intermediate
acrylonitriles 3 in the individual state: apart from the
R = H, Me
Table 1. Compositions of products 3 and 4 in DMSOꢀd6 and
CDCl3 (from 1H NMR spectra)
Scheme 2
Proꢀ
duct
R
Ar
Method A
Zꢀ3 : Eꢀ3 : 4 (%) 1 : Zꢀ3 : Eꢀ3 : 4 (%)
Method B
3a + 4a
3b
3b
3c + 4c Cl
3d + 4d
3d + 4d
H
Me
Me
Ph
Ph
Ph
30 : 52 : 18a
35 : 65 : 0a
77 : 23 : 0c
24 : 40 : 36a
08 : 15 : 77a
25 : 0 : 75c,d
35 : 60 : 5a
84 : 10 : 6c,d
25 : 27 : 44 : 4a (5)b
4 : 26 : 45 : 25a (15)b
Ph
H
H
4ꢀMeC6H4
4ꢀMeC6H4
3e + 4e Me 4ꢀMeC6H4
3e + 4e Me 4ꢀMeC6H4
4f
4f
H
H
4ꢀMeOC6H4 00 : 0 : 100a
4ꢀMeOC6H4 00 : 0 : 100c
0 : 30 : 44 : 26a (5)b
0 : 34 : 53 : 13a (5)b
3g + 4g Me 4ꢀMeOC6H4 30 : 50 : 20a
3g + 4g Me 4ꢀMeOC6H4 76 : 7 : 17c
4h
4i
4j
Cl 4ꢀMeOC6H4 00 : 0 : 100a
H
H
H
4ꢀBrC6H4
2ꢀC5H4N
2,4ꢀMe2C6H3 56 : 17 : 27a
00 : 0 : 100a
00 : 0 : 100a
3k + 4k
16 : 82 : 2 : 0c (30)b
3l + 4l Me 2,4ꢀMe2C6H3 60 : 22 : 18a
3l + 4l Me 2,4ꢀMe2C6H3 87 : 4 : 9c
4m
4n
4o
4p
H
H
H
CH2Ph
(CH2)2Ph
iꢀPr
00 : 0 : 100a,c
00 : 0 : 100a
00 : 0 : 100a
00 : 0 : 100a
Me
CH2Ph
a In DMSOꢀd6.
b The reflux time (min).
c In CDCl3.
d Earlier,12 this product has been reported to be an equilibrium
mixture of compounds 3, 4, and 5.

Reactions of 3ꢀcyanochromones with amines
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 3, March, 2010
617
Zꢀ and Eꢀisomers of products 3, the reaction mixtures
always contained impurities of chromones 1 and/or 4
(1H NMR data). At the same time, compounds 4a—e,g,k,l
can easily be obtained in 64—98% yields when the starting
reagents are refluxed in benzene for 4 h in the presence of
triethylamine (procedure C). Compounds 4 are analytiꢀ
cally pure even without recrystallization. The exception is
chromone 4p, which contains a 6% impurity (1H NMR
data) of the earlier described11 dimer 7ꢀmethylꢀ2ꢀ(6ꢀmeꢀ
thylꢀ4ꢀoxoꢀ4Hꢀchromenꢀ3ꢀyl)ꢀ5Hꢀchromeno[2,3ꢀd]pyriꢀ
midinꢀ5ꢀone (9) (Scheme 2).
The reaction studied involves nucleophilic 1,4ꢀaddiꢀ
tion of an amine to the C(2) atom of chromone 1 followed
by opening of the pyrone ring and formation of intermediꢀ
ate 3. The latter undergoes irreversible cyclization into
final product 4 through addition of the phenolic hydroxyl
to the cyano group (Scheme 3). The rate of this intramoꢀ
lecular cyclization depends on the substituents in the
chromone and aniline molecules. The first step of the reꢀ
action is rapid, which is evident from the experimental
data obtained according to procedure B. The cyclization
rate is probably determined by the acidity of the phenolic
hydroxyl and the basicity of the amine used. Although
a detailed examination of this problem was beyond the
scope of this study, the above assumption is supported by
the following experimental facts.
(1) Addition of a catalytic amount of Et3N (procedure
C) promoting the deprotonation of the phenolic hydroxyl
substantially accelerates the cyclization and affords chroꢀ
mones 4 without an impurity of the openꢀchain form 3.
(2) Being stronger bases, aliphatic amines always yield
final products 4 only, while intermediate acrylonitriles 3
are not detected even in trace amounts.
(3) In the presence of the electronꢀdonating Me group
in position 6 of chromone, the phenolic fragment is less acid
and thus the cyclization is inhibited. As a result, the reaction
products either contain no chromone 4 at all (as with 3b)
or its content is low (3e,g,l). As expected, the electronꢀ
withdrawing Cl atom produces an opposite effect (4c,h).
(4) Product 3b is stable for a day in CDCl3; in more
basic DMSOꢀd6, it undergoes spontaneous cyclization into
compound 4b with simultaneous decomposition to the
starting reagents 3ꢀcyanoꢀ6ꢀmethylchromone and aniline
over the same period of time.
Compounds 3 and 4 and their mixtures are yellow or
colorless highꢀmelting solids; they are soluble in DMSO
and moderately soluble in chloroform. The 1H NMR specꢀ
tra (400 MHz) of chromones 4 are given in Table 2; the
Scheme 3
1a—c
R = H (1a), Me (1b), Cl (1c)

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Russ.Chem.Bull., Int.Ed., Vol. 59, No. 3, March, 2010
Sosnovskikh et al.
Table 2. 1H NMR spectra of chromones 4a—p
Imine
R
Ar
1H NMR, δ, J/Hz
R, H(5)—H(8), Ar
Ha
Hb
Hc
(br.s)
(br.s)
4aa
H
H
Ph
Ph
9.43
10.64
8.98
(s)
7.19—7.26 (m, 3 H, Н(4´), Н(2´), H(6´)); 7.38—7.47 (m, 4 H,
Н(6), H(8), Н(3´), Н(5´)); 7.72 (ddd, 1 Н, Н(7), J = 8.4, 7.2,
1.7); 8.05 (ddd, 1 Н, Н(5), J = 8.1, 1.7, 0.4)
4ab
4ba
6.03
9.36
11.40
10.60
9.15
(s)
7.20—7.40 (m, 7 H, Н(6), Н(8), Ph); 7.60 (ddd, 1 H, Н(7),
J = 8.2, 7.4, 1.7); 8.24 (dd, 1 H, Н(5), J = 7.9, 1.7)
Me Ph
8.97
(s)
2.41 (s, 3 Н, Ме); 7.18—7.25 (m, 3 Н, Н(4´), Н(2´), Н(6´);
7.35 (d, 1 Н, Н(8), J = 8.4); 7.37—7.43 (m, 2 H, Н(3´), H(5´));
7.52 (ddq, 1 H, Н(7), J = 8.4, 2.3, 0.5); 7.84 (br.d, 1 H, Н(5),
J = 2.0)
4ca
4da
4db
4ea
Cl Ph
9.55
9.38
6.10
9.32
10.68
10.68
11.70
10.65
8.95
(s)
7.19—7.26 (m, 3 Н, Н(4´), Н(2´), Н(6´)); 7.38—7.43 (m, 2 Н,
Н(3´), Н(5´)); 7.52 (d, 1 H, Н(8), J = 8.8); 7.76 (dd, 1 H, Н(7),
J = 8.8, 2.7); 7.96 (d, 1 H, Н(5), J = 2.7)
H
H
4ꢀMeC6H4
8.97
(s)
2.31 (s, 3 H, Me); 7.13—7.22 (m, 4 H, Ar); 7.41—7.47 (m, 2 H,
Н(6), Н(8)); 7.72 (ddd, 1 H, H(7), J = 8.4, 7.2, 1.7); 8.05 (dd,
1 H, H(5), J = 7.9, 1.7)
4ꢀMeC6H4
9.13
(s)
2.36 (s, 3 H, Me); 7.10—7.20 (m, 4 H, Ar); 7.25 (d, 1 H, Н(8),
J = 8.2); 7.35 (td, 1 H, Н(6), J = 7.6, 0.8); 7.58 (ddd, J = 8.2,
7.4, 1.7); 8.23 (dd, 1 H, H(5), J = 7.8, 1.7)
Me 4ꢀMeC6H4
Me 4ꢀMeC6H4
8.97
(s)
2.31 and 2.41 (both s, 3 H, Me); 7.13—7.22 (m, 4 H, Ar); 7.34
(d, 1 Н, Н(8), J = 8.4); 7.52 (dd, 1 H, H(7), J = 8.4, 2.3);
7.83 (br.d, 1 Н, Н(5), J = 2.0)
4eb
5.98
9.34
11.20
10.70
9.13
(s)
2.36 and 2.43 (both s, 3 H, Me); 7.10—7.30 (m, 5 H, Ar, Н(8));
7.38 (dd, 1 H, H(7), J = 8.4, 2.0); 8.01 (d, 1 Н, Н(5), J = 2.0)
4fa,c
H
H
4ꢀMeOC6H4
4ꢀMeOC6H4
8.97
(s)
3.77 (s, 3 Н, МеО); 6.94—6.99 (m, 2 H, Ar); 7.21—7.26
(m, 2 H, Ar); 7.41—7.46 (m, 2 H, H(6), H(8)); 7.71 (ddd,
1 H, H(7), J = 8.5, 7.3, 1.7); 8.05 (dd, 1 H, H(5), J = 7.8, 1.6)
4fb
6.02
9.28
11.65
10.66
9.12
(s)
3.83 (s, 3 Н, МеО); 6.90—6.94 (m, 2 H, Ar); 7.20—7.24 (m,
2 H, Ar); 7.26 (dd, 1 H, Н(8), J = 8.3, 1.0); 7.36 (ddd, 1 H,
H(6), J = 7.8, 7.3, 1.0); 8.23 (dd, 1 H, H(5), J = 7.8, 1.7)
4ga
Me 4ꢀMeOC6H4
8.96
(s)
2.41 (s, 3 Н, Ме); 3.77 (s, 3 Н, МеО); 6.94—6.98 (m, 2 H,
H(3´), H(5´)); 7.21—7.25 (m, 2 Н, Н(2´), Н(6´)); 7.34 (d, 1 H,
H(8), J = 8.4); 7.51 (ddq, 1 H, H(7), J = 8.4, 2.3); 7.83 (br.d,
1 H, H(5), J = 2.0)
4gb
4ha
4ia,d
4ja
Me 4ꢀMeOC6H4
Cl 4ꢀMeOC6H4
5.93
9.46
9.47
9.58
11.25
10.74
10.52
10.89
9.12
(s)
2.44 (s, 3 Н, Ме); 3.83 (s, 3 Н, МеО); 6.90—6.93 (m, 2 H,
H(3´), H(5´)); 7.20—7.24 (m, 3 Н, Н(8), Н(2´), H(6´));
7.38 (dd, 1 H, H(7), J = 8.5, 2.3); 8.01 (br.d, 1 H, H(5), J = 2.0)
8.95
(s)
3.77 (s, 3 Н, МеO); 6.95—6.99 (m, 2 H, H(3´), H(5´));
7.22—7.27 (m, 2 Н, Н(2´), H(6´)); 7.51 (d, 1 H, H(8), J = 8.8);
7.75 (dd, 1 H, H(7), J = 8.8, 2.7); 7.96 (d, 1 H, H(5), J = 2.7)
H
H
4ꢀBrC6H4
2ꢀC5H4N
8.97
(s)
7.22 (d, 2 Н, H(2´), H(6´), J = 8.7); 7.42—7.46 (m, 2 H, H(6),
H(8)); 7.56 (d, 2 Н, Н(3´), H(5´), J = 8.7); 7.72 (ddd, 1 H,
H(7), J = 8.5, 7.2, 1.7); 8.05 (dd, 1 H, H(5), J = 7.8, 1.7)
9.75
(s)
7.22 (ddd, 1 Н, H(5´), J = 7.3, 4.8, 1.0); 7.36 (dt, 1 Н, Н(3´),
J = 8.1, 1.0); 7.42—7.47 (m, 2 Н, H(6), Н(8)); 7.73 (ddd,
1 H, H(7), J = 8.4, 7.2, 1.7); 8.06 (dd, 1 H, H(5), J = 7.8, 1.7);
8.47 (ddd, 1 H, H(6´), J = 4.8, 2.0, 0.7)
4ka
H
2,4ꢀMe2C6H3 9.39
10.79
8.90
(s)
2.26 and 2.28 (both s, 3 H, Me); 6.96 (d, 1 H, Н(6´), J = 7.8);
7.03—7.07 (m, 2 H, Н(3´), Н(5´)); 7.44 (td, 1 Н, Н(6),
J = 7.8, 1.0); 7.72 (ddd, 1 Н, H(7), J = 8.4, 7.2, 1.7);
7.60 (dd, 1 Н, Н(5), J = 7.8, 1.7)
(to be continued)

Reactions of 3ꢀcyanochromones with amines
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 3, March, 2010
619
Table 2 (continued)
Imine
R
Ar
1H NMR, δ, J/Hz
Ha
Hb
Hc
R, H(5)—H(8), Ar
(br.s)
(br.s)
4la
Me 2,4ꢀMe2C6H3 9.33
Me 2,4ꢀMe2C6H3 6.06
10.76
8.90
(s)
2.26, 2.28 and 2.41 (all s, 3 H, Me); 6.96 (d, 1 H, Н(6´),
7.03—7.07 (m, 4 H, Н(3´), Н(5´)); 7.35 (d, 1 Н, 7.52 (dd,
1 Н, Н(7), J = 8.4, 2.2); 7.84 (br.d, 1 H, H(5), J = 2.0)
4lb
11.25
11.60
9.07
(s)
2.32, 2.36 and 2.43 (all s, 3 H, Me); 7.03—7.10 (m, 4 H, Н(8) Ar);
7.38 (dd, 1 Н, Н(7), J = 8.4, 2.0); 6.78 (br.s, 1 H, Н(5))
4mb
H
H
CH2Ph
CH2Ph
6.31
8.98
8.83
(s)
4.74 (s, 2 H, CH2); 7.16 (dd, 1 Н, Н(8), J = 8.4, 1.0);
7.27—7.39 (m, 6 H, Ph); 7.54 (ddd, 1 Н, H(7), J = 8.4, 7.3,
1.5); 8.17 (dd, 1 Н, Н(5), J = 7.8, 1.5)
4ma
10.80
8.85
(s)
4.75 (s, 2 H, CH2); 7.25—7.37 (m, 5 H, Ph); 7.39 (ddd, 1 Н,
H(6), J = 8.0, 7.3, 1.0); 7.40 (dd, 1 Н, Н(8), J = 8.4, 1.0);
7.68 (ddd, 1 Н, H(7), J = 8.4, 7.3, 1.7); 8.02 (dd, 1 Н, Н(5),
J = 8.0, 1.7)
4me
4na
H
H
CH2Ph
—
—
9.50
(br.s)
4.90 (br.s, 2 H, CH2); 7.28—7.42 (m, 7 H, H(6), H(8), Ph);
7.64 (t, 1 Н, H(7), J = 7.5); 8.07 (d, 1 Н, Н(5), J = 7.5)
(CH2)2Ph
8.86
10.82
8.63
(s)
2.91 (t, 2 H, CH2, J = 7.2); 3.78 (t, 2 H, NCH2, J = 7.2);
7.17—7.32 (m, 5 Н, Ph); 7.36 (dd, 1 Н, Н(8), J = 8.4, 1.0);
7.37 (ddd, 1 Н, H(6), J = 8.0, 7.3, 1.0); 7.66 (ddd, 1 Н, H(7),
J = 8.4, 7.3, 1.7); 7.98 (dd, 1 Н, Н(5), J = 8.0, 1.7)
4oa
4of
H
H
H
Pri
8.84
—
10.94
—
8.70
(s)
1.20 (d, 6 H, 2 Me, J = 6.3); 3.56 (sept, 1 H, CH, J = 6.3);
7.35—7.40 (m, 2 Н, H(6), H(8)); 7.67 (ddd, 1 Н, H(7),
J = 8.3, 7.2, 1.7); 7.99 (dd, 1 Н, Н(5), J = 7.9, 1.7)
Pri
8.70
(s)
1.21 (d, 6 H, 2 Me, J = 6.3); 3.59 (sept, 1 H, CH, J = 6.3);
7.35—7.40 (m, 2 Н, H(6), H(8)); 7.67 (ddd, 1 Н, H(7),
J = 8.3, 7.2, 1.7); 8.00 (dd, 1 Н, Н(5), J = 7.9, 1.7)
4pa,g
CH2Ph
8.92
10.74
8.84
(s)
2.39 (s, 3 H, Me); 4.74 (s, 2 H, CH2); 7.24—7.38 (m, 5 H,
Ph); 7.29 (d, 1 Н, H(8), J = 8.5); 7.48 (dd, 1 Н, Н(7), J = 8.5,
2.2); 7.80 (d, 1 Н, Н(5), J = 2.2)
a In DMSOꢀd6.
b In CDCl3.
c The signals for the NH protons disappear upon the addition of CD3CO2D.
d 13C NMR (DMSOꢀd6), δ: 95.05 (C(3)), 116.73 (C(8)), 117.64 (C(4´)), 121.83 (C(4a)), 123.15 (C(2´), C(6´)), 125.09 (C(6)),
125.22 (C(5)), 132.03 (C(3´), C(5´)), 133.50 (C(7)), 150.27 (C(1´)), 152.86 (C(8a)), 156.46 (C=N), 164.25 (C(2)), 173.89 (C(4)).
e CDCl3 + CD3CO2D.
f DMSOꢀd6 + CD3CO2D.
g The product contains dimer 9 as an impurity (6%). 1H NMR (DMSOꢀd6), δ: 2.48 (s, 6 H, 2 Me); 7.68 (d, 1 H, H(8), J = 8.6 Hz); 7.71
(d, 1 H, H(8´), J = 8.6 Hz); 7.71 (dd, 1 H, H(7), J = 8.6 Hz, J = 2.3 Hz); 7.79 (dd, 1 H, H(7´), J = 8.6 Hz, J = 2.3 Hz); 7.98 (br.s, 1 H,
H(5)); 8.01 (br.s, 1 H, H(5´)); 9.09 (s, 1 H, H(2)); 9.56 (s, 1 H, CH=N).
1H NMR spectra of Zꢀ and Eꢀacrylonitriles 3 in CDCl3
and DMSOꢀd6 at 25 °C are summarized in Tables 3 and 4,
respectively. In the case of reactions of chromones 1 with
with primary amines (procedures A and C). Because the
1H NMR spectra of these products show three lowꢀfield
singlets for the Ha, Hb, and Hc protons, we excluded from
consideration amino enone structure 5, which is a nitroꢀ
gen analog of 3ꢀaminomethylidenechromaneꢀ2,4ꢀdiones
6 (earlier,12 structure 5 was assigned to openꢀchain form 3
with similar spectroscopic characteristics). We gave prefꢀ
erence to imino enamine 4 rather than imino enol 10 upon
analysis of the chemical shifts of the signals for the N atoms
in compound 4i at δ 98.9 (NH2) and 287.4 (N=C)
(2D 1H—15N HMQC and HMBC). The spectrum of tauꢀ
1
primary amines according to procedure A, the H NMR
spectra of the products show one to three sets of signals of
different intensities. This allowed assignment of all lowꢀ
field signals for the OH, NH, and =CH protons in Zꢀ and
Eꢀ3; however, signals for the aromatic protons were asꢀ
signed incompletely because of their overlap.
Our primary task was to identify the tautomeric form
of the final products in the reactions of chromones 1

620
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 3, March, 2010
Sosnovskikh et al.
Table 3. 1H NMR spectra of acrylonitriles Zꢀ and Eꢀ3a,b,d,e,g,k,l in CDCl3
Enamine
Zꢀ3a
R
H
H
Ar
1H NMR, δ, J/Hz
R, H(3)—H(6), Ar
OH
NH (br.d) =CH (d)
12.44 8.06
Ph
Ph
11.41
(s)
6.95 (ddd, 1 H, Н(5), J = 8.1, 7.4, 1.0); 7.01 (dd, 1 H, Н(3),
(J = 13.4) (J = 13.4) J = 8.2, 1.0); 7.20—7.30 (m, 3 Н, Ar); 7.40—7.50 (m, 3 Н,
H(4), Ar); 8.40 (dd, 1 H, H(6), J = 8.1, 1.6)
Eꢀ3a
11.90
(s)
18.12
8.82
6.95 (ddd, 1 H, Н(5), J = 8.1, 7.4, 1.0); 7.02 (dd, 1 H, Н(3),
(J = 15.2) (J = 15.2) J = 8.2, 1.0); 7.20—7.30 (m, 3 Н, Ar); 7.40—7.50 (m, 3 Н,
H(4), Ar); 8.31 (dd, 1 H, H(6), J = 8.1, 1.6)
Zꢀ3ba
Me Ph
Me Ph
11.17
(s)
12.45
8.05
2.34 (s, 3 Н, Ме); 6.91 (d, 1 Н, Н(3), J = 8.4); 7.22—7.32
(J = 13.4) (J = 13.4) (m, 4 Н, H(2´), H(6´), Н(4´), Н(4)); 7.46 (t, 2 H, H(3´),
Н(5´), J = 7.9); 8.19 (br.d, 1 H, Н(6), J = 1.5)
Eꢀ3bb
Zꢀ3d
11.68
(s)
8.18
(J = 15.2) (J = 15.2) (m, 6 Н, Н(4), Ar); 8.10 (br.d, 1 H, Н(6), J = 1.7)
12.45 8.01 2.38 (s, 3 H, Me); 6.94 (ddd, 1 H, Н(5), J = 8.1, 7.4, 1.0);
(J = 13.5) (J = 13.5) 7.00 (dd, 1 H, Н(3), J = 8.2, 1.0); 7.10—7.20 (m, 4 Н, Ar);
7.46 (ddd, 1 Н, H(4), J = 8.2, 7.4, 1.6); 8.39 (dd, 1 Н, H(6),
J = 8.1, 1.6)
8.80
2.35 (s, 3 Н, Ме); 6.92 (d, 1 Н, Н(3), J = 8.4); 7.21—7.50
H
4ꢀMeC6H4
11.70
(br.s)
Zꢀ3e
Eꢀ3e
Zꢀ3g
Me 4ꢀMeC6H4
Me 4ꢀMeC6H4
Me 4ꢀMeOC6H4
11.21
(br.s)
12.45
(J = 13.5) (J = 13.5) 7.10—7.30 (m, 5 Н, Н(4), Ar); 8.18 (br.d, 1 H, H(6), J = 1.5)
8.07 8.77 2.34 and 2.37 (both s, 3 H, Me); 6.92 (d, 1 H, Н(3), J = 8.4);
(J = 15.2) (J = 15.2) 7.10—7.30 (m, 5 Н, Н(4), Ar); 8.10 (br.d, 1 H, H(6), J = 1.5)
12.49 7.94 2.33 (s, 3 Н, Ме); 3.84 (s, 3 Н, МеО); 6.90 (d, 1 Н, Н(3),
8.01
2.33 and 2.38 (both s, 3 H, Me); 6.90 (d, 1 H, Н(3), J = 8.4);
11.71
(br.s)
11.25
(br.s)
(J = 13.4) (J = 13.4) J = 8.4); 6.94—7.20 (m, 4 H, Ar); 7.26 (dd, 1 Н, Н(4),
J = 8.4, 2.3); 8.18 (br.d, 1 H, H(6), J = 1.5)
Eꢀ3g
Zꢀ3k
Me 4ꢀMeOC6H4
11.72
(br.s)
8.15
8.70
2.34 (s, 3 Н, Ме); 3.84 (s, 3 Н, МеО); 7.02—7.20 (m, 5 H,
(J = 15.2) (J = 15.2) H(3), Ar); 7.28 (dd, 1 Н, Н(4), J = 8.4, 2.3); 8.10 (br.d,
1 H, H(6), J = 1.5)
H
2,4ꢀMe2C6H3 11.46
(br.s)
12.60
8.03
2.35 and 2.40 (both s, 3 H, Me); 6.95 (ddd, 1 H, Н(5),
(J = 13.3) (J = 13.3) J = 8.1, 7.2, 1.1), 7.01 (dd, 1 H, Н(3), J = 8.3, 1.1);
7.10—7.16 (m, 3 H, Ar); 7.46 (ddd, 1 H, H(4), J = 8.3, 7.2,
1.6); 8.40 (dd, 1 Н, Н(6), J = 8.1, 1.6)
Zꢀ3l
Eꢀ3l
Me 2,4ꢀMe2C6H3 11.22
(br.s)
12.61
8.02
2.34, 2.35 and 2.40 (all s, 3 H, Me); 6.91 (d, 1 H, Н(3),
(J = 13.2) (J = 13.2) J = 8.3); 7.07—7.16 (m, 3 H, Ar); 7.26 (dd, 1 Н, Н(4),
J = 8.3, 2.0); 8.19 (br.d, 1 Н, Н(6), J = 1.5)
Me 2,4ꢀMe2C6H3 11.73
(br.s)
8.09
8.71
2.30—2.40 (masked, 9 H, 3 Me); 6.90—7.16 (m, 5 H, Н(3),
(J = 15.2) (J = 15.2) H(4), Ar); 8.10 (br.s, 1 H, Н(6))
a 13C NMR (CDCl3), δ: 20.60 (Me), 82.38 (C(2)), 118.05 (C(2″), C(6″)), 118.15 (C(3´)), 119.35 (C(1´)), 120.34 (CN), 126.92 (C(4″)),
128.17 (C(5´)), 129.08 (C(6´)), 130.22 (C(3″), C(5″)), 136.78 (C(4´)), 137.84 (C(1″)), 155.03 (C(3)), 159.26 (C(2´)), 193.14 (C(1)).
b 13C NMR (CDCl3), δ: 84.02 (C(2)), 129.44 (C(6´)), 137.98 (C(1″)), 154.45 (C(3)), 160.06 (C(2´)), 188.90 (C(1)) (the signals were
identified only in part).
tomer 10 would contain two lowꢀfield signals for the imiꢀ
ne N atoms (Scheme 3).
in chromones 4a—p, which appear in DMSOꢀd6 as slightꢀ
ly broadened singlets at δ 8.8—9.6 (Ha) and 10.4—10.9
(Hb) and disappear upon addition of CD3CO2D, is probaꢀ
bly due to IntraHB between the Hb proton and the imine
N atom. The results are hindered rotation about the
C(2)—N bond, the Eꢀconfiguration of the imino group,
and the stabilization of the sꢀcisꢀconformer (see Scheme 3).
The azomethine Hc proton in these compounds resonates
in a narrow range (δ 8.6—9.0). The exception is αꢀpyridylꢀ
containing compound 4j: the signal for the Hc proton apꢀ
As another piece of evidence for structure 4, note that
the lowestꢀfield signal in the 13C NMR spectrum of comꢀ
pound 4i at δ 173.9 correlates well with the signal for the
group C=O in chromones18 and that the chemical shifts
of the signals for the H(5)—H(8) protons at δ 7.42—8.05
are very close to those for the corresponding aromatic
protons in 2ꢀaminoꢀ3ꢀformylꢀ and 2ꢀaminoꢀ3ꢀcarbamoꢀ
ylchromones.19 The nonequivalence of the NH2 protons

Reactions of 3ꢀcyanochromones with amines
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 3, March, 2010
621
Table 4. 1H NMR spectra of acrylonitriles Zꢀ and Eꢀ3a—g,k,l in DMSOꢀd6
Enamine
R
H
H
Ar
1H NMR, δ, J/Hz
OH
NH
=CH
R, H(3)—H(6), Ar
Zꢀ3a
Ph
Ph
10.18
(s)
12.32
(br.d,
J = 13.5)
8.55
(d,
6.86—6.95 (m, 2 H, Н(3), Н(5)); 7.29—7.38 (m, 5 H, Н(4),
Н(6), Н(3´), Н(4´), Н(5´));
J = 13.5) 7.56—7.59 (m, 2 Н, Н(2´), Н(6´))
Eꢀ3a
10.21
(br.s)
11.03
(br.s)
8.14
(br.s)
6.86—6.95 (m, 2 H, Н(3), Н(5)); 7.29—7.38 (m, 7 H, Н(4),
Н(6), Ph)
Zꢀ3ba
Me Ph
9.93
(s)
12.31
(br.d,
8.54
(d,
2.23 (s, 3 Н, Ме); 6.81 (d, 1 Н, Н(3), J = 8.2);
7.10—7.16 (m, 2 Н, Н(4), Н(6)); 7.24 (tt, 1 H, Н(4´),
J = 13.5)
J = 13.5) J = 7.4, 1.0); 7.41—7.46 (m, 2 H, Н(3´), Н(5´));
7.55—7.59 (m, 2 H, Н(2´), Н(6´))
Eꢀ3bb
Zꢀ3c
Me Ph
9.95
(br.s)
10.99
(br.s)
8.13
(br.s)
2.23 (s, 3 Н, Ме); 6.82 (d, 1 Н, Н(3), J = 8.2); 7.10—7.16
(m, 2 Н, Н(4), Н(6)); 7.18 (tt, 1 H, Н(4´), J = 7.4, 1.0);
7.28—7.32 (m, 2 H, Н(2´), Н(6´)); 7.36—7.41 (m, 2 H,
Н(3´), Н(5´))
Cl Ph
Cl Ph
10.43
(s)
12.26
(br.d,
J = 13.6)
8.57
(d,
6.94 (d, 1 H, H(3), J = 8.8); 7.17—7.40 (m, 3 H, Н(4),
Н(6), Н(4´)); 7.44 (br.t, 2 Н, Н(3´), Н(5´), J = 7.8);
J = 13.6) 7.58 (br.d, 2 Н, Н(2´), Н(6´), J = 7.8)
Eꢀ3c
Zꢀ3d
10.39
(br.s)
11.09
(br.s)
8.14
(br.s)
6.94 (d, 1 H, H(3), J = 8.8); 7.17—7.42 (m, 7 H, Н(4),
Н(6), Ph)
H
H
4ꢀMeC6H4
4ꢀMeC6H4
10.17
(s)
12.33
(br.d,
J = 13.6)
8.51
(d,
J = 13.6)
2.31 (s, 3 H, Me); 6.85—6.95 (m, 2 H, Н(3), Н(5));
7.20—7.48 (m, 6 H, Н(4), Н(6), Ar)
Eꢀ3d
Zꢀ3e
10.25
(br.s)
10.99
(br.s)
8.11
(br.s)
2.27 (s, 3 H, Me); 6.85—6.95 (m, 2 H, Н(3), Н(5));
7.20—7.48 (m, 6 H, Н(4), Н(6), Ar)
Me 4ꢀMeC6H4
Me 4ꢀMeC6H4
9.92
(s)
12.32
(br.d,
J = 13.5)
8.49
(d,
2.23 and 2.31 (both s, 3 H, Me); 6.81 (d, 1 H, Н(3), J = 8.2);
7.10—7.16 (m, 2 Н, Н(4), Н(6)); 7.22—7.25 (m, 2 H, Ar);
J = 13.5) 7.44—7.47 (m, 2 H, Ar)
Eꢀ3e
Zꢀ3f
9.95
(br.s)
10.95
(br.s)
8.08
(br.s)
2.22 and 2.27 (both s, 3 H, Me); 6.82 (d, 1 H, Н(3), J = 8.2);
7.10—7.16 (m, 2 Н, Н(4), Н(6)); 7.19 (s, 4 H, Ar)
H
H
4ꢀMeOC6H4
4ꢀMeOC6H4
10.16
(s)
12.37
(br.d,
J = 13.6)
8.44
(d,
J = 13.6)
3.78 (s, 3 Н, МеО); 6.85—7.02 (m, 4 H, Н(3), Н(5), Ar);
7.29—7.36 (m, 2 H, Н(4), Н(6)); 7.50—7.54 (m, 2 H, Ar)
Eꢀ3f
Zꢀ3g
10.26
(br.s)
10.96
(br.s)
8.05
(br.s)
3.74 (s, 3 Н, МеО); 6.85—7.02 (m, 4 H, Н(3), Н(5), Ar);
7.22—7.26 (m, 2 H, Ar), 7.29—7.36 (m, 2 H, Н(4), Н(6))
Me 4ꢀMeOC6H4
Me 4ꢀMeOC6H4
9.91
(s)
12.35
(br.d,
J = 13.5)
8.42
(d,
2.23 (s, 3 Н, Ме); 3.78 (s, 3 Н, МеО);
6.81 (d, 1 Н, Н(3), J = 8.3); 6.94—7.01 (m, 2 H, Ar);
J = 13.5) 7.10—7.15 (m, 2 Н, Н(4), Н(6)); 7.50—7.53 (m, 2 H, Ar)
Eꢀ3g
Zꢀ3k
9.96
(br.s)
10.93
(br.s)
8.03
(br.s)
2.22 (s, 3 Н, Ме); 3.74 (s, 3 Н, МеО); 6.81 (d, 1 Н, Н(3),
J = 8.3); 6.94—7.01 (m, 2 H, Ar); 7.10—7.15 (m, 2 Н,
Н(4), Н(6)); 7.22—7.26 (m, 2 H, Ar)
H
H
2,4ꢀMe2C6H3 10.14
(s)
12.65
(br.d,
J = 13.0)
8.61
(d,
2.28 and 2.34 (both s, 3 H, Me); 6.88 (td, 1 H, Н(5),
J = 7.5, 1.0), 6.92 (dd, 1 H, Н(3), J = 8.6, 1.0); 7.05—7.15
J = 13.0) (m, 2 H, Н(3´), Н(5´)); 7.29—7.34 (m, 2 H, H(4), Н(6));
7.60 (d, 1 Н, Н(6´), J = 8.2)
Eꢀ3k
2,4ꢀMe2C6H3 10.16
(br.s)
10.47
(br.s)
7.73
(br.s)
2.24 and 2.25 (both s, 3 H, Me); 6.84—6.94 (m, 2 H, H(5),
H(3)); 7.05—7.15 (m, 3 H, Ar); 7.26—7.34 (m, 2 H,
H(4), H(6))
(to be continued)

622
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 3, March, 2010
Sosnovskikh et al.
Table 4 (continued)
Enamine
R
Ar
1H NMR, δ, J/Hz
OH
NH
=CH
8.60
(d,
J = 13.0)
R, H(3)—H(6), Ar
Zꢀ3l
Me 2,4ꢀMe2C6H3 9.90
(s)
12.66
(br.d,
J = 13.0)
2.23, 2.28 and 2.33 (all s, 3 H, Me); 6.82 (d, 1 H, Н(3),
J = 8.5); 7.01—7.15 (m, 4 H, Н(4), Н(6), Н(3´), Н(5´));
7.59 (d, 1 Н, Н(6´), J = 8.2)
Eꢀ3l
Me 2,4ꢀMe2C6H3 9.92
(br.s)
10.44
(br.s)
7.72
(br.s)
2.20, 2.24 and 2.25 (all s, 3 H, Me); 6.78 (d, 1 H, Н(3),
J = 8.5); 7.01—7.15 (m, 5 H, Н(4), Н(6), Ar)
a 13C NMR (DMSOꢀd6), δ: 19.91 (Me), 85.48 (C(2)), 116.27 (C(3´)), 118.19 (C(2″), C(6″)), 119.92 (CN), 125.77 (C(4″)),
126.59 (C(1´)), 127.24 (C(5´)), 128.24 (C(6´)), 129.62 (C(3″), C(5″)), 132.45 (C(4´)), 138.46 (C(1″)), 152.67 (C(2´)), 153.59 (C(3)),
193.05 (C(1)).
b 13C NMR (DMSOꢀd6), δ: 19.91 (Me), 86.75 (C(2)), 116.17 (C(3´)), 116.73 (CN), 118.33 (C(2″), C(6″)), 125.20 (C(4″)),
125.63 (C(1´)), 127.70 (C(5´)), 129.19 (C(6´)), 129.62 (C(3″), C(5″)), 132.56 (C(4´)), 139.78 (C(1″)), 152.83 (C(2´)), 154.23 (C(3)),
189.69 (C(1)).
pears at δ 9.75 because of the deshielding of the pyridine N
atom (see Table 2).
amines via the opening of the pyrone ring are typical repꢀ
resentatives of pushꢀpull alkenes with the highly polarized
bond C(2)=C(3) and, accordingly, the lowered energy barꢀ
rier to rotation about this bond, which allows them to exist
in solution as an equilibrium mixture of geometric Zꢀ and
Eꢀisomers. In addition, compounds 3 can be regarded as
amide vinylogs with hindered rotation about the formally
single bonds C(1)—C(2) and C(3)—N because of the deꢀ
localized πꢀelectron density, which may give rise to conꢀ
formers (rotamers) in the equilibrium mixture. However,
the 1H NMR spectra of compounds 3 in both CDCl3 and
DMSOꢀd6 show only two sets of signals for the Zꢀ and
Eꢀisomers. The major isomer in CDCl3 is the Zꢀisomer
with IntraHB between the C=O and NH groups, while the
major isomer in DMSOꢀd6 is the Eꢀisomer with the
NH proton involved in intermolecular hydrogen bonding
to solvent molecules.
Out of two NH2 protons in chromone 4i, a cross peak
with the highꢀfield N atom is produced only by the Hb
proton (δ 10.52) involved in IntraHB (1H—15N HMQC
data). The Ha proton (δ 9.47) linked by an intermolecular
hydrogen bond (InterHB) to basic DMSOꢀd6 molecules
produces no cross peak, which has been noted earlier for
2ꢀaminoꢀ3ꢀcarbamoylchromone.19 At the same time, in
CDCl3 incapable of forming InterHB to acid hydrogen
atoms, the signal for Ha appears as a broadened singlet at
δ 5.9—6.3, while the signal for Hb is shifted downfield
(δ 11.3—11.7) because of IntraHB (compounds 4d,e,f,g,l,m).
This agrees well with the presumed formation of InterHB
and IntraHB in solutions of chromones 4 in DMSOꢀd6
(see Table 2). Upon addition of CD3CO2D to a solution of
compound 4m in CDCl3, the singlet for the azomethine
Hc proton is shifted downfield by 0.67 ppm and the singlet
for the CH2 group, by 0.16 ppm, which indicates deuteraꢀ
tion of the imine N atom in this solvent.
1
All essential signals in the H and 13C NMR spectra
for this series of compounds were assigned from 2D experꢀ
iments (1H—13C HSQC and HMBC) for compound 3b
obtained from 3ꢀcyanoꢀ6ꢀmethylchromone and aniline
(the product contained no impurity of chromone 4b).
The most informative cross peaks in the HMBC specꢀ
trum (DMSOꢀd6) are as follows: C(2)/H(3), CN/H(3),
C(1″)/H(3), C(1)/H(3), C(3´)/OH, C(1´)/OH, and
1
The H—15N HMBC spectrum of compound 4i conꢀ
tains three cross peaks with a lowꢀfield signal for the N
atom. These are produced by the azomethine Hc proton
(δ 8.97), the orthoꢀprotons of the 4ꢀbromophenyl substiꢀ
tuent, and the Hb proton (a very weak cross peak). The last
correlation is most likely due to the coupling through the
hydrogen bond (1hJN,H) rather than the longꢀrange spinꢀ
1
C(2´)/OH. The 2D H—15N HMQC spectrum of a mixꢀ
ture of Zꢀ3b and Eꢀ3b in DMSOꢀd6 exhibits only one
cross peak between the doublet for the NH proton (δH 12.3)
in Zꢀ3b and the signal for the N atom at δN 137.6
(in CDCl3, δN 140.2). Therefore, the N atom also belongs
to the Zꢀisomer (direct correlations with the Eꢀisomer
were not revealed in this experiment). The chemical
shift of the amine N atom in the Eꢀisomer (δN 132.1)
5
spin coupling with JN,H (see Ref. 20). All the signals in
1
the H and 13C NMR spectra of compound 4i were asꢀ
signed from 2D experiments (1H–13C HSQC and HMBC)
and the NOESY spectrum. The latter revealed positive
cross peaks between both NH2 protons and water because
of chemical exchange. Apparently, IntraHB in compound
4i is weakened and does not prevent the Hb proton from
participating in the exchange process.
1
was determined from the 2D H—15N HMBC data: its
signal shows a cross peak with the orthoꢀprotons of the
phenyl substituent (a similar cross peak is observed for
the Zꢀisomer).
3ꢀArylaminoꢀ2ꢀ(2ꢀhydroxyaroyl)acrylonitriles 3 obꢀ
tained from chromone 1 under the action of aromatic

Reactions of 3ꢀcyanochromones with amines
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 3, March, 2010
623
In the 1H NMR spectra of compounds 3 in CDCl3, the
major set of signals for the Zꢀisomer includes a broadened
doublet for the NH proton (δ 12.4—12.6) because of its
participation in the formation of a strong IntraHB to the
carbonyl O atom, a distinct doublet for the vinylic proton
(δ 7.9—8.1, 3J = 13.2—13.5 Hz), and a singlet for the
hydrogenꢀbonded phenolic hydroxyl (δ 11.2—11.7). The
minor set of signals (Eꢀisomer) consists of a broadened
doublet for the free NH proton (δ 8.1—8.2), a distinct
doublet for the =CH group (δ 8.7—8.8, 3J = 15.2 Hz), and
a singlet for the phenolic OH group bound by IntraHB
(δ 11.7—11.9). These data correlate well with the assumpꢀ
tion that compounds 3 exist in CDCl3 as equilibrium
mixtures of the Zꢀisomer (because of IntraHB, it is the
sꢀZ,sꢀEꢀrotamer about the bonds C(1)—C(2) and C(3)—N,
respectively) and the Eꢀisomer in the same conformation.
The considerable chemical shift difference (Δδ ~4.4 ppm)
for the NH proton in Zꢀ3 and Eꢀ3 is due to the cleavage
of IntraHB, which is inevitable for this isomerization.
The downfield shift of the signal for the =CH proton
(Δδ ~0.8 ppm) is associated with the deshielding effect of
the carbonyl group in the Eꢀisomer with the sꢀZꢀconforꢀ
mation with respect to the C(1)—C(2) bond (see Scheme 3,
Table 3).
concentration of the rotamer. When moving from Zꢀ3 to
Eꢀ3, the chemical shift of the signal for the =CH proton
in DMSOꢀd6 is shifted upfield by ~0.4 ppm (by 0.88 ppm
for compounds 3k,l containing the orthoꢀMe group in the
aniline residue)—in contrast to the solution in CDCl3, in
which the signal for this atom is shifted downfield—and
seems to be an average for the corresponding rotamers
sꢀZ,sꢀZ and sꢀE,sꢀZ in rapid equilibrium with each other
(see Scheme 3, Table 4).
As noted above, the aromatic protons were identified
incompletely because of the overlap of their signals; yet
some conclusions can be drawn. First, the 1H NMR specꢀ
tra of Zꢀ3 and Eꢀ3 in CDCl3 show the signals for the H(3)
and H(5) protons in the range expected for the phenol
fragment (δ 6.90—7.02). Along with other factors, this is
an important argument for openꢀchain amino enone 3.
In the case of the earlier proposed cyclic structure 5,
the corresponding signals would be shifted downfield
(δ 7.1—7.2). Second, the lowꢀfield signal for the H(6)
proton at δ 8.3—8.4 (R = H) and 8.1—8.2 (R = Me) in
CDCl3 confirms that the OH and C=O groups are bound
by IntraHB in both Zꢀ3 and Eꢀ3; as a result, the phenol
ring is coplanar with the enone fragment and the H(6)
proton is deshielded by the CN group. Third, in DMSOꢀd6,
the H(3) and H(5) protons resonate at δ 6.78—6.95 and
the H(4) and H(6) protons resonate at δ 7.2—7.4 (R = H)
and 7.1—7.2 (R = Me), as expected for the openꢀchain
forms Zꢀ3 and Eꢀ3. This is due to cleavage of the intramoꢀ
In DMSOꢀd6, the minor set of signals, except for
3k,l, includes a broadened doublet for the NH proton
(δ 12.3—12.7; the width of each component of the doublet
does not exceed 2.5 Hz), a distinct doublet for the =CH
3
...
group (δ 8.4—8.6, J = 13.5—13.6 Hz), and a singlet for
lecular hydrogen bond O—H O=C in this solvent and
the phenolic hydroxyl bound by InterHB (δ 9.9—10.4).
Thus, these signals relate to the IntraHBꢀstabilized
Zꢀisomer with the sꢀZ,sꢀEꢀconformation. The major set
of signals in this solvent includes three broadened singlets
in sufficiently narrow ranges (δ 7.7—8.1, 10.4—11.1, and
9.9—10.4). We assigned these signals to the vinylic proꢀ
ton, the NH protons bound by InterHB to DMSOꢀd6 molꢀ
ecules (the line width exceeds 20 Hz), and the phenolic
hydroxyl of the Eꢀisomer with the sꢀZꢀconformation about
the C(3)—N bond, respectively. The correct assignment
of the last signal to the OH proton is indirectly confirmed
by a noticeable influence of the substituent in position 5 of
the phenol residue on the chemical shift of this signal.
A rigorous proof is provided by the cross peaks between
the phenolic proton and the C(1´), C(2´), and C(3´) atꢀ
oms in the 2D HMBC spectrum of compound 3b. In so far
as the preferable form of βꢀoxo imines is amino enone
rather than imino enol (mainly because the hydrogen bond
NH...O=C is stronger than the bond OH...N=C),21—24 the
existence of acrylonitriles 3 in DMSOꢀd6 as imino enol 3´
is very unlikely. For rotamers about the C(3)—N bond,
the nonꢀcoplanarity of the phenol ring with the amino
enone residue. Fourth, in DMSOꢀd6, the H(2´) and H(6´)
protons of the aniline ring in Zꢀ3 are more strongly
deshielded than the corresponding protons in Eꢀ3. This
agrees with the assumption that Eꢀ3 exists as the
sꢀZꢀrotamer about the C(3)—N bond, in which the aryl
substituent is not coplanar, for steric reasons, with the
amino enone fragment and becomes less conjugated with
the delocalized system. In this respect, the most demonꢀ
strative is the isomer Eꢀ3e, in which the signal for the
pꢀtolyl substituent appears as a singlet at δ 7.19 (4 H).
The IR spectra of chromones 4a—p in pellets with KBr
show absorption bands at 3200—3240 (NH2 stretches),
1650—1660 (C=O stretches), and 1600—1610 cm–1 (C=C
stretches). The presence of the openꢀchain form 3 is manꢀ
ifested by a characteristic band of the cyano group at
2200—2206 cm–1
.
To sum up, the set of products in noncatalytic reacꢀ
tions of 3ꢀcyanochromones with aromatic amines in benꢀ
zene depends substantially on the substituent in position 6
of chromone and, to a less degree, on the substituents in
the aniline component. Baseꢀcatalyzed reactions of this
type yield 2ꢀaminoꢀ3ꢀ(aryl/alkylimino)methylchromones
as the sole products. 3ꢀCyanoꢀ6ꢀmethylchromone is the
most suitable reagent for the synthesis of intermediate acryꢀ
lonitriles as mixtures of their Zꢀ and Eꢀisomers.
3
the reported25—27 coupling constants are J = 13—14 Hz
(sꢀEꢀconformation) and 3J = 7—8 Hz (sꢀZꢀconformaꢀ
tion). The latter constant is not always detectable because
of intermolecular NH exchange, the exchange rate being
dependent on the amount of water in the solvent and the

624
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 3, March, 2010
Sosnovskikh et al.
J = 8.6 Hz); 7.72 (ddq, 1 H, H(7), J = 8.6 Hz, J = 2.2 Hz,
J = 0.6 Hz); 7.85 (dq, 1 H, H(5), J = 2.2 Hz, J = 0.6 Hz); 9.20
(s, 1 H, H(2)). 13C NMR (DMSOꢀd6), δ: 20.36 (Me), 100.75 (C(3)),
113.27 (CN), 118.63 (C(8)), 122.31 (C(4a)), 124.27 (C(5)),
136.55 (C(7)), 136.97 (C(6)), 153.63 (C(8a)), 165.16 (C(2)),
172.44 (C(4)).
Reactions of 3ꢀcyanochromones with amines. Procedure A.
A solution of chromone 1 (1.0 mmol) and an amine (1.0 mmol)
was refluxed in benzene (4 mL) for 4 h. The reaction mixture
was cooled and the precipitate that formed was filtered off,
washed with benzene, and dried.
Procedure B is similar but the reflux time was varied (see
Table 1).
Procedure C is similar with procedure A but two drops of
triethylamine were added.
Procedures A and C were used to obtain 2ꢀaminoꢀ3ꢀ(phenylꢀ
iminomethyl)chromone (4a), 2ꢀaminoꢀ6ꢀmethylꢀ3ꢀ(phenylꢀ
iminomethyl)chromone (4b), 2ꢀaminoꢀ6ꢀchloroꢀ3ꢀ(phenylꢀ
iminomethyl)chromone (4c), 2ꢀaminoꢀ3ꢀ(4ꢀtolyliminomethyl)ꢀ
Experimental
IR spectra were recorded on a PerkinꢀElmer Spectrum BXꢀ
II instrument (KBr pellets). 1H, 13C, and 15N NMR spectra were
recorded on a Bruker DRXꢀ400 spectrometer in DMSOꢀd6 or
CDCl3 (400.1, 100.6, and 40.5 MHz, respectively) with Me4Si
as the internal standard and with liquid ammonia as the external
standard.
The 1H NMR spectra of 2ꢀaminoꢀ3ꢀ(aryl/alkyliminomethyl)ꢀ
chromones 4a—p are given in Table 2. The H NMR spectra of
1
the Zꢀ and Eꢀisomers of 3ꢀanilinoꢀ2ꢀsalicyloylacrylonitriles 3 in
CDCl3 and DMSOꢀd6 are given in Tables 3 and 4. The yields,
melting points, elemental analysis data, and IR spectra of
chromones 4 are summarized in Table 5.
3ꢀCyanochromones 1 were prepared as described earlier.28
1
To identify the signals in the H and 13C NMR spectra of comꢀ
pound 3b, all signals for 3ꢀcyanoꢀ6ꢀmethylchromone were asꢀ
signed from 2D experiments (1H—13C HSQC and HMBC).
1H NMR (DMSOꢀd6), δ: 2.45 (s, 3 H, Me); 7.65 (d, 1 H, H(8),
Table 5. Physicochemical properties, elemental analysis data, and IR spectra of chromones 4a—p
Chromone Yield
(%)
M.p.
/°C
Molecular
formula
Found
Calculated
IR,
ν/cm–1
(%)
C
H
N
4aa
4b
4c
4db
4ec
4f
81
98
76
68
77
64
87
87
80
81
80
76
57
48
65
216—218
230—232
338—340
200—202
228—230
233—235
236—238
290—292
253—255
243—244
236—238
243—245
155—156
139—141
194—195
C16H12N2O2
72.85
72.72
73.56
73.37
64.10
64.33
73.22
73.37
74.12
73.95
69.26
69.38
70.25
70.12
62.06
62.11
55.86
56.00
67.70
67.92
73.86
73.95
74.40
74.49
73.10
73.37
74.23
73.95
67.50
67.81
4.40
4.58
5.33
5.07
3.71
3.71
5.18
5.07
5.35
5.52
4.56
4.79
4.98
5.23
3.64
3.99
3.35
3.23
4.13
4.18
5.47
5.52
6.06
5.92
4.85
5.07
5.54
5.52
5.83
6.13
10.48
10.60
10.28
10.07
9.47
3216, 3048, 1654,
1600, 1563, 1517
3203, 3070, 1650,
1608, 1565, 1512
3204, 3052, 1652,
1600, 1564, 1516
3210, 3047, 1656,
1605, 1562, 1518
3195, 3017, 1657,
1609, 1564, 1502
3197, 3037, 1656,
1607, 1564, 1501
3205, 3077, 1652,
1607, 1573, 1507
3190, 3015, 1649,
1598, 1564
3211, 3075, 1655,
1605, 1564, 1519
3185, 3042, 1614,
1575, 1554, 1510
3200, 1662, 1616,
1573, 1544
3197, 3007, 1656,
1608, 1563, 1508
3198, 1664, 1611,
1562
C
C
17H14N2O2
16H11ClN2O2
9.38
C17H14N2O2
C18H16N2O2
10.14
10.07
9.74
9.58
9.45
9.52
8.99
9.09
8.60
8.52
7.98
8.16
15.90
15.84
9.48
9.58
9.21
C
C
C
C
C
C
C
C
C
C
17H14N2O3
18H16N2O3
17H13ClN2O3
16H11BrN2O2
15H11N3O2
18H16N2O2
19H18N2O2
17H14N2O2
18H16N2O2
13H14N2O2
4g
4h
4i
4j
4k
4l
9.14
4m
4n
4o
10.09
10.07
9.72
9.58
12.12
12.17
3227, 1663, 1607,
1554
3237, 1665, 1612,
1566
3200, 1660, 1610,
1568
4pd
64
174—175
—
—
—
—
a Cf. Ref. 13: m.p. 210—214 °C.
b Cf. Ref. 12: m.p. 211 °C.
c Cf. Ref. 12: m.p. 210 °C.
d The product was isolated as a mixture with dimer 9 (6%).

Reactions of 3ꢀcyanochromones with amines
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 3, March, 2010
625
chromone (4d), 2ꢀaminoꢀ6ꢀmethylꢀ3ꢀ(4ꢀtolyliminomethyl)ꢀ
chromone (4e), 2ꢀaminoꢀ3ꢀ(4ꢀmethoxyphenyliminomethyl)ꢀ
chromone (4f), 2ꢀaminoꢀ3ꢀ(4ꢀmethoxyphenyliminomethyl)ꢀ6ꢀ
methylchromone (4g), 2ꢀaminoꢀ6ꢀchloroꢀ3ꢀ(4ꢀmethoxyphenylꢀ
iminomethyl)chromone (4h), 2ꢀaminoꢀ3ꢀ(4ꢀbromophenylimiꢀ
nomethyl)chromone (4i), 2ꢀaminoꢀ3ꢀ(2ꢀpyridyliminomethyl)ꢀ
chromone (4j), 2ꢀaminoꢀ3ꢀ(2,4ꢀdimethylphenyliminomethyl)ꢀ
chromone (4k), 2ꢀaminoꢀ3ꢀ(2,4ꢀdimethylphenyliminomethyl)ꢀ
6ꢀmethylchromone (4l), 2ꢀaminoꢀ3ꢀ(benzyliminomethyl)chroꢀ
mone (4m), 2ꢀaminoꢀ3ꢀ(phenethyliminomethyl)chromone (4n),
2ꢀaminoꢀ3ꢀ(isopropyliminomethyl)chromone (4o), and 2ꢀamiꢀ
noꢀ3ꢀbenzyliminomethylꢀ6ꢀmethylchromone (4p).
13. H. Hagen, G. Nilz, H. Walter, A. Landes, W. Freund, DE
Patent 4 039 281, 1992; Chem. Abstr., 1992, 117, 111473.
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This work was financially supported by the Russian
Foundation for Basic Research (Project No. 06ꢀ03ꢀ32388).
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2008, 46, 599.
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Received May 5, 2009;
in revised form August 31, 2009