A simple method for the synthesis of 5-substituted 2-cyanofurans

Article abstract of DOI:10.1023/A:1019544726068

A new method based on the Schmidt reaction was developed for the production of 5-R-2-cyanofurans from 5-R-furfurals.

Full text of DOI:10.1023/A:1019544726068

Chemistry of Heterocyclic Compounds, Vol. 38, No. 5, 2002
A SIMPLE METHOD FOR THE
SYNTHESIS OF 5-SUBSTITUTED
2-CYANOFURANS
P. A. Pavlov
A new method based on the Schmidt reaction was developed for the production of 5-R-2-cyanofurans
from 5-R-furfurals.
Keywords: hydrazoic acid, nitrile, furancarbaldehyde, cyanofuran, 2-cyanofurans.
The Schmidt reaction [1] differs favorably from other methods for the production of nitriles, since it is
conducted in one stage using readily obtainable initial reagents and provides a simple method for treatment of
the reaction mixture. However, with all its merits it has been considered unsuitable for the production of nitriles
from aldehydes of the furan series on account of the need to use high concentrations of strong mineral acids or
classical Lewis acids, which lead to resinification of the reaction mass as a result of the high sensitivity of furan
compounds to acids.
In the methods we developed for the synthesis of 5-R-2-cyanofurans benzene solutions of hydrazoic acid
and a catalytic system containing perchloric acid and anhydrous magnesium perchlorate in various ratios were
used [2-5]. The procedure can be simplified by avoiding the presence of the strong mineral acid (HClO4) and the
poorly available magnesium perchlorate in the reaction mixture [6]. Here the yield of the targeted products is
increased by 5-7% (in the case of 2-cyano-5-nitrofuran the yield is practically quantitative), the safety of the
process is increased on account of the absence of the perchloric acid oxidizing agent and benzene, and the
reaction becomes more controllable with uniform release of gaseous nitrogen. The effect is achieved by
replacing the benzene solutions of hydrazoic acid by chloroform solutions and using the readily available
hydrated magnesium perchlorate Mg(ClO4)2·(2-2.5)H2O (anhydrone) as catalyst.
HN3
+
H2O + N2
Mg(ClO4)2· 2.5 H2O
R
CHO
O
R
CN
O
1a–u
2a–u
The identities of R and the physicochemical and spectral characteristics of compounds 2a-u are given in
Tables 1 and 2.
The use of anhydrone as catalyst is based on its strong dehydrating power and characteristics that are in
the opinion of a series of authors typical of "soft" Lewis acids [6, 7]. It can be concluded on the basis of
experimental data on the synthesis of 5-R-2-cyanofurans that anhydrone (hydrated magnesium perchlorate) is
not inferior to the anhydrous salt in its catalytic characteristics.
__________________________________________________________________________________________
Kuban State University, Krasnodar, Russia; e-mail: NMR_ESR@chem.kubsu.ru. Translated from
Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 603-608, May, 2002. Original article submitted October
24, 1999; revision submitted December 21, 2000.
524
0009-3122/02/3805-0524$27.00©2002 Plenum Publishing Corporation

TABLE 1. The Physicochemical Characteristics of 5-R-2-Cyanofurans 2a-u
Found, %
——————
Com-
Empirical
formula
bp, °С
20
20
Yield, %
Calculated, %
R
7
nD
d4
pound
(mm Hg)/mp, °С
C
3
H
4
N
5
1
2
6
147
8
1.4797
1.4849
—
9
10
84
91
90
94
88
85
96
96
85
79
81
C5H3NO
64.44
64.52
3.16
3.25
14.91
15.05
H
1.0850
1.0398
—
2a
2b
2c
2d
2e
2f
C6H5NO
67.36
4.58
13.00
74-76 (33)
73
Me
67.28
4.71
13.08
C11H7NO
C13H7NO
C5H2BrNO
C5H2INO
78.17
78.09
4.07
4.17
—
Ph
80.91
3.54
7.23
7.25
76
PhC≡C
Br
—
—
80.82
3.65
35.03
34.92
1.20
1.17
8.17
78 (14)
36-37
65
1.5408
—
1.8976
—
8.14
27.50
0.87
6.29
6.40
I
27.42
0.92
C5H2N2O3
C6H4CINO
C11H6N2O3
C12H9NO2
C11H6CINO2
43.63
43.49
1.40
1.46
20.18
NO2
ClCH2
—
—
2g
2h
2i
20.29
51.15
2.85
9.79
9.89
93 (4)
171
1.5260
—
1.3614
—
50.91
2.85
61.84
61.69
2.74
2.82
13.07
4-O2NC6H4
4-MeC6H4O
4-ClC6H4O
13.08
72.49
4.51
6.92
7.03
155 (4)
43
1.5563
—
1.2851
—
2j
72.35
4.55
60.37
60.16
2.69
2.75
6.30
2k
6.38

TABLE 1 (continued)
1
2
3
4
5
6
7
8
9
10
C6H5NOS
52.06
51.78
3.54
3.62
10.05
10.06
111 (25)
161 (8)
126
MeS
1.5622
1.5178
—
1.3644
1.3453
—
79
78
93
92
89
2l
C9H9NO3S
C11H5N3O5S
C10H4N2O2S
C9H5NO3S
51.42
4.19
6.65
EtOOCCH2S
2m
2n
2o
2p
51.17
4.29
6.63
45.51
45.37
1.68
1.73
14.32
14.43
2,4-(O2N)2C6H3S
5-Cyano-2-furylthio
55.70
1.80
12.83
63
—
—
55.55
1.86
12.96
52.68
52.17
1.98
2.43
6.71
6.76
82
5-Oxo-2,5-dihydro-
2-furylthio
—
—
C12H7NO2S
C12H6BrNO2S
C10H5NO3S
C11H7NO3S
C12H9NO3S
63.01
3.00
6.12
100
113
76
PhCOS
—
—
—
—
—
—
—
—
—
—
90
91
90
98
98
2q
2r
2s
2t
62.87
3.08
6.11
46.90
46.77
1.91
1.96
4.45
4.55
3-BrC6H4COS
2-Furoylthio
PhSO2
55.07
2.22
6.32
54.79
2.30
6.39
56.89
56.65
2.93
3.03
5.95
6.01
81
58.58
3.60
5.61
121
4-MeC6H4SO2
2u
58.29
3.67
5.66

TABLE 2. The Spectral Characteristics of 5-Substituted 2-Cyanofurans 2a-u
IR spectrum, cm-1
UV spectrum,
1Н NMR spectrum
Compound
λmax, nm
(log ε)
δ, ppm
H(4) (d)
6
SSCC, J, Hz
other SSCC
νCN
other bands
4
H(3) (d)
5
HR
7
J3,4
8
1
2
3
9
240 (3.97)
2200
7.33
6.63 (dd)
7.82 (d)
3.7
0.75 (J3,5);
2a
ν
ν
3110 ( CH); 1575 (
)
cycl
1.8 (J4,5
)
ν
ν
ν
250 (4.17)
2200
2210
3130 ( CH); 1580 (
)
)
7.15
7.01
6.23
6.60
2.32 (s)
7.47 (m)
4.0
4.0
—
2b
2c
cycl
ν
210 (4.27),
3130 ( CH); 1575 (
cycl
—
293 (4.37)
ν
ν
205 (4.36),
303 (4.83),
318 (4.75)
255 (4.13)
258 (4.48)
2200
3115 ( CH); 1573 (
)
cycl
6.96
6.85
7.33 (m)
4.0
2d
—
ν
ν
2205
2200
3118 ( CH); 1575 (
)
cycl
7.28
6.92
7.65
6.61
—
—
—
4.0
4.0
—
—
2e
2f
ν
3112 (
1580 (
1505 (
)
CH
ν
ν
)
cycl
290 (4.32)
248 (4.43)
2244
2220
2231
)
7.60
6.99
7.65
7.71
6.45
7.47
3.9
4.0
4.0
—
—
2g
2h
2i
NO2
—
ν
ν
ν
205 (4.08),
1515; 1345 (
1230; 1260 (
1230; 1260 (
)
8.30 (d, m-HAr);
9.0 (Jo,m
)
NO2
333 (4.66)
8.03 (d, o-HAr
)
217 (4.12),
262 (4.52)
2205
2205
)
6.80
6.93
5.25
5.46
7.03 (d, m-HAr);
8.80 (d, o-HAr
7.27 (d, m-HAr);
6.97 (d, o-HAr
4.0
4.0
10.0 (Jo,m)
2j
C–O–C
C–O–C
)
222 (4.09),
)
9.0 (Jo,m)
2k
260 (4.55)
)

TABLE 2 (continued)
1
2
3
4
5
6
7
8
9
237 (3.94),
285 (4.46)
2220
2205
—
6.98
7.08
6.28
6.54
2.45 (s)
4.0
4.0
—
2l
243 (4.09),
—
1.02 (t, CH3);
7.0
2m
2.79 (4.24)
(q, CH2–CH3);
3.51 (s, CH2–S–)
ν
232 (3.87),
271 (4.41)
2205
2220
2205
1365, 1340, 1535 (
)
7.00
7.00
7.38
6.72
6.69
6.88
7.60 (m)
4.0
4.0
4.0
—
—
2n
2o
2p
NO2
244 (4.40),
—
—
267 (4.53)
6.10 (dd, Н-4');
6.40 (t, H-2');
7.67 (dd, H-3')
1.75 (J2'3'),
2.00 (J2'4'),
ν
212 (4.13),
255 (4.19),
333 (3.83)
1740, 1780 (
)
C=O
5.50 (J3'4'
)
ν
205 (4.12),
257 (4.39),
337 (3.75)
205 (4.08),
256 (3.87),
333 (3.69)
212 (4.19),
248 (4.41),
329 (3.73)
2220
2220
2220
1680 (
1700 (
1690 (
)
)
)
7.09
6.55
7.10
6.78
6.01
6.79
7.68 (m)
3.7
4.0
—
2q
2r
2s
C=O
C=O
C=O
ν
ν
6.60 (m)
—
6.55 (q, H-4');
7.44 (d, H-3');
7.58 (d, H-5')
3.85
3.80 (J3'4'),
2.0 (J4'5'),
0.7 (J3'5'
)
—
222 (4.35),
256 (4.60)
2205
2205
1130, 1150,
7.44
7.36
7.55
7.51
7.85 (m)
4.0
4.0
2t
ν
1340 (
)
SO2
229 (4.39),
1130, 1155,
2.38 (s, CH3);
7.40 (d, m-H);
7.85 (d, o-H)
8.00 (Jo,m)
2u
259 (4.55)
ν
1330 (
)
SO2

EXPERIMENTAL
The IR spectra of the synthesized compounds were recorded in Vaseline oil on a UR-20 spectrometer.
1
The UV spectra were recorded in ethanol on a Specord UV-vis spectrometer. The H NMR spectra were
obtained on a Tesla BS-467 spectrometer (60 MHz) in hexadeuteroacetone for compounds 2a,b,e,g,j,k and in
carbon tetrachloride for compounds 2c,f,h,i,e,u with HMDS as internal standard. The purity of the compounds
was monitored by TLC (Silufol UV-254, ethanol–toluene, 3:20).
The solutions of hydrazoic acid in chloroform were prepared by the method described in [1]; the
anhydrone was of pure grade supplied by the Altaikhimprom company.
2-Furonitrile (2a), 5-Methyl-2-furonitrile (2b), 5-Phenyl-2-furonitrile (2c), 5-Phenylethynyl-2-
furonitrile (2d), 5-Bromo-2-furonitrile (2e), 5-Iodo-2-furonitrile (2f), 5-Nitro-2-furonitrile (2g),
5-Chloromethyl-2-furonitrile (2h), 5-(4-Nitrophenyl)-2-furonitrile (2i), 5-(4-Methylphenoxy)-2-furonitrile
(2j), 5-(4-Chlorophenoxy)-2-furonitrile (2k), 5-Methylthio-2-furonitrile (2l), Ethyl S-(5-Cyano-2-
furyl)thioglycolate (2m), 5-(2,4-Dinitrophenylthio)-2-furonitrile (2n), 5-(5-Cyano-2-furylthio)-2-
furonitrile (2o), 5-(5-Oxo-2,5-dihydro-2-furylthio)-2-furonitrile (2p), S-(5-Cyano-2-furyl) Thiobenzoate
(2q), S-(5-Cyano-2-furyl) 3-Bromothiobenzoate (2r), S-(5-Cyano-2-furyl) 2-Thiofuroate (2s),
5-Phenylsulfonyl-2-furonitrile (2t), 5-(4-Methylphenylsulfonyl)-2-furonitrile (2u) (General Procedure). In
a three-necked flask with a mechanical stirrer and a reflux condenser to the initial furfural (0.1 mol) and a
solution of hydrazoic acid in chloroform (0.11 mol) anhydrone (25.0 g, 0.1 mol) was added. The release of
gaseous nitrogen began after 5 min. The flow of nitrogen became strongest after 10-15 min. When the release of
nitrogen had stopped the reaction mixture was brought to boiling point and kept for 2 h. The contents of the
flask were cooled to room temperature, water was added, and the mixture was filtered. The organic layer was
washed twice with water, dried with anhydrous sodium sulfate, and evaporated. The residue was distilled under
vacuum or recrystallized from ethanol. Compound 2g was recrystallized from a mixture of chloroform and
hexane, and compound 2p from carbon tetrachloride.
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1.
2.
G. Wolf, in: Organic Reactions [in Russian], Vol. 3, Izd. Inostr. Lit., Moscow (1951), p. 293.
P. A. Pavlov and V. G. Kul'nevich, USSR Inventor's Certificate No. 1130566; Byull. Izobr., No. 47, 81
(1984).
3.
P. A. Pavlov, in: Chemistry and Technology of Furan Compounds [in Russian], Mezhvuz. Sb. Nauch.
Tr. Krasnodar. Politekh. In-ta, Krasnodar (1983), p. 33.
4.
5.
6.
P. A. Pavlov and V. G. Kulnevich, in: Abstracts of V Intern. Symp. of Furan Chem., Riga (1988), p. 68.
P. A. Pavlov and V. G. Kul'nevich, Khim. Geterotsikl. Soedin., 181 (1986).
I. L. Knunyants (Ed.), Chemical Encyclopedia [in Russian], Vol. 2, Sovetskaya Entsiklopediya, Moscow
(1990), p. 628.
I. L. Knunyants (Ed.), Chemical Encyclopedia [in Russian], Vol. 3, Bol'shaya Russkaya Entsiklopediya,
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529