Reduction of derivatives of α-arylidene-α-(2-thiazolyl)acetonitrile with lithium aluminum hydride

Article abstract of DOI:10.1007/s10593-005-0126-3

The action of lithium aluminum hydride on derivatives of α-arylidene-α-(2-thiazolyl)acetonitrile in absolute ether leads to reduction of the nitrile group without affecting the double bond conjugated with it. The reaction products are the corresponding su

Full text of DOI:10.1007/s10593-005-0126-3

Chemistry of Heterocyclic Compounds, Vol. 41, No. 2, 2005
REDUCTION OF DERIVATIVES OF
α-ARYLIDENE-α-(2-THIAZOLYL)ACETONITRILE
WITH LITHIUM ALUMINUM HYDRIDE
A. A. Zubarev, V. K. Zav'yalova, and V. P. Litvinov
The action of lithium aluminum hydride on derivatives of α-arylidene-α-(2-thiazolyl)acetonitrile in
absolute ether leads to reduction of the nitrile group without affecting the double bond conjugated with
it. The reaction products are the corresponding substituted allylamines.
Keywords: α-arylidene-α-(2-thiazolyl)acetonitriles, β-arylidene-β-(2-thiazolyl)ethylamines, lithium
aluminum hydride, reduction.
Lithium aluminum hydride is widely used in synthetic practice for the reduction of the nitrile group. In
the case of α,β-unsaturated nitriles the direction of the reaction depends strongly on the structure of the
compound and the conditions of conducting the synthesis [1]. In many cases hydrogenation of only the double
bond occurs without affecting the nitrile group [2] or simultaneous reduction of both functions occurs [3]. Esters
of arylidenecyanoacetic acid are reduced with lithium aluminum hydride even in the cold to the corresponding 2-
(arylmethyl)-3-aminopropanols [4]. Only the double bond is reduced in substituted esters of 2-cyanocrotonic and
2-cyanoacrylic acids, and the nitrile and carbalkoxy groups are not affected [5]. The behavior of certain
compounds of the stilbene series is of interest. For example, α,β-diphenyl-β-methoxyacrylonitrile undergoes
reduction of the double bond with fission of the methoxy group with the formation of α-cyano-α,β-
diphenylethane [6].
Ph
Ph
R1COCl
3a,b
N
N
LiAlH4
Et2O
CN
CHR
NH2
S
S
CHR
1a,b
2a,b
Ph
N
O
N
H
S
R1
CHR
4a,b
1a, 2a, 4a,b R = 2-ClC6H4; 1b, 2b R = 2-furyl, 3, 4, a R1 = 2-Me-3-O2NC6H3; b R1 = 4-ClC6H4
__________________________________________________________________________________________
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 119991; e-mail:
vpl@ioc.ac.ru. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 221-224, February, 2005.
Original article submitted July 10, 2002.
192
0009-3122/05/4102-0192©2005 Springer Science+Business Media, Inc.

The reduction of α,α'-dicyano-4,4'-dimethoxystilbene with lithium aluminum hydride in THF solution
leads to 2,3-di(4-methoxyphenyl)propylamine [7]. There is therefore significant interest in the study of the
reduction of derivatives of α-arylidene-α-(2-thiazolyl)acetonitrile having a structure similar to the structure of
the stilbenes mentioned above.
We have studied the interaction of LiAlH4 with derivatives of α-arylidene-α-(2-thiazolyl)acetonitrile,
the reduction products of which may be of interest both as new biologically active compounds and as synthons
in organic synthesis.
It was found that on reduction of derivatives of α-arylidene-α-(2-thiazolyl)-acetonitrile 1a,b with
LiAlH4 in ether with subsequent treatment with water the corresponding β-arylidene-β-(2-thiazolyl)ethylamines
2a,b were formed in 55-70% yield (see Scheme). The structure of amines 2a,b, which form crystals of a bright
yellow color with sharp melting points, was confirmed by data of IR, 1H NMR, and mass spectra. The signal of
the CN group (2200 cm-1) was absent in the IR spectra, there were absorption bands for an NH2 group
1
(3450-3470 cm-1) and an intense absorption band for the C=C group (1630 cm-1). In the H NMR spectra of
amines 2a,b a singlet was observed for the methylene group at 3.6-3.8 and for the alkene fragment at
6.5-6.7 ppm.
Amine 2a is readily acylated by carboxylic acid chlorides 3a,b in the presence of an equimolar amount
of triethylamine in acetonitrile with the formation of amides 4a,b. An intense absorption band was present in
1
their IR spectra for the C=O group (1680 cm-1), and in the H NMR spectra a doublet was observed for the NH
group at 12.6-12.75 ppm (Table 2).
EXPERIMENTAL
Melting points were determined on a Kofler block. The IR spectra were recorded on a Specord M 80
1
spectrophotometer in KBr disks, and H NMR spectra on a Bruker WM 250 (250 MHz) spectrometer in
DMSO-d6, internal standard was the signal of the solvent (δH = 2.50 ppm). Elemental analysis was carried out on
a Perkin-Elmer 2400 instrument.
β-Arylidene-β-(2-thiazolyl)ethylamines (2a,b). A solution of thiazole 1a,b (3 mmol) in abs. Et2O
(50 ml) was added dropwise with stirring during 20 min to a suspension of LiAlH4 (6 mmol) in abs. Et2O
(50 ml). The suspension was stirred for 1 h at the boiling point, cooled, and water (100 ml) was added dropwise.
The organic layer was separated, and the aqueous phase with the solid was extracted with Et2O (2 × 25 ml). The
combined organic phase was dried over MgSO4, and evaporated. The residue was recrystallized from hexane.
TABLE 1. Characteristics of Compounds 2a,b and 4a,b
Found, %
——————
Calculated, %
Com-
pound
Empirical
formula
mp, °С
(solvent)
Yield, %
69
C
H
Cl
N
S
2a
2b
4a
4b
C18H15ClN2S
C16H14N2OS
66.03
66.15
4.69
4.63
10.59
10.85
8.73
8.57
9.96
9.81
101-103
(C6H14)
68.31
68.06
4.87
5.00
—
9.81
9.92
11.55
11.36
80-82
(C6H14)
55
26
62
C26H20ClN3O3S
C25H18Cl2N2OS
63.45
63.73
4.20
4.11
7.11
7.24
8.47
8.58
6.72
6.54
86-87
(AcOEt)
64.69
64.52
3.84
3.90
15.05
15.24
5.89
6.02
7.07
6.89
162-163
(AcOEt)
193

TABLE 2. Spectral Characteristics of Compounds 2a,b and 4a,b
IR spectrum,
Com-
pound
Mass spectrum,
m/z (I, %)
1H NMR spectrum, δ, ppm (J, Hz)
ν, cm-1
2a
3456 (NH2),
3112 (CH=C),
1632 (C=C)
326 [M]+ (87),
309 (13),
291 (100),
274 (27), 215 (18),
155 (31), 145 (32),
134 (99), 102 (34),
89 (77), 77 (34)
3.82 (2H, s, CH2); 6.47 (3H, m, C=CH, NH2);
7.17 (3H, m, HPh-3,4,5); 7.32 (2H, m,
2-ClC6H4 (H-4,5)); 7.41 (3H, m,
2-ClC6H4 (H-3,6), thyazole);
7.87 (2H, d, J = 7.9, HPh-2,6)
2b
4a
3464 (NH2),
3112 (CH=C),
1628 (C=C)
3.62 (2H, s, CH2); 6.12 (1H, m, (H-4) furan);
6.34 (1H, d, J = 3.7, (H-3) furan); 6.75 (1H, s,
CH=C); 7.3-7.5 (4H, m, HPh-3,4,5,
(H-5 furan)); 7.66 (1H, s, thyazole); 7.9 (2H,
d, J = 7.9, HPh-2,6)
—
3440 (NH), 3072 489 [M]+ (42),
(CH=C),
1680 (C=O),
1632 (C=C)
2.65 (3H, s, СH3); 4.01 (2H, br. s, CH2);
7.24 (1H, m, 2-ClC6H4 (H-5)); 7.26-7.30 (4H,
m, HPh-3,4,5, 2-ClC6H4 (H-4));
7.32-7.37 (2H, m, 2-ClC6H4 (H-3), CH=C);
7.4 (1H, s, thyazole); 7.46 (2H, m,
2-ClC6H4 (H-6), 2-СH3-3-NO2C6H3 (H-5));
7.58 (2H, d, J = 7.9, HPh-2,6); 7.88 (1H, d,
J = 7.7, 2-СH3-3-NO2C6H3 (H-6)); 7.98 (1H, d,
J = 8.2, 2-СH3-3-NO2C6H3 (H-4));
327 (25), 325 (49),
289 (56), 262 (23),
187 (18), 164 (97),
134 (58), 125 (21),
118 (64), 90 (100)
12.75 (1H, d, J = 5.6, NH)
4b
3464 (NH),
464 [M]+ (16),
429 (5), 325 (22),
289 (18),
4.01 (2H, br. s, CH2); 7.22-7.35 (6H, m,
C=CH, o-ClC6H4 (H-4,5), HPh-3,4,5);
7.4 (1H, m, o-ClC6H4 (H-3));
3064 (CH=C),
1680 (C=O),
1636 (C=C)
139 (100), 125 (6),
111 (46), 102 (8),
91 (26), 75 (19),
51 (6)
7.49 (2H, m, п-ClC6H4CO (H-3,5));
7.61 (2-H, m, HPh-2,6); 7.69 (2H, m,
п-ClC6H4CO (H-2,6)); 7.78 (1H, d, J = 7.6,
o-ClC6H4 (H-6)); 7.9 (1H, s, thyazole);
12.58 (1H, d, J = 5.6, CONH)
Amides of β-Methylidene-β-(2-thiazolyl)ethylamines (4a,b). Triethylamine (1 mmol) and carboxylic
acid chlorides 3a,b were added to a suspension of amine 2a (1 mmol) in MeCN (5 ml). The mixture obtained
was heated to boiling, cooled, and left for 24 h at 20°C. The reaction mixture was diluted with water (30 ml),
acidified with aqueous 3% HCl solution, and extracted with chloroform (3 × 15 ml). The organic phase was
dried over MgSO4, and evaporated. The residue was recrystallized from ethyl acetate.
The work was carried out with the financial support of the Russian Fund for Fundamental Investigations
(Project No. 02-03-32063).
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