Heterocyclic syntheses on the basis of arylation products of unsaturated compounds: X. 3-aryl-2-chloropropanals as reagents for the synthesis of 2-amino-1,3-thiazole derivatives

Article abstract of DOI:10.1023/B:RUJO.0000034976.75646.85

Meerwein reaction of arenediazonium chlorides with acrolein gave 3-aryl-2-chloropropanals which were brought into cyclocondensation with thiourea. The resulting 2-amino-5-benzyl-1,3-thiazoles were acylated with carboxylic acid chlorides and phthalic anhydride to afford, respectively, 2-acylamino-5-benzyl-1,3-thiazoles and N-(5-benzyl-1,3-thiazol-2-yl) phthalimides.

Full text of DOI:10.1023/B:RUJO.0000034976.75646.85

Russian Journal of Organic Chemistry, Vol. 40, No. 3, 2004, pp. 383–389. Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 3, 2004,
pp. 412–417.
Original Russian Text Copyright © 2004 by Obushak, Matiichuk, Vasylyshin, Ostapyuk.
Heterocyclic Syntheses on the Basis
of Arylation Products of Unsaturated Compounds:
X.* 3-Aryl-2-chloropropanals as Reagents for the Synthesis
of 2-Amino-1,3-thiazole Derivatives
N. D. Obushak, V. S. Matiichuk, R. Ya. Vasylyshin, and Yu. V. Ostapyuk
Ivan Franko L’viv National University, ul. Kirilla i Mefodiya 6, L’viv, 79005 Ukraine
e-mail: obushak@in.lviv.ua
Received November 6, 2002
Abstract—Meerwein reaction of arenediazonium chlorides with acrolein gave 3-aryl-2-chloropropanals which
were brought into cyclocondensation with thiourea. The resulting 2-amino-5-benzyl-1,3-thiazoles were
acylated with carboxylic acid chlorides and phthalic anhydride to afford, respectively, 2-acylamino-5-benzyl-
1,3-thiazoles and N-(5-benzyl-1,3-thiazol-2-yl)phthalimides.
Arylation of unsaturated compounds with arene-
diazonium salts according to Meerwein provides
a convenient method for the synthesis of polyfunc-
tional compounds [2–8]. Numerous examples of pur-
poseful utilization in organic synthesis of products
obtained by these reactions have been reported [8, 9].
In the preceding communications of this series we
demonstrated the potential of such compounds for the
synthesis of heterocycles.
products are often formed instead of the desired
haloarylation products [4–8]; also, the available data
are insufficient to draw some conclusions and practical
recommendations. A procedure for the preparation of
2-chloro(bromo)-3-phenylpropanals was reported in
[12, 13], but it received no further development in later
studies [8]. An attempt was made to extend the scope
of this reaction; however, 3-aryl-2-chloropropanals
were obtained in poor yields [14]. Therefore, elabora-
tion of a preparative procedure for chloroarylation of
acrolein seems to be important, for it would open
a simple synthetic route to α-chloro-substituted alde-
hydes as reagents for heterocyclizations.
Scheme 1.
R2
R2
Cu2+
–N2
+
R1
R3
R1
R3
ArN2 Hlg–
+
Hlg
In the present work we examined the reaction of
arenediazonium salts with acrolein and found con-
ditions for the preparation of α-chloro aldehydes IIa–
IIm in moderate yields (Scheme 2; see table), which
may be regarded as a good result for such reactions
[4–8]. The first results were reported in [15]. The reac-
tions of arenediazonium chlorides Ia–Im with acrolein
were carried out in aqueous acetone in the presence of
CuCl2 as catalyst. The yields of the products strongly
depend on the acidity of the medium. The best yields
of aldehydes IIa–IId from toluene- and methoxy-
benzenediazonium chlorides Ia–Id were obtained in
a nearly neutral medium. Diazonium salts having
electron-acceptor substituents in the aromatic ring
successfully react with acrolein in acidic medium.
Here, contrary to published data [14], the yields of
O
Ar
O
R1, R2, R3 = Alk, Ar.
Classical reagents for cyclizations are α-halo-
carbonyl compounds. Unlike α-halo ketones, the series
of α-halo aldehydes available for the synthesis of
heterocycles is strongly limited [10, 11] due to dif-
ficulties in their preparation. From the synthetic view-
point, an attractive procedure for the preparation of
α-halo aldehydes may be that involving the Meerwein
reaction according to Scheme 1. However, α,β-un-
saturated carbonyl compounds can react with arene-
diazonium salt along different pathways, and arylation
* For communication IX, see [1].
1070-4280/04/4003-0383 © 2004 MAIK “Nauka/Interperiodica”

OBUSHAK et al.
384
Scheme 2.
+
N2 Cl–
CHO
CuCl2
O
R
+
R
Cl
Ia–Im
IIa–IIm
I, II, R = 3-Me (a), 4-Me (b), 4-MeO (c), 3-Me-4-Cl (d), 4-F (e), 4-Cl (f), 4-Br (g), 3-CF3 (h), 2,3-Cl2 (i), 2,4-Cl2 (j), 2,5-Cl2 (k),
3,4-Cl2 (l), 4-FCH2S (m).
compounds IIe–IIm were not lower. However, it is
advisable to perform the synthesis in a two-phase
system (rather than in aqueous acetone) using an
aqueous solution of diazonium salt I and CuCl2–
acrolein or a solution of acrolein in benzene. Addition
of acetone reduces the yield of aldehydes IIe–IIl and
favors formation of tarry products, presumably via side
aldol condensation processes. The latter were likely to
be responsible for the poor yields of 3-aryl-2-chloro-
propanals in [14]. Our attempts to avoid tarring by
reacting acrolein with diazonium salts having electron-
acceptor substituents in neutral medium were unsuc-
cessful: as a result, the contribution of side trans-
formations of diazonium salts increased. When the
reactions were carried out in a two-phase system, the
fraction of tarry product was considerably reduced, and
the procedure for isolation of compounds IIe–IIm was
more facile.
salts. The proposed procedure is much more advan-
tageous than the other methods for the preparation of
α-chloro aldehydes: it utilizes accessible initial react-
ants and is simple to perform.
Aldehydes IIa–IIm were subjected to hetero-
cyclization with thiourea on heating in alcohol
(Scheme 3). The reaction was not accompanied by
elimination of HCl with formation of substituted
cinnamaldehydes, and the corresponding 2-amino-5-
benzyl-1,3-thiazoles IIIa–IIIm were obtained in high
yields. The cyclization can also be effected in other
solvents. Compounds IIIa–IIIm were isolated by
treatment of aqueous solutions of the respective hydro-
chlorides with bases. Thiazoles IIIa–IIIm are readily
soluble in DMF, DMSO, alcohol, and dioxane, and
some products, in benzene and toluene.
Aldehydes IIa–IIm were also brought into reaction
with acylthioureas IV. However, these reactions
resulted in formation of mixtures of products, and
products Va–Vo were difficult to isolate. Therefore,
Thus we have shown that chloroarylation of ac-
rolein is a general reaction for different diazonium
Yields, boiling points, refractive indices, C=O stretching vibration frequencies, and elemental analyses of 3-aryl-2-
chloropropanals IIa–IIm
Comp.
no.
bp, °C
(3 mm)
IR spectrum,
Yield, %
nD20
Found Cl, %
Formula
Calculated Cl, %
ν(C=O), cm–1
42
39
30
44
42
43
41
49
49
45
46
56
42
105
106
110
119
100
115
172
110
165
169
170
178
190
1.5370
1.5382
1.5469
1.5378
1.5320
1.5518
1.5801
1.5622
1.5722
1.5752
1.5790
1.5779
1.6120
1706
1706
1705
1707
1709
1705
1706
1717
1711
1710
1708
1709
1710
19.28
19.20
17.66
32.30
19.04
35.01
a46.30a
15.10
44.45
44.69
44.57
44.50
14.03
C10H11ClO
C10H11ClO
C10H11ClO2
C10H10Cl2O
C9H8ClFO
C9H8Cl2O
C9H8BrClO
C10H8ClF3O
C9H7Cl3O
C9H7Cl3O
C9H7Cl3O
C9H7Cl3O
C10H9ClF2OS
19.41
19.41
17.85
32.66
19.00
34.92
a 46.61a
14.98
44.78
44.78
44.78
44.78
14.14
IIa
IIb
IIc
IId
IIe
IIf
IIg
IIh
IIi
IIj
IIk
IIl
IIm
a
Cl + Br.
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HETEROCYCLIC SYNTHESES ON THE BASIS OF ARYLATION PRODUCTS ... X.
385
Scheme 3.
N
N
H2NC(S)NH2
B
IIa–IIm
R
R
NH2 ·HCl
NH2
S
S
IIIa–IIIm
this procedure for the synthesis of 2-acylamino-5-
benzyl-1,3-thiazoles V (method b) cannot be regarded
as preparative (Scheme 4). An alternative route in-
volves acylation of aminothiazoles III (method a). The
latter were treated with aliphatic and aromatic acid
chlorides and substituted cinnamoyl chlorides. In all
cases, the acylation occurred at a high rate and with
high selectivity at the exocyclic nitrogen atom. Amino-
thiazoles III were also acylated with phthalic
anhydride. As a result, N-substituted phthalimides
VIa–VIg were isolated in high yields. This reaction
was also performed with aminothiazoles IIIn (R =
2-Cl) and IIIo (R = 3-NO2) which were described by
us previously [15].
chemical shifts were measured relative to the solvent
signal (DMSO, δ 2.50 ppm). The IR spectra were
obtained on a Specord 75IR spectrometer.
3-Aryl-2-chloropropanals IIa–IIm (general proce-
dure). A three-necked flask equipped with a stirrer,
a dropping funnel, and a gas-outlet tube (attached to
a bubble counter) was charged with 0.2 mol (13.5 ml)
of acrolein, 10 g of CuCl2·2H2O, and 50 ml of acetone
(in the synthesis of IIa–IId) or 50 ml of benzene
(in the synthesis of IIe–IIm). A cold aqueous solution
of arenediazonium chloride Ia–Im (prepared by di-
azotization of 0.2 mol of the corresponding aromatic
amine) was added dropwise under vigorous stirring. In
the synthesis of aldehydes IIa–IId, the diazonium salt
was preliminarily neutralized with NaHCO3 to pH 6–7,
and 2 g of MgO was added to the mixture. The
temperature was maintained within 10–30°C. When
the reaction was complete, the organic layer was
separated, and the aqueous layer was extracted with
chloroform. The extract was combined with the
organic phase, dried over MgSO4, and evaporated, and
the residue was distilled under reduced pressure. The
yields, boiling points, refractive indices, C=O
stretching vibration frequencies, and elemental
analyses of 3-aryl-2-chloropropenals IIa–IIm are
given in table.
Thus, the results of our study made 3-aryl-2-chloro-
propanal accessible. These compounds were used to
synthesize poorly studied [16] 2-amino-5-benzyl-1,3-
thiazoles which attract interest as reagents for organic
synthesis.
EXPERIMENTAL
1
The H NMR spectra were recorded from solutions
in DMSO-d6 on Bruker instruments operating at 400
(IIId, IIIm, VIb–VIf), 300 (IIIa–IIIc, IIIe–IIIl,
Va–Vg, Vi–Vo), and 200 MHz (Vh, VIa, VIg). The
Scheme 4.
R1CONHC(S)NH2 (IV)
R1COCl
N
R
II
NHCOR1
S
Va–Vo
O
III
O
O
N
N
O
R
S
O
VIa–VIg
V, R = 4-F, R1 = Me (a); R = 2,5-Cl2, R1 = Me (b); R = 2,3-Cl2, R1 = CH3(CH2)3 (c); R = 2,5-Cl2, R1 = (CH3)2CHCH2 (d); R =
4-MeO, R1 = CH3(CH2)5 (e); R = 4-F, R1 = 2-tetrahydrofuryl (f); R = 3-CF3, R1 = 4-ClC6H4 (g); R = 4-Cl, R1 = 2-furyl (h); R =
4-MeO, R1 = 2-thienyl (i); R = 3-Me, R1 = 2-MeC6H4CH=CH (j); R = 4-Me, R1 = 4-EtOC6H4CH=CH (k); R = 4-MeO, R1 =
3-CF3C6H4CH=CH (l); R = Cl, R1 = 3-CF3C6H4CH=CH (m); R = 4-F, R1 = 4-ClC6H4CH=CH (n); R = 4-Cl, R1 = 2-(2-furyl)-
ethenyl (o); VI, R = 2-Cl (a), 4-Cl (b), 4-Br (c), 3-NO2 (d), 2,3-Cl2 (e), 2,5-Cl2 (f), 3-CF3 (g).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 3 2004

OBUSHAK et al.
386
2-Amino-5-benzyl-1,3-thiazoles IIIa–IIIm (general
2-Amino-5-(4-bromobenzyl)-1,3-thiazole (IIIg).
1
Yield 84%, mp 123–125°C. H NMR spectrum, δ,
procedure). A mixture of 0.8 g of thiourea and
0.01 mol of aldehyde IIa–IIm in 10 ml of ethanol was
heated for 1.5–2 h under reflux. The mixture was
cooled, diluted with 100 ml of water, and made
alkaline by adding aqueous ammonia. The precipitate
was filtered off and recrystallized from CCl4 or
CHCl3–CCl4.
ppm: 3.86 s (2H, CH2), 6.61 s (2H, NH2), 6.64 s (1H,
4-H, thiazole), 7.15 d (2H, C6H4), 7.42 d (2H, C6H4,
J = 8.1 Hz). Found, %: C 44.38; H 3.38; N 10.26.
C10H9BrN2S. Calculated, %: C 44.62; H 3.37; N 10.41.
2-Amino-5-(3-trifluoromethylbenzyl)-1,3-thia-
1
zole (IIIh). Yield 77%, mp 121–123°C. H NMR
spectrum, δ, ppm: 3.97 s (2H, CH2), 6.45 s (2H, NH2),
6.60 s (1H, 4-H, thiazole), 7.40–7.50 m (4H, C6H4).
Found, %: C 51.10; H 3.56; N 10.62. C11H9F3N2S.
Calculated, %: C 51.16; H 3.51; N 10.85.
2-Amino-5-(3-methylbenzyl)-1,3-thiazole (IIIa).
1
Yield 72%, mp 101–102°C. H NMR spectrum, δ,
ppm: 2.28 s (3H, Me), 3.83 s (2H, CH2), 6.56 s (2H,
NH2), 6.62 s (1H, 4-H, thiazole), 6.93–7.02 m (3H,
C6H4), 7.14 t (1H, C6H4, J = 7.5 Hz). Found, %:
C 64.32; H 5.90; N 13.78. C11H12N2S. Calculated, %:
C 64.67; H 5.92; N 13.71.
2-Amino-5-(2,3-dichlorobenzyl)-1,3-thiazole
1
(IIIi). Yield 79%, mp 126–128°C. H NMR spectrum,
δ, ppm: 4.01 s (2H, CH2), 6.68 s (1H, 4-H, thiazole),
6.73 s (2H, NH2), 7.26–7.36 m (2H, C6H3), 7.47 d.d
2-Amino-5-(4-methylbenzyl)-1,3-thiazole (IIIb).
4
3
(1H, C6H3, J = 1.2, J = 7.8 Hz). Found, %: C 46.09;
H 3.05; N 10.80. C10H8Cl2N2S. Calculated, %:
C 46.35; N 3.11; N 10.81.
1
Yield 69%, mp 142–143°C. H NMR spectrum, δ,
ppm: 2.28 s (3H, Me), 3.82 s (2H, CH2), 6.55 s (2H,
NH2), 6.60 s (1H, 4-H, thiazole), 7.06 s (4H, C6H4).
Found, %: C 64.48; H 5.75; N 13.67. C11H12N2S.
Calculated, %: C 64.67; H 5.92; N 13.71.
2-Amino-5-(2,4-dichlorobenzyl)-1,3-thiazole
1
(IIIj). Yield 91%, mp 112–113°C. H NMR spectrum,
δ, ppm: 3.99 s (2H, CH2), 6.70 s (1H, 4-H, thiazole),
6.79 s (2H, NH2), 7.38 m (2H, C6H3), 7.60 d (1H,
C6H3). Found, %: C 46.51; H 3.14; N 10.55.
C10H8Cl2N2S. Calculated, %: C 46.35; H 3.11; N 10.81.
2-Amino-5-(4-methoxybenzyl)-1,3-thiazole (IIIc).
1
Yield 78%, mp 133–134°C. H NMR spectrum, δ,
ppm: 3.72 s (3H, MeO), 3.80 s (2H, CH2), 6.54 s (2H,
NH2), 6.59 s (1H, 4-H, thiazole), 6.80 d (2H, C6H4),
7.09 d (2H, C6H4, J = 8.4 Hz). Found, %: C 60.05;
H 5.36; N 12.58. C11H12N2OS. Calculated, %: C 59.98;
H 5.49; N 12.72.
2-Amino-5-(2,5-dichlorobenzyl)-1,3-thiazole
(IIIk). Yield 85%, mp 124–125°C. 1H NMR spectrum,
δ, ppm: 3.98 s (2H, CH2), 6.67 s (1H, 4-H, thiazole),
4
3
6.69 s (2H, NH2), 7.26 d.d (1H, C6H3, J = 2.4, J =
8.7 Hz), 7.34 d (1H, C6H3, J = 2.4 Hz), 7.40 d (1H,
C6H3, J = 8.7 Hz). Found, %: C 46.27; H 2.97;
N 10.58. C10H8Cl2N2S. Calculated, %: C 46.35; H 3.11;
N 10.81.
2-Amino-5-(4-chloro-3-methylbenzyl)-1,3-thia-
1
zole (IIId). Yield 82%, mp 125–127°C. H NMR
spectrum, δ, ppm: 2.28 s (3H, Me), 3.87 s (2H, CH2),
6.72 s (1H, 4-H, thiazole), 6.75 s (2H, NH2), 7.08 d
(1H, C6H3, J = 8.0 Hz), 7.24 s (1H, C6H3), 7,26 d
(1H, C6H3). Found, %: C 55.39; H 4.50; N 11.54.
C11H11ClN2S. Calculated, %: C 55.34; H 4.64;
N 11.73.
2-Amino-5-(3,4-dichlorobenzyl)-1,3-thiazole
1
(IIIl). Yield 83%, mp 92–94°C. H NMR spectrum, δ,
ppm: 3.90 s (2H, CH2), 6.67 s (3H, 4-H, thiazole,
NH2), 7.17 d.d (1H, C6H3, 4J = 1.8, 3J = 8.4 Hz), 7.40 d
(1H, C6H3), 7.47 d (1H, J = 8.4 Hz). Found, %:
C 46.08; H 3.05; N 10.97. C10H8Cl2N2S. Calculated,
%: C 46.35; H 3.11; N 10.81.
2-Amino-5-(4-fluorobenzyl)-1,3-thiazole (IIIe).
1
Yield 85%, mp 135–136°C. H NMR spectrum, δ,
ppm: 3.87 s (2H, CH2), 6.62 s (2H, NH2), 6.63 s (1H,
4-H, thiazole), 7.03 t (2H, C6H4, J = 8.4 Hz), 7.21 d.d
(2H, C6H4, J = 5.7 Hz). Found, %: C 57.67; H 4.17;
N 13.16. C10H9FN2S. Calculated, %: C 57.67; H 4.36;
N 13.45.
2-Amino-5-(4-difluoromethylsulfanylbenzyl)-1,3-
1
thiazole (IIIm). Yield 74%, mp 78–80°C. H NMR
spectrum, δ, ppm: 3.94 s (2H, CH2), 6.74 s (1H, 4-H,
thiazole), 6.78 s (2H, NH2), 7.44 t (1H, SCHF2, JFH
=
56 Hz), 7.31 d (2H, C6H4), 7.51 d (2H, C6H4, J =
8.0 Hz). Found, %: C 48.18; H 3.69; N 10.25.
C11H10F2N2S2. Calculated, %: C 48.51; H 3.70; N 10.29.
2-Amino-5-(4-chlorobenzyl)-1,3-thiazole (IIIf).
1
Yield 88%, mp 122–124°C. H NMR spectrum, δ,
ppm: 3.88 s (2H, CH2), 6.62 s (2H, NH2), 6.64 s (1H,
4-H, thiazole), 7.21 d (2H, C6H4), 7.27 d (2H, C6H4,
J = 7.2 Hz). Found, %: C 53.33; H 3.97; N 12.50.
C10H9ClN2S. Calculated, %: C 53.45; H 4.04; N 12.47.
2-Acylamino-5-benzyl-1,3-thiazoles Va–Vo
(general procedure). a. To a solution of 0.01 mol of
2-aminothiazole III and 1 ml of triethylamine in 30 ml
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HETEROCYCLIC SYNTHESES ON THE BASIS OF ARYLATION PRODUCTS ... X.
387
of anhydrous dioxane we added under stirring
0.01 mol of the corresponding acid chloride. The mix-
ture was left to stand for 0.5 h and diluted with water,
and the precipitate was filtered off, washed with water,
and recrystallized from alcohol, DMF, or their mixture.
b. A mixture of 0.01 mol of acylthiourea IV and
0.01 mol of aldehyde II in 20 ml of ethanol was heated
for 1.5–2 h under reflux. The mixture was cooled,
diluted with 100 ml of water, and made alkaline by
adding aqueous ammonia. The oily residue was
repeatedly treated with water and alcohol, and the
precipitate was filtered off and recrystallized.
N-[5-(4-Fluorobenzyl)-1,3-thiazol-2-yl]tetra-
hydrofuran-2-carboxamide (Vf). Yield 65%, mp 127–
128°C. H NMR spectrum, δ, ppm: 1.80–1.98 m (3H),
1
2.17 m (1H), 3.80 m (1H), 3.95 m (1H), 4.49 m (1H,
tetrahydrofuran), 4.08 s (2H, CH2), 7.22 s (1H, 4-H,
thiazole), 7.10 t (2H, C6H4), 7.30 d.d (2H, C6H4),
11.57 br.s (1H, NH). Found, %: N 8.97; S 10.39.
C15H15FN2O2S. Calculated, %: N 9.14; S 10.47.
N-[5-(3-Trifluoromethylbenzyl)-1,3-thiazol-2-yl]-
4-chlorobenzamide (Vg). Yield 86%, mp 165–166°C.
1H NMR spectrum, δ, ppm: 4.23 s (2H, CH2), 7.24 s
(1H, 4-H, thiazole), 7.47–7.63 m (4H, 3-CF3C6H4),
7.51 d (2H, C6H4), 8.12 d (2H, C6H4), 12.32 br.s (1H,
NH). Found, %: N 6.93; S 8.05. C18H12ClF3N2OS.
Calculated, %: N 7.06; S 8.08.
N-[5-(4-Fluorobenzyl)-1,3-thiazol-2-yl]acetamide
1
(Va). Yield 86%, mp 184–185°C. H NMR spectrum,
δ, ppm: 2.11 s (3H, Me), 4.05 s (2H, CH2), 7.10 s
(1H, 4-H, thiazole), 7.05 t (2H, C6H4), 7.21–7.30 m
(2H, C6H4), 11.82 br.s (1H, NH). Found, %: N 10.95;
S 12.78. C12H11FN2OS. Calculated, %: N 11.19;
S 12.81.
N-[5-(4-Chlorobenzyl)-1,3-thiazol-2-yl]furan-2-
1
carboxamide (Vh). Yield 75%, mp 135–137°C. H
NMR spectrum, δ, ppm: 4.09 s (2H, CH2), 7.15–
7.48 m (5H, 4-H, thiazole, C6H4), 6.70 m (1H, 4-H,
furan), 7.55 d (1H, 3-H, furan), 7.97 br.s (1H, 5-H,
furan), 12.46 br.s (1H, NH). Found, %: N 8.71; S 10.08.
C15H11ClN2O2S. Calculated, %: N 8.79; S 10.06.
N-[5-(2,5-Dichlorobenzyl)-1,3-thiazol-2-yl]acet-
1
amide (Vb). Yield 77%, mp 186–187°C. H NMR
spectrum, δ, ppm: 2.11 s (3H, Me), 4,16 s (2H, CH2),
7.15 s (1H, 4-H, thiazole), 7.28 d.d (1H, C6H3), 7.39–
7.46 m (2H, C6H3), 11.88 br.s (1H, NH). Found, %:
N 9.19; S 10.53. C12H10Cl2N2OS. Calculated, %:
N 9.30; S 10.65.
N-[5-(4-Methoxybenzyl)-1,3-thiazol-2-yl]thio-
phene-2-carboxamide (Vi). Yield 89%, mp 193–
1
194°C. H NMR spectrum, δ, ppm: 3.73 s (3H, MeO),
4.03 s (2H, CH2), 6.88 d (2H, C6H4), 7.20 d (2H,
C6H4), 7.22 m (1H, 4-H, thiophene), 7.27 s (1H, 4-H,
thiazole), 7.91 d (1H, 3-H, thiophene), 8.16 d (1H,
5-H, thiophene), 12.48 br.s (1H, NH). Found, %:
N 8.28; S 19.31. C16H14N2O2S2. Calculated, %: N 8.48;
S 19.41.
N-[5-(2,3-Dichlorobenzyl)-1,3-thiazol-2-yl]pen-
1
tanamide (Vc). Yield 75%, mp 141–142°C. H NMR
spectrum, δ, ppm: 0.93 t (3H, Me), 1.37 sext (2H,
CH2), 1.61 quint (2H, CH2), 2.39 t (2H, CH2CO),
4.23 s (2H, CH2), 7.11 s (1H, 4-H, thiazole), 7.22–
7.35 m (2H, C6H3), 7.43 d (1H, C6H3), 11.68 br.s (1H,
NH). Found, %: N 8.03; S 9.27. C15H16Cl2N2OS. Cal-
culated, %: N 8.16; S 9.34.
N-[5-(3-Methylbenzyl)-1,3-thiazol-2-yl]-3-(2-
methylphenyl)acrylamide (Vj). Yield 80%, mp 196–
1
198°C. H NMR spectrum, δ, ppm: 2.32 s (3H, Me),
2.47 s (3H, Me), 4.05 s (2H, CH2), 6.76 d (1H, CH=),
7.18 s (1H, 4 H, thiazole), 7.03 d (1H), 7.12–7.28 m
(6H), 7.58 d (1H, C6H4), 7.90 d (1H, CH=), 11.98 br.s
(1H, NH). Found, %: N 7.97; S 9.15. C21H20N2OS.
Calculated, %: N 8.04; S 9.20.
N-[5-(2,5-Dichlorobenzyl)-1,3-thiazol-2-yl]-4-
methylbutanamide (Vd). Yield 56%, mp 134–136°C.
1H NMR spectrum, δ, ppm: 0.96 d (6H, Me), 2.11 m
(1H, CH), 2.28 d (2H, CH2CO), 4.17 s (2H, CH2),
7.12 s (1H, 4 H, thiazole), 7.26 m (1H, C6H3), 7.35–
7.44 m (2H, C6H3), 11.69 br.s (1H, NH). Found, %:
N 7.99; S 9.40. C15H16Cl2N2OS. Calculated, %: N 8.16;
S 9.34.
N-[5-(4-Methylbenzyl)-1,3-thiazol-2-yl]-3-(4-
ethoxyphenyl)acrylamide (Vk). Yield 76%, mp 215–
1
217°C. H NMR spectrum, δ, ppm: 1.40 t (3H, Me),
2.31 s (3H, Me), 4.02 s (2H, CH2), 4.10 q (2H, CH2O),
6.70 d (1H, CH=), 7.12 s (1H, 4-H, thiazole), 7.10 d
(2H, 4-MeC6H4), 7.15 d (2H, 4-MeC6H4), 7.59 d
(1H, CH=), 6.90 d (2H, C6H4), 7.50 d (2H, C6H4),
11.84 br.s (1H, NH). Found, %: N 7.41; S 8.29.
C22H22N2O2S. Calculated, %: N 7.40; S 8.47.
N-[5-(4-Methoxybenzyl)-1,3-thiazol-2-yl]heptan-
1
amide (Ve). Yield 59%, mp 135–136°C. H NMR
spectrum, δ, ppm: 0.90 t (3H, Me), 1.32 br.s (6H,
CH2), 1.61 m (2H, CH2), 2.36 t (2H, CH2SO), 3.77 s
(3H, MeO), 3.99 s (2H, CH2), 7.05 s (1H, 4-H, thia-
zole), 6.81 d (2H, C6H4), 7.15 d (2H, C6H4), 11.63 br.s
(1H, NH). Found, %: N 8.38; S 9.50. C18H24N2O2S.
Calculated, %: N 8.43; S 9.64.
N-[5-(4-Methoxybenzyl)-1,3-thiazol-2-yl]-3-(3-
trifluoromethylphenyl)acrylamide (Vl). Yield 81%,
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OBUSHAK et al.
388
1
mp 227–228°C. H NMR spectrum, δ, ppm: 3.78 s
(3H, MeO), 4.04 s (2H, CH2), 6.99 d (1H, CH=),
7.15 s (1H, 4-H, thiazole), 6.84 d (2H, 4-MeOC6H4),
7.17 d (2H, 4-MeOC6H4), 7.72 d (1H, CH=), 7.60–
7.69 m (2H, C6H4), 7.87 m (2H, C6H4), 11.96 br.s
(1H, NH). Found, %: N 6.89; S 8.01. C21H17F3N2O2S.
Calculated, %: N 6.69; S 7.66.
N-[5-(4-Bromobenzyl)-1,3-thiazol-2-yl]phthal-
imide (VIc). Yield 86%, mp 193–194°C. H NMR
1
spectrum, δ, ppm: 4.22 s (2H, CH2), 7.30 d (2H,
4-BrC6H4), 7.54 d (2H, 4-BrC6H4, J = 8.4 Hz), 7.63 s
(1H, 4-H, thiazole), 7.91–7.95 m (2H, C6H4), 7.96–
8.01 m (2H, C6H4). Found, %: C 53.85; H 2.71.
C18H11BrN2O2S. Calculated, %: C 54.15; H 2.78.
N-[5-(4-Chlorobenzyl)-1,3-thiazol-2-yl]-3-(3-tri-
fluoromethylphenyl)acrylamide (Vm). Yield 75%,
N-[5-(3-Nitrobenzyl)-1,3-thiazol-2-yl]phthal-
imide (VId). Yield 79%, mp 222–223°C. H NMR
1
1
mp 228–229°C. H NMR spectrum, δ, ppm: 4.10 s
spectrum, δ, ppm: 4.43 s (2H, CH2), 7.70 s (1H, 4-H,
thiazole), 7.90–7.95 m (2H, C6H4), 7.96–8.01 m (2H,
C6H4), 7.65 t (1H, 3-NO2C6H4, J = 7.6 Hz), 7.83 d (1H,
3-NO2C6H4, J = 7.6 Hz), 8.13 d.d (1H, 3-NO2C6H4,
(2H, CH2), 6.99 d (1H, CH=), 7.19 s (1H, 4-H,
thiazole), 7.73 d (1H, CH=), 7.24–7.35 m (4H), 7.60–
7.69 m (2H), 7.86 m (2H, C6H4), 11.97 br.s (1H, NH).
Found, %: N 6.39; S 7.50. C20H14ClF3N2OS. Calcu-
lated, %: N 6.62; S 7.58.
3
4J = 2.4, J = 8.0 Hz), 8.25 br.s (1H, 3-NO2C6H4).
Found, %: C 58.88; H 2.97. C18H11N3O4S. Calculated,
%: C 59.17; H 3.03.
N-[5-(4-Fluorobenzyl)-1,3-thiazol-2-yl]-3-(4-
chlorophenyl)acrylamide (Vn). Yield 89%, mp 245–
N-[5-(2,3-Dichlorobenzyl)-1,3-thiazol-2-yl]-
phthalimide (VIe). Yield 80%, mp 142–144°C.
1H NMR spectrum, δ, ppm: 4.40 s (2H, CH2), 7.38 t
(1H, C6H3, J = 8.0 Hz), 7.50 d (1H, C6H3, J = 7.6 Hz),
7.58 d (1H, C6H3, J = 8.0 Hz), 7.63 s (1H, 4-H,
thiazole), 7.90–7.94 m (2H, C6H4), 7.96–8.01 m (2H,
C6H4). Found, %: C 55.36; H 2.53. C18H10Cl2N2O2S.
Calculated, %: C 55.54; H 2.59.
1
246°C. H NMR spectrum, δ, ppm: 4.09 s (2H, CH2),
6.86 d (1H, CH=), 7.16 s (1H, 4-H, thiazole), 7.05 t
(2H, 4-FC6H4), 7.23–7.33 m (2H, 4-FC6H4), 7.42 d
(2H, C6H4), 7.60 d (2H, C6H4), 7.62 d (1H, CH=),
11.94 br.s (1H, NH). Found, %: N 7.25; S 8.56.
C19H14ClFN2OS. Calculated, %: N 7.51; S 8.60.
N-[5-(4-Chlorobenzyl)-1,3-thiazol-2-yl]-3-(2-
furyl)acrylamide (Vo). Yield 85%, mp 252–253°C.
1H NMR spectrum, δ, ppm: 4.09 s (2H, CH2), 6.54 m
(1H, 4-H, furan), 6.77 d (1H, 3-H, furan), 6.68 d (1H,
CH=), 7.16 s (1H, 4-H, thiazole), 7.27 d (2H, C6H4),
7.31 d (2H, C6H4), 7.45 d (1H, CH=), 7.68 br.s (1H,
5-H, furan), 11,92 br.s (1H, NH). Found, %: N 7.96;
S 9.22. C17H13ClN2O2S. Calculated, %: N 8.12; S 9.30.
N-[5-(2,5-Dichlorobenzyl)-1,3-thiazol-2-yl]-
phthalimide (VIf). Yield 82%, mp 199–200°C.
1H NMR spectrum, δ, ppm: 4.33 s (2H, CH2), 7.39 d.d
4
3
(1H, C6H3, J = 2.4, J = 8.0 Hz), 7.52 d (1H, C6H3,
J = 8.0 Hz), 7.64 d (1H, C6H3, J = 2.4 Hz), 7.63 s
(1H, 4-H, thiazole), 7.90–7.94 m (2H, C6H4), 7.96–
8.01 m (2H, C6H4). Found, %: C 55.51; H 2.39.
C18H10Cl2N2O2S. Calculated, %: C 55.54; H 2.59.
N-(5-Benzyl-1,3-thiazol-2-yl)phthalimides VIa–
VIg. 2-Aminothiazole III, 0.01 mol, was fused with
0.01 mol of phthalic anhydride until water no longer
liberated. The melt was ground with alcohol, and the
product was recrystallized from DMF.
N-[5-(3-Trifluoromethylbenzyl)-1,3-thiazol-2-yl]-
phthalimide (VIg). Yield 84%, mp 154–155°C.
1H NMR spectrum, δ, ppm: 4.40 s (2H, CH2), 7.64 s
(1H, 4-H, thiazole), 7.53–7.76 m (4H, 3-CF3C6H4),
7.91–7.95 m (2H, C6H4), 7.96–8.01 m (2H, C6H4).
Found, %: C 58.81; H 2.76. C19H11F3N2O2S. Calcu-
lated, %: C 58.76; H 2.85.
N-[5-(2-Chlorobenzyl)-1,3-thiazol-2-yl]phthal-
1
imide (VIa). Yield 87%, mp 190–192°C. H NMR
spectrum, δ, ppm: 4.34 s (2H, CH2), 7.60 s (1H,
4-H, thiazole), 7.27–7.56 m (4H, 2-ClC6H4), 7.87–
8.03 m (4H, C6H4). Found, %: C 60.90; H 3.05.
C18H11ClN2O2S. Calculated, %: C 60.93; H 3.12.
REFERENCES
N-[5-(4-Chlorobenzyl)-1,3-thiazol-2-yl]phthal-
imide (VIb). Yield 82%, mp 177–178°C. H NMR
1. Obushak, N.D., Martyak, R.L., and Matiychuk, V.S., Pol.
J. Chem., 2002, vol. 76, p. 1419.
1
spectrum, δ, ppm: 4.24 s (2H, CH2), 7.36 d (2H,
4-ClC6H4), 7.41 d (2H, 4-ClC6H4, J = 8.4 Hz), 7.63 s
(1H, 4-H, thiazole), 7.91–7.95 m (2H, C6H4), 7.97–
8.01 m (2H, C6H4). Found, %: C 60.74; H 3.16.
C18H11ClN2O2S. Calculated, %: C 60.93; H 3.12.
2. Saunders, K.H. and Allen, R.L.M., Aromatic Diazo
Compounds, London: Edward Arnold, 1985, p. 594.
3. Zollinger, H., Diazo Chemistry. I. Aromatic and Hetero-
aromatic Compounds, Weinheim: VCH, 1994, p. 243.
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HETEROCYCLIC SYNTHESES ON THE BASIS OF ARYLATION PRODUCTS ... X.
389
4. Dombrovskii, A.V., Reaktsii i metody issledovaniya
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York: Wiley, 1957, vol. 5. Translated under the title
Geterotsiklicheskie soedineniya, Moscow: Inostrannaya
Literatura, 1960, vol. 5, p. 402.
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1962–1963, vol. 31, p. A5–A8; Ref. Zh., Khim., 1968,
no. 15Zh311.
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