L-Proline as an efficient catalyst for synthesis of aldimines at ambient temperature condition

Article abstract of DOI:10.1155/2011/185981

Some new aldimines were synthesized from substituted 2-amino thiazoles and different aromatic aldehydes using L-proline as an efficient catalyst. The structure elucidation of aldimines has been made on the basis of elemental analysis and spectral data. Th

Full text of DOI:10.1155/2011/185981

ISSN: 0973-4945; CODEN ECJHAO
E-Journal of Chemistry
2011, 8(4), 1859-1863
http://www.e-journals.net
L-Proline as an Efficient Catalyst for Synthesis of
Aldimines at Ambient Temperature Condition
S. S. KOTTAWAR, S. V. GOSWAMI, P. B. THORAT and S. R. BHUSARE*
Department of Chemistry
Dnyanopasak College, Parbhani-431401, MS, India
bhusare71@yahoo.com
Received 26 September 2010; Accepted 21 November 2010
Abstract: Some new aldimines were synthesized from substituted 2-amino
thiazoles and different aromatic aldehydes using L-proline as an efficient
catalyst. The structure elucidation of aldimines has been made on the basis of
elemental analysis and spectral data. The easy work up, higher yield and shorter
reaction time are the advantages of the method.
Keywords: 2-Amino thiazole, Aldehydes, L-Proline, Aldimines
Introduction
Utility of aldimines lies in their potent biological activity and their usefulness as a starting
material for the synthesis of various heterocyclic compounds such as azetidinones and
thiazolidinones. One interesting role of imines (Schiff bases) is as intermediate in the biologically
important transamination reaction. In living systems the amino group of an amino acid is
transferred to the carbonyl group of another molecule, promoted by an enzyme called
transaminase. All the important transaminase enzymes appear to have common coenzymes,
pyridoxal phosphate.
The Schiff bases constitute one of the most active class of the compounds possessing
diversified biological activity such as antitubercular1, anticancer2, antibacterial3, antifungal3,
analgesic4, CNS depressant4, anti-inflammatory5, anticonvulsant6, insecticidal7 and plant
growth inhibitors8. The biological transformation is not simple transfer of an amino group
from one molecule to another. The carbonyl group of the coenzyme pyridoxal actually forms
an imine with amino group of the donor amino acid. Subsequent reaction of this adducts
with the "acceptor" carbonyl compound results in the formation of a new amino acid and
regeneration of the pyridoxal fragment. Pyridoxal is the carrier of the amino group from one
reactant to the other where in the first step, the Schiff bases formation occurs.

L-Proline as an Efficient Catalyst for Synthesis of Aldimines
1860
Literature survey reveals that various aldimines attracted considerable attention as they are
also endowed with wide range of pharmaceutical activities. Its reactivity is greatly influenced by
different substituent. Aldimines and its derivatives possess different therapeutic activities.
Proline and its derivatives are often used as catalysts in organic reactions. The CBS reduction
and proline catalyzed aldol condensation are prominent examples. L-Proline is an osmoprotectant
and therefore is used in many pharmaceutical, biotechnological applications. Recently9, the use
of L-Proline as an organo-catalyst for the multicomponent Hantzsch reaction under benign
reaction conditions is reported. L-Proline is a very effective, environmentally friendly catalyst for
the four component condensations of dimedone, ethylacetoacetate, aromatic aldehyde and
ammonium acetate to form polyhydroquinoline in excellent yields9.
Here in we report the synthesis of several new heterocyclic aldimines first time using
L-proline as organocatalyst from various substituted 2-amino thiazoles and aromatic aldehydes.
Our results demonstrate that L-proline is very effective, environmentally friendly catalyst for the
condensation of aromatic aldehyde and thiazole to form the aldimines in excellent yield (Scheme 1).
CHO
S
R1
S
N
N
a
NH2
+
N
R1
R
R
3a-j
1
2
Scheme 1. Reaction conditions: (a) Methanol, L-proline (10 mol%), 80-85%, 4-6 h.
Experimental
Melting points were determined in open capillary tube and are uncorrected. The purity of the
compounds has been checked by TLC. The IR spectra were recorded on Varian FTIR 640
spectrometer. 1H NMR and 13C NMR spectra were recorded on Burker 400 MHz
spectrometer in CDCl3 as a solvent and TMS as an internal standard.
General procedure for the synthesis of aldimines (3a-j)
A mixture of equimolar quantities of substituted benzaldehydes 1 (10 mmol) and substituted
2-amino thiazole 2 (10 mmol) in methanol was stirred at room temperature and added
catalytic amount of L-Proline (10 mole%). Reaction mixture was stirred till the completion
of reaction at room temperature as indicated by TLC (ethyl acetate: n-hexane, 2:8). After the
completion of reaction, the reaction mixture was concentrated and added water. Solid was
precipitated out and filtered to get crude compound. Crude compound was crystallized from
ethanol to get pure compound (3a-j) (Table 1).
Table 1. Synthesis of aldimines (3a-j)
Entry
1.
R
R1
4-Phenyl
Time, h
4.5
4.5
Yield, %
85
82
3a-j
3a
3b
3c
3d
3e
3f
3,4,5-Trimethoxy
3,4,5-Trimethoxy
5-Bromo-2-hydroxy
5-Bromo-2-hydroxy
5-Bromo-2-hydroxy
5-Bromo-2-hydroxy
3-Chloro
2.
4-Chlorophenyl
4-Naphthalene
3-Nitrophenyl
4-Chlorophenyl
4-Phenyl
3.
5.5
5.0
5.0
5.0
76
78
75
79
4.
5.
6.
7.
4-Naphthalene
4-Chlorophenyl
3-Nitrophenyl
4-Chlorophenyl
4.0
5.5
84
82
3g
3h
3i
8.
3-Chloro
2-Hydroxy
2-Hydroxy
9.
10.
6.0
4.5
85
83
3j

1861
S. R. BHUSARE et al.
4-Phenyl-N-(3,4,5-trimetoxybenzylidene)thiazol-2-amine (3a)
1H NMR: δ 3.61 (s, 9H, CH3), 7.1-7.8 (m, 7H, ArH), 8.41(s, 1H, thiazole H), 9.35 (s, 1H,
=CH); 13C NMR: δ 55.4, 59.5, 103.4, 110.8, 126.4, 127.1, 128.5, 131.6, 131.8, 140.8, 150.9,
151.1, 161.2, 170.8; ESMS: 353.1 (M-1); Elemental Analysis: C19H18N2O3S; Calcd. C,
64.39; H, 5.12; N, 7.90; O, 13.54; S, 9.05; Found C, 64.40; H, 5.11; N, 7.89; O, 13.56; S,
9.04; m. p. 165-167 °C;
4-(4-Chlorophenyl)-N-(3,4,5-trimethoxybenzylidene)thiazol-2-amine (3b)
1H NMR: δ 3.61(s, 9H, CH3), 7.1 (s, 2H, ArH), 7.6 (d, 2H, ArH), 7.85 (d, 2H, ArH), 8.40 (s,
1H, thiazole H), 9.31 (s, 1H, =CH); 13C NMR: δ 55.4, 59.5, 103.4, 110.8, 126.7, 127.6,
128.6, 131.6, 131.8, 140.8, 150.9, 151.1, 161.2, 170.8; ESMS: 387.1 (M-1); Elemental
Analysis: C19H17ClN2O3S; Calcd. C, 58.68; H, 4.41; Cl, 9.12; N, 7.20; O, 12.35; S, 8.25;
Found C, 58.69; H, 4.42; Cl, 9.13; N, 7.21; O, 12.36; S, 8.24; m. p. 179-181 °C.
4-Naphthalene-N-(2-hydroxy-5-bromobenzylidene)thiazol-2-amine (3c)
1H NMR: δ 6.95 (d, 1H, ArH), 7.4-8.0 (m, 9H, ArH), 8.45 (s, 1H, thiazole H), 9.35 (s, 1H,
=CH), 12.35 (s, 1H, OH); 13C NMR: δ 110.80, 114.62, 119.27, 121.84, 123.97, 124.77,
126.35, 127.61, 128.26, 128.36, 131.31, 131.91, 132.73, 133.13, 136.98, 152.55, 159.19,
161.11, 170.63; ESMS: 407.5 (M-1); Elemental Analysis: C20H13BrN2OS; Calcd. C, 58.69;
H, 3.20; Br, 19.52; N, 6.84; O, 3.91; S, 7.83. Found C, 58.70; H, 3.19; Br, 19.50; N, 6.82; O,
3.93; S, 7.82; m. p.169-171 °C.
4-(3-Nitrophenyl)-N-(2-hydroxy-5-bromobenzylidene)thiazol-2-amine (3d)
1H NMR: 6.9 (d, 1H, ArH), 7.3 (d, 1H, ArH), 7.7- 8.3 (m, 5H, ArH), 8.7 (s, 1H, ArH), 9.41
(s, 1H, =CH); 13C NMR: δ 110.6, 110.8, 118.3, 119.6, 128.5, 128.9, 131.1, 132.1, 133.9,
134.1, 152.4, 160.2, 161.4, 170.6; ESMS: 401.9 (M-1); Elemental Analysis:
C16H10BrN3O3S: Calcd. C, 47.54; H, 2.49; Br, 19.77; N, 10.39; O, 11.87; S, 7.93. Found C,
47.55; H, 2.47; Br, 19.78; N, 10.36; O, 11.89; S, 7.94; m. p. 238-240 °C.
4-(4-Chlorophenyl)-N-(2-hydroxy-5-bromobenzylidene)thiazol-2-amine (3e)
1H NMR: δ 6.95-7.91 (m, 8H, ArH), H), 9.35 (s, 1H, =CH), 12.35 (s, 1H, OH); 13C NMR: δ
110.6, 110.8, 118.3, 119.6, 121.5, 122.1, 128.4, 131.1, 132.3, 132.9, 134.3, 150.1, 152.5,
160.1, 161.4, 170.6; ESMS: 390.9 (M-1); Elemental Analysis: C16H10ClN2OS: Calcd. C,
48.81; H, 2.56; Br, 20.30; Cl, 9.01; N, 7.12; O, 4.06; S, 8.14; Found C, 48.82; H, 2.58; Br,
20.31; Cl, 9.03; N, 7.11; O, 4.07; S, 8.12; m. p.198-201 °C.
4-Phenyl-N-(2-hydroxy-5-bromobenzylidene)thiazol-2-amine (3f)
1H NMR: δ 6.91 (d, 1H, ArH), 7.4-7.8 (m, 7H, ArH), 8.44 (s, 1H, thiazole H), 9.32 (s, 1H,
=CH); 13C NMR: δ 110.5, 110.8, 118.4 119.7, 126.8, 127.4, 128.6, 130.4, 131.9, 134.2,
160.2, 161.4, 170.6; ESMS: 356.9 (M-1); Elemental Analysis: C16H11BrN2OS: Calcd. C,
53.49; H, 3.09; Br, 22.24; N, 7.80; O, 4.45; S, 8.93; Found C, 53.48; H, 3.11; Br, 22.23; N,
7.81; O, 4.44; S, 8.94; m. p.130-131°C.
4-Naphthalene-N-(3-chlorobenzylidene)thiazol-2-amine (3g)
1H NMR: δ 7.4-8.0 (m, 11H, ArH), 8.41 (s, 1H, thiazole H), 9.35 (s, 1H, =CH); 13C NMR: δ
110.81, 114.92, 119.35, 121.89, 123.77, 124.77, 126.35, 126.58, 128.26, 131.41, 131.81,
132.93, 133.23, 136.98, 152.15, 159.09, 161.23, 170.68; ESMS: 347.1 (M-1); Elemental
Analysis: C20H13ClN2S: Calcd. C, 68.86; H, 3.76; Cl, 10.16; N, 8.03; S, 9.19; Found C,
68.87; H, 4.78; Cl, 10.12; N, 7.02; S, 9.18; m. p.125-128 °C.

L-Proline as an Efficient Catalyst for Synthesis of Aldimines
1862
4-(4-Chlorophenyl)-N-(3-chlorobenzylidene)thiazol-2-amine (3h)
1H NMR: δ 7.4-8.0 (m, 8H, ArH), 8.40 (s, 1H, thiazole H), 9.30 (s, 1H, =CH); 13C NMR: δ
110.8, 125.8, 125.9, 127.5, 127.6, 129.4, 130.8, 132.8, 132.9, 135.4, 159.09, 161.23, 170.68.
ESMS: 331.1 (M-1); Elemental Analysis: C16H10Cl2N2S: Calcd. C, 57.67; H, 3.02; Cl, 21.28;
N, 8.41; S, 9.62; Found C, 57.68; H, 3.03; Cl, 21.30; N, 8.38; S, 9.60; m. p. 145-147 °C.
4-(3-Nitrophenyl)-N-(2-hydroxybenzylidene)thiazol-2-amine (3i)
1H NMR: δ 7.0-8.2 (m, 7H ArH), 8.40 (s, 1H, thiazole H), 8.55 (s, 1H, ArH), 9.30 (s, 1H,
=CH); 13C NMR: δ 110.8, 117.5, 119.4, 120.7, 122.5, 123.2, 131.5, 132.2, 132.6, 132.9,
133.0, 149.6, 152.5, 159.09, 161.23, 170.68; ESMS: 324.1(M-1); Elemental Analysis:
C16H11ClN3O3S: Calcd. C, 59.07; H, 3.41; N, 12.92; O, 14.75; S, 9.86; Found C, 58.05; H,
3.42; N, 12.91; O, 14.76; S, 9.85; m. p.218-220 °C.
4-(4-Chlorophenyl)-N-(2-hydroxybenzylidene)thiazol-2-amine (3j)
1H NMR: δ 6.91-7.1(m, 2H, ArH), 7.4-7.6 (m, 4H, ArH and s, 1H, thiazole H), 7.87 (d, 2H,
ArH), 9.35 (s, 1H, =CH); 13C NMR: δ 110.8, 116.5, 119.6, 120.5, 127.6, 127.9, 131.1, 131.9,
135.6, 152.5, 159.09, 161.23, 170.68; ESMS: 313.1 (M-1); Elemental Analysis:
C16H11ClN2OS: Calcd. C, 61.05; H, 3.52; Cl, 11.26; N, 8.90; O, 5.08; S, 10.19; Found C,
61.06; H, 3.54; Cl, 11.27; N, 8.91; O, 5.06; S, 10.20; m. p.159-161 °C.
Results and Discussion
The experimental procedure is very simple and easy to carry out. A mixture of aromatic
aldehyde and substituted 2-amino thiazole was vigorously stirred in methanol in the
presence of catalyst L-proline (10 mol%) at room temperature until the completion of
reaction. Progress of reaction was monitored by Thin-Layer Chromatography (TLC). On
completion of the reaction, concentrated the crude reaction mixture and extracted the
product in ethyl acetate followed by evaporation of solvent gave crude product, which was
further crystallized with ethanol to get pure product in excellent yields. All the products
were characterized by melting point, 1H NMR, 13C NMR spectral and elemental analysis. To
the best of our knowledge, this is the first approach for the synthesis of aldimines carried out
in methanol in presence of L-Proline catalyst at ambient temperature. It can be observed that
almost all reactions were complete in 4-6 h in methanol and L-Proline as a catalyst at
ambient temperature. The amount of solvent used in the reaction did not have significant
influence on the overall rate of the reaction and yields of products. The reaction went to
completion in identical time and with the same isolated yields as for the diluted reaction
mixture. This observation assumes great significance for optimizing reactor volumes during
scale-up operations. A highly efficient stirring is required for the success of this reaction.
The good results obtained following our simple procedure are a pleasant surprise in view of
the numerous catalysts employed in organic solvents to synthesize this class of compounds.
Conclusion
In conclusion, we describe a mild and efficient method for the synthesis of aldimines by
using L-proline as a Lewis acid catalyst method. This method not only provides an excellent
complement to aldimines synthesis but also avoids the use of hazardous acids or bases and
harsh reaction conditions. The advantages of this method include the use of inexpensive
reagents and catalyst under mild condition and experimental operational ease.
Acknowledgment
We acknowledge Dr. P. L. More and Dr. W. N. Jadhav, Dnyanopasak College, Parbhani for
providing necessary facilities and UGC, New Delhi for financial support (MRP-47-125/06).

1863
S. R. BHUSARE et al.
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