LiCl catalyzed Claisen-Schmidt condensation in solvent-free conditions using microwaves

Article abstract of DOI:10.1081/SCC-120015561

Microwave assisted Claisen-Schmidt condensation of 2-(4-acetylphenyl-amino)-3-(4-methoxyphenyl)-1,8-naphthyridine 3 with various aromatic aldehydes under solvent-free conditions to prepare α,β-unsaturated ketones 4 using LiCl as catalyst has been describe

Full text of DOI:10.1081/SCC-120015561

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
LiCl Catalyzed Claisen–Schmidt Condensation in
Solvent-Free Conditions Using Microwaves
K. Mogilaiah & N. Vasudeva Reddy
To cite this article: K. Mogilaiah & N. Vasudeva Reddy (2003) LiCl Catalyzed Claisen–Schmidt
Condensation in Solvent-Free Conditions Using Microwaves, Synthetic Communications, 33:1,
73-78, DOI: 10.1081/SCC-120015561
To link to this article: http://dx.doi.org/10.1081/SCC-120015561
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 1, pp. 73–78, 2003
LiCl Catalyzed Claisen–Schmidt Condensation in
Solvent-Free Conditions Using Microwaves
*
K. Mogilaiah and N. Vasudeva Reddy
Department of Chemistry, Kakatiya University, Warangal, India
ABSTRACT
Microwave assisted Claisen–Schmidt condensation of 2-(4-acetyl-
phenyl-amino)-3-(4-methoxyphenyl)-1,8-naphthyridine 3 with vari-
ous aromatic aldehydes under solvent-free conditions to prepare
a,b-unsaturated ketones 4 using LiCl as catalyst has been described.
The products are obtained in good yields and excellent purities.
In recent years the use of microwave irradiation in organic reac-
tions is rapidly increasing because of the short reaction time, operational
simplicity and formation of cleaner reaction products. It has been
commonly employed as thermal energy source in various organic
*Correspondence: K. Mogilaiah, Department of Chemistry, Kakatiya University,
Warangal, 506 009, India. E-mail: mogilaiah_k@yahoo.co.in.
73
DOI: 10.1081/SCC-120015561
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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Mogilaiah and Reddy
reactions.[1–3] The use of domestic microwave oven in this regard is
now a well-established procedure in MORE[4] chemistry. It has been
reported that the rate of a variety of organic reactions such as
Michael addition,[5] Claisen rearrangement,[6] Fisher-indole synthesis,[7]
Hantzsch synthesis,[8] Knoevenagel condensation[9] could be enhanced by
microwave irradiation. Chalkones, more generally a,b-unsaturated
ketones are widely recognized as versatile synthons for a variety of
organic transformations.[10,11] Usually, the preparation of chalkones is
Scheme 1.

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LiCl Catalyzed Claisen–Schmidt Condensation
75
achieved with NaOH, KOH, or Ba(OH)2 frombenzaldehyde and methyl
ketones.[12–14]
In view of this and in continuation of our interest on microwave
assisted organic transformations,[15–17] we report here our results related
to the preparation of a,b-unsaturated ketones, without solvent, catalyzed
by LiCl under microwave irradiation, which to our knowledge, was not
attempted up to now.
Interaction of 2-chloro-3-(4-methoxyphenyl)-1,8-naphthyridine 1[18]
with 4-aminoacetophenone 2 in glacial acetic acid under micro-
wave irradiation yielded 2-(4-acetylphenylamino)-3-(4-methoxyphenyl)-
1,8-naphthyridine 3 in 85% yield. Claisen–Schmidt condensation of 3
with various aromatic aldehydes in the presence of LiCl in solvent-free
conditions under microwave irradiation afforded the respective 2-(4-
cinnamoylphenylamino)-3-(4-methoxyphenyl)-1,8-naphthyridines 4. The
reaction is fairly general, facile, and efficient and devoid of any
by-products. The reaction did not proceed at all when performed without
LiCl. The optimum results were obtained when equimolar amounts of the
substrates were reacted in the presence of LiCl under microwave irradia-
tion. Furthermore, it is to be noted that highly pure products were
obtained using this simple procedure and in most cases no further
purification was needed. The reactions proceed efficiently in high yields
at ambient pressure within a few minutes. The process in environmentally
benign.
In conclusion, we have realized a very simple, fast and useful method
for the preparation of various a,b-unsaturated ketones by simple mixing
of the reactants without solvent and irradiation under microwaves. The
other notable advantages offered by this protocol are the reduced reac-
tion times, high purity, easy work-up, better yields of the products and
inexpensive LiCl. Due to the simplicity and environmentally friendly
conditions this methodology should find utility in organic synthesis.
EXPERIMENTAL SECTION
Melting points were determined in open capillary tubes using Cintex
apparatus and were uncorrected. IR spectra in KBr were recorded in a
1
Perkin–Elmer spectrum BX series FT-IR spectrophotometer, H NMR
spectra on a Varian Gemini 200 MHz spectrometer using TMS as an
internal standard and mass spectra (EI) on a Jeol JMS D-300 spectrom-
eter. Analytical TLC was performed on Merck 60F-254 silica gel plates.

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Mogilaiah and Reddy
2-(4-Acetylphenylamino)-3-(4-methoxyphenyl)-1,8-naphthyridine 3
A mixture of 1 (2.70 g, 0.01 mol) and 4-aminoacetophenone 2 (1.35 g,
0.01 mol) in glacial acetic acid (25 mL) was subjected to microwave irra-
diation at 450 watts for 4 min, the completion of the reaction was mon-
itored by TLC and poured into ice cold water. The solid obtained was
collected and washed with water. It was dried and recrystallized from
methanol to give 3 (3.14 g, 85%) as a yellow compound, m.p. 240ꢀC. IR
(KBr) 3250, 1662, 1605 cmꢁ1; 1H NMR (CDCl3, 200 MHz) ꢀ 2.60 (s, 3H,
COCH3), 3.85 (s, 3H, OCH3), 6.90–7.26 (m, 8H, Ar-H), 7.78 (m, 2H,
C4-H, C6-H), 7.96 (m, 1H, C5-H), 8.75 (m, 1H, C7-H), 12.09 (s, 1H, NH);
EIMS m/z 369 (Mþ). Anal. Calcd for C23H19N3O2: C, 74.80; H, 5.15; N,
11.38. Found C, 74.99; H, 5.22; N, 11.49.
General Procedure for the Preparation of
2-(4-Cinnamoylphenylamino)-3-(4-methoxyphenyl)-
1,8-naphthyridines 4
LiCl (0.01 mol) was added to a mixture of 3 (0.01 mol) and appro-
priate aromatic aldehyde (0.01 mol) and irradiated at 300 watts for
1.5–4.5 min, the completion of the reaction was monitored by TLC.
The reaction mixture was allowed to attain room temperature and treated
with water. The resulting precipitate was filtered, dried and recrystallized
frommethanol to afford 4.
4a: Reaction time 2 min, yield 86%, m.p. 220ꢀC. IR (KBr) 3280,
1
1640, 1607, 980 cmꢁ1; H NMR (CDCl3 þ DMSO-d6 200 MHz) ꢀ 3.86
(s, 3H, OCH3), 6.95 (d, J ¼ 15.6 Hz, 1H, olefinic Ca-H), 7.45 (d,
J ¼ 15.6 Hz, olefinic Cb-H), 7.56–7.98 (m, 13H, Ar-H), 8.10 (m, 3H, C4-
H, C5-H, C6-H), 8.52 (m, 1H, C7-H), 12.20 (s, 1H, NH); EIMS m/z 457
(Mþ). Anal. Calcd for C30H23N3O2: C, 78.77; H, 5.03; N, 9.19. Found: C,
78.98; H, 5.10; N, 9.28.
4b: Reaction time 3 min, yield 83%, m.p. 245ꢀC. IR (KBr) 3310, 1645,
1605, 970 cmꢁ1; EIMS m/z 471 (Mþ). Anal. Calcd for C31H25N3O2: C,
78.98; H, 5.31; N, 8.92. Found C, 78.83; H, 5.38; N, 8.83.
4c: Reaction time 1.5 min, yield 80%, m.p. 260ꢀC. IR (KBr) 3250,
1640, 1605, 984 cmꢁ1; EIMS m/z 487 (Mþ) Anal. Calcd for C31H25N3O3:
C, 76.39; H, 5.13; N, 8.62. Found: C, 76.60; H, 5.19; N, 8.75.
4d: Reaction time 4 min, yield 82%, m.p. 290ꢀC; IR (KBr) 3240, 1640,
1606, 975 cmꢁ1; EIMS m/z 491 (Mþ). Anal. Calcd for C30H22N3O2Cl: C,
73.25; H, 4.48; N, 8.55. Found: C, 73.46; H, 4.55; N, 8.69.

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LiCl Catalyzed Claisen–Schmidt Condensation
77
4e: Reaction time 4.5 min, yield 84%, m.p. 205ꢀC; IR (KBr)
3270, 1650, 1607, 980 cmꢁ1; EIMS m/z 491 (Mþ). Anal. Calcd for
C30H22N3O2Cl: C, 73.25; H, 4.48; N, 8.55. Found: C, 73.43; H, 4.57;
N, 8.68.
4f: Reaction time 3 min, yield 81%, m.p. 270ꢀC; IR (KBr) 3290, 1655,
1607, 978 cmꢁ1; EIMS m/z 473 (Mþ). Anal. Calcd for C30H23N3O3: C,
76.11; H, 4.86; N, 8.88. Found: C, 76.30; H, 4.81; N, 8.98.
4g: Reaction time 3.5 min, yield 82%, m.p. 223ꢀC; IR (KBr) 3210,
1640, 1600, 982 cmꢁ1
;
EIMS m/z 500 (Mþ). Anal. Calcd for
C32H28N4O2: C, 76.80; H, 5.60; N, 11.20. Found: C, 76.97; H, 5.67; N,
11.32.
4h: Reaction time 1.5 min, yield 85%, m.p. 255ꢀC; IR (KBr) 3320,
1650, 1605, 970 cmꢁ1
;
EIMS m/z 502 (Mþ). Anal. Calcd for
C30H22N4O4: C, 71.71; H, 4.38; N, 11.16. Found: C, 71.52; H, 4.32; N,
11.28.
4i: Reaction time 3 min, yield 83%, m.p. 180ꢀC; IR (KBr) 3280, 1645,
1606, 972 cmꢁ1; EIMS m/z 501 (Mþ). Anal. Calcd for C31H23H3O4: C,
74.25; H, 4.59; N, 8.38. Found: C, 74.43; H, 4.53; N, 8.52.
ACKNOWLEDGMENT
One of the authors (NVR) is grateful to CSIR, New Delhi for the
award of a senior research fellowship.
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Received in Japan November 5, 2001