One-pot synthesis of 3-phenacylphthalides

Article abstract of DOI:10.1081/SCC-200048976

Acid catalyzed condensation of phthalaldehydic acid (1) with aromatic methyl ketones (2) providing 3-phenacylphthalides (3) is described. Copyright Taylor & Francis, Inc.

Full text of DOI:10.1081/SCC-200048976

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One‐Pot Synthesis of
3‐Phenacylphthalides
Madhusudan V. Paradkar a , Suhas Y. Gadre a
,
Twarita A. Pujari a , Priti P. Khandekar a & Virendra
B. Kumbhar a
a Department of Chemistry, Post Graduate &
Research Center, A.G. College, Karve Road, Pune,
411 004, India
Version of record first published: 28 Jul 2007
To cite this article: Madhusudan V. Paradkar, Suhas Y. Gadre, Twarita A. Pujari, Priti P.
Khandekar & Virendra B. Kumbhar (2005): One‐Pot Synthesis of 3‐Phenacylphthalides,
Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 35:3, 471-474
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Synthetic Communicationsw, 35: 471–474, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200048976
One-Pot Synthesis of 3-Phenacylphthalides
Madhusudan V. Paradkar, Suhas Y. Gadre, Twarita A. Pujari,
Priti P. Khandekar, and Virendra B. Kumbhar
Department of Chemistry, Post Graduate & Research Center, A.G.
College, Pune, India
Abstract: Acid catalyzed condensation of phthalaldehydic acid (1) with aromatic
methyl ketones (2) providing 3-phenacylphthalides (3) is described.
Keywords: One-pot synthesis, 3-phenacylphthalides, phthalaldehydic acid
3-aryl phthalides are widely accepted synthons for the elaboration to polycyc-
lic compounds. 3-phenacylphthalides, i.e., 3-[2-Oxo-2-phenyl-ethyl 3H iso-
benzofuran 1-one], and its derivatives are used as softening agents.[1] These
phthalides are easily converted into a) 3-phenacylidene phthalides, known
for their plant growth regulatory activity[2,3] b) 3-alkylidene phthalides,
known for their biological importance,[4] and c) 3-styryl phthalides which
are used as color formers for heat and pressure-sensitive recording
materials.[5] The literature survey revealed that 3-phenacylphthalides are syn-
thesized by reacting 2-bromo benzaldehyde with 1,3 dicarbonyl compounds
under catalytic[6] conditions in the presence of alkali.[2,7] The method to
obtain 3-phenacylphthalides in one step was not reported yet. Recently we
reported that the reaction of phthalaldehydic acid with various aromatic
methyl ethers in the presence of TFA provided 3-aryl phthalides in good
yields.[8] This observation led us to explore the reaction of phthaladehydic
acid (1) with acetophenone which gave 3-phenacylphthalide (3a) in 69%
yield. Substituted acetophenones (2b–2f) and phthaladehydic acid gave
Received in India September 25, 2004
Address correspondence to Suhas Y. Gadre, Department of Chemistry, Post
Graduate & Research Center, A.G. College, Karve Road, Pune 411 004, India.
E-mail: syg46@rediffmail.com

472
M. V. Paradkar et al.
1
products (3b–3f) which were fully characterized by H NMR, 13C NMR, IR
and elemental analysis.
EXPERIMENTAL
General Procedure for the Synthesis of 3-Phenacylphthalides
A solution of phthalaldehydic acid (1) (3.3 mmol), aromatic methyl ketones
(2a–2f) (3.3 mmol), in trifluoroacetic acid (13 mmol) was refluxed and
monitored by TLC. The reaction mixture was cooled and was poured over
crushed ice. The solid was filtered and recrystallized using hexane: ethyl
acetate (80:20).
3-Phenacylphthalide (3a): 69% yield; M.P. 1458C;[9] IR (KBr); 1772,
1
1679 cm21, H NMR (CDCl3, 300 MHz). data d 3.4 (dd, J ¼ 17.3 Hz, 7.3 Hz,
1H), 3.8 (dd, J ¼ 17.6Hz, 5.57Hz, 1H), 6.19 (t, J ¼ 6.7 Hz, 1H), 7.4–7.8
(m, 6H), 7.9 (m, 3H). 13C NMR (DMSO-d6, 200 MHz); data 43.61 (-CH2),
0
0
78.00 (C3), 123.74–137.0 (C4–C9, C1 –C6 ), 170.71 (lactone carbonyl), 197.30
(-CO-). Anal. Calcd. for C16H12O3: C, 76.12; H, 4.76. Found: C, 76.02; H, 4.70.
3-(4-Methyl phenacyl)phthalide (3b) 68% yield; M.P. 1498C; IR (KBr);
1
1762, 1674 cm 21; H NMR (CDCl3, 300 MHz); data d 2.5 (s, 3H), 3.4 (dd,
J ¼ 17.6 Hz, 7.61 Hz, 1H), 3.8 (dd, J ¼ 17.6 Hz, 5.6 Hz, 1H), 6.22
(t, J ¼ 6.7 Hz, 1H), 7.25–7.35 (m, 2H), 7.5–7.8 (m, 3H), 7.9 (m, 3H). 13C
NMR (DMSO-d6, 200 MHz); data 22.0 (-CH3), 43.31 (-CH2), 78.17 (C3),
0
0
0
0
0
0
123.73–135.27 (C4–C9, C1 , C2 , C3 , C5 , and C6 ), 145.10 (C4 ), 170.85
(lactone carbonyl), 196.83 (-CO-). Anal. Calcd. for C17H14O3: C, 76.69; H,
5.2. Found: C, 76.60; H, 5.13.

One-Pot Synthesis of 3-Phenacylphthalides
473
3-(4-Methoxy phenacyl)phthalide (3c): 81% yield; M.P. 1208C3; IR
(KBr); 1760, 1666 cm21 1H NMR (CDCl3, 300 MHz); data d 3.35 (dd,
;
J ¼ 17.6 Hz, 7.6 Hz, 1H), 3.75 (dd, J ¼ 17.6 Hz, 5.6 Hz, 1H), 3.83 (s, 3H),
6.18 (t, J ¼ 5.6 Hz, 1H), 6.95 (d, 2 H), 7.65 (m, 3H), 7.95 (m, 3H). 13C NMR
(CDCl3, 200 MHz); data 43.61 (-CH2), 55.96 (-OCH3), 77.84 (C3), 114.35
0
0
0
0
0
0
(C3 , C5 ), 123.35–134.69 (C4–C9, C1 , C2 , and C6 ), 164.44 (C4 ), 170.65
(lactone carbonyl), 194.82 (-CO-). Anal. Calcd. for C17H14O4: C, 72.34;
H, 4.96. Found: C, 72.14; H, 4.88.
3-(4-Chlorophenacyl)phthalide (3d): 77% yield; M.P. 1468C; IR (KBr);
1
1751, 1681 cm21; H NMR (CDCl3, 300 MHz) data d 3.38 (dd, J ¼ 17.6 Hz,
7.0 Hz, 1H), 3.76 (dd, J ¼ 17.6Hz, 5.86 Hz,1H), 6.16 (t, J ¼ 6.5 Hz, 1H), 7.44–
7.72 (m, 5H), 7.88–7.96 (m, 3H).13C NMR (DMSO-d6, 200 MHz); data 43.67
0
0
(-CH2), 77.88 (C3), 123.75–139.50 (C4–C9 and C1 –C6 ), 170.65 (lactone
carbonyl), 196.36 (-CO-). Anal. Calcd. for C16H11O3Cl: C, 67.01; H, 3.83.
Found: C, 66.97; H, 3.78.
3-(4-Nitrophenacyl)phthalide (3e): 86% yield; M.P. 2108C; IR (KBr);
1
1747, 1689cm -1; H NMR (CDCl3, 300 MHz); data d 3.46 (dd, J ¼ 17.6 Hz,
6.4 Hz, 1H), 3.78 (dd, J ¼ 17.6 Hz, 6.5 Hz, 1H), 6.17 (t, J ¼ 6.5Hz, 1H), 7.55–
7.72 (m, 3H), 8.10 (m, 3H) 8.40 (d, J ¼ 8 Hz, 2H). 13C NMR (DMSO-d6,
0
200 MHz); data 44.20 (-CH2), 77.68 (C3), 123.76–135.25 (C4–C9, C2 , C3 ,
0
0
0
0
0
C5 , and C6 ), 141.51 (C1 ), 151.62 (C4 ) 170.62 (lactone carbonyl), 196.66
(-CO-). Anal. Calcd. for C16H11NO5: C, 64.65; H, 3.7. Found: C, 64.58; H, 3.68.
3-(2-Hydroxy-5-methylphenacylphthalide (3f): 56% yield; M.P. 132–
1358C; IR (KBr); 1755.1 cm21; H NMR (CDCl3, 300 MHz); data d 2.3
1
(s, 3H), 3.48 (dd, J ¼ 17.6 Hz, 6.7 Hz, 1H), 3.82 (dd, J ¼ 17.6 Hz, 6.1 Hz,
1H), 6.21 (t, 6.7 Hz, 1 Hz, 1H), 7.45–7.80 (m, 5H), 8 (d, J ¼ 7.9 Hz, 2H),
12 (s, 1H). 13C NMR (DMSO-d6, 200 MHz); data s20.73 (-CH3), 45.11
0
0
0
0
0
(-CH2), 77.78 (C3), 118.38–137.7 (C4–C9, C1 , C3 , C4 , C5 , and C6 ),
0
159.17 (C2 ), 170.63 (lactone carbonyl), 201.92 (-CO-). Anal. Calcd. for
C17H14O4: C, 72.34; H, 4.96. Found: C, 72.28; H, 4.90.
ACKNOWLEDGMENT
We are thankful to Dr. A. S. Inamdar, principal, and Dr. H. G. Damle, head,
Department of Chemistry, Abasaheb Garware College, Pune, for providing the
necessary facilities. We are also thankful to the Department of Chemistry,
University of Pune, for providing spectral and elemental analyses.
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