Organic reactions in water: Synthesis of phenacyl esters from phenacyl bromide and potassium salts of aromatic acids in the presence of β-cyclodextrin

Article abstract of DOI:10.1081/SCC-200061672

A convenient and facile synthesis of phenacyl esters is reported by the reaction of phenacyl bromide with potassium salts of aromatic acids in the presence of β-cyclodextrin in water under neutral conditions. Copyright Taylor & Francis, Inc.

Full text of DOI:10.1081/SCC-200061672

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Organic Reactions in Water:
Synthesis of Phenacyl Esters
from Phenacyl Bromide and
Potassium Salts of Aromatic
Acids in the Presence of
β‐Cyclodextrin
M. Narender a , M. Somi Reddy a , V. Pavan Kumar a
& K. Rama Rao a
a Organic Chemistry Division‐I , Indian Institute of
Chemical Technology , Hyderabad, India
Published online: 16 Aug 2006.
To cite this article: M. Narender , M. Somi Reddy , V. Pavan Kumar & K. Rama Rao
(2005) Organic Reactions in Water: Synthesis of Phenacyl Esters from Phenacyl
Bromide and Potassium Salts of Aromatic Acids in the Presence of β‐Cyclodextrin,
Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 35:12, 1681-1686, DOI: 10.1081/SCC-200061672
To link to this article: http://dx.doi.org/10.1081/SCC-200061672
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Synthetic Communicationsw, 35: 1681–1686, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200061672
Organic Reactions in Water: Synthesis of
Phenacyl Esters from Phenacyl Bromide
and Potassium Salts of Aromatic Acids
in the Presence of b-Cyclodextrin
M. Narender, M. Somi Reddy, V. Pavan Kumar, and K. Rama Rao
Organic Chemistry Division-I, Indian Institute of Chemical Technology,
Hyderabad, India
Abstract: A convenient and facile synthesis of phenacyl esters is reported by the
reaction of phenacyl bromide with potassium salts of aromatic acids in the presence
of b-cyclodextrin in water under neutral conditions.
Keywords: b-Cyclodextrin, phenacylbromide, phenacyl esters, potassium salts of
carboxylic acids, water
INTRODUCTION
The synthesis of phenacyl esters has many advantages in organic chemistry
because they are usually solids and provide a useful means of characterizing
acids and phenols. The classical synthesis of phenacyl esters consists of
treating the sodium or potassium salts of acids with a-bromoacetophenones,[1]
but are associated with problems such as low yields, slow reaction times,
hydrolysis of the alkylating agents,[2] and contamination of the product with
the starting alkylating reagent. To overcome these disadvantages, a number
of methods have been developed such as potassium fluoride in glacial acetic
acid,[3] polymer-supported reagents,[4] crown ether in conjunction with
Received in the USA November 11, 2005
IICT Communication 050211.
Address correspondence to K. Rama Rao, Organic Chemistry Division-I, Indian
Institute of Chemical Technology, Hyderabad 500 007, India. Tel.: þ91-40-
27193164; Fax: þ91-40-27160757; E-mail: drkrrao@yahoo.com
1681

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M. Narender et al.
phase transfer catalyst (PTC),[5] crown ether under reflux conditions,[6] and
1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in benzene,[7] which is carcino-
genic. Even recently, Liu et al.[8] reported the synthesis of phenacyl esters
from a-tosyloxy ketones in ionic liquids. We saw the need to develop a
mild and widely applicable approach for the synthesis of phenacyl esters in
water under neutral conditions.
RESULTS AND DISCUSSION
Cyclodextrins, which are cyclic oligosaccharides, have excited much
interest as enzyme models because of their ability to bind substrates selec-
tively and catalyze chemical reactions by supramolecular catalysis
involving the reversible formation of host–guest complexes with the sub-
strates by noncovalent bonding as seen in enzyme complexation
processes.[9] Complexation depends on the size, shape, and hydrophobicity
of the guest molecule. The synthesis of phenacyl esters in the presence of
b-cyclodextrin has been examined (Scheme 1). In general, these reactions
were carried out by dissolving b-cyclodextrin in water, followed by the
addition of phenacyl bromide 1 and potassium salt of carboxylic acid 2 to
obtain the corresponding phenacyl ester. All the products were characterized
by 1H NMR, IR, and mass spectroscopy. Although these reactions were
carried out in situ, the cyclodextrin complexes were isolated and characterized
by 1H NMR in D2O. There is an upfield shift of C3 and C5 protons of cyclo-
dextrin indicating the formation of inclusion complex.[10] These reactions did
not proceed in the absence of b-cyclodextrin. We believe that b-cyclodextrin
activates the phenacyl bromide by forming the hydrogen bond and also acts as
a solubilizing agent. These cyclodextrins can also be recovered and reused.
This method has many advantages over the existing methodologies,
offering an environmentally benign protocol with the practical convenience
of not having to handle flammable and anhydrous organic solvents, and is a
practical method involving carboxylic acid salts.
Scheme 1.

Organic Reactions in Water
EXPERIMENTAL
Materials
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All reactions were carried out without any special precautions in an
atmosphere of air. Chemicals and solvents were purchased from Fluka and
S. D. Fine Chemicals and used as received. The 1H NMR spectra were
recorded on a 300 or 400 MHz spectrometer. IR spectra were recorded on a
NICOLET FT-IR spectrometer. Mass spectra were observed on V. G. Auto
spectrometer.
General Procedure
To a solution of b-cyclodextrin (1 mmol) in water (25 mL) at 508C phenacyl
bromide (1 mmol) in acetone (1 mL) was added. After 10 min, the potassium
salt of carboxylic acid (1.2 mmol) was added. After completion of the
reaction, the organic material was extracted with ethyl acetate, washed with
sodium bicarbonate and brine, and dried over sodium sulphate. On solvent
removal, the crude product was purified on silica gel by using ethylacetate–
hexane (2:98) as an eluent.
1-(2-Phenylcarbonyloxyacetyl) benzene (1). White solid, yield 90%, mp
1
116–1188C; IR (KBr) 1720 cm21, 1685 cm21; H NMR (CDCl3, 300 MHz)
d: 5.55 (s, 2H), 7.40–7.70 (m, 6H), 7.95 (d, 2H, J ¼ 7.9 Hz), 8.15 (d, 2H,
J ¼ 7.5 Hz); Anal. calcd. for C15H12O3 requires C, 74.99; H, 5.03; found:
C, 74.85; H, 5.12.
2-Oxo-2-phenylethyl 2-phenylacetate (2). Brown oil, yield 95%, IR (KBr)
1
1715 cm21, 1660 cm21; H NMR (CDCl3, 400 MHz) d: 3.82 (s, 2H), 5.32
(s, 2H), 7.25–7.40 (m, 5H), 7.47 (t, 2H, J ¼ 9.4 Hz), 7.63 (t, 1H,
J ¼ 9.4 Hz), 7.93 (d, 2H, J ¼ 9.4 Hz). Anal. calcd. for C16H14O3 requires
C, 75.58; H, 5.55; found: C, 75.45; H, 5.65.
2-Oxo-2-phenylethyl 3-phenyl-(E)-2-propenoate (3). White solid, yield
88%, mp 1108C; IR (KBr) 1702 cm21, 1630 cm21 1H NMR (CDCl3,
;
300 MHz) d: 5.45 (s, 2H), 6.60 (d, 1H, J ¼ 16.4 Hz), 7.37–7.42 (m, 3H),
7.45–7.70 (m, 5H), 7.80 (d, 1H, J ¼ 16.4 Hz), 7.95 (d, 2H, J ¼ 9.6 Hz).
Anal. calcd. for C17H14O3 requires C, 76.68; H, 5.30; found: C, 76.52;
H, 5.40.
4-Chloro-1-(2-phenylcarbonyloxyacetyl) benzene (4). White solid, yield
1
92%, mp 117–1198C; IR (KBr) 1732 cm21, 1702 cm21; H NMR (CDCl3,
400 MHz) d: 5.48 (s, 2H), 7.40–7.50 (m, 4H), 7.59 (t, 1H, J ¼ 9.3 Hz),
7.93 (d, 2H, J ¼ 9.0 Hz), 8.12 (d, 2H, J ¼ 9.0 Hz); Anal. calcd. for

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M. Narender et al.
C15H11O3Cl requires C, 65.59; H, 4.04; Cl, 12.91; found: C, 65.45; H, 4.13;
Cl, 12.79.
2-(4-Chlorophenyl)-2-oxoethyl 2-phenylacetate (5). White solid, yield
1
90%, mp 73–758C; IR (KBr) 1750 cm21, 1695 cm21; H NMR (CDCl3,
400 MHz) d: 3.80 (s, 2H), 5.25 (s, 2H), 7.25–7.40 (m, 5H), 7.47 (d, 2H,
J ¼ 9.2 Hz), 7.85 (d, 2H, J ¼ 9.2 Hz). Anal. calcd. for C16H13O3Cl requires
C, 66.56; H, 4.54; Cl, 12.28; found: C, 66.43; H, 4.65; Cl, 12.44.
2-(4-Chlorophenyl)-2-oxoethyl 3-phenyl-(E)-2-propenoate (6). white solid,
1
yield 90%, mp 1358C; IR (KBr) 1709 cm21, 1632 cm21; H NMR (CDCl3,
400 MHz) d: 5.40 (s, 2H), 6.60 (d, 1H, J ¼ 14.6 Hz), 7.35–7.45 (m, 3H),
7.45–7.55 (m, 4H), 7.80 (d, 1H, J ¼ 14.6 Hz), 7.95 (d, 2H, J ¼ 9.3 Hz).
Anal. calcd. for C17H13O3Cl requires C, 67.89; H, 4.36; Cl, 11.79; found:
C, 67.75; H, 4.53; Cl, 11.53.
4-Bromo-1-(2-phenylcarbonyloxyacetyl) benzene (7). White solid, yield
1
93%, mp 119–1208C; IR (KBr) 1734 cm21, 1701 cm21; H NMR (CDCl3,
400 MHz) d: 5.52 (s, 2H), 7.46 (t, 2H, J ¼ 9.4 Hz), 7.57 (t, 1H, J ¼ 9.4 Hz),
7.67 (d, 2H, J ¼ 9.4 Hz), 7.85 (d, 2H, J ¼ 10.0 Hz), 8.13 (d, 2H,
J ¼ 10.0 Hz); Anal. calcd. for C15H11O3Br requires C, 56.45; H, 3.47; Br,
25.04; found: C, 56.30; H, 3.67; Br, 25.18.
2-(4-Bromophenyl)-2-oxoethyl 2-phenylacetate (8). White solid, yield
88%, mp 778C; IR (KBr) 1749 cm21, 1697 cm21 1H NMR (CDCl3,
;
300 MHz) d: 3.80 (s, 2H), 5.30 (s, 2H), 7.30–7.40 (m, 5H), 7.60 (d, 2H,
J ¼ 9.0 Hz), 7.75 (d, 2H, J ¼ 9.0 Hz). Anal. calcd. for C16H13O3Br requires
C, 57.68; H, 3.93; Br, 23.98; found: C, 57.53; H, 4.18; Br, 23.86.
2-(4-Bromophenyl)-2-oxoethyl 3-phenyl-(E)-2-propenoate (9). White
1
solid, yield 86%, mp 1378C; IR (KBr) 1720 cm21, 1701 cm21; H NMR
(CDCl3, 300 MHz) d: 5.40 (s, 2H), 6.55 (d, 1H, J ¼ 16.7 Hz), 7.35–7.85
(m, 10H). Anal. calcd. for C17H13O3Br requires C, 59.15; H, 3.80; Br,
23.15; found: C, 59.28; H, 3.71; Br, 23.02.
4-Methyl-1-(2-phenylcarbonyloxyacetyl) benzene (10). White solid, yield
88%, mp 1058C; IR (KBr) 1732 cm21, 1697 cm21 1H NMR (CDCl3,
;
400 MHz) d: 2.45 (s, 3H), 5.51 (s, 2H), 7.30 (d, 2H, J ¼ 8.2 Hz), 7.45
(t, 2H, J ¼ 8.9 Hz), 7.56 (t, 1H, J ¼ 8.9 Hz), 7.87 (d, 2H, J ¼ 8.2 Hz), 8.13
(d, 2H, J ¼ 8.9 Hz); Anal. calcd. for C16H14O3 requires C, 75.58; H, 5.55;
found: C, 75.41; H, 5.41.
2-(4-Methylphenyl)-2-oxoethyl 2-phenylacetate (11). White solid, yield
,
90%, mp 778C; IR (KBr) 1745 cm21
(CDCl3, 400 MHz) d: 2.45 (s, 3H), 3.80 (s, 2H), 5.30 (s, 2H), 7.20–7.40
1699 cm21
;
1H NMR

Organic Reactions in Water
1685
(m, 7H), 7.80 (d, 2H, J ¼ 9.5 Hz). Anal. calcd. for C17H16O3 requires C,
76.10; H, 6.01; found: C, 76.30; H, 5.87.
2-(4-Methylphenyl)-2-oxoethyl 3-phenyl-(E)-2-propenoate (12). White solid,
1
yield 87%, mp 1308C; IR (KBr) 1725 cm21, 1695 cm21; H NMR (CDCl3,
300 MHz) d: 2.45 (s, 3H), 5.40 (s, 2H), 6.55 (d, 1H, J ¼ 15.0 Hz), 7.27
(d, 2H, J ¼ 8.8 Hz), 7.35–7.40 (m, 3H), 7.50–7.60 (m, 2H), 7.80 (d, 1H,
J ¼ 15.0 Hz), 7.87 (d, 2H, J ¼ 8.8 Hz). Anal. calcd. for C18H16O3 requires
C, 77.13; H, 5.75; found: C, 77.28; H, 5.88.
4-Nitro-1-(2-phenylcarbonyloxyacetyl) benzene (13). Pale yellow solid,
yield 90%, mp 140–1428C; IR (KBr) 1726 cm21, 1705 cm21 1H NMR
;
(CDCl3, 300 MHz) d: 5.53 (s, 2H), 7.46 (t, 2H, J ¼ 7.8 Hz), 7.60 (t, 1H,
J ¼ 7.8 Hz), 8.10–8.18 (m, 4H), 8.39 (d, 2H, J ¼ 8.4 Hz); Anal. calcd. for
C15H11O5N requires C, 63.16; H, 3.89; N, 4.91; found: C, 63.31; H, 3.74;
N, 4.76.
2-(4-Nitrophenyl)-2-oxoethyl 2-phenylacetate (14). Pale yellow solid, yield
89%, mp 878C; IR (KBr) 1728 cm21, 1705 cm21; 1H NMR (CDCl3, 300 MHz)
d: 3.80 (s, 2H), 5.40 (s, 2H), 7.40–7.50 (m, 3H), 7.55–7.65 (m, 2H), 8.15
(d, 2H, J ¼ 8.8 Hz), 8.40 (d, 2H, J ¼ 8.8 Hz). Anal. calcd. for C16H13O5N
requires C, 64.28; H, 4.38; N, 4.68; found: C, 64.43; H, 4.51; N, 4.82.
2-(4-Nitrophenyl)-2-oxoethyl 3-phenyl-(E)-2-propenoate (15). Pale yellow
1
solid, yield 93%, mp 1528C; IR (KBr) 1728 cm21, 1705 cm21; H NMR
(CDCl3, 300 MHz) d: 5.40 (s, 2H), 6.55 (d, 1H, J ¼ 16.6 Hz), 7.35–7.45
(m, 3H), 7.50–7.60 (m, 2H), 7.80 (d, 1H, J ¼ 16.6 Hz), 8.15 (d, 2H,
J ¼ 9.2 Hz), 8.40 (d, 2H, J ¼ 9.2 Hz). Anal. calcd. for C17H13O5N requires
C, 65.59; H, 4.21; N, 4.50; found: C, 65.76; H, 4.05; N, 4.35.
ACKNOWLEDGMENTS
MN and MSR thank to CSIR, New Delhi, India, for financial assistance.
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