An efficient method for the preparation of benzyl γ-ketohexanoates

Article abstract of DOI:10.2478/s11696-012-0282-8

Twenty acid chlorides, 4-(mono/di-benzyloxy)-4-ketobutanoyl chlorides (Ia-XXa) were synthesised by the reaction of monoesters of succinic acid with thionyl chloride. The product thus obtained (4-benzyloxy-4-ketobutanoyl chlorides) was treated with diethyl

Full text of DOI:10.2478/s11696-012-0282-8

Chemical Papers 67 (4) 444–455 (2013)
DOI: 10.2478/s11696-012-0282-8
ORIGINAL PAPER
An efficient method for the preparation of benzyl γ-ketohexanoates
Muhammad Iqbal*, Imam B. Baloch, Musa K. Baloch
Department of Chemistry, Gomal University, 29050 Dera Ismail Khan, Pakistan
Received 4 August 2012; Accepted 12 September 2012
Twenty acid chlorides, 4-(mono/di-benzyloxy)-4-ketobutanoyl chlorides (Ia–XXa) were synthe-
sised by the reaction of monoesters of succinic acid with thionyl chloride. The product thus ob-
tained (4-benzyloxy-4-ketobutanoyl chlorides) was treated with diethylcadmium to convert it into
the corresponding keto-esters (Ib–XXb), the mono/di-benzyl-γ-ketohexanoates, with a good yield.
All the compounds thus prepared were characterised by physical, spectroscopic (UV-VIS, IR, 1H
NMR, 13C NMR), and mass measurements techniques.
c
ꢀ 2012 Institute of Chemistry, Slovak Academy of Sciences
Keywords: γ-ketoesters, mono/disubstituted-benzyl alcohols, diethylcadmium, monoesters of suc-
cinic acid
Introduction
metal complexes, their ions or oxides as catalysts
and toxic solvents such as ketoacids, strong inorganic
acids, nitrogenous and halogenated solvents, the use
of which can be harmful to the environment (Poli-
akoff et al., 2002; Larock, 1999; Sheldon & Arends,
2004; Tojo & Fernández, 2006; Bandgar et al., 2005;
Csende, 2002; Hilgenkamp & Zercher, 2001; Kashima
et al., 2001; Wang et al., 2009; Williams et al., 2001,
2002; Huang et al., 2005). The other common tech-
nique is anaerobic oxidation; this faces criticism on the
grounds that it is difficult to control and to obtain a
well-defined product (Csende et al., 1993; Stájer et al.,
1994; Poliakoff et al., 2002; Hudlicky, 1990). However,
the contribution made by Von Rudloff (1958), Cason
(1942, 1946), and Cason and Prout (1944, 1948) to
the synthesis of γ-ketoesters is essential as it provides
basic and important information in this respect.
The above aspects prompted us to synthesise
new mono/di-benzyl-γ-ketohexanoates (Ib–XXb) from
the corresponding acid chlorides (Ia–XXa) using the
methodology devised by Cason and Prout (1944, 1948)
and Von Rudloff (1958). The compounds reported (Ia–
XXa and Ib–XXb) were synthesised by following a
two-step reaction using diethyl ether as solvent and
diethyl cadmium as ethylating agent. In the first step,
the benzyl hydrogen succinates (I–XX) were converted
into the corresponding acid chlorides (Ia–XXa) by al-
The γ-ketohexanoates are bi-functional com-
pounds having ketone and ester groups. They are con-
sidered to be the precursors of numerous important
compounds used in the pharmaceutical and agrochem-
ical industries (Dahl et al., 1999; Forni et al., 1994; Fu-
jisawa et al., 1994; Nakamura et al., 2003; Shafiee et
al., 1998). These are synthons of some biologically ac-
tive compounds like sex hormones and pheromones,
anti-asthma drugs, enzyme inhibitors, additives in
food, and perfumes (Hayakawa et al., 1998; Heiss et
al., 2001; Itoh et al., 2002; Kataoka et al., 1999; Kizaki
et al., 2001; Larock, 1999; Sheldon & Arends, 2004;
Tojo & Fernández, 2006; Yamamoto et al., 2002a,
2002b). Hence, a number of techniques for their syn-
thesis have been proposed and some significant routes
leading to the synthesis of γ-ketoesters have been de-
scribed by Ballini et al. (2002), Izquierdo et al. (2011),
Wehrli and Chu (1973, 1978), Ronsheim et al. (2002),
Brockman & Fabio (1957), and Taylor (1958). A great
deal of work has been reported in this area of organic
chemistry over the last decade (Bandgar et al., 2005;
Csende, 2002; Hilgenkamp & Zercher, 2001; Huang et
al., 2005; Kashima et al., 2001; Wang et al., 2009;
Williams et al., 2001, 2002).
These methods require very expensive transition
*Corresponding author, e-mail: miqbal 44@yahoo.com

M. Iqbal et al./Chemical Papers 67 (4) 444–455 (2013)
Table 1. Physical characteristics of Ia–XXa
445
wi(calc.)/%
Time Yield
wi(found)/%
Entry Ara
Formula
Mr Physical
min
165
165
165
%
state
C
H
N
–
–
–
–
–
–
–
–
Cl
Br
–
–
–
–
–
–
–
–
–
–
–
–
–
–
I
Ia
2-MeO-C6H4
3-MeO-C6H4
75 C12H13ClO4
70 C12H13ClO4
74 C12H13ClO4
79 C13H15ClO5
79 C13H15ClO5
75 C13H15ClO5
72 C13H15ClO5
74 C13H15ClO5
256.68 Viscous oil 56.15
5.10
4.78
5.10
5.22
5.10
5.23
5.27
5.31
5.27
5.11
5.27
5.13
5.27
5.16
5.27
5.16
3.71
3.65
3.71
3.58
3.71
3.88
3.86
3.65
3.86
3.79
3.86
3.68
3.30
3.45
3.30
3.21
3.30
3.26
2.86
2.77
2.86
2.67
2.86
2.98
13.81
13.94
13.81
13.33
13.81
13.86
12.37
12.66
12.37
12.56
12.37
12.14
12.37
12.48
12.37
12.22
13.05
12.84
13.05
12.97
13.05
12.82
27.16
27.33
27.16
27.32
27.16
26.98
11.60
11.26
11.60
11.53
11.60
11.76
10.06
10.32
10.06
9.97
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
56.23
256.68 Viscous oil 56.15
56.34
IIa
IIIa 4-MeO-C6H4
256.68 Viscous oil 56.15
56.33
IVa 2,3-(MeO)2-C6H3 150
Va 2,4-(MeO)2-C6H3 150
286.70 Viscous oil 54.46
54.37
286.70 Viscous oil 54.46
54.64
VIa 2,5-(MeO)2-C6H3 150
VIIa 3,4-(MeO)2-C6H3 150
VIIIa 3,5-(MeO)2-C6H3 150
286.70 Viscous oil 54.46
54.55
286.70 Viscous oil 54.46
54.61
286.70 Viscous oil 54.46
54.59
IXa 2-NO2-C6H4
Xa 3-NO2-C6H4
180
180
180
210
210
210
225
225
225
210
210
210
70 C11H10ClNO5 271.66 Viscous oil 48.63
5.16
5.31
5.16
5.10
5.16
5.23
–
48.86
69 C11H10ClNO5 271.66 Viscous oil 48.63
48.33
XIa 4-NO2-C6H4
XIIa 2-Cl-C6H4
XIIIa 3-Cl-C6H4
XIVa 4-Cl-C6H4
VIa 2-Br-C6H4
XVIa 3-Br-C6H4
XVIIa 4-Br-C6H4
XVIIIa 2-I-C6H4
XIXa 3-I-C6H4
XXa 4-I-C6H4
67 C11H10ClNO5 271.66 Viscous oil 48.63
48.42
63 C11H10Cl2O3 260.95 Viscous oil 50.60
50.76
65 C11H10Cl2O3 260.95 Viscous oil 50.60
–
–
–
–
–
–
–
–
50.47
66 C11H10Cl2O3 260.95 Viscous oil 50.60
50.67
68 C11H10BrClO3 305.76 Viscous oil 43.24
26.15
26.45
26.15
26.24
26.15
26.08
–
43.16
67 C11H10BrClO3 305.76 Viscous oil 43.24
43.35
72 C11H10BrClO3 305.76 Viscous oil 43.24
43.17
63 C11H10ClIO3 352.65 Viscous oil 37.47
36.00
35.98
36.00
36.23
36.00
35.76
37.42
64 C11H10ClIO3 352.65 Viscous oil 37.47
–
–
37.56
66 C11H10ClIO3 352.65 Viscous oil 37.47
37.41
10.06
9.98
a) Aromatic substituent (Fig. 2).
lowing them to react with thionyl chloride and in the
second step the acid chlorides thus obtained were con-
verted into novel benzyl γ-ketohexanoates (Ib–XXb)
by treating them with diethyl cadmium.
13C NMR (75 MHz) (1D, 2D, homo/hetero-nuclear)
spectra were procured in CDCl3 on a Bruker Biospin,
AMX 300 MHz FT NMR spectrometer (Bruker, Ger-
many). EI-MS were acquired with a direct insertion
probe on a double-focusing Finnigan MAT 112 at
70 eV. HR-EI-MS measurements were made on a
JEOL HX 110 spectrometer (Jeol, Japan). Elemental
analyses were performed by Midwest Microlab (USA).
Column chromatography was carried out using sil-
ica gel (PF254, mesh size 60–70; Merck, Germany),
and thin layer chromatography was performed on pre-
coated silica gel plates (20 cm × 20 cm, 0.2 mm
thickness) with UV fluorescence (PF254) (Merck, Ger-
many).
Experimental
All the required chemicals were of analytical grade,
purchased from Merck (Germany) and used as re-
ceived. The UV-VIS spectrum was recorded in abso-
lute methanol on an Irmeco UV/VIS Model U-2020
spectrophotometer (Germany). IR spectra were ob-
tained on a Tensor 27 FT-IR spectrophotometer sup-
1
plied by Bruker (Germany). H NMR (300 MHz) and

446
M. Iqbal et al./Chemical Papers 67 (4) 444–455 (2013)
Table 2. Spectroscopic data of acid halides (Ia–XXa)
Compound
Spectral data
—
—
Ia
IIa
IIIa
IVa
Va
IR, ν˜/cm−1: 3056 (ArH), 1792 (COCl), 1737 (C O), 1595, 1546 (C C, ArH), 1026 (C—O), 723 (C—Cl)
—
—
1H NMR (CDCl3), δ: 2.60 (t, 2H, J = 6.5 Hz, C-2), 2.74 (t, 2H, J = 6.5 Hz, C-3), 3.89 (s, 3H, OMe), 5.14 (s, 2H,
C-1ꢀꢀ), 6.96 (m, 2H, ArH), 7.46 (m, 1H, ArH), 7.80 (m, 1H, ArH)
13C NMR (CDCl3), δ: 31.5 (C-2), 36.6 (C-3), 56.6 (OMe), 67.8 (C-1ꢀꢀ), 113.8 (C-3ꢀ), 120.1 (C-5ꢀ), 121.2 (C-1ꢀ),
128.1 (C-4ꢀ), 128.9 (C-6ꢀ), 159.1 (C-2ꢀ), 169.9 (C-1), 175.6 (C-4)
MS, m/z (Ir/%): 256.68 (11) (M+
UV-VIS (MeOH), λmax/nm (log ε): 278 (3.7)
)
IR, ν˜/cm−1: 3057 (ArH), 1793 (COCl), 1738 (C O), 1592, 1541 (C C, ArH), 1021 (C—O), 721 (C—Cl)
—
—
—
—
1H NMR (CDCl3), δ: 2.60 (t, 2H, J = 6.5 Hz, C-2), 2.74 (t, 2H, J = 6.5 Hz, C-3), 3.89 (s, 3 H, OMe), 5.14 (s, 2H,
C-1ꢀꢀ), 6.96 (m, 2H, ArH), 7.46 (m, 1H, ArH), 7.80 (m, 1H, ArH)
13C NMR (CDCl3), δ: 30.9 (C-2), 36.2 (C-3), 56.7 (OMe), 67.5 (C-1ꢀꢀ), 112.5 (C-2ꢀ), 115.6 (C-3ꢀ), 112.2 (C-4ꢀ),
118.4 (C-6ꢀ), 128.3 (C-5ꢀ), 137.6 (C-1ꢀ), 169.1 (C-1), 175.3 (C-4)
MS, m/z (Ir/%): 256.68 (13) (M+
UV-VIS (MeOH), λmax/nm (log ε): 278 (3.7)
)
IR, ν˜/cm−1: 3057 (ArH), 1793 (COCl), 1738 (C=O), 1593, 1542 (C C, ArH), 1023 (C—O), 722 (C—Cl)
—
—
1H NMR (CDCl3), δ: 2.61 (t, 2H, J = 6.5 Hz, C-2), 2.76 (t, 2H, J = 6.5 Hz, C-3), 3.82 (s, 3H, OMe), 5.18 (s, 2H,
C-1ꢀꢀ), 6.97 (m, 2H, ArH), 7.25 (m, 2H, ArH)
13C NMR (CDCl3), δ: 30.1 (C-2), 37.6 (C-3), 55.5 (O-Me), 67.8 (C-1ꢀꢀ), 112.4 (C-5ꢀ), 112.5 (C-3ꢀ), 126.4 (C-6ꢀ),
127.2 (C-1ꢀ), 127.3 (C-2ꢀ), 157.5 (C-4ꢀ), 168.9 (C-1), 176.5 (C-4)
MS, m/z (Ir/%): 256.68 (16) (M+
UV-VIS (MeOH), λmax/nm (log ε): 278 (3.7)
)
IR, ν˜/cm−1: 3065 (ArH), 1797 (COCl), 1741 (C O), 1598, 1547 (C C, 1027 (C—O), 725 (C—Cl)
—
—
—
—
1H NMR (CDCl3), δ: 2.64 (t, 2H, J = 6.5 Hz, C-2), 2.79 (t, 2H, J = 6.5 Hz, C-3), 3.87 (s, 6H, 2 × OMe), 5.23 (s,
2H, C-1ꢀꢀ), 6.96–6.98 (m, 2H, ArH), 7.12–7.31 (m, 2H, ArH)
13C NMR (CDCl3), δ: 30.5 (C-2), 36.7 (C-3), 56.1 (OMe), 58.6 (OMe), 67.7 (C-1ꢀꢀ), 112.3 (C-4ꢀ), 120.1 (C-6ꢀ), 120.7
(C-5ꢀ), 127.2 (C-1ꢀ), 143.8 (C-3ꢀ), 156.5 (C-2ꢀ), 169.9 (C-1), 177.4 (C-4)
MS, m/z (Ir/%): 286.70 (17) (M+
UV-VIS (MeOH), λmax/nm (log ε): 282 (3.7)
IR, ν˜/cm−1: 3067 (ArH), 1799 (COCl), 1743 (C O), 1591, 1544, 1431 (C C, ArH), 1245, 1135, 1029 (C—O), 727
)
—
—
—
—
(C—Cl)
1H NMR (CDCl3), δ: 2.66 (t, 2H, J = 6.5 Hz, C-2), 2.78 (t, 2H, J = 6.5 Hz, C-3), 3.82 (s, 6H, 2 × OMe), 5.23 (s,
2H, C-1ꢀꢀ), 6.73 (m, 1H, ArH), 6.92 (m, 1H, ArH), 7.18 (m, 1H, ArH)
13C NMR (CDCl3), δ: 29.4 (C-2), 36.3 (C-3), 56.3 (2 × OMe), 67.2 (C-1ꢀꢀ), 99.8 (C-3ꢀ), 105.9 (C-5ꢀ), 115.8 (C-1ꢀ),
128.2 (C-6ꢀ), 158.6 (C-2ꢀ), 159.6 (C-4ꢀ), 169.2 (C-1), 176.7 (C-4)
MS, m/z (Ir/%): 286.70 (18) (M+
UV-VIS (MeOH), λmax/nm (log ε): 282 (3.7)
IR, ν˜/cm−1: 3069 (ArH), 1790 (COCl), 1747 (C O), 1594, 1541, 1433 (C C, ArH), 1249, 1131, 1022 (C—O), 724
)
—
—
—
—
VIa
VIIa
VIIIa
(C—Cl)
1H NMR (CDCl3), δ: 2.60 (t, 2H, J = 6.5 Hz, C-2), 2.74 (t, 2H, J = 6.5 Hz, C-3), 3.89 (s, 6H, 2 × OMe), 5.14 (s,
2H, C-1ꢀꢀ), 6.96 (m, 2H, ArH), 7.46 (m, 1H, ArH), 7.80 (m, 1H, ArH)
13C NMR (CDCl3), δ: 29.6 (C-2), 36.1 (C-3), 56.6 (2 × OMe), 64.8 (C-1ꢀꢀ), 113.3 (C-3ꢀ), 120.1 (C-6ꢀ), 121.1 (C-1ꢀ),
128.8 (C-4ꢀ), 128.8 (C-6ꢀ), 159.2 (C-2ꢀ), 169.9 (C-1), 179.7 (C-4)
MS, m/z (Ir/%): 286.70 (14) (M+
UV-VIS (MeOH), λmax/nm (log ε): 282 (3.7)
IR, ν˜/cm−1: 3077 (ArH), 1799 (COCl), 1738 (C O), 1598, 1547, 1431 (C C, ArH), 1241, 1129, 1021 (C—O), 725
)
—
—
—
—
(C—Cl)
1H NMR (CDCl3), δ: 2.79 (t, 2H, J = 6.5 Hz, C-2), 2.93 (t, 2H, J = 6.5 Hz, C-3), 3.84 (s, 6H, 2 × OMe), 5.19 (s,
2H, C-1ꢀꢀ), 6.66 (m, 1H, ArH), 6.91 (m, 1H, ArH), 7.40 (m, 1H, ArH)
13C NMR (CDCl3), δ: 29.5 (C-2), 36.3 (C-3), 55.2 (2 × OMe), 68.4 (C-1ꢀꢀ), 111.7 (C-5ꢀ), 113.3 (C-2ꢀ), 120.7 (C-6ꢀ),
123.5 (C-1ꢀ), 147.8 (C-4ꢀ), 149.1 (C-3ꢀ), 167.4 (C-1), 176.6 (C-4)
MS, m/z (Ir/%): 286.70 (19) (M+
UV-VIS (MeOH), λmax/nm (log ε): 282 (3.7)
)
IR, ν˜ cm−1: 3046 (ArH), 1789 (COCl), 1733 (C O), 1601, 1548, 1432 (C C, ArH), 1243, 1127, 1019 (C—O), 726
—
—
—
—
(C—Cl)
1H NMR (CDCl3), δ: 2.67 (t, 2H, J = 6.5 Hz, C-2), 2.87 (t, 2H, J = 6.5 Hz, C-3), 3.83, 3.84 (s, 6H, 2 × OMe), 5.16
(s, 2H, C-1ꢀꢀ), 6.92–6.53 (m, 3H, ArH)
13C NMR (CDCl3), δ: 29.2 (C-2), 36.1 (C-3), 57.4 (2 × OMe), 68.9 (C-1ꢀꢀ), 98.2 (C-4ꢀ), 104.6 (C-2ꢀ, C-6ꢀ), 136.7
(C-1ꢀ), 160.7 (C-3ꢀ, C-5ꢀ), 168.5 (C-1), 173.3 (C-4)
MS, m/z (Ir/%): 286.70 (11) (M+
UV-VIS (MeOH), λmax/nm (log ε): 278 (3.4)
)

M. Iqbal et al./Chemical Papers 67 (4) 444–455 (2013)
447
Table 2. (continued)
Compound
Spectral data
IR, ν˜/cm−1: 3085 (ArH), 1788 (COCl), 1734 (C O), 1602, 1549, 1433 (C C, ArH), 1365 (NO2), 1244, 1128, 1018
—
—
—
—
IXa
(C—O), 724 (C—Cl)
1H NMR (CDCl3), δ: 2.81 (t, 2H, J = 6.5 Hz, C-2), 2.98 (t, 2H, J = 6.5 Hz, C-3), 5.14 (s, 2H, C-1ꢀꢀ), 7.54–7.59
(2H, m, ArH), 7.75 (1H, m, ArH), 7.92 (1H, m, ArH)
13C NMR (CDCl3), δ: 30.2 (C-2), 35.5 (C-3), 64.7 (C-1ꢀꢀ), 113.7 (C-6ꢀ), 126.2 (C-3ꢀ), 129.5 (C-4ꢀ), 131.1 (C-5ꢀ),
135.3 (C-1ꢀ), 148.3 (C-2ꢀ), 169.7 (C-1), 172.3 (C-4)
MS, m/z (Ir/%): 271.66 (16) (M+
UV-VIS (MeOH), λmax/nm (log ε): 238 (3.1)
IR, ν˜/cm−1: 3087 (ArH), 1786 (COCl), 1735 (C O), 1603, 1559, 1443 (C C, ArH), 1371 (NO2), 1255, 1138, 1028
)
—
—
—
—
Xa
(C—O), 722 (C—Cl)
1H NMR (CDCl3), δ: 2.83 (t, 2H, J = 6.5 Hz, C-2), 2.99 (t, 2H, J = 6.5 Hz, C-3), 5.21 (s, 2H, C-1ꢀꢀ), 7.45 (m, 1H,
ArH), 7.76 (1H, m, ArH), 7.95–7.99 (m, 2H, ArH)
13C NMR (CDCl3), δ: 29.8 (C-2), 36.7 (C-3), 66.7 (C-1ꢀꢀ), 121.9 (C-4ꢀ), 123.6 (C-2ꢀ), 128.9 (C-5ꢀ), 132.3 (C-6ꢀ),
141.2 (C-1ꢀ), 147.2 (C-3ꢀ), 167.8 (C-1), 173.6 (C-4)
MS, m/z (Ir/%): 271.66 (14) (M+
UV-VIS (MeOH), λmax/nm (log ε): 238 (3.1)
IR, ν˜/cm−1: 3083 (ArH), 1785 (COCl), 1734 (C O), 1601, 1558, 1441 (C C, ArH), 1375 (NO2), 1251, 1134, 1025
)
—
—
—
—
XIa
(C—O), 727 (C—Cl)
1H NMR (CDCl3), δ: 2.78 (t, 2H, J = 6.5 Hz, C-2), 2.98 (t, 2H, J = 6.5 Hz, C-3), 5.19 (s, 2H, C-1ꢀꢀ), 7.57 (m, 2H,
ArH), 7.98–8.05 (m, 2H, ArH)
13C NMR (CDCl3), δ: 29.3 (C-2), 35.8 (C-3), 66.9 (C-1ꢀꢀ), 123.2 (C-3ꢀ, C-5ꢀ), 127.1 (C-2ꢀ, C-6ꢀ), 141.6 (C-1ꢀ), 145.7
(C-4ꢀ), 169.5 (C-1), 173.2 (C-4)
MS, m/z (Ir/%): 271.66 (14) (M+
UV-VIS (MeOH), λmax/nm (log ε): 238 (3.1)
IR, ν˜/cm−1: 3053 (ArH), 1787 (COCl), 1738 (C O), 1603, 1551, 1439 (C C, ArH), 1257, 1138, 1021 (C—O), 721
)
—
—
—
—
XIIa
XIIIa
XIVa
XVa
(C—Cl)
1H NMR (CDCl3), δ: 2.67 (t, 2H, J = 6.5 Hz, C-2), 2.85 (t, 2H, J = 6.5 Hz, C-3), 5.11 (s, 2H, C-1ꢀꢀ), 7.22 (m, 1H,
ArH), 7.29–7.34 (m, 2H, ArH), 7.65 (m, 1H, ArH)
13C NMR (CDCl3), δ: 29.7 (C-2), 35.6 (C-3), 66.7 (C-1ꢀꢀ), 126.2 (C-5ꢀ), 127.2 (C-6ꢀ), 128.1 (C-3ꢀ), 128.3 (C-4ꢀ),
129.8 (C-2ꢀ), 137.8 (C-1ꢀ), 169.9 (C-1), 174.3(C-4)
MS, m/z (Ir/%): 260.95 (17) (M+
UV-VIS (MeOH), λmax/nm (log ε): 268 (4.1)
IR, ν˜/cm−1: 3059 (ArH), 1791 (COCl), 1736 (C O), 1605, 1548, 1432 (C C, ArH), 1251, 1132, 1019 (C—O), 726
)
—
—
—
—
(C—Cl)
1H NMR (CDCl3), δ: 2.68 (t, 2H, J = 6.5 Hz, C-2), 2.87 (t, 2H, J = 6.5 Hz, C-3), 5.19 (s, 2H, C-1ꢀꢀ), 7.31–7.36 (m,
2H, ArH), 7.43 (m, 1H, ArH), 7.59 (m, 1H, ArH)
13C NMR (CDCl3), δ: 29.7 (C-2), 35.5 (C-3), 64.4 (C-1ꢀꢀ), 123.7 (C-6ꢀ), 125.4 (C-2ꢀ), 126.2 (C-4ꢀ), 128.8 (C-5ꢀ),
133.0 (C-3ꢀ), 137.6 (C-1ꢀ), 168.5 (C-1), 174.4 (C-4)
MS, m/z (Ir/%): 260.95 (18) (M+
UV-VIS (MeOH), λmax/nm (log ε): 268 (4.1)
IR, ν˜/cm−1: 3061 (ArH), 1789 (COCl), 1737 (C O), 1606, 1549, 1436 (C C, ArH), 1252, 1131, 1018 (C—O), 724
)
—
—
—
—
(C—Cl)
1H NMR (CDCl3), δ: 2.72 (t, 2H, J = 6.5 Hz, C-2), 2.88 (t, 2H, J = 6.5 Hz, C-3), 5.21 (s, 2H, C-1ꢀꢀ), 7.28 (m, 2H,
ArH), 7.39 (m, 2H, ArH)
13C NMR (CDCl3), δ: 29.6 (C-2), 35.7 (C-3), 65.9 (C-1ꢀꢀ), 128.5 (C-3ꢀ, C-5ꢀ), 129.2 (C-2ꢀ, C-6ꢀ), 132.7 (C-4ꢀ), 133.7
(C-1ꢀ), 168.9 (C-1), 174.5 (C-4)
MS, m/z (Ir/%): 260.95 (15) (M+
UV-VIS (MeOH), λmax/nm (log ε): 268 (4.1)
IR, ν˜/cm−1: 3063 (ArH), 1788 (COCl), 1739 (C O), 1602, 1575, 1431 (C C, ArH), 1258, 1139, 1028 (C—O), 722
)
—
—
—
—
(C—Cl), 521 (C—Br)
1H NMR (CDCl3), δ: 2.75 (t, 2H, J = 6.5 Hz, C-2), 2.83 (t, 2H, J = 6.5 Hz, C-3), 5.12 (s, 2H, C-1ꢀꢀ), 7.23–7.33 (m,
3H, ArH), 7.55 (m, 1H, ArH)
13C NMR (CDCl3), δ: 29.3 (C-2), 35.5 (C-3), 63.9 (C-1ꢀꢀ), 125.2 (C-2ꢀ), 126.2 (C-5ꢀ), 128.0 (C-3ꢀ), 128.3 (C-4ꢀ),
130.2 (C-6ꢀ), 136.6 (C-1ꢀ), 168.8 (C-1), 174.4 (C-4)
MS, m/z (Ir/%): 305.76 (12) (M+
UV-VIS (MeOH), λmax/nm (log ε): 268 (4.1)
)

448
M. Iqbal et al./Chemical Papers 67 (4) 444–455 (2013)
Table 2. (continued)
Compound
Spectral data
IR, ν˜/cm−1: 3064 (ArH), 1786 (COCl), 1729 (C O), 1599, 1567, 1443 (C C, ArH), 1253, 1144, 1024, 723 (C—Cl),
—
—
—
—
XVIa
523 (C—Br)
1H NMR (CDCl3), δ: 2.73 (t, 2H, J = 6.5 Hz, C-2), 2.84 (t, 2H, J = 6.5 Hz, C-3), 5.18 (s, 2H, C-1ꢀꢀ), 7.25 (m, 1H,
ArH), 7.43 (m, 1H, ArH), 7.50–7.54 (m, 2H, ArH)
13C NMR (CDCl3), δ: 29.8 (C-2), 36.6 (C-3), 66.8 (C-1ꢀꢀ), 121.7 (C-3ꢀ), 124.5 (C-6ꢀ), 128.1 (C-5ꢀ), 128.9 (C-4ꢀ),
130.3 (C-2ꢀ), 141.8 (C-1ꢀ), 167.6 (C-1), 173.5 (C-4)
MS, m/z (Ir/%): 305.76 (15) (M+
UV-VIS (MeOH), λmax/nm (log ε): 268 (4.1)
)
IR, ν˜/cm−1: 3061 (ArH), 1787 (COCl), 1731 (C O), 1598, 1569, 1441 (C C, ArH), 1257, 1142, 1021, 725 (C—Cl),
—
—
—
—
XVIIa
525 (C—Br)
1H NMR (CDCl3), δ: 2.73 (t, 2H, J = 6.5 Hz, C-2), 2.82 (t, 2H, J = 6.5 Hz, C-3), 5.22 (s, 2H, C-1ꢀꢀ), 7.21 (m, 2H,
ArH), 7.86 (m, 2H, ArH)
13C NMR (CDCl3), δ: 29.4 (C-2), 36.5 (C-3), 66.2 (C-1ꢀꢀ), 121.4 (C-4ꢀ), 128.7 (C-2ꢀ, C-6ꢀ), 130.6 (C-3ꢀ, C-5ꢀ), 136.3
(C-1ꢀ), 167.8 (C-1), 173.6 (C-4)
MS, m/z (Ir/%): 305.76 (13) (M+
UV-VIS (MeOH), λmax/nm (log ε): 268 (4.1)
)
XVIIIa IR, ν˜/cm−1: 3075 (ArH), 1791 (COCl), 1736 (C O), 1593, 1561, 1446 (C C, ArH), 1261, 1147, 1025, 723 (C—Cl),
—
—
—
—
487 (C—I)
1H NMR (CDCl3), δ: 2.76 (t, 2H, J = 6.9 Hz, C-2), 2.85 (t, 2H, J = 7.3 Hz, C-3), 5.20 (s, 2H, C-1ꢀꢀ), 7.11–7.14 (m,
2H, ArH), 7.34 (m, H, ArH), 7.81 (m, H, ArH)
13C NMR (CDCl3), δ: 29.1 (C-2), 36.6 (C-3), 66.9 (C-1ꢀꢀ), 94.5 (C-2ꢀ), 126.7 (C-5ꢀ), 127.5 (C-6ꢀ), 128.6 (C-4ꢀ), 138.5
(C-3ꢀ), 139.3 (C-1ꢀ), 167.7 (C-1), 173.3 (C-4)
MS, m/z (Ir/%): 352.65 (12) (M+
UV-VIS (MeOH), λmax/nm (log ε): 278 (3.7)
)
IR, ν˜/cm−1: 3077 (ArH), 1793 (COCl), 1738 (C O), 1595, 1562, 1448 (C C, ArH), 1263, 1148, 1026, 723 (C—Cl),
—
—
—
—
XIXa
485 (C—I)
1H NMR (CDCl3), δ: 2.77 (t, 2H, J = 6.9 Hz, C-2), 2.88 (t, 2H, J = 6.9 Hz, C-3), 5.25 (s, 2H, C-1ꢀꢀ), 7.16 (t, 1H,
J = 7.8 Hz, ArH), 7.31 (d, 1H, J = 7.8 Hz, ArH), 7.67 (d, J = 7.8 Hz, 1H, ArH), 7.72 (s, 1H, ArH)
13C NMR (CDCl3), δ: 29.3 (C-2), 36.2 (C-3), 66.5 (C-1ꢀꢀ), 94.6 (C-3ꢀ), 126.7 (C-6ꢀ), 129.6 (C-5ꢀ), 135.8 (C-4ꢀ), 138.5
(C-2ꢀ), 139.4 (C-1ꢀ), 167.4 (C-1), 173.5 (C-4)
MS, m/z (Ir/%): 352.65 (11) (M+
UV-VIS (MeOH), λmax/nm (log ε): 278 (3.7)
)
IR, ν˜/cm−1: 3064 (ArH), 1786 (COCl), 1729 (C O), 1599, 1567, 1443 (C C, ArH), 1253, 1144, 1024, 723 (C—Cl),
—
—
—
—
XXa
523 (C—Br)
1H NMR (CDCl3), δ: 2.73 (t, 2H, J = 6.5 Hz, C-2), 2.84 (t, 2H, J = 6.5 Hz, C-3), 5.18 (s, 2H, C-1ꢀꢀ), 7.25 (m, 1H,
ArH), 7.43 (m, 1H, ArH), 7.50–7.54 (m, 2H, ArH)
13C NMR (CDCl3), δ: 29.8 (C-2), 36.6 (C-3), 66.8 (C-1ꢀꢀ), 121.7 (C-3ꢀ), 124.5 (C-6ꢀ), 128.1 (C-5ꢀ), 128.9 (C-4ꢀ),
130.3 (C-2ꢀ), 141.8 (C-1ꢀ), 167.6 (C-1), 173.5 (C-4)
MS, m/z (Ir/%): 352.65 (15) (M+
UV-VIS (MeOH), λmax/nm (log ε): 268 (4.1)
)
Twenty (I–XX ) benzyl hydrogen succinates were
prepared by following the procedure described pre-
viously (Iqbal et al., 2012; Cason & Prout, 1944,
1948; Von Rudloff, 1958). In brief, the correspond-
ing benzyl alcohols (15 mmol) were added to succinic
anhydride (15 mmol), p-toluenesulfonic acid (12.5 g,
0.06 mmol), and toluene (15 mL) in a single-necked
round-bottom flask (100 mL) equipped with a mag-
netic stirrer, Dean–Stark trap, and a reflux condenser.
After refluxing the mixture for 14 h under nitrogen,
it was cooled to ambient temperature, treated with
a saturated aqueous solution of sodium bicarbonate
and extracted with hexane (3 × 50 mL). The extract
was dried over MgSO4, the solvent was removed, and
the residue was subjected to open column chromatog-
raphy on silica gel using a mixture of hexane/ethyl
acetate (ϕr = 4 : 1 → 1 : 4) as the eluent to obtain
the pure monoesters I–XX.
General procedure for preparation of 4-mono/
di-benzyloxy-4-ketobutanoyl chlorides
(Ia–XXa)
Acid chlorides (Ia–XXa) were prepared by a pub-
lished procedure (Cason & Prout, 1944, 1948; Von
Rudloff, 1958). In brief, the required monoester (I–
XX; 8 mmol) and thionyl chloride (1.64 mL, 22.5
mmol) were mixed in a round-bottom reaction flask
(100 mL) fitted with a reflux condenser. The mixture
was heated to 30–40◦C for different lengths of time
(Table 1) and the excess thionyl chloride was removed
by heating at reduced pressure. The residue was sub-
jected to open column chromatography on silica gel
using a mixture of hexane/ethyl acetate (ϕr = 4 : 1 →
1 : 4) as the eluent to obtain pure Ia–XXa. The prod-
uct was characterised by the physical characteristics
(Table 1) and spectroscopic data (Table 2).

M. Iqbal et al./Chemical Papers 67 (4) 444–455 (2013)
449
Table 3. Physical characteristics of Ib–XXb
wi(calc.)/%
Time Yield
wi(found)/%
Entry Ar
Formula
Mr
Physical
state
h
%
C
H
N
–
–
–
–
–
–
–
–
Cl
–
–
–
–
–
–
–
–
–
–
–
Br
–
–
–
–
–
–
–
–
–
–
–
–
–
–
I
Ib
2-MeO-C6H4
3-MeO-C6H4
13
12
13
69 C14H18O4
73 C14H18O4
71 C14H18O4
74 C15H20O5
79 C15H20O5
75 C15H20O5
74 C15H20O5
71 C15H20O5
250.29 Viscous oil 67.18
7.25
7.16
7.25
7.13
7.25
7.36
7.19
7.14
7.19
7.23
7.19
7.11
7.19
7.11
7.19
7.35
5.70
5.56
5.70
5.67
5.70
5.66
5.94
5.77
5.94
5.83
5.94
5.45
5.05
5.12
5.05
4.87
5.05
5.02
4.37
4.16
4.37
4.46
4.37
4.15
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
67.43
250.29 Viscous oil 67.18
67.32
IIb
IIIb 4-MeO-C6H4
250.29 Viscous oil 67.18
67.13
IVb 2,3-(MeO)2-C6H3 11
Vb 2,4-(MeO)2-C6H3 11
280.11 Viscous oil 64.27
64.12
280.11 Viscous oil 64.27
64.18
VIb 2,5-(MeO)2-C6H3 13
VIIb 3,4-(MeO)2-C6H3 14
VIIIb 3,5-(MeO)2-C6H3 12
280.11 Viscous oil 64.27
64.23
280.11 Viscous oil 64.27
64.34
280.11 Viscous oil 64.27
64.19
IXb 2-NO2-C6H4
Xb 3-NO2-C6H4
13
13
13
12
13
14
12
14
14
15
16
14
68 C13H15NO5 265.12 Viscous oil 58.86
5.28
5.32
5.28
5.38
5.28
5.45
–
58.95
66 C13H15NO5 265.12 Viscous oil 58.86
56.73
XIb 4-NO2-C6H4
XIIb 2-Cl-C6H4
XIIIb 3-Cl-C6H4
XIVb 4-Cl-C6H4
XVb 2-Br-C6H4
XVIb 3-Br-C6H4
XVIIb 4-Br-C6H4
XVIIIb 2-I-C6H4
XIXb 3-I-C6H4
XXb 4-I-C6H4
59 C13H15NO5 265.12 Viscous oil 58.86
56.95
59 C13H15ClO3 254.71 Viscous oil 61.30
13.92
13.99
13.92
13.87
13.92
13.88
–
61.28
64 C13H15ClO3 254.71 Viscous oil 61.30
–
–
–
–
–
–
–
–
61.19
64 C13H15ClO3 254.71 Viscous oil 61.30
61.55
63 C13H15BrO3 299.11 Viscous oil 52.19
26.71
25.72
26.71
26.68
26.71
26.85
–
52.23
59 C13H15BrO3 299.11 Viscous oil 52.19
–
–
–
–
–
52.33
60 C13H15BrO3 299.11 Viscous oil 52.19
52.21
59 C13H15IO3
67 C13H15IO3
66 C13H15IO3
346.09 Viscous oil 45.11
36.66
36.55
36.66
36.45
36.66
36.67
45.31
346.09 Viscous oil 45.11
44.87
–
–
346.09 Viscous oil 45.11
45.24
Preparation of diethylcadmium reagent
General procedure for preparation of benzyl-γ-
ketohexanoates (Ib–XXb)
The diethylcadmium reagent was prepared from a
freshly prepared Grignard solution (Cason & Prout,
1944, 1948; Von Rudloff, 1958). Dry CdCl2 (2.15 g,
11.8 mmol) was added to the Grignard reagent (pre-
pared from ethyl bromide (1.06 g, 11.8 mmol) and
magnesium metal (0.26 g, 11.8 mmol) and cooled to
0◦C) and dry diethylether (60 mL) over a period of 10
min with vigorous stirring. Stirring was continued for
a further hour and the diethylcadmium reagent was
used as prepared.
All γ-ketohexanoates (Ib–XXb) were prepared from
acid chlorides (Ia–XXa), by following the method-
ologies described by Cason and Prout (1944, 1948)
and Von Rudloff (1958). For the preparation of com-
pounds Ib–XXb, the corresponding 4-benzyloxy-4-
ketobutanoyl chloride (5 mmol) was slowly added to
the freshly prepared solution of diethyl cadmium. Af-
ter maintaining reflux for different lengths of time (Ta-
ble 3), the mixture was allowed to stand overnight.
The material was then poured into a beaker contain-

450
M. Iqbal et al./Chemical Papers 67 (4) 444–455 (2013)
Table 4. Spectroscopic data of synthesised γ-ketohexanoates (Ib–VIIb) from acid halides
Compound
Spectral data
—
—
Ib
IR, ν˜/cm−1: 3057 (ArH), 1749 (C O), 1717 (RO—C O), 1595, 1546, 1429 (C C, ArH), 1239, 1127, 1026
— —
— —
1H NMR (CDCl3), δ: 1.05 (t, 3H, J = 4 Hz, C-6), 2.55 (q, J = 7.4 Hz, 2H, C-5), 2.72 (t, 2H, J = 6.8 Hz, C-2), 2.82
(t, 2H, J = 6.8 Hz, C-3), 3.86 (s, 3H, OMe), 5.22 (s, 1H, C-1ꢀꢀ), 6.81–6.98 (m, 3H, ArH), 7.26 (m, 1H, ArH)
13C NMR (CDCl3), δ: 7.7 (C-6), 28.3 (C-2), 34.2 (C-3), 36.1 (C-5), 56.3 (OMe), 62.8 (C-1ꢀꢀ), 123.7 (C-5ꢀ), 124.7
(C-1ꢀ), 127.5 (C-6ꢀꢀ), 128.9 (C-4ꢀ), 129.3 (C-3ꢀ), 155.6 (C-2ꢀ), 172.2 (C-1), 212.1 (C-4)
MS, m/z (Ir/%): 250.29 (23) (M+
UV-VIS (MeOH), λmax/nm (log ε): 271.3 (3.3)
)
—
—
IIb
IR, ν˜/cm−1: 3065 (ArH), 1725, 1714 (C O), 1592, 1545, 1431 (C C), 1230, 1128, 1025
—
—
1H NMR (CDCl3), δ: 1.05 (t, 3H, J = 7.4 Hz, C-6), 2.57 (q, 2H, J = 7.4 Hz, C-5), 2.72 (t, 2H, J = 6.8 Hz, C-2),
2.83 (t, 2H, J = 6.8 Hz, C-3), 3.82 (s, 3H, OMe), 5.21 (s, 2H, C-1ꢀꢀ), 6.96–6.99 (m, 2H, ArH), 7.11 (m, 1H, ArH),
7.32 (m, 1H, ArH)
13C NMR (CDCl3), δ: 7.7 (C-6), 29.3 (C-2), 31.3 (C-3), 36.1 (C-5), 54.9 (OMe), 65.4 (C-1ꢀꢀ), 112.2 (C-2ꢀ), 113.3
(C-4ꢀ), 118.3 (C-6ꢀ), 129.3 (C-5ꢀ), 138.8 (C-1ꢀ), 159.4 (C-3ꢀ), 172.2 (C-1), 212.1 (C-4)
MS, m/z (Ir/%): 250.29 (29) (M+
UV-VIS (MeOH), λmax/nm (log ε): 271.6 (3.5)
)
—
—
IIIb
IR, ν˜/cm−1: 3069 (ArH), 1747 (C O), 1722 (CO2Ar), 1596, 1543, 1430 (C C), 1243, 1129, 1023
—
—
1H NMR (CDCl3), δ: 1.04 (t, 3H, J = 7.4 Hz, C-6), 2.56 (q, 2H, J = 7.4 Hz, C-5), 2.72 (t, 2H, J = 6.8 Hz, C-2),
2.82 (t, 2H, J = 6.8 Hz, C-3), 3.76 (s, 3H, OMe), 5.21 (s, 2H, C-1ꢀꢀ), 6.94–6.96 (m, 2H, ArH), 7.17–7.19 (m, 2H,
ArH)
13C NMR (CDCl3), δ: 7.7 (C-6), 27.8 (C-2), 33.4 (C-3), 34.2 (C-5), 55.4 (OMe), 66.2, (C-1ꢀꢀ), 113.6 (C-3ꢀ, C-5ꢀ),
129.2 (C-1ꢀ), 129.3 (C-2ꢀ, C-6ꢀ), 159.1 (C-4ꢀ), 172.2 (C-1), 212.1 (C-4)
MS, m/z (Ir/%): 250.29 (25) (M+
UV-VIS (MeOH), λmax/nm (log ε): 271.1 (3.6)
)
—
—
IVb
IR, ν˜/cm−1: 3085 (ArH), 2850, 1757 (C O), 1723 (CO2Ar), 1592, 1538, 1435 (C C), 1237, 1133, 1041
—
—
1H NMR (CDCl3), δ: 1.02 (t, 3H, J = 7.4 Hz, C-6), 2.61 (q, 2H, J = 7.4 Hz, C-5), 2.72 (t, 2H, J = 6.8 Hz, C-2),
2.85 (t, 2H, J = 6.8 Hz, C-3), 3.79 (s, 3H, OMe), 3.82 (s, 3H, OMe), 5.13 (s, 2H, C-1ꢀꢀ), 6.67–6.99 (m, 3H, ArH)
13C NMR (CDCl3), δ: 7.7 (C-6), 27.3 (C-2), 32.4 (C-3), 34.9 (C-5), 55.6 (OMe), 59.7 (OMe), 62.0 (C-1ꢀꢀ), 115.5
(C-4ꢀ), 119.1 (C-6ꢀ), 124.2 (C-5ꢀ), 127.6 (C-1ꢀ), 138.9 (C-2ꢀ), 147.2 (C-3ꢀ), 174.2 (C-1), 213.1 (C-4)
MS, m/z (Ir/%): 280.11 (27) (M+
UV-VIS (MeOH), λmax/nm (log ε): 278.8 (3.7)
)
—
—
Vb
IR, ν˜/cm−1: 3054 (ArH), 1754 (C O), 1726 (CO2Ar), 1600, 1540, 1436 (C C), 1290, 1135
—
—
1H NMR (CDCl3), δ: 1.05 (t, 3H, J = 7.4 Hz, C-6), 2.62 (q, 2H, J = 7.4 Hz, C-5), 2.79 (t, 2H, J = 6.8 Hz, C-2),
2.85 (t, 2H, J = 6.8 Hz, C-3), 3.78 (s, 3H, OMe), 3.85 (s, 6H, 2 × OMe), 5.21 (s, 2H, C-1ꢀꢀ), 6.63 (s, 1H, ArH), 6.63
(m, 1H, ArH), 6.84 (m, 1H, ArH), 7.41 (m, 1H, ArH)
13C NMR (CDCl3), δ: 7.7 (C-6), 29.3 (C-2), 33.2 (C-3), 36.1 (C-5), 55.4 (OMe), 56.5 (OMe), 62.8 (C-1ꢀꢀ), 100.4
(C-3ꢀ), 108.5 (C-5ꢀ), 116.1 (C-1ꢀ), 128.8 (C-6ꢀ), 158.3 (C-2ꢀ), 162.6 (C-4ꢀ), 171.2 (C-1), 214.1 (C-4)
MS, m/z (Ir/%): 280.11 (24) (M+
UV-VIS (MeOH), λmax/nm (log ε): 278.6 (3.87)
)
—
—
VIb
VIIb
VIIIb
IR, ν˜/cm−1: 3092 (ArH), 1753 (C O), 1722 (ArO—C O), 1605, 1595, 1435 (C C), 1245 (C—O), 1125
— —
— —
1H NMR (CDCl3), δ: 1.04 (t, 3H, J = 7.4 Hz, C-6), 2.49 (q, 2H, J = 7.4 Hz, C-4), 2.73 (t, 2H, J = 6.8 Hz, C-2),
2.86 (t, 2H, J = 6.8 Hz, C-3), 3.82 (s, 6H, 2 × OMe), 5.21 (s, 2H, C-1ꢀꢀ), 6.82–7.33 (m, 3H, ArH)
13C NMR (CDCl3), δ: 7.7 (C-6), 29.6 (C-2), 32.6 (C-3), 35.3 (C-5), 56.3 (2 × OMe), 63.4 (C-1ꢀꢀ), 114.8 (C-6ꢀ), 115.8
(C-4ꢀ), 124.6 (C-3ꢀ), 128.7 (C-1ꢀ), 148.5 (C-2ꢀ), 155.5 (C-5ꢀ), 171.4 (C-1), 214.7 (C-4)
MS, m/z (Ir/%): 280.11 (18) (M+
UV-VIS (MeOH), λmax/nm (log ε): 282.5 (3.6)
)
IR, ν˜/cm−1: 3086 (ArH), 1755 (C O), 1721 (CO2Ar), 1603, 1592, 1433 (C C), 1247, 1128
—
—
—
—
1H NMR (CDCl3), δ: 1.03 (t, 3H, J = 7.4 Hz, C-6), 2.48 (q, 2H, J = 7.4 Hz, C-5), 2.75 (t, 2H, J = 6.8 Hz, C-2),
2.85 (t, 2H, J = 6.8 Hz, C-3), 3.81 (s, 6H, 2 × OMe), 5.17 (s, 2H, C-1ꢀꢀ), 6.43–7.21 (m, 3H, ArH)
13C NMR (CDCl3), δ: 7.7 (C-6), 31.2 (C-2), 35.8 (C-3), 36.1 (C-5), 55.7 (2 × OMe), 66.3 (C-1ꢀꢀ), 111.4 (C-5ꢀ), 121.2
(C-6ꢀ), 124.7 (C-1ꢀ), 146.3 (C-4ꢀ), 147.3 (C-2ꢀ), 148.7 (C-3ꢀ), 171.8 (C-1), 214.4 (C-4)
MS, m/z (Ir/%): 280.11 (18) (M+
UV-VIS (MeOH), λmax/nm (log ε): 279.7 (3.8)
)
IR, ν˜/cm−1: 1751 (C O), 1726 (CO2Ar), 1592, 1538, 1515, 1435 (C C), 1235, 1155, 1141, 1133, 1041, 1022
—
—
—
—
1H NMR (CDCl3), δ: 1.03 (t, 3H, J = 7.4 Hz, C-6), 2.44 (q, 2H, J = 7.4 Hz, C-5), 2.71 (t, 2H, J = 6.8 Hz, C-2),
2.81 (t, 2H, J = 6.8 Hz, C-3), 3.84 (s, 6H, 2 × OMe), 5.19 (s, 2H, C-1ꢀꢀ), 6.45–6.99 (m, 3H, ArH)
13C NMR (CDCl3), δ: 7.7 (C-6), 27.2 (C-2), 32.7 (C-3), 36.4 (C-5), 55.6 (s, 2 × OMe), 66.7 (C-1ꢀꢀ), 98.7 (C-4ꢀ),
105.1 (C-2ꢀ, C-6ꢀ), 137.2 (C-1ꢀ), 158.4 (C-3ꢀ, C-5ꢀ), 171.1 (C-1), 215.4 (C-4)
MS, m/z (Ir/%): 280.11 (22) (M+
UV-VIS (MeOH), λmax/nm (log ε): 279.9 (3.8)
)

M. Iqbal et al./Chemical Papers 67 (4) 444–455 (2013)
451
Table 4. (continued)
Compound
Spectral data
—
—
IXb
IR, ν˜/cm−1: 3092 (ArH), 1746 (C O), 1723 (CO2R), 1596, 1530, 1441 (C C, ArH), 1375 (NO2), 1244, 1139, 1045
—
—
1H NMR (CDCl3), δ: 1.06 (t, J = 7.4 Hz, 3H, CH3, C-6), 2.57 (q, J = 7.4 Hz, 2H, CH2, C-5), 2.72 (t, J = 6.8 Hz,
2H, C-2), 2.85 (t, J = 6.8 Hz, 2H, C-3), 5.19 (s, 2H, C-1ꢀꢀ), 7.62 (m, H, ArH), 7.83 (m,1H, ArH), 8.19–8.26 (m, 2H,
ArH)
13C NMR (CDCl3), δ: 7.7 (C-6), 29.1 (C-2), 32.6 (C-3), 36.7 (C-5), 65.1 (C-1ꢀꢀ), 124.7 (C-3ꢀ), 129.2 (C-4ꢀ), 129.9
(C-5ꢀ), 134.3 (C-1ꢀ), 134.3 (C-6ꢀ), 147.4 (C-2ꢀ), 171.2 (C-1), 213.2 (C-4)
MS, m/z (Ir/%): 265.12 (16) (M+
UV-VIS (MeOH), λmax/nm (log ε): 267 (4.0)
)
—
—
Xb
XIb
XIIb
IR, ν˜/cm−1: 3086 (ArH), 1757, 1721 (C O), 1597, 1539, 1440 (C C), 1374 (NO2), 1249, 1137, 1044
—
—
1H NMR (CDCl3), δ: 1.06 (t, 3H, J = 7.4 Hz, C-6), 2.57 (q, 2H, J = 7.4 Hz, C5), 2.72 (t, 2H, J = 6.8 Hz, C-2),
2.80 (t, 2H, J = 6.8 Hz, C-3), 5.19 (s, 2H, C-1ꢀꢀ), 7.57 (m, 1H, ArH), 7.79 (m, 1H, ArH), 8.18–8.24 (m, 2H, ArH)
13C NMR (CDCl3), δ: 7.7 (C-6), 29.3 (C-2), 36.1 (C-3), 36.2 (C-5), 65.6 (C-1ꢀ), 123.3 (C-2ꢀ), 123.8 (C-4ꢀ), 130.6
(C-5ꢀ), 132.4 (C-6ꢀ), 143.2 (C-1ꢀ), 147.8 (C-3ꢀ), 171.4 (C-1), 213.8 (C-4)
MS, m/z (Ir/%): 265.12 (19) (M+
UV-VIS (MeOH), λmax/nm (log ε): 267.5 (4.0)
)
IR, ν˜/cm−1: 3071 (ArH), 1753, 1722 (C O), 1595, 1535, 1440 (C C), 1372 (NO2), 1248, 1136, 1045
—
—
—
—
1H NMR (CDCl3), δ: 1.03 (t, 3H, J = 7.4 Hz, C-6), 2.57 (q, 2H, J = 7.4 Hz, C-5), 2.72 (t, 2H, J = 6.8 Hz, C-2),
2.82 (t, 2H, J = 6.8 Hz, C-3), 5.18 (s, 2H, C-1ꢀꢀ), 7.59 (m, 2H, ArH), 8.20 (m, 2H, ArH)
13C NMR (CDCl3), δ: 7.7 (C-6), 27.8 (C-2), 31.4 (C-3), 36.6 (C-5), 66.3 (C-1ꢀꢀ), 123.7 (C-3ꢀ, C-5ꢀ), 129.9 (C-2ꢀ,
C-6ꢀ), 143.4 (C-1ꢀ), 147.4 (C-4ꢀ), 171.6 (C-1), 214.2 (C-4)
MS, m/z (Ir/%): 265.12 (14) (M+
UV-VIS (MeOH), λmax/nm (log ε): 267.6 (4.2)
)
IR, ν˜/cm−1: 3077 (ArH), 1748 (C O), 1721 (CO2R), 1597, 1529, 1497, 1456 (C C), 1387, 1251, 1237, 1134, 1208,
—
—
—
—
1094, 1047, 1015, 723 (C—Cl)
1H NMR (CDCl3), δ: 1.04 (t, 3H, J = 7.4 Hz, C-6), 2.59 (q, 2H, J = 7.4 Hz, C-5), 2.72 (t, 2H, J = 6.8 Hz, C-2),
2.82 (t, 2H, J = 6.8 Hz, C-3), 5.10 (s, 2H, C-1ꢀꢀ), 7.28 (m, 1H, ArH), 7.31–7.33 (m, 2H, ArH), 7.65 (m, 1H, ArH)
13C NMR (CDCl3), δ: 7.7 (C-6), 28.5 (C-2), 30.6 (C-3), 36.1 (C-5), 62.2 (C-1ꢀꢀ), 127.1 (C-6ꢀ), 127.4 (C-5ꢀ), 129.2
(C-3ꢀ), 129.6 (C-2ꢀ), 131.2 (C-4ꢀ), 138.4 (C-1ꢀ), 174.2 (C-1), 213.2 (C-4)
MS, m/z (Ir/%): 254.71 (19) (M+
UV-VIS (MeOH), λmax/nm (log ε): 266.5 (4.1)
)
—
—
XIIIb
XIVb
XVb
IR, ν˜/cm−1: 3079 (ArH), 1739, 1722 (C O), 1599, 1525, 1452 (C C), 1248, 1133, 727 (C—Cl)
—
—
1H NMR (CDCl3), δ: 1.03 (t, 3H, J = 7.4 Hz, C-6), 2.42 (q, 2H, J = 7.4 Hz, C-5), 2.72 (t, 2H, J = 6.8 Hz, C-2),
2.81 (t, 2H, J = 6.8 Hz, C-3), 5.19 (s, 2H, C-1ꢀꢀ), 7.33–7.36 (m, 2H, ArH), 7.46 (m, 1H, ArH), 7.59 (m, 1H, ArH)
13C NMR (CDCl3), δ: 7.7 (C-6), 29.3 (C-2), 36.1 (C-3), 36.2 (C-5), 65.7 (C-1ꢀꢀ), 124.1 (C-6ꢀ), 125.8 (C-2ꢀ), 128.1
(C-4ꢀ), 130.1 (C-5ꢀ), 133.5 (C-3ꢀ), 138.6 (C-1ꢀ), 172.0 (C-1), 212.1 (C-4)
MS, m/z (Ir/%): 254.71 (16) (M+
UV-VIS (MeOH), λmax/nm (log ε): 266.8 (3.7)
)
IR, ν˜/cm−1: 3093 (ArH), 1754, 1720 (C O), 1597, 1529 (C C), 1383, 1251, 1047, 721 (C—Cl)
—
—
—
—
1H NMR (CDCl3), δ: 1.03 (t, 3H, J = 7.4 Hz, C-6), 2.42 (q, 2H, J = 7.4 Hz, C-5), 2.73 (t, J = 6.8 Hz, 2H, C-2),
2.83 (t, J = 6.8 Hz, 2H, C-3), 5.19 (s, 2H, C-1ꢀꢀ), 7.38 (m, 2H, ArH), 7.45 (m, 2H, ArH)
13C NMR (CDCl3), δ: 7.7 (C-6), 28.7 (C-2), 32.3 (C-3), 35.7 (C-5), 66.5 (C-1ꢀꢀ), 128.6 (C-3ꢀ, C-5ꢀ), 128.8 (C-2ꢀ,
C-6ꢀ), 133.8 (C-4ꢀ), 133.9 (C-1ꢀ), 171.7 (C-1), 213.0 (C-4)
MS, m/z (Ir/%): 254.71 (15) (M+
UV-VIS (MeOH), λmax/nm (log ε): 266.1 (3.7)
)
IR, ν˜/cm−1: 3085 (ArH), 1736, 1715 (C O), 1596, 1527 (C C), 1413, 1254, 1054, 535 (C—Br)
—
—
—
—
1H NMR (CDCl3), δ: 1.03 (t, 3H, J = 7.4 Hz, C-6), 2.42 (q, 2H, J = 7.4 Hz, C-5), 2.73 (t, 2H, J = 6.8 Hz, C-2),
2.82 (t, 2H, J = 6.8 Hz, C-3), 5.10 (s, 2H, C-1ꢀꢀ), 7.24–7.28 (m, 2H, ArH), 7.37 (m, 1H, ArH), 7.51 (m, 1H, ArH)
13C NMR (CDCl3), δ: 7.7 (C-6), 27.7 (C-2), 32.2 (C-3), 37.1 (C-5), 66.3 (C-1ꢀꢀ), 123.7 (C-2ꢀ), 127.5 (C-5ꢀ), 128.6
(C-3ꢀ), 128.7 (C-4ꢀ), 131.2 (C-6ꢀ), 139.7 (C-1ꢀ), 173.2 (C-1), 214.2 (C-4)
MS, m/z (Ir/%): 299.11 (18) (M+
UV-VIS (MeOH), λmax/nm (log ε): 263.6 (3.9)
)
—
—
XVIb
IR, ν˜/cm−1: 3085 (ArH), 1739, 1718 (C O), 1591, 1522, 1451 (C C), 1417, 1271, 1252, 1140, 1051, 528 (C—Br)
—
—
1H NMR (CDCl3), δ: 1.03 (t, 3H, J = 7.4 Hz, C-6), 2.43 (q, 2H, J = 7.4 Hz, C-5), 2.75 (t, 2H, J = 6.8 Hz, C-2),
2.83 (t, 2H, J = 6.8 Hz, C-3), 5.20 (s, 2H, C-1ꢀꢀ), 7.29 (m, 1H, ArH), 7.44 (m, 1H, ArH), 7.50–7.55 (m, 2H, ArH)
13C NMR (CDCl3), δ: 7.7 (C-6), 27.8 (C-2), 32.3 (C-3), 37.2 (C-5), 66.3 (C-1ꢀꢀ), 123.5 (C-3ꢀ), 125.8 (C-6ꢀ), 129.1
(C-5ꢀ), 130.3 (C-4ꢀ), 131.7 (C-2ꢀ), 143.6 (C-1ꢀ), 173.4 (C-1), 214.4 (C-4)
MS, m/z (Ir/%): 299.11 (21) (M+
UV-VIS (MeOH), λmax/nm (log ε): 263.2 (3.8)
)

452
M. Iqbal et al./Chemical Papers 67 (4) 444–455 (2013)
Table 4. (continued)
Compound
Spectral data
—
—
XVIIb
IR, ν˜/cm−1: 3083 (ArH), 1743, 1717 (C O), 1598, 1532, 1455 (C C, 1419, 1266, 531 (C—Br)
—
—
1H NMR (CDCl3), δ: 1.03 (t, 3H, J = 7.4 Hz, C-6), 2.44 (q, 2H, J = 7.4 Hz, C-5), 2.76 (t, 2H, J = 6.8 Hz, C-2),
2.85 (t, 2H, J = 6.8 Hz, C-3), 5.21 (s, 2H, C-1ꢀꢀ), 7.22 (m, 2H, ArH), 7.87 (m, 2H, ArH)
13C NMR (CDCl3), δ: 7.7 (C-6), 27.3 (C-2), 32.7 (C-3), 37.4 (C-5), 66.5 (C-1ꢀꢀ), 121.6 (C-4ꢀ), 132.3 (C-3ꢀ, C-5ꢀ),
134.6 (C-1ꢀ), 139.7 (C-2ꢀ, C-6ꢀ), 173.8 (C-1), 214.7 (C-4)
MS, m/z (Ir/%): 299.11 (22) (M+
UV-VIS (MeOH), λmax/nm (log ε): 263.9 (3.9)
)
XVIIIb IR, ν˜/cm−1: 3046 (ArH), 1735, 1718 (C O), 1592, 1524, 1456 (C C, 1258, 1156, 488 (C—I)
—
—
—
—
1H NMR (CDCl3), δ: 1.04 (t, 3H, J = 7.4 Hz, C-6), 2.41 (q, 2H, J = 7.4 Hz, C-5), 2.66 (t, 2H, J = 6.8 Hz, C-2),
2.79 (t, 2H, J = 6.8 Hz, C-3), 5.10 (s, 2H, C-1ꢀꢀ), 7.11–7.15 (m, 2H, ArH), 7.39 (m, 1H, ArH), 7.83 (m, 1H, ArH)
13C NMR (CDCl3), δ: 7.7 (C-6), 29.2 (C-2)ꢀ, 31.7 (C-3), 35.4 (C-5), 67.6 (C-1ꢀꢀ), 92.5 (C-2ꢀ), 126.8 (C-6ꢀ), 127.7
ꢀ
ꢀ
ꢀ
—
—
(C-5 ), 129.3 (C-4 ), 138.2 (C-3 ), 142.7 (C-1 ), 169.2 (C-1), 208.5 (C O)
MS, m/z (Ir/%): 346.09 (11) (M+
)
UV-VIS (MeOH), λmax/nm (log ε): 260.3 (3.6)
—
—
XIXb
IR, ν˜/cm−1: 3042 (ArH), 1732, 1719 (C O), 1591, 1529, 1467 (C C, 1251, 1161, 1058, 492 (C—I)
—
—
1H NMR (CDCl3), δ: 1.03 (t, 3H, J = 7.4 Hz, C-6), 2.40 (q, 2H, J = 7.4 Hz, C-5), 2.64 (t, 2H, J = 6.8 Hz, C-2),
2.77 (t, 2H, J = 6.8 Hz, C-3), 5.18 (s, 2H, C-1ꢀꢀ), 7.15 (m, 1H, ArH), 7.43 (m, 1H, ArH), 7.75 (m, 1H, ArH), 7.84
(m, H, ArH)
13C NMR (CDCl3), δ: 7.7 (C-6), 29.4 (C-2), 31.3 (C-3), 35.6 (C-5), 65.1 (C-1ꢀꢀ), 94.2 (C-3ꢀ), 127.3 (C-6ꢀ), 129.7
(C-5ꢀ), 136.1 (C-2ꢀ), 137.1 (C-4ꢀ), 142.2 (C-1ꢀ), 169.7 (C-1), 208.1 (C-4)
MS, m/z (Ir/%): 346.09 (8) (M+
UV-VIS (MeOH), λmax/nm (log ε): 263.2 (3.9)
)
—
—
XXb
IR, ν˜/cm−1: 3048 (ArH), 1733, 1715 (C O), 1599, 1521, 1460 (C C), 1255, 1151, 1054, 483 (C—I)
—
—
1H NMR (CDCl3), δ: 1.03 (t, 3H, J = 7.4 Hz, C-6), 2.38 (q, 2H, J = 7.4 Hz, C-5), 2.65 (t, 2H, J = 6.8 Hz, C-2),
2.76 (t, 2H, J = 6.8 Hz, C-3), 5.19 (s, 2H, C-1ꢀꢀ), 7.15 (m, 2H, ArH), 7.65 (m, 2H, ArH)
13C NMR (CDCl3), δ: 7.7 (C-6), 29.0 (C-2), 31.7 (C-3), 35.8 (C-5), 66.1 (C-1ꢀꢀ), 92.3 (C-4ꢀ), 129.6 (C-2ꢀ, C-6ꢀ),
134.2 (C-1ꢀ), 136.9 (C-3ꢀ, C-5ꢀ), 169.3 (C-1ꢀ), 208.9 (C-4)
MS, m/z (Ir/%): 346.09 (9) (M+
UV-VIS (MeOH), λmax/nm (log ε): 263.8 (3.9)
)
ing ice and aq. H2SO4 (1 M, 30 mL). The organic layer
was extracted with diethyl ether (3 × 20 mL), washed
with an aq. NaHCO3 solution (20 mL), and dried over
anhydrous Na2SO4. After removal of the solvent, the
material thus obtained was subjected to open column
chromatography on silica gel eluting it with the mix-
ture of hexane/ethyl acetate (ϕr = 4 : 1 → 1 : 4)
to gain pure compounds (Ib–XXb) which were charac-
terised by their physical characteristics (Table 3) and
spectroscopic data (Table 4). The reactions were car-
ried out in an efficient fuming hood and the wastes
were disposed of safely.
Fig. 1. General structure of γ-ketoesters.
Our γ-ketoesters differ from those previously reported,
mainly in the nature of R, R1, and R2 (Fig. 1). In
almost all reported examples, R3 is an alkyl or an
un-substituted benzyl (Cason et al., 1951) (Fig. 1),
whereas in our case R is ethyl, R1 and R2 are H, and
Results and discussion
In the present work, twenty new compounds (Ib–
XXb) were synthesised from acid chlorides (Ia–XXa).
Fig. 2. Preparation of compounds Ia–XXa and Ib–XXb: i) SOCl2, 3 h, 30–40◦C, 63–79 %; ii) diethylcadmium, diethylether,
11–16 h, reflux, 59–79 %.

M. Iqbal et al./Chemical Papers 67 (4) 444–455 (2013)
453
Fig. 4. Tetrahedral intermediate from reaction of RCdCl with
CH3COCl.
Bansal (1996) proposed a mechanism for the reac-
tion of dimethylcadmium with acid halides. The same
can apply to diethylcadmium because of the similarity
in structure and reactivity of the two. This mechanism
is further supported by Roberts and Caserio (1964),
who reported on the formation of a tetrahedral inter-
mediate from the reaction of RCdCl and CH3COCl
(Fig. 4).
The proposed mechanism for the reaction of di-
ethylcadmium with acid halide is given below (Fig. 5).
The structures of the synthesised compounds (Ia–XXa
and Ib–XXb) were established by various spectroscopic
techniques.
Compounds Ia and Ib were identified as representa-
tive of the respective series Ia–XXa and Ib–XXb, and
discussed in detail. The IR spectrum of Ia showed no
OH peak for the initial monoester I. The two new
Fig. 3. Atom numbering in compounds for assignment of spec-
tral data.
R3 is a mono- or di-substituted benzyl group (Ia–XXa
and Ib–XXb) (Figs. 1 and 2). The carbon atoms in
acid chlorides (Ia–XXa) and ketoesters (Ib–XXb) are
numbered for spectral data assignment as shown in
Fig. 3.
Fig. 5. Proposed mechanism for ketone formation from acid chlorides and diethylcadmium.

454
M. Iqbal et al./Chemical Papers 67 (4) 444–455 (2013)
peaks observed (723 cm−1 and 1792 cm−1) were as-
10.1021/ja01575a053.
Cason, J. (1942). Branched-chain fatty acids. I. Synthesis of 17-
methyloctadecanoic acid. Journal of the American Chemical
Society, 64, 1106–1110. DOI: 10.1021/ja01257a029.
Cason, J. (1946). Branched-chain fatty acids. IV. A further
study of the preparation of ketones and keto esters by means
of orgaocadmium reagents. Journal of the American Chem-
ical Society, 68, 2078–2081. DOI: 10.1021/ja01214a061.
Cason, J., & Prout, F. S. (1944). Branched-chain fatty acids.
II. Syntheses in the C19 and C25 series. Preparation of keto
esters. Journal of the American Chemical Society, 66, 46–50.
DOI: 10.1021/ja01229a015.
Cason, J., & Prout, F. S. (1948). Methyl 4-keto-7-methyloctano-
ate. Organic Syntheses, 28, 75.
Cason, J., Taylor, P. B., & Williams, D. A. (1951). Branched-
chain fatty acids. XX. Synthesis of compounds useful for re-
lating melting point to structure. Journal of Organic Chem-
istry, 16, 1187–1192. DOI: 10.1021/jo50002a002.
Csende, F. (2002). Some alternative synthetic routes to γ- and
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—
signed to C—Cl and Cl—C O, respectively, confirm-
—
ing the formation of Ia. In the 13C NMR spectra,
compound Ia displaying a peak at δ 175.6 supported
1
the conclusion; this was also verified by H NMR and
13C NMR (Table 2). The assignment was also ver-
ified by HMBC spectrum, in which the proton res-
onating at δ 2.74, which displayed interactions with
carbon resonating at δ 175.6, was attributed to COCl
(Fig. 5). In the high resolution electron impact MS
(HRMS) spectrum, Ia displayed a molecular ion peak
at m/z 256.6823 (calc. 256.6813) corresponding to
C12H13ClO4. Chemical analysis data of Ia supported
the molecular formula C12H13ClO4.
The structure of the remaining compounds (IIa–
XXa) was established in the same way. Conversion of
Ia into Ib was established by mass spectrum display-
ing a molecular ion peak in HRMS at m/z 250.2905
for C14H18O4 (calc. 250.2903). 1D (1H NMR and 13C
NMR) spectra similarly supported the predicted for-
mation of Ib (Fig. 3, Table 4). Its formation was fur-
ther verified by the presence of an ethyl moiety by dis-
playing peaks at δ 1.05 (t, 3H, J = 7.4 Hz, C-6) and
2.55 (q, 2H, J = 7.4 Hz, C-5) and 13C NMR peaks at
7.7 (C-6) and 36.1 (C-5).
Conclusions
A highly convenient synthesis of γ-ketoesters is de-
scribed, using diethyl ether as solvent and diethylcad-
mium as ethylating agent. Twenty novel γ–ketoesters
(mono-/dibenzyl γ–ketohexanoates), denoted as Ib–
XXb, were successfully prepared employing a two-step
reaction strategy. In the first step, reaction of the mo-
noesters (Ia–XXa) of succinic acid with thionyl chlo-
ride delivered new mono-/di-benzyl 4-ketobutanoyl
chlorides with good yields. In the second step, the
products obtained in the reaction with diethylcad-
mium led to formation of the desired γ-ketoesters.
Heiss, C., Laivenieks, M., Zeikus, J. G., & Phillips, R. S.
(2001). The stereospecificity of secondary alcohol dehydroge-
nase from Thermoanaerobacter ethanolicus is partially deter-
mined by active site water. Journal of the American Chem-
ical Society, 123, 345–346. DOI: 10.1021/ja005575a.
Hilgenkamp, R.,
& Zercher, C. K. (2001). Tandem chain
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