Convenient preparation of benzylseleno- and phenylselenoalkanoic acids: Reagents for synthesis of organoselenium compounds

Article abstract of DOI:10.1080/00397910601133540

An efficient and operationally simple route to benzylseleno- and phenylselenoalkanoic acids from ethyl benzyl/phenylselenoalkanoates is described. This involves preparation of ethyl benzyl/phenylselenoalkanoates as substrates by reaction of dibenzyl/diphenyl diselenide and sodium borohydride with ethyl chloroalkanoates in ethanol followed by basic hydrolysis and subsequent acidification. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910601133540

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Convenient Preparation of Benzylseleno‐ and
Phenylselenoalkanoic Acids: Reagents for
Synthesis of Organoselenium Compounds
Aman Bhalla a , Sitansh Sharma a , Kuldip K. Bhasin a & Prof. Shamsher S.
Bari a
a Department of Chemistry, Panjab University, Chandigarh, India
Published online: 10 Mar 2007.
To cite this article: Aman Bhalla , Sitansh Sharma , Kuldip K. Bhasin & Prof. Shamsher S. Bari (2007):
Convenient Preparation of Benzylseleno‐ and Phenylselenoalkanoic Acids: Reagents for Synthesis of
Organoselenium Compounds, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 37:5, 783-793
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Synthetic Communicationsw, 37: 783–793, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910601133540
Convenient Preparation of Benzylseleno-
and Phenylselenoalkanoic Acids: Reagents
for Synthesis of Organoselenium
Compounds
Aman Bhalla, Sitansh Sharma, Kuldip K. Bhasin, and
Shamsher S. Bari
Department of Chemistry, Panjab University, Chandigarh, India
Abstract: An efficient and operationally simple route to benzylseleno- and phenylse-
lenoalkanoic acids from ethyl benzyl/phenylselenoalkanoates is described. This
involves preparation of ethyl benzyl/phenylselenoalkanoates as substrates by
reaction of dibenzyl/diphenyl diselenide and sodium borohydride with ethyl chloroalk-
anoates in ethanol followed by basic hydrolysis and subsequent acidification.
Keywords: benzylselenoalkanoic acid, ethyl benzylselenoalkanoates, ethyl phenyl-
selenoalkanoates, phenylselenoalkanoic acid
INTRODUCTION
Selenium, which is an essential trace element, has been recognized to function
as an active center of redox enzymes, such as glutathione peroxidase, and as a
modifying factor in the toxicities of heavy metals.[1,2] Apart from this, selenium
is an integral part of factor 3, a dietary agent that prevents liver necrosis in the rat
and exudative diathesis in the chick.[3] Many organoselenium compounds are
useful reagents or synthons in organic synthesis.[4,5] Over the past few years,
a few synthetic strategies for the selenium-containing higher heterocycles,
such as 5-deoxy-5-selenopyranose sugars,[6] and novel selenium analogs[7] of
an important antioxidant, a-tocopherol, have been reported.
Received July 24, 2006
Address correspondence to Prof. Shamsher S. Bari, Department of Chemistry,
Panjab University, Chandigarh, U.T. 160014, India. E-mail: ssbari@pu.ac.in
783

784
A. Bhalla et al.
Recently, b-lactams have been found to exhibit a wide spectrum of biologi-
cal activity such as cholesterol absorption inhibiting activity,[8] antiviral
activity,[9] and antitumor activity.[10] A lot of studies involving C-3 functionali-
zation of azetidin-2-ones have been carried out in our laboratory,[11–16] and
further interest in the development of synthetic methodologies for the
synthesis of novel seleno-b-lactams was initiated by the discovery of novel
selenium azetidin-2-ones, such as selenopenams and selenocephams, exhibiting
potential b-lactamase inhibitory properties.[17] We envisaged synthesizing
3-seleno-b-lactams from selenoethanoic acids. These studies required a con-
venient method of preparating benzylseleno- and phenylselenoalkanoic acids.
A literature survey revealed the availability of a few methods for the
synthesis of higher benzylselenoalkanoic acids. One of the methods
involves the reaction of diseleno-dicarboxylic acid, ammonia, rongalite, and
benzyl chloride.[18] However, it suffered from some disadvantages such as
(i) the requirement for pungent-smelling ammonia, (ii) the need for
rongalite, (iii) the multistep procedure, (iv) the use of excess of benzyl
chloride, (v) a longer reaction time, and (vi) low to moderate yields of
products. The second method involves the reaction of 5-bromopentanoic
acid with dibenzyl diselenide and sodium borohydride.[19] However, this
also involves much longer reaction time (i.e., 15 h of stirring), coupled with
unpredictable performance of the reaction in large-scale preparations.
We have successfully employed ethyl benzyl/phenylselenoalkanoates as
the most appropriate substrates for the synthesis of ethyl benzyl/phenylsele-
noalkanoic acids. The most convenient method for the preparation of ethyl
2-benzylselenoethanoate so far appears to be the BiCl3-Sm-catalyzed
reaction of dibenzyl diselenide with ethyl a-bromoacetate in water and
THF.[20] However, use of this synthetic approach is also restricted because
of the requirement of BiCl3-Sm catalyst and low yield of product. We
report here a facile method for the preparation of ethyl benzyl/phenylsele-
noalkanoates from ethyl chloroalkanoates involving a reaction with sodium
borohydride in ethanol under varied reaction conditions.
RESULTS AND DISCUSSION
Starting substrates, such as ethyl 2-chloroethanoate 3a and ethyl 3-chloropro-
panoate 3b, were prepared by esterification of 2-chloroethanoic acid with
ethanol in the presence of benzene using p-toluene sulfonic acid and 3-chlor-
oproanoyl chloride with ethanol in the presence of pyridine in dry benzene at
08C, respectively. Whereas, commercially available ethyl 4-chlorobutanoate
3c was used without further purification.
Initial studies were carried out by treating dibenzyl diselenide 1 and
sodium borohydride with ethyl 2-chloroethanoate 3a in ethanol. Cleavage
of dibenzyl diselenide 1 by sodium borohydride in ethanol leads to the
formation of nucleophilic selenium reagent PhCH2Se2Naþ, which on

Benzylseleno- and Phenylselenoalkanoic Acids
785
treatment with ethyl 2-chloroethanoate 3a affords ethyl 2-benzylselenoethano-
ate 4a in quantitative yield (Scheme 1). The selenide anion (PhCH2Se2)
generated in situ was observed to be very unstable at room temperature or
higher temperature because it led to the regeneration of dibenzyl diselenide
1 and a semisolid product that could not be isolated in pure form. The
stability of this anionic species was enhanced by carrying out the reaction at
08C temperature. Dropwise addition of ethyl 2-chloroethanoate 3a was
completed in 5 min after the generation of selenide anion, which was
indicated by the disappearance of yellow color of the solution. At this stage,
the addition of ethyl 2-chloroethanoate 3a resulted in the formation of ethyl
2-benzylselenoethanoate 4a.
In an effort to demonstrate the synthetic potential of this reaction,
the reaction was carried out with ethyl 3-chloropropanoate 3b and ethyl
4-chlorobutanoate 3c, and the results are summarized in Table 1. Ethyl
3-benzylselenopropanoate 4b and ethyl 4-benzylselenobutanoate 4c were effi-
ciently formed at higher temperature (Table 1, entries 2 and 3). Similarly,
ethyl phenylselenoalkanoates 5a–c were synthesized by the reaction of the
appropriate substrates, ethyl chloroalkanoates 3a–c with PhSe2Naþ in
ethanol,[21] prepared in situ from diphenyl diselenide 2 and sodium borohy-
dride (Scheme 1, Table 1). However, in this case, after the addition of ethyl
chloroalkanoates 3a–c at 08C, the reaction temperature was slowly
increased to 55–608C and stirring continued. Progress of the reaction was
monitored by thin-layer chromatography (TLC), and disappearance of the
spot for starting diphenyl diselenide on TLC confirmed the completion of
reaction.
The ethyl benzyl/phenylselenoalkanoates 4, 5(a–c) on hydrolysis using
KOH in methanol afforded precipitates of potassium benzyl/phenylselenoalk-
anoates 6, 7(a–c). These were further acidified with conc. hydrochloric acid to
obtain benzyl/phenylselenoalkanoic acids 8, 9(a–c) as crystalline solids in
excellent yields (Scheme 2, Table 2). The structures of these ethyl benzyl/
phenylselenoalkanoates 4, 5(a–c) and corresponding benzyl/phenylsele-
noalkanoic acids 8, 9(a–c) were established on the basis of their spectral
data such as IR, 1H NMR, 13C NMR, and 77Se NMR.
In conclusion, we report here new procedure for the synthesis of 2-benzyl-
seleno- and 2-phenylselenoalkanoic acids, which is operationally simple and
superior to the methodologies reported earlier.
Scheme 1.

Table 1. Synthesis of ethyl benzyl/phenylselenoalkanoates 4, 5(a–c)
Entry
Reactants
Product
Temp. (8C)
Time (min)
5
Yielda (%)
90
1
0
2
1
1
0–15
15
87
3
4
0–40
25
45
84
94
3a
50–55
5
6
2
2
3b
3c
55–60
55–60
75
90
90
89
1
aYields quoted are for the isolated products characterized by IR, H NMR, 13C NMR, and 77Se NMR.

Benzylseleno- and Phenylselenoalkanoic Acids
787
Scheme 2.
EXPERIMENTAL
Melting points were determined in an open capillary and are uncorrected. IR
spectra were recorded on a FTIR spectrophotometer (ymax in cm21). 1H NMR
Table 2. Benzyl/phenylselenoalkanoic acids 8, 9(a–c)
Entry
Product
Yielda(%)
96
Mp(8C)
1
63–64
2
92
67–68
3
4
89
95
70–71
42–43
5
6
91
90
45–46
49–50
aYields quoted are for the isolated products characterized by IR, 1H NMR,
13C NMR, and 77Se NMR.

788
A. Bhalla et al.
(300 MHz), 13C NMR (75 MHz), and 77Se NMR (57 MHz) spectra were
recorded on Jeol 300-MHz NMR spectrometer. Chemical shifts are given in
parts per million (ppm) relative to TMS as an internal standard (d ¼ 0 ppm)
for 1H NMR, CDCl3 (d ¼ 77.0 ppm) for 13C NMR spectra, and SeMe2
(d ¼ 0 ppm) for 77Se NMR spectra. Elemental analysis (C, H, Se) were
recorded on Perkin-Elmer 2400 elemental analyzer. Column chromatography
was performed using Merck silica gel (60–120 mesh). TLC was performed
using Merck silica gel G. For visualization, TLC plates were stained with
iodine vapors. All commercially available compounds/reagents were used
without further purification.
Ethyl Benzylselenoalkanoates (4a–c)
General Procedure
Sodium borohydride (2.3 mmol) was added slowly over 10 min, in portions, to
a stirred solution of dibenzyl diselenide (1, 1.0 mmol) in absolute ethanol
(80 mL) at 08C under nitrogen. After the complete addition of NaBH4, the
reaction mixture was stirred for 10 min until the characteristic yellow disele-
nide color had disappeared. Sodium borohydride was added cautiously
because reduction of the diselenide is exothermic and vigorous evolution of
hydrogen occurs after each addition. After the evolution of hydrogen had
ceased (ca.10 min), ethyl chloroalkanoate (3, 2.2 mmol) in ethanol (5 mL)
was added dropwise over 5 min with the immediate precipitation of a
white solid. The reaction mixture was stirred, and progress of the reaction
was monitored by TLC. Disappearance of the spot for starting dibenzyl
diselenide 1 and appearance of a spot having an Rf lower than that of disele-
nide confirmed the completion of the reaction. A small amount of water
(3 mL) was added to slow down the reaction. Thereafter, sodium chloride
(5 g) was added to saturate it, and the product was extracted with ether
(4 ꢀ 50 mL). The ether extract was washed with brine (2 ꢀ 15 mL) and
dried over anhydrous sodium sulfate. After, evaporation of the solvent
under reduced pressure, the residue was chromatographed using silica gel
(60–120 mesh), eluting with 1% ethyl acetate in hexanes to give pure ethyl
benzylselenoalkanoates 4a–c.
Data
Ethyl 2-benzylselenoethanoate (4a): Yield: 90%; greenish-yellow semisolid;
IR (CCl4): 1734 (C55O) cm21
;
1H NMR (CDCl3, 300 MHz): dH ¼ 1.20
(t, 3H, J ¼ 7.2 Hz, –CH3), 2.87 (s, 2H, –SeCH2), 3.83 (s, 2H, PhCH2–),
4.04 (q, 2H, J ¼ 7.2 Hz, –OCH2), 7.06–7.24 (m, 5H, ArH); 13C NMR
(CDCl3, 75 MHz): dC ¼ 12.24, 21.61, 28.10, 60.77, 126.90, 128.40, 129.17,

Benzylseleno- and Phenylselenoalkanoic Acids
789
138.21, 170.91; 77Se NMR (CDCl3, 57 MHz): dSe ¼ 305.11; anal. calcd. for
C11H14O2Se: C, 51.37; H, 3.64; Se, 30.70; found: C, 51.28; H, 3.53; Se, 30.61.
Ethyl 3-benzylselenopropanoate (4b): Yield: 87%; yellow oil; IR (CCl4):
1737 (C55O) cm21
;
1H NMR (CDCl3, 300 MHz): dH ¼ 1.23 (t, 3H,
J ¼ 7.2 Hz, –CH3), 2.55 (t, 2H, J ¼ 6.9 Hz, –SeCH2), 2.66 (t, 2H,
J ¼ 7.1 Hz, –CH2CO), 3.77 (s, 2H, PhCH2–), 4.07 (q, 2H, J ¼ 7.2 Hz,
–OCH2), 7.12–7.26 (m, 5H, ArH); 13C NMR (CDCl3, 75 MHz):
dC ¼ 14.47, 17.61, 27.43, 35.51, 60.41, 126.86, 128.57, 129.00, 139.08,
171.63; anal. calcd. for C12H16O2Se: C, 53.14; H, 5.94; Se, 29.11; found: C,
53.02; H, 5.87; Se, 29.06.
Ethyl 4-benzylselenobutanoate (4c): Yield: 84%; yellow oil; IR (CCl4): 1735
1
(C55O) cm21; H NMR (CDCl3, 300 MHz): dH ¼ 1.17 (t, 3H, J ¼ 7.2 Hz,
–CH3), 1.84–1.93 (m, 2H, –CH2CH2CH2–), 2.22 (t, 2H, J ¼ 7.1 Hz,
–SeCH2), 2.47 (t, 2H, J ¼ 7.1 Hz, –CH2CO), 3.67 (s, 2H, PhCH2–), 3.67
(q, 2H, J ¼ 7.2 Hz, –OCH2), 7.11–7.26 (m, 5H, ArH); 13C NMR (CDCl3,
75 MHz): dC ¼ 14.12, 16.31, 18.03, 26.53, 34.07, 60.24, 126.72, 128.50,
128.88, 140.02, 172.08; anal. calcd. for C13H18O2Se: C, 54.74; H, 6.35; Se,
27.68; found: C, 54.61; H, 6.24; Se, 27.62.
Ethyl Phenylselenoalkanoates (5a–c)
General Procedure
The ethyl phenylselenoalkanoates 5a–c were prepared from diphenyl disele-
nide (2, 1.0 mmol) following the general procedure as reported for benzylse-
lenoalkanoates 4a–c, however, in this case the reaction temperature was
slowly increased to 55–608C.
Data
Ethyl 2-phenylselenoethanoate (5a): Yield: 94%; yellow oil; IR (CCl4):
1734 (C55O) cm21
;
1H NMR (CDCl3, 300 MHz): dH ¼ 1.19 (t, 3H,
J ¼ 7.2 Hz, –CH3), 3.45 (s, 2H, –SeCH2), 4.06 (q, 2H, J ¼ 7.2 Hz,
–OCH2), 7.22–7.58 (m, 5H, ArH); 13C NMR (CDCl3, 75 MHz):
dC ¼ 14.20, 27.50, 61.09, 127.78, 129.15, 129.40, 133.56, 170.45;
77Se NMR (CDCl3, 57 MHz): dSe ¼ 333.78; anal. calcd. for C10H12O2Se:
C, 49.39; H, 4.97; Se, 32.47; found: C, 49.32; H, 4.84; Se, 32.40.
Ethyl 3-phenylselenopropanoate (5b): Yield: 90%; yellow oil; IR (CCl4):
1738 (C55O) cm21
;
1H NMR (CDCl3, 300 MHz): dH ¼ 1.16 (t, 3H,
J ¼ 7.2 Hz, –CH3), 2.58 (t, 2H, J ¼ 7.1 Hz, –SeCH2), 2.95 (t, 2H,

790
A. Bhalla et al.
J ¼ 7.1 Hz, –CH2CO), 4.00 (q, 2H, J ¼ 7.2 Hz, –OCH2), 7.13–7.43 (m, 5H,
ArH); 13C NMR (CDCl3, 75 MHz): dC ¼ 14.35, 21.85, 35.38, 60.49, 127.27,
129.12, 129.46, 133.40, 171.69; anal. calcd. for C11H14O2Se: C, 51.37; H,
5.48; Se, 30.70; found: C, 51.29; H, 5.43; Se, 30.64.
Ethyl 4-phenylselenobutanoate (5c): Yield: 89%; colorless oil; IR (CCl4):
1735 (C55O) cm21
;
1H NMR (CDCl3, 300 MHz): dH ¼ 1.09 (t, 3H,
J ¼ 7.2 Hz, –CH3), 1.84–1.94 (m, 2H, –CH2CH2CH2–), 2.31 (t, 2H, J ¼
7.2 Hz, –SeCH2), 2.77 (t, 2H, J ¼ 7.1 Hz, –CH2CO), 3.95 (q, 2H,
J ¼ 7.2 Hz, –OCH2), 7.07–7.38 (m, 5H, ArH); 13C NMR (CDCl3, 75 MHz):
dC ¼ 14.13, 25.12, 26.75, 33.59, 59.93, 126.59, 128.73, 129.85, 132.49,
172.08; anal. calcd. for C12H16O2Se: C, 53.14; H, 5.94; Se, 29.11; found: C,
53.05; H, 5.89; Se, 29.08.
Benzylselenoalkanoic Acids (8a–c)
General Procedure
To a solution of potassium hydroxide (1.4 mmol) in methanol/water (3/1;
4 mL) at 08C, ethyl benzylselenoalkanoate (4, 1 mmol) in methanol
(60 mL) was added dropwise. The resultant mixture was stirred for 1 h.
Progress of the reaction was monitored by TLC. White fluffy precipitates of
potassium benzylselenoalkanoates 6a–c were obtained, which were further
dissolved in a minimum amount of water and acidified with conc. hydro-
chloric acid. The completion of the reaction was monitored by change of
pH, which was checked at regular intervals. The product was extracted with
dichloromethane (4 ꢀ 35 mL) and dried over anhydrous sodium sulfate.
After evaporation of solvent under reduced pressure, the residue was recrys-
tallized from dichloromethane–hexanes to afford benzylselenoalkanoic
acids 8a–c.
Data
Ethyl 2-benzylselenoethanoic acid (8a): Yield: 96%; white crystalline solid;
1
mp 63–648C; IR (KBr): 3009 (OH), 1690 (C55O) cm21; H NMR (CDCl3,
300 MHz): dH ¼ 2.92 (s, 2H, –SeCH2), 3.91 (s, 2H, PhCH2–), 7.10–7.27
(m, 5H, ArH), 9.05 (br s, 1H, COOH); 13C NMR (CDCl3, 75 MHz):
dC ¼ 21.36, 28.52, 127.20, 128.61, 129.33, 137.99, 178.43; 77Se NMR
(CDCl3, 57 MHz): dSe ¼ 305.11; anal. calcd. for C9H10O2Se: C, 47.18; H,
4.40; Se, 34.46; found: C, 47.09; H, 4.36; Se, 34.41.
Ethyl 3-benzylselenopropanoic acid (8b): Yield: 92%; white crystalline
1
solid; mp 67–688C; IR (KBr): 3120 (OH), 1694 (C55O) cm21; H NMR

Benzylseleno- and Phenylselenoalkanoic Acids
791
(CDCl3, 300 MHz): dH ¼ 2.68 (t, 2H, J ¼ 6.9 Hz, –SeCH2), 2.79 (t, 2H,
J ¼ 7.1 Hz, –CH2CO), 3.82 (s, 2H, PhCH2–), 7.16–7.41 (m, 5H, ArH),
9.01 (br s, 1H, COOH); 13C NMR (CDCl3, 75 MHz): dC ¼ 17.87, 27.82,
35.76, 127.10, 128.77, 129.20, 140.50, 172.20; anal. calcd. for C10H12O2Se:
C, 49.39; H, 4.96; Se, 32.47; found: C, 49.35; H, 4.90; Se, 32.38.
Ethyl 4-benzylselenobutanoic acid (8c): Yield: 89%; white crystalline solid;
1
mp 70–718C; IR (KBr): 3256 (OH), 1697 (C55O) cm21; H NMR (CDCl3,
300 MHz): dH ¼ 1.86–1.95 (m, 2H, –CH2CH2CH2–), 2.32 (t, 2H,
J ¼ 7.1 Hz, –SeCH2), 2.51 (t, 2H, J ¼ 7.1 Hz, –CH2CO), 3.71 (s, 2H,
PhCH2–), 7.11–7.26 (m, 5H, ArH), 10.94 (br s, 1H, COOH); 13C NMR
(CDCl3, 75 MHz): dC ¼ 16.49, 18.27, 26.83, 34.24, 127.00, 128.69, 129.10,
140.70, 172.61; anal. calcd. for C11H14O2Se: C, 51.37; H, 5.48; Se, 30.70;
found: C, 51.32; H, 5.50; Se, 30.66.
Phenylselenoalkanoic Acids (9a–c)
General Procedure
The phenylselenoalkanoic acids 9a–c were prepared from ethyl phenylsele-
noalkanoates 5a–c following the general procedure as reported for benzylse-
lenoalkanoic acids 8a–c.
Data
Ethyl 2-phenylselenoethanoic acid (9a): Yield: 95%; white crystalline solid;
1
mp 42–438C; IR (KBr): 3289 (OH), 1706 (C55O) cm21; H NMR (CDCl3,
300 MHz): dH ¼ 3.86 (s, 2H, –SeCH2), 7.06–7.24 (m, 5H, ArH), 10.94 (br
s, 1H, COOH); 13C NMR (CDCl3, 75 MHz): dC ¼ 27.33, 128.09, 129.17,
129.31, 133.61, 177.73; 77Se NMR (CDCl3, 57 MHz): dSe ¼ 340.56; anal.
calcd. for C8H8O2Se: C, 44.67; H, 3.75; Se, 36.70; found: C, 44.59; H,
3.71; Se, 36.62.
Ethyl 3-phenylselenopropanoic acid (9b): Yield: 91%; white crystalline
1
solid; mp 45–468C; IR (KBr): 3324 (OH), 1706 (C55O) cm21; H NMR
(CDCl3, 300 MHz): dH ¼ 2.65 (t, 2H, J ¼ 7.1 Hz, –SeCH2), 2.97 (t, 2H,
J ¼ 7.0 Hz, –CH2CO), 7.12–7.26 (m, 5H, ArH), 10.77 (br s, 1H, COOH);
13C NMR (CDCl3, 75 MHz): dC ¼ 26.54, 30.54, 127.36, 129.20, 131.04,
133.60, 178.12; anal. calcd. for C9H10O2Se: C, 47.17; H, 4.39; Se, 34.46;
found: C, 47.12; H, 4.29; Se, 34.38.
Ethyl 4-phenylselenobutanoic acid (9c): Yield: 90%; white crystalline solid;
1
mp 49–508C; IR (KBr): 3362 (OH), 1708 (C55O) cm21; H NMR (CDCl3,
300 MHz): dH ¼ 1.85–1.96 (m, 2H, –CH2CH2CH2–), 2.38 (t, 2H,

792
A. Bhalla et al.
J ¼ 7.2 Hz, –SeCH2), 2.81 (t, 2H, J ¼ 7.1 Hz, –CH2CO), 7.12–7.42
(m, 5H, ArH), 10.68 (br s, 1H, COOH); 13C NMR (CDCl3, 75 MHz):
dC ¼ 24.99, 26.91, 33.71, 127.00, 129.02, 129.82, 132.99, 179.46; anal.
calcd. for C10H12O2Se: C, 49.39; H, 4.96; Se, 32.47; found: C, 49.31; H,
4.92; Se, 32.36.
ACKNOWLEDGMENTS
We gratefully acknowledge the financial support for this work from Council of
Scientific and Industrial Research, New Delhi, and Department of Science and
Technology, New Delhi, Government of India (Project No. SP/S1/G-50/99).
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