Enzyme-catalyzed chemoselective transesterification reactions on hydroxymethylated phenolic compounds

Article abstract of DOI:10.1006/bioo.1998.1117

The chemoselective capabilities of porcine pancreatic lipase (PPL) in tetrahydrofuran and Candida rugosa lipase (CRL) in diisopropyl ether have been investigated for selective acetylation and deacetylation of hydroxymethylated phenols and hydroxyaryl alky

Full text of DOI:10.1006/bioo.1998.1117

Bioorganic Chemistry 27, 119–134 (1999)
Article ID bioo.1998.1117, available online at http://www.idealibrary.com on
Enzyme-Catalyzed Chemoselective Transesterification Reactions
on Hydroxymethylated Phenolic Compounds
Virinder S. Parmar,*,1 Ashok K. Prasad,* Hari N. Pati,* Rajesh Kumar,*
Abul Azim,* Sucharita Roy,* and William Errington†
*Department of Chemistry, University of Delhi, Delhi-110 007, India; and
†Department of Chemistry, University of Warwick, Coventry CV4 7AL,
England, United Kingdom
Received October 30, 1998
The chemoselective capabilities of porcine pancreatic lipase (PPL) in tetrahydrofuran and
Candida rugosa lipase (CRL) in diisopropyl ether have been investigated for selective acetyla-
tion and deacetylation of hydroxymethylated phenols and hydroxyaryl alkyl ketones and their
peracetylated derivatives. Both PPL and CRL exhibited exclusive selectivity for the acetylation
of alcoholic hydroxyl group over the phenolic hydroxyl group(s) of the hydroxymethylated
phenols 1–5 and aryl alkyl ketones 6–9, and for the deacetylation of ester group involving the
phenolic hydroxyl group over the ester group involving alcoholic hydroxyl of the peracetates
19–24. The preliminary results indicate that this strategy of chemoselective acetylation can
also be used in the enantiomeric resolution of racemic ketones 6–9. Single crystal X-ray
diffraction studies have confirmed the structures of compounds 4, 15, and 17.
᭧ 1999 Aca-
demic Press
INTRODUCTION
In recent years, chemoenzymatic synthetic strategies have become standard tech-
niques for the preparation of a variety of chiral and nonchiral precursors and target
molecules (1,2). Among the different enzymatic methodologies, lipase-catalyzed acyl-
ations and deacylations represent an important class of enzymatic transformations in
organic synthesis (3), wider applications of lipases are attributed to their low-cost
and tolerance toward a variety of organic molecules (4). In recent years, we have
successfully used lipases from porcine pancreas (PPL) and Candida rugosa (CRL)
for the regioselective deacetylation of peracetates of different classes of polyphenolics
(5) and for the regioselective and enantioselective esterifications of polyols (6). It
has been observed that the change of enzyme may lead to complementary result.
For example, use of lipases from Aspergillus species for the deacetylation of 2,4-
diacetoxyphenyl alkyl ketones led to the formation of 2-hydroxy-4-acetoxy ketones
(7), which is complementary to the result of deacetylation catalyzed by PPL or CRL (5).
1 To whom correspondence and reprint requests should be addressed. Fax: 91-11-725 7206. E-mail:
vparmar.duchem@axcess.net.in.
119
0045-2068/99 $30.00
Copyright ᭧ 1999 by Academic Press
All rights of reproduction in any form reserved.

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PARMAR ET AL.
So far, enzymes have seldom been employed for the chemoselective discrimination
between the phenolic and alcoholic hydroxyl groups present in the same molecule,
there is only one report in literature where such selection is achieved on 2- and 4-
hydroxymethylphenols via enzymatic catalysis with Aspergillus niger lipase (8). We
have employed PPL in tetrahydrofuran (THF) and CRL in diisopropyl ether (DIPE),
relatively cheaper and more easily accessible enzymes than Aspergillus niger lipase
for the selective acetylation of hydroxymethylated phenols and aryl alkyl ketones,
novel precursors for the synthesis of phenyl alkyl carbinols (9), and 3-alkyl/aryl
chromanones and their bioactive analogs (10). Further, the enzyme substrate ratio
used in the present investigation is just half of that used during selective acetylation
with A. niger lipase (8). The enzymatic methodology developed for chemoselective
acetylation of hydroxymethylated phenols and aryl alkyl ketones has successfully
been used for the enantioselective resolution of racemic hydroxymethylated aryl alkyl
ketones 6–9, which in turn can be used for the synthesis of optically pure isoflavanones
and 3-alkylchromanones (10), which have not been synthesized in optically enriched/
pure form thus far.
RESULTS AND DISCUSSION
The starting phenol, 2-hydroxymethylphenol (1) was procured from Aldrich Chemi-
cal Co. (U.S.A.) and other hydroxymethylated phenols; i.e., 4-hydroxymethylphenol
(2), 4-hydroxymethyl-2-methoxyphenol (3), 5-hydroxymethyl-2-methoxyphenol (4),
and 2-hydroxymethyl-6-methoxyphenol (5) were prepared by reduction of the corres-
ponding aldehydes, i.e., 4-hydroxybenzaldehyde, 4-hydroxy-3-methoxybenzaldehyde,
3-hydroxy-4-methoxybenzaldehyde, and 2-hydroxy-3-methoxybenzaldehyde, respec-
tively, with NaBH4 in 80–90% yields. The diacetates of hydroxymethylated phenols
1–5; i.e., 2-acetoxymethylphenyl acetate (19), 4-acetoxymethylphenyl acetate (20),
4-acetoxymethyl-2-methoxyphenyl acetate (21), 5-acetoxymethyl-2-methoxyphenyl
acetate (22), and 2-acetoxymethyl-6-methoxyphenyl acetate (23) were prepared by
SCHEME 1. Preparation of 2-ethyl-3-hydroxy-1-(2Ј,4Ј-dihydroxyphenyl)propanone (7).

CHEMOSELECTIVE O-ACETYLATIONS CATALYZED BY LIPASES
121
SCHEME 2
the acetic anhydride-pyridine method in the presence of catalytic amounts of dimethy-
laminopyridine (DMAP) in quantitative yields. The hitherto unknown diacetates 19
and 23 were identified on the basis of their spectral analysis, whereas the known
hydroxymethylated phenols 2–5 and the known diacetates 20–22 were characterized
by analysis of their spectral data and by comparison of their spectral and/or physical

122
PARMAR ET AL.
data with those reported in literature (11–13). The structure of 5-hydroxymethyl-2-
methoxyphenol (4) was also confirmed by its single crystal X-ray diffraction studies
(Table 5). Though compound 22 has been synthesized earlier (13), its spectral data
has not been reported and we herein report its complete data (cf. Experimental). The
compound 3-hydroxy-1-(4Ј-hydroxyphenyl)-2-methylpropanone (6) was prepared by
stirring a suspension of 4-hydroxypropiophenone in 37% formaldehyde and 0.5 N
sodium hydroxide solution in a molar ratio of 1.0:1.1:1.1 at 28–30ЊC for 15 h (14).
Further, 2-ethyl-3-hydroxy-1-(2Ј,4Ј-dihydroxyphenyl)propanone (7) was prepared by
hydroxymethylation of 4-benzyloxy-2-hydroxybutyrophenone (25) (15) as above, fol-
lowed by debenzylation of the hydroxymethylated ketone, 1-(4Ј-benzyloxy-2Ј-hydro-
xyphenyl)-2-ethyl-3-hydroxypropanone (26) by catalytic hydrogenation (Scheme 1).
The hydroxypropanones, 3-hydroxy-1-(2Ј-hydroxy-4Ј-methoxyphenyl)-2-phenylpro-
panone (8) and 3-hydroxy-1-(2Ј-hydroxyphenyl)-2-(4Љ-methoxybenzyl)propanone (9)
were prepared by reacting 2-hydroxy-4-methoxydesoxybenzoin (16) and 2Ј-hydroxy-
4-methoxydihydrochalcone (17) with ethoxymethyl chloride in the presence of dry
potassium carbonate in dry acetone in 65 and 70% yields, respectively. The diacetate,
3-acetoxy-1-(4Ј-acetoxyphenyl)-2-methylpropanone (24) was prepared as in the case
of hydroxymethylated phenols in 98% yield. Attempts to prepare di/triacylated deriva-
tives of 7, 8, and 9 resulted in the enolization of ketonic carbonyl group and subsequent
formation of the corresponding enolic peracetates as per our earlier observation in
similar compounds (18). The hitherto unknown compounds 7, 9, 24, and 26 were
characterized on the basis of their spectral analysis and the known compounds 6 and
8 were characterized by their spectral analysis and comparison with the data reported
in the literature (14,16).
To examine the chemoselective capabilities of PPL and CRL for the selective
acetylation of two different types of hydroxyl groups, hydroxymethylated phenols
1–5 were incubated with vinyl acetate and PPL or CRL in THF and DIPE, respectively.
Both the enzymes exhibited exclusive selectivity for the acetylation of aliphatic
hydroxyl function over the phenolic hydroxyl, though the rate of acetylation catalyzed
by CRL in DIPE was too slow with respect to PPL in THF. Thus, PPL-catalyzed
acetylation of the hydroxymethylated phenols 1–5 afforded the monoacetates 2-
acetoxymethylphenol (10), 4-acetoxymethylphenol (11), 4-acetoxymethyl-2-me-
thoxyphenol (12), 5-acetoxymethyl-2-methoxyphenol (13), and 2-acetoxymethyl-6-
methoxyphenol (14) exclusively in 95, 80, 90, 95, and 85% yields, respectively
(Table 1). The results indicate that the turn over in PPL-catalyzed acetylation of
hydroxymethylated phenols is almost quantitative. In addition to the selective acetyla-
tion studies on hydroxymethylated phenols, chemoselective capabilities of PPL and
CRL were also investigated for the selective acetylation of hydroxymethylated aryl
alkyl ketones. As in the case of acetylation of hydroxymethylated phenols, PPL and
CRL exhibited 100% selectivity for the acetylation of aliphatic hydroxyl group with
respect to phenolic hydroxyl group in hydroxymethylated aryl alkyl ketones. Thus,
incubation of compounds 6 and 7 with PPL in THF afforded the monoacetoxy products,
3-acetoxy-1-(4Ј-hydroxyphenyl)-2-methylpropanone (15) and 3-acetoxy-2-ethyl-1-
(2Ј,4Ј-dihydroxyphenyl)propanone (16) in 65 and 55% yields in 12 and 38 h (Table
1), respectively. It has been observed that PPL in THF catalyzes the acetylation of
aliphatic hydroxyl group of 6 and 7 faster than CRL in DIPE, the rate of selective

CHEMOSELECTIVE O-ACETYLATIONS CATALYZED BY LIPASES
123
TABLE 1
Selective Acetylation of Hydroxymethylated Phenols 1–5 and Aryl alkyl Ketones 6–9 Mediated by
PPL in THF (A) and/or CRL in DIPE (B) at 42–45ЊCa
Reaction Time
condition (h)
Percentage
yield
Substrate
Product
2-Hydroxymethylphenol (1)
4-Hydroxymethylphenol (2)(11a)
4-Hydroxymethyl-2-methoxyphenol
(3)(11b)
A
A
A
120 2-Acetoxymethylphenol (10)(8)
48 4-Acetoxymethylphenol (11)(12)
24 4-Acetoxymethyl-2-methoxy-
phenol (12)(12)
95
80
90
5-Hydroxymethyl-2-methoxyphenol
(4)(11b)
2-Hydroxymethyl-6-methoxyphenol
(5)(11c)
3-Hydroxy-1-(4Ј-hydroxyphenyl)-
2-methylpropanone (6)(14)
2-Ethyl-3-hydroxy-1-(2Ј,4Ј-
dihydroxyphenyl)propanone (7)
3-Hydroxy-1-(2Ј-hydroxy-4Ј-
methoxyphenyl)-2-
A
A
96 5-Acetoxymethyl-2-methoxy-
phenol (13)(19)
120 2-Acetoxymethyl-6-methoxy-
phenol (14)
12/30 3-Acetoxy-1-(4Ј-hydroxyphenyl)-
2-methylpropanone (15)
38/72 3-Acetoxy-2-ethyl-1-(2Ј,4Ј-
dihydroxyphenyl)propanone (16)
95
85
65
55
70
A/B
A/B
B
8
3-Acetoxy-1-(2Ј-hydroxy-4Ј-
methoxyphenyl)-2-
phenylpropanone (8)(16)
3-Hydroxy-1-(2Ј-hydroxyphenyl)-2-
(4Љ-methoxybenzyl)propanone (9)
phenylpropanone (17)(16)
3-Acetoxy-1-(2Ј-hydroxyphenyl)-2-
(4Љ-methoxybenzyl)propanone
(18)
B
8
75
a All these reactions, when performed under identical conditions but without adding the lipase, did not
yield any product.
acetylation of aliphatic hydroxyl function by the former is about 2.5 and 2 times
faster, respectively, than the latter (Table 1). The hydroxymethylated aryl alkyl ketones
8 and 9 were poor substrates for PPL and no appreciable acetylation was observed
even upon incubation for several days. However, CRL in DIPE catalyses the acetylation
of compounds 8 and 9 to afford the monoacetates involving the aliphatic hydroxyl
group, i.e., 3-acetoxy-1-(2Ј-hydroxy-4Ј-methoxyphenyl)-2-phenylpropanone (17) and
3-acetoxy-1-(2Ј-hydroxyphenyl)-2-(4Љ-methoxybenzyl)propanone (18) in 70 and 75%
yields, respectively (Table 1). This result indicates that the substituent at C-2 position
in compounds 6–9 plays an important role during their binding with PPL and CRL.
The hitherto unknown monoacetates 14, 15, 16, and 18 were identified on the basis
of their spectral analysis, while the known monoacetates 10–13 and 17 were identified
on the basis of spectral analysis and their comparison with those reported in the
literature (8,12,16,19). The formation of monoacetates involving aliphatic hydroxyl
group during enzyme-catalyzed acetylation reactions has been well established as the
carbinol protons in all the monoacetates (except in 16) are deshielded (by ⌬␦ 0.35–0.68
ppm) with respect to the corresponding protons in the respective hydroxylated com-
pounds (Table 2). The presence of chelated and free phenolic hydroxyl groups at ␦
12.87 and 9.99, respectively, and the absence of any resonance due to aliphatic
1
hydroxyl group in the H NMR spectrum of 16 in deuterated chloroform establishes
the acetylation of aliphatic hydroxyl group in this compound as well. The compounds
16, 17, and 18 gave dark brown Fe3ϩ coloration when their TLC spots were sprayed

124
PARMAR ET AL.
TABLE 2
Comparison of Chemical Shift Values of Methylene Protons of the Starting Carbinols and in Their
Corresponding Acetates
Deshielding effect
Carbinol
␦ CH2OH
4.78
4.54
4.51
4.49
4.70
3.59 and 3.66
4.33
3.74 and 4.20
3.88
Acetate
␦ CH2OCOCH3
(ppm)
1
10
11
12
13
14
15
16
17
18
5.20
5.08
5.00
5.05
0.42
0.54
0.49
0.56
0.48
0.51 and 0.68
2
3
4
5
6
7
8
9
5.18
4.10 and 4.34
4.23 and 4.32
4.35 and 4.75
4.23 and 4.38
0.61 and 0.55
0.35 and 0.50
with 3% alcoholic FeCl3 solution, thus indicating that the ortho (phenolic) hydroxy
function to the nuclear carbonyl group is not acetylated in any of them. This is further
proved by the presence of chelated hydroxyl group at ␦ 12.87, 12.68, and 12.31 in
the 1H NMR spectra of 16, 17, and 18, respectively. The X-ray crystallographic studies
on the monoacetates 15 and 17 (Figs. 1 and 2) finally confirmed the involvement of
the aliphatic hydroxyl group of 6 and 8 in ester formation during enzyme-catalyzed
acetylation reaction.
In addition to the capabilities of PPL and CRL to catalyze the chemoselective
FIG. 1. Molecular structure of compound 15. Displacement ellipsoids are shown at the 50% probabil-
ity level.

CHEMOSELECTIVE O-ACETYLATIONS CATALYZED BY LIPASES
125
FIG. 2. Molecular structure of compound 17. Displacement ellipsoids are shown at the 50% probabil-
ity level.
acetylation of aliphatic hydroxyl groups of hydroxymethylated phenols and aryl alkyl
ketones, we tried to extend these studies to enantiomeric resolution of racemic ketones
6–9. The racemic hydroxymethylated aryl alkyl ketones 6 and 7, and 8 and 9 were
incubated with PPL in THF and CRL in DIPE, respectively, and the reactions were
stopped by filtering off the enzyme after about 45% conversion of the dihydroxy
ketone to monoacetate. The monoacetates and the unreacted dihydroxy ketones were
separated on silica gel column with a gradient solvent system of petrol:ethyl acetate
and their optical rotations measured. The monoacetates and the unreacted dihydroxy
compounds were found to be optically active in each case (Table 3). The monoacetates
were deacetylated enzymatically and the rotations of the dihydroxy compounds thus
obtained were measured, the rotations of these compounds were found to be of the
same order and had opposite sign to the rotation of the corresponding unreacted
dihydroxy compound (Table 3). These observation revealed that the chemoselective
acetylation is also accompanied by enantiomeric resolution of the racemic ketones
6–9. The evaluation of enantiomeric excess (ee) of the monoacetates in each case is
in progress by 1H NMR spectral studies using diamagnetic anthryl chiral shift reagent
and on chiral HPLC columns.
Together with enzyme-catalyzed acetylation, deacetylation reactions of peracetates

126
PARMAR ET AL.
TABLE 3
Optical Rotations of Products Obtained after Enzymatic Acetylation of Compounds 6–9a and
Deacetylation of the Monoacetoxy Productsb
[␣]25 Values of the compounds obtained by incubation with enzymes
D
Dihydroxypropanones obtained
Unreacted
Dihydroxy-
propanones
by the CRL-catalyzed deacetylation
of the monoacetoxypropanones
in DIPE (containing n-butanol)c
Substrate
(racemic)
Enzyme/
solvent
Monoacetoxy-
propanones
6
7
8
9
PPL/THF
PPL/THF
CRL/DIPE
CRL/DIPE
ϩ23.7
ϩ3.7
Ϫ46.0
ϩ30.8
Ϫ26.2
ϩ6.6
ϩ16.0
Ϫ25.6
ϩ29.9
Ϫ10.8
Ϫ12.7
ϩ29.5
a All the enzyme-assisted reactions carried out for enantiomeric resolution studies were stopped by
filtering off the enzyme after about 45% conversion (as seen on HPLC) of the starting racemic substrate
to the product.
b All these acetylation and deacetylation reactions, when performed under identical conditions but
without adding the lipase, did not yield any product.
c The specific rotations of the unreacted dihydroxypropanones are less than those of the corresponding
dihydroxypropanones obtained by enzymatic deacetylation of the monoacetates, except in the case of
compound 8. This may be due to partial racemization of the unreacted dihydroxypropanones taking place
during their separation from the monoacetoxypropanones on silica gel column, the deacetylated products
of monoacetates did not require purification as they were found to be sufficiently pure on TLC/HPLC
examination. Such partial racemization on silica gel due to its acidic nature is known in literature (24).
of hydroxymethylated phenols 19–23 and hydroxymethylated aryl alkyl ketone 24
catalysed by PPL in THF and CRL in DIPE were also studied. It has been found that
the incubation of compounds 19–23 with CRL in DIPE catalyzes the deacetylation
of ester group involving the phenolic hydroxyl function and afforded the monoacetates
10, 11, 12, 13, and 14 (Table 4), respectively. None of the diacetates was a substrate
for PPL in THF. In general, the deacetylation reactions on peracetates 19–23 catalyzed
by CRL in DIPE were slow than the acetylation reactions on corresponding dihydroxy
compounds 1–5 (Tables 1 and 4). In contrast to the selective deacetylation reactions
on 19–23 which were catalysed by CRL in DIPE, the deacetylation reaction on
3-acetoxy-1-(4Ј-acetoxyphenyl)-2-methylpropanone (24) was catalyzed by PPL in
THF affording the monoacetate 15 in 60% yield due to the selective deacetylation
of ester function involving phenolic hydroxyl group over alcoholic hydroxyl (Table
4). The incubation of compound 24 with CRL in DIPE led to the formation of an
inseparable mixture.
The enzymatic method developed for the chemoselective acetylation of hydroxy-
methylated phenols and aryl alkyl ketones may find applications in the efficient
synthesis of phenyl alkyl carbinols, known for their chloretic properties, and for
the synthesis of bioactive analogs of naturally occurring 3-alkylchromanones and
isoflavanones, respectively. It has been demonstrated that this strategy of selective
esterification also leads to enantiomeric resolution of racemic aryl alkyl ketones which
in turn can be used for the synthesis of optically pure isoflavanones. Further, in the

CHEMOSELECTIVE O-ACETYLATIONS CATALYZED BY LIPASES
127
TABLE 4
Selective Deacetylation of Peracetates of Hydroxymethylated Phenols 19–23 and Aryl alkyl Ketone
24 Mediated by PPL in THF (A) and CRL in DIPE (B) at 42–45ЊCa
Reaction Time
condition (days)
Percentage
yield
Substrate
Product
2-Acetoxymethylphenyl acetate (19)
4-Acetoxymethylphenyl acetate
(20)(11a, 12)
B
B
15 2-Acetoxymethylphenol (10)(8)
4-Acetoxymethylphenol (11)(12)
40
60
2
4-Acetoxymethyl-2-methoxyphenyl
acetate (21)(12)
5-Acetoxymethyl-2-methoxyphenyl
acetate (22)(13)
2-Acetoxymethyl-6-methoxyphenyl
acetate (23)
3-Acetoxy-1-(4Ј-acetoxyphenyl)-
2-methylpropanone (24)
B
B
B
A
12 4-Acetoxymethyl-2-
methoxyphenol (12)(12)
10 5-Acetoxymethyl-2-
methoxyphenol (13)(19)
50
55
50
60
10 2-Acetoxymethyl-6-
methoxyphenol (14)
3
3-Acetoxy-1-(4Ј-hydroxyphenyl)-
2-methylpropanone (15)
a All these reactions, when performed under identical conditions but without adding the lipase, did not
yield any product.
course of this enzyme-assisted selective acetylation studies, 10 new compounds, i.e.,
7, 9, 14, 15, 16, 18, 19, 23, 24, and 26 have been obtained.
X-RAY CRYSTALLOGRAPHY
The molecular structures of the compounds 4, 15, and 17 were confirmed by single
crystal X-ray diffraction studies. Some of the crystallographic data are summarized
in Table 5. All bond lengths and angles are unexceptional. In the molecular structure
of hydroxymethylated phenol 4, the carbinol oxygen atom is twisted out of the plane
of the phenyl ring to give a C6-C1-C7-O1 torsion angle of 80.2(2)Њ; in contrast the
methoxy group is almost coplanar with the phenyl group and has a C8-O3-C4-C3
torsion angle of 176.5(1)Њ. Intermolecular H-bonding interactions are responsible for
the integrity of the solid state.
The structures of compounds 15 and 17 are illustrated in Figs. 1 and 2, respectively.
Both molecules deviate considerably from planarity as illustrated by torsion angles
C1Ј-C1-C2-C4 of 83.4(2)Њ and 77.9(2)Њ, respectively. Both structures are stabilized
by hydrogen bonding; in compound 15, intermolecular H-bonding occurs between
the hydrogen of phenolic hydroxyl group and the acetyl oxygen of an adjacent
molecule, while in 17 there is intramolecular H-bonding between the phenolic hydroxyl
group and the ketonic carbonyl group.
EXPERIMENTAL
Melting points were determined on a Mettler FP62 instrument and are uncorrected.
The IR spectra were recorded on a Perkin–Elmer model 435 spectrophotometer. The
1H NMR and 13C NMR spectra were recorded either on Bruker AC-250, Bruker AC-
300, or Bruker AC-400 spectrometer at 250, 300, and 400 MHz, and at 62.8, 75.0,
and 100.0 MHz, respectively, using TMS as internal standard. The chemical shift

128
PARMAR ET AL.
TABLE 5
Crystal Data and Structure Refinement for Compounds 4, 15, and 17.
Compounds
4
15
17
Formula
M
C8H10O3
154.16
C12H14O4
222.23
C18H18O5
314.32
Crystal system
Orthorhombic
Pbca
14.9898(10)
6.0337(4)
16.5351(11)
90
90
90
1495.5(2)
180(2)
Monoclinic
P2(1)/c
10.8613(3)
9.0667(2)
11.9286(3)
90.00
101.059(2)
90.00
1152.87(5)
210(2)
Monoclinic
P2(1)
8.2127(3)
9.0559(4)
10.5774(5)
90.00
99.036(1)
90.00
776.91(6)
200(2)
Space Group
˚
a/A
˚
b/A
˚
c/A
␣/Њ
␤/Њ
␥/Њ
˚
V/A3
T/K
Z
␭/A
8
4
2
˚
0.71073
1.369
0.105
0.71073
1.280
0.096
0.71073
1.344
0.098
␳(calcd.)/Mg/m3
␮/mmϪ1
hkl ranges
Ϫ19, 19; Ϫ5, 7;
Ϫ21, 20
8208
1807
0.9834, 0.9495
0.045
0.124
1.055
0.479, Ϫ0.415
1807, 0, 106
Ϫ13, 13; Ϫ12, 12;
Ϫ10, 15
6673
2693
0.9051, 0.6049
0.049
0.135
0.929
0.192, Ϫ0.229
2693, 0, 151
Ϫ10, 10; Ϫ10, 11;
Ϫ7, 13
4724
3254
0.9844, 0.9768
0.033
0.079
0.918
0.130, Ϫ0.176
3254, 1, 211
Number of data collected
Independent reflections
Transmission coefficients
R(F) [IϾ2␴(I)]
wR(F2) (all data)
Goodness of fit on F2
˚
Peak diff. & hole/eAϪ3
Data, restraints, parameters
values are on ␦ scale and the coupling constants (J) are in Hz. The EI mass spectra
were recorded on a Jeol JMSDX 303 or on a Jeol AX 505 W instrument at 70 eV.
The enzymes, porcine pancreatic lipase (PPL, Type II) and Candida rugosa lipase
(CRL, Type VII) were purchased from Sigma Chemical Co. (U.S.A.) and used after
keeping in vacuo over P2O5 for 24 h. The organic solvents (THF and DIPE) used
˚
were distilled and dried over molecular sieves (4 A), while n-butanol was dried
and distilled over ignited potassium carbonate. Analytical TLCs were performed on
precoated Merck silica gel 60 F254 plates; the developing agent was alcoholic FeCl3
solution (3%). Reactions were monitored at ␭254 nm on a Shimadzu LC-10AS HPLC
instrument with SPD-10A UV-VIS detector and Shimpack CLC-ODS (4.6 ϫ 150
mm) reverse phase column, solvent system used was methanol–water (3:2) at the
flow rate of 0.50 ml/min.
The hydroxymethylated phenols 2–5 were prepared by the reduction of their respec-
tive aldehydes with NaBH4 in methanol at ice temperature in 80–90% yields, 2-
hydroxymethylphenol (1) was purchased from Aldrich Chemical Co. (U.S.A.). The
peracetates of hydroxymethylated phenols, i.e., the compounds 19–24, were prepared
in quantitative yields by stirring a solution of the corresponding phenolic compounds

CHEMOSELECTIVE O-ACETYLATIONS CATALYZED BY LIPASES
129
1–6 in acetic anhydride-pyridine in the presence of catalytic amount of dimethylamino-
pyridine either at room temperature (28–30ЊC) or at 40–45ЊC.
General Method of Enzymatic Acetylation of Hydroxymethylated Phenolic
Compounds 1–9
The hydroxymethylated phenolic compounds (1–9, 2 mmol) were dissolved in dry
tetrahydrofuran or diisopropyl ether (25–30 ml), vinyl acetate (4 mmol), and porcine
pancreatic lipase or C. rugosa lipase (200 mg) were added to the solution. The
suspension was stirred at 42–45ЊC and progress of the reaction was monitored by
TLC and/or HPLC. After completion, the reaction was quenched by filtering off the
enzyme, solvent removed under reduced pressure, and the crude product was purified
by column/preparative thin layer chromatography and/or by crystallization to afford
the pure monoacetates 10–18 involving the aliphatic hydroxyl group. The hitherto
unknown monoacetates 14, 15, 16, and 18 obtained were fully characterized on the
basis of their spectral analysis. The known monoacetates 10 (8), 11 (12), 12 (12), 13
(19), and 17 (16) were identified on the basis of their spectral analysis and their
comparison with those reported in the literature.
General Method of Enzymatic Deacetylation of Peracetates of Hydroxymethylated
Phenols 19–23and Aryl Alkyl Ketone 24
The peracetates (19–24, 2 mmol) were dissolved in dry tetrahydrofuran or diisopro-
pyl ether (25–30 ml) containing n-butanol (4 mol eq.), porcine pancreatic lipase, or
C. rugosa lipase (200 mg) was added to the solution. The suspension was stirred at
42–45ЊC and progress of the reaction was monitored by TLC and/or HPLC. After
completion, the reaction was quenched by filtering off the enzyme, solvent removed
under reduced pressure, and the crude product was purified by column/preparative
thin layer chromatography and/or by crystallization to afford the pure monoacetates
10–15, which were fully characterized as mentioned in the preceding paragraph.
2-Ethyl-3-hydroxy-1-(2Ј, 4Ј-dihydroxyphenyl)propanone (7)
To a solution of 1-(4Ј-benzyloxy-2Ј-hydroxyphenyl)-2-ethyl-3-hydroxypropanone
(26, 1.20 g, 4 mmol) in ethyl acetate (40 ml), Pd-C (10%)was added and the reaction
mixture was stirred under hydrogen at atmospheric pressure at 25–30ЊC for 2 h, TLC
examination of the reaction showed 100% conversion to the product. The catalyst
was filtered off, solvent removed, and the residue was kept under high vaccum to
remove the traces of toluene formed during debenzylation to afford pure 7 as a
colorless oil (0.82g), 98% yield; Rf 0.30 (petrol:ethyl acetate, 3:2); IR (thin film):
1
3254, 2967, 2361, 1632, 1514, 1455, 1385, 1314, 1233, 1146, and 1036 cmϪ1; H
NMR (300 MHz, CD3 OD) ␦: 1.61(t, J ϭ 7.5 Hz, 3H, CH3), 2.38(m, 2H, CH2-CH3),
4.33(m, 2H, CH2-OH), 4.48(m, 1H, C-2H), 5.50(brs, 1H, CH2-OH), 7.08(d, J ϭ 1.8
Hz, 1H, C-3ЈH), 7.20(d, J ϭ 9.0 Hz, 1H, C-5ЈH), 8.67(d, J ϭ 9.0 Hz, 1H, C-6ЈH),
11.50(brs, 1H, phenolic OH), and 13.83(s, 1H, chelated OH); 13C NMR (75 MHz,
CD3OD) ␦: 12.00(CH3), 23.76(CH2CH3), 50.51(C-2), 64.28(C-3), 103.78 and
108.25(C-3Ј and C-5Ј), 115.03(C-1Ј), 133.92(C-6Ј), 166.37 and 166.67(C-2Ј and C-
4Ј) and 208.54(CO); EIMS, m/z (% rel. int.): 210[M+](10), 192(10), 180(4), 163(6),
149(14), 137(100), 121(23), 98(6), 81(9) and 77(3).

130
PARMAR ET AL.
3-Hydroxy-1-(2Ј-hydroxyphenyl)-2-(4Љ-methoxybenzyl)propanone (9)
A solution of 2Ј-hydroxy-4-methoxydihydrochalcone (17) (1.28g, 5 mmol) in dry
acetone (100 ml) and anhydrous potassium carbonate (3.5 g, 25 mmol) was treated
with a solution of ethoxymethyl chloride (20) (0.75 ml, 5.5 mmol) in dry acetone (8
ml). The resulting mixture was refluxed at 60–70ЊC for 2.5 h. The reaction mixture
was filtered and the filterate concentrated at reduced pressure. The light brown residue
was purified by column chromatography on silica gel to afford compound 9 as a light
yellow colored oil (0.72 g), 50% yield; Rf 0.35 (petrol:ethyl acetate, 4:1); IR (thin
film): 3435, 2934, 2837, 1633, 1512, 1487, 1446, 1290, 1246, 1179 and 1035 cmϪ1;
1H NMR (400 MHz, CDCl3) ␦: 2.10 and 2.92(2m, 1H each, 2H, PhCH␣ and PhCH␤),
3.02(m, 1H, C-2H), 3.76(s, 3H, OCH3), 3.84(brm, 1H, OH), 3.88(m, 2H, C-3H),
6.80(d, J ϭ 8.8Hz, 2H, C-3ЉH and C-5ЉH), 6.88(m, 1H, C-5ЈH), 6.98(dd, J ϭ 1.1
and 8.4Hz, 1H, C-3ЈH), 7.11(d, J ϭ 8.8 Hz, 2H, C-2ЉH, and C-6ЉH), 7.48(m, 1H, C-
4ЈH), 7.73(dd, J ϭ 1.8 and 8.1Hz, 1H, C-6ЈH) and 12.31(s, 1H, chelated OH);
13C NMR (100 MHz, CDCl3) ␦: 34.31(CH2), 49.59(C-2), 55.13(OCH3), 62.39(C-3),
113.92(C-3Ј, C-3Љ and C-5Љ), 118.68 and 118.95(C-1Ј and C-5Ј), 129.82 and 130.04(C-
4Ј, C-1Љ, C-2Љ and C-6Љ), 136.72(C-6Ј), 158.22(C-4Љ), 162.99(C-2Ј), and 209.27(C-
1); EIMS, m/z (% rel. int.): 286[M+](35), 255(92), 147(52), 121(100), 97(55), 91(58),
and 65(98).
2-Acetoxymethyl-6-methoxyphenol (14)
The column chromatographic purification of the crude product on silica gel afforded
compound 14 as a colorless viscous oil in 85% yield; Rf ϭ 0.40 (petrol:ethyl acetate,
4:1); IR (thin film): 3437, 2941, 2844, 2361, 1734, 1620, 1597, 1484, 1443, 1382,
1
1362, 1275, 1084, and 1027 cmϪ1; H NMR (300 MHz, CDCl3) ␦: 2.06(s, 3H,
OCOCH3), 3.84(s, 3H, OCH3), 5.18(s, 2H, CH2OCOCH3), 6.82(m, 2H, C-3H and C-
5H), and 6.90(m, 1H, C-4H); 13C NMR(75 MHz, CDCl3) ␦: 20.73(CH3), 55.91(CH2),
61.33(OCH3), 110.90(C-4), 119.41 and 121.68(C-3 and C-5), 121.17(C-2), 144.15
and 146.65 (C-1 and C-6) and 171.14(CO); EIMS, m/z (% rel. int.): 196[M+] (20),
153(3), 136(100), 122(7), 118(7), 107(33), 106(33), 93(16), 80(12), and 77(10).
3-Acetoxy-1-(4Ј-hydroxyphenyl)-2-methylpropanone (15)
The column chromatographic purification of the crude product on silica gel afforded
compound 15 as a colorless solid that was crystallized from petrol:chloroform as
white shining powder in 60% yield. Mp 136ЊC; Rf 0.30 (petrol:ethyl acetate, 4:1); IR
(thin film): 3305, 2979, 2818, 1714, 1667, 1601, 1514, 1442, 1371, 1219, 1174, 1153
1
and 1039 cmϪ1; H NMR (250 MHz, DMSO-d6) ␦: 1.17(d, J ϭ 6.8 Hz, 3H, CH3),
1.92(s, 3H, OCOCH3), 3.88(m, 1H, C-2H), 4.10(dd, J ϭ 6.2 and 10.6 Hz, 1H, C-3
H␣), 4.34(dd, J ϭ 7.9 and 10.6Hz, 1H, C-3H␤), 6.94(d, J ϭ 8.9 Hz, 2H, C-3ЈH and
C-5ЈH), 7.94(d, J ϭ 8.9 Hz, 2H, C-2ЈH and C-6ЈH) and 9.25(brs, 1H, phenolic OH);
13C NMR(62.8 MHz, CDCl3) ␦: 15.03(CH3), 20.58(COCH3), 39.95(C-2), 66.61(C-
3), 116.14(C-3Ј and C-5Ј), 129.26(C-1Ј), 131.64(C-2Ј and C-6Ј), 162.91(C-4Ј),
170.83(CO) and 199.85(C-1); EIMS, m/z (% rel. int.): 222[M+] (3), 180(17), 122(15),
121(100), 93(17), 77(3), and 71(3).

CHEMOSELECTIVE O-ACETYLATIONS CATALYZED BY LIPASES
131
3-Acetoxy-2-ethyl-1-(2Ј, 4Ј-dihydroxyphenyl)propanone (16)
The column chromatographic purification of the crude product on silica gel afforded
compound 16 as a light brownish oil in 55% yield; Rf 0.60 (petrol:ethyl acetate, 3:2);
IR (thin film): 3337, 2969, 2879, 2361, 1714, 1630, 1512, 1447, 1376, 1231 and
1
1042 cmϪ1; H NMR (300 MHz, CD3OD) ␦: 0.91(t, J ϭ 7.5 Hz, 3H, CH3), 1.62(m,
1H, CH␣H␤CH3), 1.71(m, 1H, CH␣H␤CH3), 1.92(s, 3H, OCOCH3), 3.77(dt, J ϭ 2.4
and 8.0 Hz, 1H, C-2H), 4.23(dd, J ϭ 5.1 and 10.8 Hz, 1H, C-3H␣), 4.32(dd, J ϭ 8.7
and 10.5 Hz, 1H, C-3H␤) 6.29(d, J ϭ 2.4 Hz, 1H, C-3ЈH), 6.39(dd, J ϭ 2.4 and 9.0
1
Hz, 1H, C-5ЈH), 7.78(d, J ϭ 9.0 Hz, 1H, C-6ЈH) and 12.83(s, 1H, chelated OH); H
NMR (300 MHz, CDCl3) ␦: 0.92(t, J ϭ 7.5 Hz, 3H, CH3), 1.62(m, 1H, CH␣H␤CH3),
1.76(m, 1H, CH␣H␤CH3), 1.96(s, 3H, OCOCH3), 3.65(m, 1H, C-2H), 4.24(dd, J ϭ
6.0 and 12.0 Hz, 1H, C-3H␣), 4.34(dd, J ϭ 8.0 and 9.0 Hz, 1H, C-3H␤), 6.42(m, 2H,
C-3ЈH and C-5ЈH), 7.63(d, J ϭ 8.4 Hz, 1H, C-6ЈH), 9.99(brs, 1H, phenolic OH), and
12.87(s, 1H, chelated OH); 13C NMR (75 MHz, CDCl3) ␦: 11.52(CH3), 20.83 and
23.08(CH2 and COCH3), 45.67(C-2), 64.99(C-3), 103.59 and 108.30 (C-3Ј and C-5Ј),
113.85 (C-1Ј), 132.27(C-6Ј), 164.23 and 165.79(C-2Ј and C-4Ј) and 171.48(COCH3);
EIMS, m/z (% rel. int.): 252[M+](4), 192(18), 177(3), 163(7), 149(4), 137(100),
121(19), 84(6), and 81(6).
3-Acetoxy-1-(2Ј-hydroxyphenyl)-2-(4Љ-methoxybenzyl)propanone (18)
The column chromatographic purification of the crude product on silica gel afforded
compound 18 as a colorless oil in 75% yield; Rf 0.50 (petrol:ethyl acetate, 4:1); IR
(thin film): 2956, 2934, 2837, 1743, 1635, 1613, 1581, 1514, 1488, 1446, 1375, 1247,
1
1179, 1158, and 1036 cmϪ1; H NMR (400 MHz, CDCl3) ␦: 1.92(s, 3H, OCOCH3),
2.81(dd, J ϭ 14.0 and 7.4Hz, 1H, PhCH␣H␤), 3.05(dd, J ϭ 14.0 and 7.0Hz, 1H,
PhCH␣H␤), 3.75(s, 3H, OCH3), 4.01(m, 1H, C-1H), 4.23(dd, J ϭ 10.5 and 4.5Hz,
1H, C-3H␣), 4.38(dd, J ϭ 10.9 and 8.8Hz, 1H, C-3H␤), 6.78(d, J ϭ 8.8Hz, 2H, C-
3ЉH and C-5ЉH), 6.85(dtd, J ϭ 1.1, 1.0 and 1.4Hz, 1H, C-5ЈH), 6.97(dd, J ϭ 1.1 and
8.4Hz, 1H, C-3ЈH), 7.05(d, J ϭ 8.8Hz, 2H, C-2ЉH and C-5ЉH), 7.45(dtd, J ϭ 1.7,
1.4 and 1.4Hz, 1H, C-4ЈH), 7.68(dd, J ϭ 8.0 and 1.4Hz, 1H, C-6ЈH), and 12.31(s,
1H, chelated OH); 13C NMR (100 MHz, CDCl3) ␦: 20.61(COCH3), 34.60(ArCH2),
46.51(C-2), 55.11(OCH3), 64.38(C-3), 113.94(C-3Љ and C-5Љ), 118.57, 118.87 and
119.28(C-1Ј, C-3Ј and C-5Ј), 129.55(C-1Љ), 129.73 and 129.79(C-4Ј, C-2Љ and C-6Љ),
136.64(C-6Ј), 158.28(C-4Љ), 162.85(C-2Ј), 171.00(CO) and 206.48(C-1); EIMS, m/z
(% rel. int.): 328[M+](9), 268(58), 255(17), 237(8), 148(13), 147(33), 121(100),
93(11), and 77(10).
2-Acetoxymethylphenyl acetate (19)
The column chromatographic purification of the crude product on silica gel column
afforded compound 19 as a colorless oil in 92% yield; Rf 0.35 (petrol:ethyl acetate,
19:1); IR (KBr): 1739, 1600, 1492, 1458, 1370, 1232, 1178, 1110 and 1027 cmϪ1;
1H NMR (250 MHz, CDCl3)␦: 2.04 and 2.28(2s, 3H each, 2 ϫ OCOCH3), 5.07(s,
2H, CH2OCOCH3), and 7.08, 7.32, 7.23 and 7.42(4dd, J ϭ 1.3 and 8.0 Hz, 1.3 and
7.5 Hz, 1.8 and 7.7 Hz, and 1.7 and 7.3 Hz, respectively, 1H each, 4H, C-3H, C-4H,
C-5H and C-6H); 13C NMR (62.5 MHz, CDCl3)␦: 20.57(2 ϫ OCOCH3), 61.14(CH2),
122.49 and 125.94(C-3 and C-6), 127.90(C-2), 129.40 and 130.18(C-4 and C-5),

132
PARMAR ET AL.
148.94(C-1), and 169.01 and 170.35(2 ϫ CO); EIMS m/z (% rel. int.): 208[M]+(9),
166(61), 149(17), 124(7), 106(100), 97(8), 78(28), 71(9), 57(16), and 43(32).
5-Acetoxymethyl-2-methoxyphenyl acetate (22)
The column chromatographic purification of the crude product on silica gel afforded
compound 22 as a colorless oil in 90% yield; Rf 0.30 (petrol:ethyl acetate, 19:1); IR
(thin film): 2941, 1767, 1739, 1620, 1516, 1444, 1370, 1271, 1227, 1203, 1126, and
1025 cmϪ1; 1H NMR(250 MHz, CDCl3) ␦: 2.06 and 2.30(2s, 3H each, 2 ϫ OCOCH3),
3.81(s, 3H, OCH3), 5.02(s, 2H, CH2OCOCH3), 6.94(d, J ϭ 9.5 Hz, 1H, C-5H), 7.08(d,
J ϭ 1.8 Hz, 1H, C-2H) and 7.19(dd, J ϭ 9.5 and 1.8 Hz, 1H, C-4H); 13C NMR
(CDCl3, 62.5 MHz) ␦: 20.50 and 20.88(2 ϫ OCOCH3), 55.85(CH2), 65.42(OCH3),
121.16, 123.13 and 127.10(C-2, C-4 and C-5), 128.48(C-3), 139.57(C-1), 151.05(C-
6), and 168.82 and 170.73(2 ϫ CO); EIMS, m/z (% rel. int.): 238[M]+(17), 196(100),
179(7), 154(84), 137(55), 136(18), 122(17), 93(8), 65(6), and 43(28).
2-Acetoxymethyl-6-methoxyphenyl acetate (23)
The column chromatographic purification of the crude product on silica gel afforded
compound 23 as a light yellow viscous oil in 85% yield; Rf 0.30 (petrol:ethyl acetate,
19:1); IR (thin film): 2942, 2843, 1769, 1739, 1614, 1589, 1483, 1368, 1282, 1227,
1176, 1085, and 1028 cmϪ1 1H NMR (250 MHz, CDCl3) ␦: 2.04 and 2.31(2s, 3H
each, 2 ϫ OCOCH3), 3.80(s, 3H, OCH3), 5.06(s, 2H, CH2OCOCH3), 6.95(dd, J ϭ
8.2 and 1.4 Hz, 1H, C-3H), 7.00(dd, J ϭ 7.78 and 1.48 Hz, 1H, C-5H) and 7.18(t,
J ϭ 10.00 Hz, 1H, C-4H); 13C NMR (62.5 MHz, CDCl3)␦: 20.24 and 20.64(2 ϫ
OCOCH3), 55.86(CH2), 61.15(OCH3), 112.40, 121.49 and 126.40(C-3, C-4 and C-
5), 129.29(C-2), 138.34(C-1), 151.22(C-6), and 168.47 and 170.48(2 ϫ CO); EIMS,
m/z(% rel. int.): 238[M+](9), 196(28), 136(100), 135(26), 107(17), 93(4), 65(5),
and 43(18).
3-Acetoxy-1-(4Ј-acetoxyphenyl)-2-methylpropanone (24)
The column chromatographic purification of the crude product on silica gel afforded
compound 24 as a thick oil in 92% yield; Rf 0.50 (petrol:ethyl acetate, 19:1); IR (thin
1
film): 2979, 1764, 1742, 1683, 1599, 1504, 1370, 1196, 1167 and 1039 cmϪ1; H
NMR (200 MHz, CDCl3) ␦: 1.25(d, J ϭ 7.0 Hz, 3H, CH3), 2.01 and 2.36(2s, 3H
each, 2 ϫ OCOCH3), 3.87(m, 1H, C-2H), 4.20(dd, J ϭ 10.8 and 5.6 Hz, 1H, C-3
H␣), 4.45(dd, J ϭ 10.8 and 8.0 Hz, 1H, C-3 H␤), 7.24(d, J ϭ 10.0 Hz, 2H, C-3ЈH
and C-5ЈH) and 8.03(d, J ϭ 10.0 Hz, 2H, C-2ЈH and C-6ЈH); 13C NMR (75 MHz,
CDCl3)␦: 14.23 (CH3), 20.35 and 20.69(2 ϫ COCH3), 39.59(C-2), 65.52(C-3),
121.65(C-3Ј and C-5Ј), 129.66(C-2Ј and C-6Ј), 133.41(C-1Ј), 154.26(C-4Ј), and 168.40
and 170.42 (2 ϫ COCH3); EIMS, m/z (% rel. int.): 264[M+](1), 222(18), 180(10),
163(40), 121(100), and 93(10).
1-(4Ј-Benzyloxy-2Ј-hydroxyphenyl)-2-ethyl-3-hydroxypropanone (26)
To a solution of 4-benzyloxy-2-hydroxybutyrophenone (15) (2.70 g, 10 mmol) in
37% formaldehyde (11 mmol) and tetrahydrofuran (2 ml), 0.5 N sodium hydroxide
solution (22 mmol) was added and the reaction mixture stirred at 25–30ЊC for 5 h,
it was acidified to pH 4 with dilute hydrochloric acid and extracted with ether (2 ϫ

CHEMOSELECTIVE O-ACETYLATIONS CATALYZED BY LIPASES
133
50 ml). The organic layer was separated, washed with brine (2 ϫ 50 ml), dried, and
the solvent was removed under reduced pressure. The residue was purified by column
chromatography on silica gel eluting with petrol:ethyl acetate (23:2) and finally by
crystallization from petrol:chloroform mixture to afford 26 as a white fluffy solid
(1.65 g), 55% yield; Mp 76ЊC; Rf 0.50 (petrol:ethyl acetate, 17:1); IR (KBr): 3432,
1
2929, 2871, 1635, 1581, 1515, 1401, 1272, 1243, 1158, 1074, and 1005 cmϪ1; H
NMR (300 MHz, CDCl3) ␦: 0.93(t, J ϭ 7.4Hz, 3H, CH3), 1.68(m, 2H, CH2), 2.46(brs,
1H, aliphatic OH), 3.45(m, 1H, C-2H), 3.78(dd, J ϭ 10.9 and 3.9 Hz, 1H, C-3H␣),
3.93(dd, J ϭ 10.8 and 7.1Hz, 1H, C-3H␤), 5.06(s, 2H, CH2C6H5), 6.49(brs, 1H, C-
3ЈH), 6.51(d, J ϭ 8.5Hz, 1H, C-5ЈH), 7.38(m, 5H, C6H5) and 7.68(d, J ϭ 8.5Hz, 1H,
C-6ЈH); 13C NMR (75 MHz, CDCl3) ␦: 11.82(CH3), 22.84(CH2), 48.91(C-2), 62.67(C-
3), 70.24(CH2C6H5), 102.12(C-3Ј), 108.32(C-5Ј), 113.90(C-1Ј), 127.51, 128.31,
128.69, 129.19 and 135.82 (aromatic carbons), 131.80(C-6Ј), and 165.45 and
165.94(C-2Ј and C-4Ј); EIMS, m/z (% rel. int): 300[M+](9), 282(6), 270(18), 227(20),
91(100) and 65(7).
X-Ray Crystallography of Compounds 4, 15, and 17
All data were collected using a Siemens SMART CCD area-detector diffractometer.
A full hemisphere of reciprocal space was scanned by a combination of three sets of
exposures; each set had a different ␾ angle for the crystal and each exposure of 10
s covered 0.3Њ in ␻. The crystal to detector distance was 5.01 cm. Crystal decay was
monitored by repeating the initial frames at the end of the data collection and analyzing
the duplicate refractions, and was found to be negligible in all cases. A multiscan
absorption correction was applied using SADABS(21).
The structures were solved by direct methods using SHELXTL-PC (22) and refined
by full matrix least-squares on F2 for all data using SHELXL-97 (23). Hydrogen
atoms were added at calculated positions and refined using a riding model. Anisotropic
temperature factors were used for all non-H atoms; H-atoms were given isotropic
temperature factors equal to 1.2 times (or 1.5 for methyl hydrogens) the equivalent
isotropic displacement parameter of the atom to which they are attached.
ACKNOWLEDGMENT
We thank the Council of Scientific and Industrial Research (CSIR, New Delhi, India) for financial
assistance.
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