An efficient synthesis of thioesters via TFA-catalyzed reaction of carboxylic acid and thiols: Remarkably facile C-S bond formation

Article abstract of DOI:10.1080/10426507.2012.664220

A general, facile, and efficient new synthetic path to thioesters was established by employing defined TFA-catalyzed reaction of carboxylic acid and thiol under mild conditions. The structure of the newly synthesized compounds was determined by infrared spectroscopy, nuclear magnetic resonance, and a single crystal X-ray crystallographic analysis. Supplemental materials are available for this paper. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. Copyright

Full text of DOI:10.1080/10426507.2012.664220

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An Efficient Synthesis of Thioesters Via
TFA-Catalyzed Reaction of Carboxylic
Acid and Thiols: Remarkably Facile C–S
Bond Formation
Adel S. El-Azab a b & Alaa A.-M. Abdel-Aziz a c
a Department of Pharmaceutical Chemistry, College of Pharmacy,
King Saud University, Riyadh, Saudi Arabia
b Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar
University, Nasr City, Cairo, Egypt
c Department of Medicinal Chemistry, Faculty of Pharmacy,
University of Mansoura, Mansoura, Egypt
Accepted author version posted online: 13 Feb 2012.Version of
record first published: 19 Jun 2012.
To cite this article: Adel S. El-Azab & Alaa A.-M. Abdel-Aziz (2012): An Efficient Synthesis of
Thioesters Via TFA-Catalyzed Reaction of Carboxylic Acid and Thiols: Remarkably Facile C–S Bond
Formation, Phosphorus, Sulfur, and Silicon and the Related Elements, 187:9, 1046-1055
To link to this article: http://dx.doi.org/10.1080/10426507.2012.664220
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Phosphorus, Sulfur, and Silicon, 187:1046–1055, 2012
Copyright ꢀC King Saud University
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2012.664220
AN EFFICIENT SYNTHESIS OF THIOESTERS VIA
TFA-CATALYZED REACTION OF CARBOXYLIC ACID AND
THIOLS: REMARKABLY FACILE C–S BOND FORMATION
Adel S. El-Azab1,2 and Alaa A.-M. Abdel-Aziz1,3
1Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud
University, Riyadh, Saudi Arabia
2Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar University,
Nasr City, Cairo, Egypt
3Department of Medicinal Chemistry, Faculty of Pharmacy, University
of Mansoura, Mansoura, Egypt
GRAPHICAL ABSTRACT
Abstract A general, facile, and efficient new synthetic path to thioesters was established by
employing defined TFA-catalyzed reaction of carboxylic acid and thiol under mild conditions.
The structure of the newly synthesized compounds was determined by infrared spectroscopy,
nuclear magnetic resonance, and a single crystal X-ray crystallographic analysis.
Supplemental materials are available for this paper. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.
Keywords Synthesis; trifluroacetic acid; carboxylic acid; thioester; ester; x-ray crystallography
INTRODUCTION
The driving force for the development of new methodologies in organic synthesis
has been a need for simple and efficient strategies to obtain complex products.1–4 Over the
past few decades, extensive efforts have been made to develop methodologies that form
carbon–sulfur bonds in the synthesis of molecules with various biological applications.4–10
Received 6 December 2011; accepted 21 January 2012.
The authors extend their appreciation to the Deanship of Scientific Research at King Saud University for
funding the work through the research group project No. RGP-VPP-163.
Address correspondence to Adel S. El-Azab, Department of Pharmaceutical Chemistry, College of Pharmacy,
P.O. Box 2457, King Saud University, Riyadh 11451, Saudi Arabia. E-mail: adelazaba@yahoo.com
1046

SYNTHESIS OF THIOESTERS VIA TFA-CATALYZED REACTION OF CARBOXYLIC ACID 1047
Although a great deal of effort has been directed toward the use of nucleophilic thiols11–17
for the formation of C S bond, thioacids18–25 have not been explored in organic synthesis,
as they are less nucleophilic and hence less reactive. On the other hand, protection of thiol
groups as thioesters is important in many areas of organic research, particularly in peptide,
protein, and β-lactam synthesis.19 Thioesters are formed and cleaved in the same way as
oxygen esters; they are more reactive against nucleophilic substitution and used as activated
esters.26 Moreover, it is widely agreed that thioesters are one of the most useful building
blocks for organic transformations. They have found application in C C coupling, for
the synthesis of carbonyl compounds, in asymmetric aldol reactions, and more recently,
their α-β-unsaturated analogs have been successfully applied for asymmetric additions,
which allow the access to chiral intermediates for the synthesis of more complex com-
pounds.27–31 Furthermore, they found application in native chemical ligation for peptide
bond formation,4–10 in natural product synthesis,32,33 and also acting as biologically relevant
substances finding application for in vivo tumor suppression.34 These valuable compounds
have been prepared through the activation of carboxylic acids with diphosgene35 or N-
acylbenzotriazoles36 followed by the addition of thiol, or by reaction of acyl chlorides
with zinc and thiols.37 They have also been accessed from thiols and carbon monoxide by
carbonylation of organic substrates catalyzed by transition metals such as Pt38 or Pd.39 The
conversion of alkyl halides to thioesters using potassium thioacetate is well reported in
the literature.40 Other methods include the reaction of thioacids with suitable electrophilic
reagents, such as alkyl halides, and Michael acceptors.20–22,41 These methodologies, how-
ever, suffer from limitations, such as the limited availability of starting thioacids and thiols
and also the practical difficulty associated in handling them. Besides, the drawback of
these methodologies is associated with undesirable side reactions owing to the oxidation
of thiols. In order to minimize or eliminate the encountered problems, the method has
been developed in recent years for the synthesis of thioesters by the reaction of anhydrides
or acyl halides with thiol or disulfides in the presence of various promoting agents, such
as In or InI, Sm/CoCl2, SmI2, Sm/Cp2TiCl2, Sm/NiCl2, Zn/AlCl3, Zn/ZrCl4, K2CO3, and
RhCl(PPh3)3/H2.42–47 Recently, Yamaguchi and co-workers48 reported rhodium catalyzed
alkylthio exchange reaction of thioester with disulfide. However, these methods usually
suffer from one or more limitations, such as the use of expensive, toxic, or metallic cat-
alysts, long reaction times, unsatisfactory yields, as well as elevated temperature. On the
other hand, only a few of them have been studied with more complete anhydride scope,
and substrates bearing sensitive groups, such as furanyl and thienyl, might not be fully
compatible.
RESULTS AND DISCUSSION
As a part of our ongoing program on the development of novel methods in organic
synthesis under mild conditions,2–4 we describe a new efficient and practical route for the
one-step conversion of carboxylic acid into the corresponding thioesters using trifluroacetic
acid in CH3CN at 60 ◦C in high yield under mild conditions. To the best of our knowledge,
the applicability of trifluroacetic acid in the synthesis of thioesters from carboxylic acid
and thiol has not been reported (Table 1).
Attempts to prepare benzoic acid thioesters using trifluroacetic acid at 0 ◦C temper-
ature furnished low yields (10%). The best results were obtained using CH3CN as solvent
at 60 ◦C. As can be seen in Table 1, we first examined the effect of solvent, temperature,

1048
A. S. EL-AZAB ET AL.
Table 1 Effect of solvent, temperature, and reaction time on formation of thioester of benzoic acid and thiophenol
promoted by trifluoroacetic acid
Conditions
Entry
Solvent
Temp (oC)
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
CH3CN
CH3CN
THF
25a
60
25
Reflux
25
Reflux
25
8
4
12
7
24
24
24
24
50
95
10
30
15
25
0
THF
CH2Cl2
CH2Cl2
Tolueneb
Toluene
60
5
a0 ◦C temperature furnished low yields (10%).
bSimilarly, no reaction was proceeded using benzene as a solvent.
reaction time on the treatment of benzoic acid (1) with thiophenol (2). Among the solvents
that we examined, CH3CN worked most effectively for the conversion of benzoic acid
(1) to the corresponding thioester 3 (Entries 1, 2). In the case of other solvents, such as
CH2Cl2, THF, and ether, lower yield was obtained, which could not be observed with the
use of toluene or benzene as a solvent (entries 3–8). The mechanism for the formation of
thioester may proceed through either a standard proton-catalyzed esterification or in situ
mixed anhydride formation mechanism (Figure 1). It is noteworthy that the observed nu-
cleophilic displacement of the reaction was highly dependent on the nature of solvent, and
the tendency of the preferred formation of the formed in situ intermediate approximately
correlated with the reactivity of the formed anhydride (Figure 1).
Furthermore, the temperature of the reaction also affected the reaction◦yield. The
◦
result of the reaction at 60 C was completely in contrast with that at 0 C, that is,
appropriate temperature afforded thioester exclusively (Table 2).
Figure 1 Plausible mechanism for thioester formation.

SYNTHESIS OF THIOESTERS VIA TFA-CATALYZED REACTION OF CARBOXYLIC ACID 1049
Table 2 Conversion of benzoic acid into phenyl benzothioate in the presence of different organic acids in CH3CN
at 60 ◦C
Entry
Organic acid catalyst
Time (h)
Yield (%)
1
2
3
4
Trifluoroacetic acid
Trichloroacetic acid
Dichloroacetic acid
Acetic acid
4
24
24
24
95
5
0
0
Acid catalyst other than trifluoroacetic acid, such as acetic acid, dichloroacetic acid,
and trichloroacetic acid, was examined (Table 2). There was no thioester formation between
benzoic acid and thiophenol in the presence of acetic acid or dicholoroacetic acid even
under reflux temperature for 24 h. Performing such transformation in the presence of
trichloroacetic acid required reflux temperature and a long reaction time affording the
required thioester in very low yield. Is seems that the acidic behavior of trifluoroacetic acid
not only activate the acid but also enhances the reactivity of used thiol. It has the additional
advantage of being freely soluble in water and is thus extracted and recovered for reuse.49
In order to explore the generality and scope of this methodology, diverse carboxylic
acids were studied to illustrate this novel and general method for the synthesis of thioesters,
and the results are summarized in Table 3. It is important to note that carboxylic acid
possessing electron-withdrawing groups, such as chloro group, furnished excellent yields
of the corresponding thioesters in shorter reaction times compared with carboxylic acid
Table 3 TFA promoted condensation of thiophenol or cyclohexyl thiol with different carboxylic acids
Entry
Compd. No.
R1
R2
Time (h)
Yield (%)
150
251
336
4
3
4
5
6
7
8
9
10
11
12
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
4
3
4
5
2
2
4
4
5
5
95
92
97
84
99
96
91
99
86
85
4-Methoxyphenyl
4-Chlorophenyl
3-Pyridyl
552,53
6
Benzyl
4-Chlorobenzyl
2-Chlorobenzyl
1-Naphthylmethyl
1-Adamantyl
2-Methoxy-7,7-dimethylbicyclo
[2.2.1]heptan-1-yl
Ph
4-Methoxyphenyl
4-Chlorophenyl
4-Chlorobenzyl
2-Chlorobenzyl
1-Naphthylmethyl
1-Adamantyl
7
854
955
10
1156
12
13
14
15
16
17
18
13
14
15
16
17
18
19
20
Cyclohexyl
Cyclohexyl
Cyclohexyl
Cyclohexyl
Cyclohexyl
Cyclohexyl
Cyclohexyl
Cyclohexyl
2
2
5
5
5
4
4
5
95
90
98
92
96
98
88
89
2-Methoxy-7,7-
dimethylbicyclo[2.2.1]heptan-1-yl

1050
A. S. EL-AZAB ET AL.
Table 4 Trifluoroacetic acid promoted the formation of carboxylic acid ester
Entry
R
Time (h)
Yield (%)
1
2
3
4
5
Phenyl
5
4
4
2
2
90
91
95
89
92
4-Chlorophenyl
4-Methoxyphenyl
Methyl
Ethyl
with electron-donating substituents, such as CH3O group, which required longer times
(Table 3, entries 1–3, 11–13). These phenomena may be attributed to the reactivity of the
proposed anhydride formed in situ.
Aromatic carboxylic acids as well as aliphatic carboxylic acids were also converted
smoothly to the corresponding thioesters in good yields (Table 3, entries 1, 8–11, 17,
and 18). Heterocyclic carboxylic acid, such as nicotinic acid, was transformed into the
corresponding thioesters in good yields under these mild conditions (Table 3, entry 4).
Moreover, replacement of thiophenol with cyclohexyl thiol gave excellent yields of the
corresponding thioesters using the same reaction conditions (Table 3, entries 11–18).
In order to support the nucleophilic activation mechanism, we performed the reaction
of benzoic acid with phenol or alcohol to afford the corresponding ester in high yield
(89–90%) under such mild condition (Table 4).
However, a successful attempt was made to prepare esters from the corresponding
phenol, 4-chlorophenol, 4-methoxyphenol, ethanol, and methanol in CH3CN (Table 4).
Finally, the mild reaction conditions, simple work-up, short reaction time, and good
to excellent yields are important features of this novel methodology as compared with
other reported methods. The structure of thioester 4 was confirmed by single crystal x-ray
crystallography (Figure 2; Tables 5 and 6).
Figure 2 X-ray molecular structure of S-phenyl 4-methoxybenzothioate (4).

SYNTHESIS OF THIOESTERS VIA TFA-CATALYZED REACTION OF CARBOXYLIC ACID 1051
Table 5 Summary of crystal data, intensity data collection, and structure refinement for compound S-phenyl
4-methoxybenzothioate (4) at 20.0 ◦C
Compound
4
Empirical formula
Formula weight
C14H12O2S
244.31
Crystal system/space group
Orthorhombic/P 212121
a/Å
5.4472 (1)
b/Å
8.2115 (2)
c/Å
27.3671 (7)
90
90
90
α/◦
β/◦
γ /◦
V/Å3
1224.12 (5)
Z
4
Dcalc (g/cm3)
2.075
2.68
µ (mm−1
)
F000
804.00
Color/shape
Colorless/plate
No. of reflections used for unit cell determination (2θ range)
Omega scan peak width at half-height
Structure solution
25 (59.2–59.9◦)
0.28◦
Direct methods (SIR92)
Refinement
Full-matrix least-squares
p-factor
0.0800
1.26
6.05
0.043
0.037
860
Goodness of fit indicator
Reflection/parameter ratio
Residuals: R, Rw
Residuals R1
No. of reflections to calc R1
Table 6 Geometric parameters (Å, ◦) of S-phenyl 4-methoxybenzothioate (4)
S1–C4
S1–C7
O2–C11
O2–C14
C4–C5
C4–C3
C8–C13
C8–C9
1.767 (3)
1.775 (3)
1.357 (3)
1.421 (3)
1.368 (4)
1.374 (3)
1.374 (3)
1.385 (3)
1.476 (3)
120.0 (3)
117.8 (3)
120.6 (3)
119.4 (3)
121.0 (3)
120.7 (3)
116.0 (3)
125.0 (3)
118.9 (3)
121.7 (3)
C2–C1
1.365 (4)
1.379 (3)
1.380 (3)
1.368 (3)
1.379 (3)
1.380 (3)
1.383 (3)
1.201 (3)
1.377 (3)
120.0 (3)
120.2 (3)
120.1 (3)
119.6 (3)
124.0 (3)
121.9 (2)
114.1 (2)
C11–C12
C13–C12
C6–C1
C6–C5
C10–C9
C3–C2
O1–C7
C8–C7
C10–C11
C11–C12–C13
C1–C6–C5
C4–C5–C6
C2–C1–C6
O1–C7–C8
O1–C7–S1
C8–C7–S1
C5–C4–C3
C13–C8–C9
C11–C10–C9
C4–C3–C2
C10–C9–C8
C1–C2–C3
O2–C11–C10
O2–C11–C12
C10–C11–C12
C8–C13–C12

1052
A. S. EL-AZAB ET AL.
CONCLUSION
An efficient new methodology has been developed for synthesis of thioester from the
parent carboxylic acid by their reaction with thiol under mild condition using trifluoroacetic
acid as a catalyst.
EXPERIMENTAL
Melting points (uncorrected) were recorded on Barnstead Electrothermal 9100 melt-
ing apparatus. Infrared (IR) spectra were recorded on a FT-IR Perkin-Elmer spectrometer
(ν in cm−1) and NMR spectra on Bruker (500 MHz) spectrometer using TMS as an internal
standard (chemical shift, δ ppm). Mass spectral (MS) data were obtained on a Perkine-
Elmer, Clarus 600 GC/MS mass spectrometers at Central Research Laboratories, College
of Pharmacy, King Saud University. Single crystal x-ray crystallography was recorded on
Bruker APEXII CCD diffractometer, and structure refinement and resolve was carried out
using SHELXS97.57 Supplemental materials contain some additional characterization data.
General Method for Preparation of Carboxylic Acid Ester and Thioester
The trifluoroacetic acid (0.4 equiv) was added dropwise to a stirred solution of
carboxylic acid (1 equiv) and thiol or phenol (1 equiv) in dry CH3CN (0.01 mol/L) over a
period of 15 min at room temperature. After being stirred for 2–5 h at 60 ◦C, the mixture
was quenched by adding ammonium chloride solution (5 mL) extract with ethylacetate,
washed with brine, and dried over anhydrous sodium sulfate; the product obtained after
evaporation of solvent was purified by column chromatography using mixture of hexane
and CHCl3 as eluent.
◦
1
S-phenyl pyridine-3-carbothioate (6). Mp: 67–68 C, 84% yield, H NMR
(CDCl3): δ 9.23 (s, 1H), 8.84 (s, 1H), 8.40 (d, 1H, J = 8.0 Hz), 7.59 (d, 1H, J = 1.5 Hz),
7.44–7.43 (m, 5H). 13C NMR (CDCl3): δ 125.0, 125.5, 129.6, 130.2, 135.0, 137.4, 146.1,
151.0, 187.8. MS: M+ = 215.
1
S-phenyl 2-(2-chlorophenyl)ethanethioate (9). Colorless oil, 91% yield, H
NMR (CDCl3): δ 7.44–7.39 (m, 7H), 7.31–7.29 (m, 2H), 4.12 (s, 2H). 13C NMR (CDCl3):
δ 47.8, 127.0, 127.6, 129.2, 129.3, 129.5, 129.7, 131.7, 132.0, 134.5, 134.9, 194.6. MS:
M+ = 262.
S-phenyl 2-((1S,2R,4R)-2-methoxy-7,7-dimethylbicyclo[2.2.1]heptan-1-
yl)ethanethioate (12). Mp: 48 ◦C, 85% yield. 1H NMR (CDCl3): δ 7.32–7.26 (m, 5H),
3.60–3.59 (m, 1H), 3.23 (s, 3H), 2.02–2.01 (m, 1H), 1.84–1.81 (m, 1H), 1.69–1.60 (m,
3H), 1.51–1.49 (m, 1H), 1.21 (s, 3H), 1.04–1.03 (m, 1H), 0.95 (s, 3H). 13C NMR (CDCl3):
δ 20.9, 21.2, 26.9, 29.8, 38.7, 45.9, 48.7, 57.2, 63.4, 66.4, 128.0, 128.2, 129.0, 135.1,
197.4. MS: M+ = 290.
S-cyclohexyl 4-methoxybenzothioate (14). Colorless oil, 98% yield. 1H NMR
(CDCl3): δ 7.86 (d, 2H, J = 9.0 Hz), 6.81 (d, 2H, J = 8.5 Hz), 3.72 (s, 3H), 3.64 (s, 1H),
1.94 (d, 2H, J = 8.5 Hz), 1.68–1.66 (m, 2H), 1.55–1.37 (m, 5H), 1.25–1.23 (m, 1H).
13C NMR (CDCl3): δ 25.6, 26.0, 33.2, 42.3, 55.3, 113.6, 129.3, 130.0, 163.5, 190.0. MS:
M+ = 250.
1
S-cyclohexyl 4-chlorobenzothioate (15). Colorless oil, yield 90%. H NMR
(CDCl3): δ 7.91 (d, 2H, J = 8.5 Hz), 7.46 (d, 2H, J = 8.5 Hz), 3.74 (s, 1H), 2.02–2.00 (m,

SYNTHESIS OF THIOESTERS VIA TFA-CATALYZED REACTION OF CARBOXYLIC ACID 1053
2H), 1.91–1.78 (m, 2H), 1.55–1.53 (m, 1H), 1.55–1.47 (m, 4H), 1.35–1.33 (m, 1H). 13C
NMR (CDCl3): δ 25.6, 26.0, 33.1, 42.8, 128.5, 128.8, 135.8, 139.5, 190.7. MS: M+ = 254.
S-cyclohexyl 2-(4-chlorophenyl)ethanethioate (16). Yellow oil , 96% yield.
IR (KBr): 1646 cm−1 (CO), 1H NMR (CDCl3): δ 7.42–7.40 (m, 2H), 7.32–7.31 (m, 1H),
7.27–7.25 (m, 2H), 3.97 (s, 2H), 3.54 (s, 1H), 2.19–2.18 (m, 2H), 1.71–1.69 (m, 2H),
1.61–1.59 (m, 1H), 1.41–1.38 (m, 4H), 1.27–1.25 (m, 1H). 13C NMR (CDCl3): δ 25.5,
26.0, 32.9, 42.7, 48.2, 126.9, 128.9, 129.6, 131.9, 132.1, 134.8, 196.3. MS: M+ = 268.
◦
S-cyclohexyl 2-phenylethanethioate (17). Mp: 54 C, 92% yield. 1H NMR
(CDCl3): δ 7.30 (d, 2H, J = 8.0 Hz), 7.21 (d, 2H, J = 8.0 Hz), 3.75 (s, 2H), 3.51 (s, 1H),
1.90–1.89 (m, 2H), 1.69–1.67 (m, 2H), 1.60–1.57 (m, 1H), 1.41–1.40 (m, 4H), 1.27–1.25
(m, 1H). 13C NMR (CDCl3): δ 25.5, 25.9, 30.9, 42.8, 49.8, 128.7, 130.9, 132.6, 133.3,
196.7. MS: MS: M+ = 268.
S-cyclohexyl naphthalene-1-carbothioate (18). Colorless oil, 98% yield. 1H
NMR (CDCl3): δ 8.04 (d, 1H, J = 8.0 Hz),), 7.91 (d, 1H, J = 8.0 Hz), 7.86 (d, 1H, J =
7.0 Hz),), 7.55–7.47 (m, 4H), 4.28 (s, 2H), 3.52 (d, 1H, J = 3.0 Hz),), 1.90 (d, 2H, J =
5.5 Hz),), 1.69–1.59 (m, 3H), 1.42–1.24 (m, 5H). 13C NMR (CDCl3): δ 25.5, 26.0, 32.9,
42.7, 48.5, 124.0, 125.5, 125.8, 126.4, 128.4, 128.7, 128.8, 130.4, 132.2, 133.9, 197.6. MS:
M+ = 284.
◦
S-cyclohexyl adamantane-1-carbothioate (19). Mp: 97 C, 88% yield. 1H
NMR (CDCl3): δ 3.44 (s, 1H), 2.05–2.03 (m, 3H s-like), 1.91–1.89 (m, 8H), 1.76–1.72 (m,
8H), 1.61–1.59 (m, 1H), 1.44–1.38 (m, 4H), 1.28–1.27 (m, 1H). 13C NMR (CDCl3): δ 25.6,
26.1, 28.2, 30.9, 32.2, 36.5, 39.3, 41.3, 48.4, 206.5. MS: M+ = 278.
S-cyclohexyl 2-((1S,2R,4R)-2-methoxy-7,7-dimethylbicyclo[2.2.1]heptan-
1
1-yl)ethanethioate (20). Yellow oil, 89% yield. H NMR (CDCl3): δ 3.57–3.54 (m,
2H), 3.25 (s, 3H), 2.00–1.86 (m, 4H), 1.77–70 (m, 5H), 1.68–1.67 (m, 1H), 1.59–1.38 (m,
6H), 1.30 (s, 3H), 1.25–1.11 (m, 1H), 1.09 (s, 3H). 13C NMR (CDCl3): δ 21.0, 21.2, 25.6,
26.1, 26.2, 26.8, 30.9, 33.3, 41.5, 45.9, 48.3, 57.2, 65.9, 89.2, 199.7. MS: M+ = 296.
4-chlorophenyl Benzoate. Mp: 84 ◦C, 91% yield. 1H NMR (CDCl3): δ 8.11 (d,
2H, J = 7.0 Hz), 7.57–7.56 (m, 1H), 7.44–7.41 (m, 2H), 7.30 (d, 2H, J = 9.0 Hz), 7.08
(d, 2H, J = 9.0 Hz). 13C NMR (CDCl3): δ 123.1, 128.7, 129.2, 130.2, 131.3, 133.8, 149.4,
165.0.
Data Collection and Refinement
APEX2 (Bruker) was used to solve structure, cell refinement, and data reduction.
SHELXS97 program57 was used to refine the structure.
All electrostatic discharge (esd) (except the esd in the dihedral angle between two l.s.
planes) are estimated using the full covariance matrix. The cell esds are taken into account
individually in the estimation of esds in distances, angles, and torsion angles; correlations
between esds in cell parameters are only used when they are defined by crystal symmetry.
An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s.
planes.
Refinement of F2 against ALL reflections was applied. The weighted R-factor wR
and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set
to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating
R-factors (gt) etc. and is not relevant to the choice of reflections for refinement. R-factors

1054
A. S. EL-AZAB ET AL.
based on F2 are statistically about twice as large as those based on F, and R-factors based
on ALL data will be even larger.
Supporting information available
Crystallographic data for the structure in this paper have been deposited with the Cam-
bridge Crystallographic Data Centre as the supplementary publication No. CCDC 805232.
Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK (fax: +44 1223 336033 or e-mail: deposit@ccdc.cam.ac.uk).
Table S1 (Supplemental Materials) contains a selection of torsion angles for (4).
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