Bismuth triflate catalyzed friedel-crafts acylation of 3-phenyl-and 3-(2-Carboalkoxyphenyl)sydnones under microwaveirradiation

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Bismuth Triflate Catalyzed Friedel-
Crafts Acylation of 3-Phenyl- and 3-
(2-Carboalkoxyphenyl)sydnones under
Microwave Irradiation
Amanda M. Balaguera, Amber C. Rumplea & Kenneth Turnbulla
a Department of Chemistry, Wright State University, Dayton, OH,
45435, USA
Published online: 10 Jul 2014.
To cite this article: Amanda M. Balaguer, Amber C. Rumple & Kenneth Turnbull (2014) Bismuth
Triflate Catalyzed Friedel-Crafts Acylation of 3-Phenyl- and 3-(2-Carboalkoxyphenyl)sydnones under
Microwave Irradiation, Organic Preparations and Procedures International: The New Journal for
Organic Synthesis, 46:4, 363-369, DOI: 10.1080/00304948.2014.922379
To link to this article: http://dx.doi.org/10.1080/00304948.2014.922379
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Organic Preparations and Procedures International, 46:363–369, 2014
Copyright © Taylor & Francis Group, LLC
ISSN: 0030-4948 print / 1945-5453 online
DOI: 10.1080/00304948.2014.922379
Bismuth Triflate Catalyzed Friedel-Crafts Acylation
of 3-Phenyl- and 3-(2-Carboalkoxyphenyl)sydnones
under Microwave Irradiation
Amanda M. Balaguer, Amber C. Rumple, and Kenneth Turnbull
Department of Chemistry, Wright State University, Dayton, OH, 45435, USA
Mesoionic sydnones (cf. 1)1 undergo electrophilic aromatic substitution, including
acylation,2–5 at the C-4 position.6–14 In earlier work from our laboratory, we showed that
C-4 acetylation of arylsydnones 1 could be effected using acetic anhydride and Mont-
morillonite K-10 as catalyst15 and a model study for the acetylation of 3-phenylsydnone
(1a) [to form 2a] was conducted using various metal triflates as catalysts.16 More recently,
we have extended this latter study to an exhaustive examination of the acetylation of 1a
using lanthanum, gadolinium, scandium, yttrium, indium, or hafnium triflate catalysts.17
Our preliminary experiments16,17 had shown bismuth triflate18,19 (with lithium perchlorate
as co-catalyst20) to be the most effective catalyst for the acetylations and, accordingly,
the study was extended to explore its scope and limitations.16 In contrast to previous
investigations, the sydnone could be acylated utilizing less than stoichiometric amounts
of the catalyst and the amount of acetic anhydride as the typical acylating agent was
optimized at four molar equivalents (rather than the common practice of using the an-
hydride as solvent). However, even this improved procedure suffered from drawbacks, in
that freshly-prepared bismuth triflate catalyst was required for satisfactory product yields
and reaction times were long. Since the synthesis of the catalyst is non-trivial24,25 and
its effective shelf life is relatively short, it seemed reasonable to expect that the use of
microwave irradiation might shorten reaction times and minimize the degradation of the
bismuth triflate during the reaction, allowing it to perform optimally. While previous acy-
lation studies with sydnones have been performed using conventional heating there has
been no examination of the corresponding reactions under the influence of microwave
irradiation.
The present study is a continuation of our previous work with bismuth triflate,16 but the
experiments were conducted under microwave irradiation, and extrapolated to the synthesis
of new acyl sydnones from 3-(2-carbalkoxy)phenylsydnones.26,27
Received September 27, 2013; in final form March 10, 2014.
Address correspondence to Kenneth Turnbull, Department of Chemistry, Wright State
University, Dayton, OH 45435, USA. E-mail: kenneth.turnbull@wright.edu
363

364
Turnbull et al.
Acylation of 1 with Anhydrides Under Microwave Irradiation
The previous protocol16 for the synthesis of 2a using conventional heating (100◦C,
18 h) was chosen for the initial optimization of the microwave process. Three temperatures
(100, 125, and 150◦C) were utilized for 15 to 45 min each, with the amounts of catalysts
set at 25 mole% of both bismuth triflate and lithium perchlorate in acetonitrile as solvent.
The results are displayed in Table 1. The first trial (Entry 1) was performed at 100◦C for
30 minutes and gave a 69% yield of 2a. Raising the temperature to 125◦C for 15 minutes
reduced the yield (Entry 2) but even higher yields of 2a were obtained at 125◦C for 30
minutes or at 150◦C for 15 minutes (Entries 3 & 4). The best yield for 2a was 94% at 125◦C
for 30 minutes (Entry 3). The results of the other experiments are shown in Table 1.
The optimum yields of 3-phenyl-4-propanoylsydnone (2b) [92%, Entry 6], 4-butanoyl-
3-phenylsydnone (2c) [88%, Entry 9] and 4-isobutanoyl-3-phenylsydnone (2d) [92%, Entry
14] were obtained at 125◦C for 30 min, 15 min and 45 min, respectively. These yields
greatly surpassed those obtained under conventional heating conditions16 and took place in
a fraction of the time.
From these results, it can be concluded that the best conditions for microwave-induced
acylations with 3-phenylsydnone (1a) are ∼30 minutes at 125◦C with 25 mole% of both
bismuth triflate and lithium perchlorate and 4 eq of the corresponding anhydride in acetoni-
trile. With this protocol in hand, different sydnones 1b and 1c were subjected to analogous
microwave conditions. These sydnones were chosen, both because the corresponding acy-
lated products 2e-2l were needed for another study and to explore the effect (if any) upon
acylation due to the steric hindrance presented by an ortho substituent on the phenyl ring.
These results are tabulated also in Table 1. Overall, yields ranged from moderate to poor
depending on the sydnone and anhydride employed and, in general, were slightly better
with 1b and slightly worse with 1c than those obtained using conventional heating (Entries
16–23). For Entries 22 and 23, the reaction time was raised to 40 minutes in an unsuccessful
attempt to increase the yields.

Friedel-Crafts Acylation of Sydnones under Microwave Irradiation
365
Table 1
Microwave-induced Acylation of 3-Phenyl- and 3-(2-Carbalkoxyphenyl)sydnones
Temp.
(◦C)
Time
Yielda
(%)
mp.
(◦C)
lit. mp.
(◦C)
Entry Product
(min.)
1
2
3
4
5
6
7
8
2a
2a
2a
2a
2b
2b
2b
2b
2c
2c
2c
2c
2d
2d
2d
2e
2f
100
125
125
150
125
125
150
150
125
125
150
150
125
125
150
125
125
125
125
125
125
125
125
30
15
30
15
15
30
15
30
15
30
15
30
30
45
15
30
30
30
30
30
30
40
40
69
53
94
80
55
92
42
55
88
88
43
36
30
92
28
140–141
143–14415
89–91
70–72
92.5–942
9
72.5–742
10
11
12
13
14
15
16
17
18
19
20
21
22
23
109–111
113.5–1152
54 [49]a
58 [31]a
36 [17]a
21 [3]a
22 [47]a
26 [30]a
27 [41]a
11 [0]a
116–118
107–108
85–87
121–122
123–124
64–66
118–11915
—
—
—
—
—
—
—
2g
2h
2i
2j
2k
2l
59–60
84–86
aThe yields in square brackets for the preparation of 2e-2l (Entries 16–23) are those obtained by
conventional heating and will be reported elsewhere in due course.
From these results, it is clear that the presence of an electron-withdrawing substituent
at the ortho position of the aryl ring negatively affects the acylation process, however,
without further experimentation, it is unclear which of the two parameters (electronic or
steric) has the greater effect.
The identity of 4-acetyl-3-(2-carbomethoxyphenyl)sydnone (2e), was confirmed by
comparison to an authentic sample previously synthesized in this laboratory.15 In gen-
eral, the previously unknown acylated products 2f-2l exhibited the spectral charac-
teristics expected for such species. Thus, the IR spectra displayed three carbonyl
peaks at 1761–1786 cm−1 (sydnone carbonyl), 1717–1736 cm−1 (ester carbonyl), and
1667–1675 cm−1 (ketone carbonyl); the 3150 cm−1 peak of the C-4 hydrogen of the start-
1
ing sydnone was absent. The H NMR spectra showed the expected aromatic and alkyl
signals, as well as the absence of the C-4 proton (δ 6.8), and their 13C NMR spectra also

366
Turnbull et al.
contained the expected peaks, including those for the sydnone C-4 carbon at δ 106–108,
the carbonyl of the ester at δ 162–163, the C-5 carbon of the sydnone at δ 165–166 and the
carbonyl of the keto group at δ 184–191.
In conclusion, the microwave-induced acylation process offers an attractive alternative
to our previous acylation protocols15–17 since the former provides the corresponding acyl
products in good to excellent yields and takes only minutes in comparison to the many
hours required for the reactions under conventional heating conditions.
Experimental Section
General Notes
3-Phenylsydnone (1a),28 3-(2-carbomethoxyphenyl)sydnone (1b),26 3-(2-carboethoxy-
phenyl)sydnone (1c)27 and bismuth triflate18 were synthesized according to reported pro-
cedures. All other starting materials and catalysts (including lithium perchlorate; see
CAUTION ref. 20) were purchased commercially and used without purification unless
otherwise noted. Melting points were determined on a Mel-Temp melting point device and
are uncorrected. The infrared spectra were performed as KBr pellets and were taken on a
Nicolet 6700 FTIR. NMR spectra were obtained on a Bruker Advance 300 MHz NMR in
CDCl3 and are reported relative to tetramethylsilane as an internal standard. Column chro-
matography was performed on an Isco CombiFlash Separator System Sg100c. Microwave
reactions were conducted in a 300 W, monomode CEM Discover microwave reactor us-
ing 10-mL (total volume) sealed reaction vessels. Elemental analyses were carried out by
Midwest Microlab LLC, Indianapolis, Indiana 46250.
General Procedure for the Acylation of 3-Arylsydnones using Bismuth Triflate
and Lithium Perchlorate under Microwave Irradiation (MWI). To the sydnone (1)
[0.6 mmol] was added freshly-prepared bismuth triflate (0.106g, 25 mole%),24 lithium per-
chlorate (0.016g, 25 mole%), acetonitrile (1.5 mL) and the anhydride (4 molar equivalents;
acetic anhydride, 0.23 mL; propionic anhydride, 0.31 mL; n-butyric anhydride, 0.39 mL;
isobutyric anhydride, 0.39 mL). The reaction mixture was subjected to microwave irradi-
ation at 100◦C, 125◦C, or 150◦C until complete disappearance of the starting material, as
determined by TLC (dichloromethane as eluent) on silica. The mixture was neutralized
(10% aq. NaHCO3) and then extracted with dichloromethane (3 × 20 mL). The combined
organic layers were dried (MgSO4), filtered, and evaporated in vacuo. The resultant crude
material was then separated via flash chromatography (12 g silica gel column, gradient of
hexanes to dichloromethane to ethyl acetate) to yield the desired material (see Table).
4-Acetyl-3-[2-(carbomethoxy)phenyl]sydnone (2e)
Reaction of 1b with acetic anhydride according to the general procedure yielded tan crystals
(54%) of 2e, identical (TLC, mp, IR) to an authentic sample.15
3-[2-Carbomethoxy)phenyl]-4-propanoylsydnone (2f)
Reaction of 1b with propionic anhydride according to the general procedure yielded light
tan crystals (58%) of 2f, mp. 107–108◦C. IR: 2946, 1778 (sydnone C=O), 1722 (C=O),
1667 (C=O) cm−1. 1H NMR: δ 1.1 (t, 3 H), 2.9 (q, 2 H), 3.8 (s, 3 H), 7.4 (m, 1 H), 7.7 (m,

Friedel-Crafts Acylation of Sydnones under Microwave Irradiation
367
2 H), 8.25 (m, 1 H). 13C NMR: δ 188.24 (C=O), 165.71 (sydnone C=O), 163.13 (C=O),
134.96, 133.47, 132.14, 131.77, 126.93, 126.39, 107.33 (sydnone C-4), 52.79, 33.32, 7.09.
Anal. Calcd. for C13H12N2O5: C, 56.52; N, 10.14; H, 4.38. Found: C, 56.78; N, 9.90;
H, 4.49.
4-Butanoyl-3-[2-(carbomethoxy)phenyl]sydnone (2g)
Reaction of 1b with butyric anhydride according to the general procedure yielded 2g as a
pale yellow solid (36%), mp. 85–87◦C. IR: 2962, 2934, 1770 (sydnone C=O), 1731 (C=O),
1668 (C=O) cm−1. 1H NMR: δ 0.93 (t, 3H), 1.60 (m, 2H), 2.86 (s, 3H), 3.82 (s, 3H), 7.41
(m, 1H), 7.78 (m, 2H), 8.25 (m, 1H). 13C NMR: δ 187.77 (C=O), 165.68 (sydnone C=O),
163.11 (C=O), 135.00, 133.45, 132.12, 131.77, 126.90, 126.43, 107.47 (sydnone C-4),
52.78, 41.58, 16.86, 13.52.
Anal. Calcd. for C14H14N2O5: C, 57.93; N, 9.65; H, 4.86. Found: C, 57.91; N, 9.44;
H, 4.92.
3-[2-(Carbomethoxy)phenyl]-4-isobutanoylsydnone (2h)
Reaction of 1b with isobutyric anhydride according to the general procedure yielded 2h as
a colorless solid (21%), m.p. 121–122◦C. IR: 2972, 1776 (sydnone C=O), 1724 (C=O),
1669 (C=O) cm−1. 1H NMR: δ 1.0 (d, 3H), 3.5 (sept, 1H), 3.7 (s, 3H), 7.9 (m, 3H), 8.2 (m,
1H). 13C NMR: δ 191.98 (C=O), 165.24 (sydnone C=O), 163.13 (C=O), 135.08, 133.47,
132.07, 131.75, 126.86, 126.34, 106.99 (sydnone C-4), 52.74, 35.60, 17.66.
Anal. Calcd. for C14H14N2O5: C, 57.93; N, 9.65; H, 4.86. Found: C, 57.65; N, 9.64;
H, 5.15.
4-Acetyl-3-[2-(carboethoxy)phenyl]sydnone (2i)
Reaction of 1c with acetic anhydride according to the general procedure yielded light tan
crystals (22%) of 2i, mp 123–124◦C. IR: 1770 (sydnone C=O), 1717 (C=O), 1674 (C=O)
1
cm−1. H NMR: δ 1.28 (t, 3H), 2.48 (s, 3H), 4.26 (q, 2H), 7.40 (m, 1H), 7.77 (m, 2H),
8.27 (m, 1H). 13C NMR: δ 184.50 (C=O), 165.87 (sydnone C=O), 162.69 (C=O), 134.73,
133.29, 132.15, 131.93, 126.84, 126.80, 108.05 (sydnone C-4), 62.05, 29.67, 27.49.
Anal. Calcd. for C13H12N2O5: C, 56.52; N, 10.14; H, 4.38. Found: C, 56.64; N, 10.08;
H, 4.40.
3-[2-(Carboethoxy)phenyl]-4-propanoylsydnone (2j)
Reaction of 1c with propionic anhydride according to the general procedure yielded light
tan crystals (26%) of 2j, mp. 64–66◦C. IR: 2982, 1774 (sydnone C=O), 1723 (C=O), 1673
(C=O) cm−1. 1H NMR: δ 0.94 (t, 3H), 1.16 (t, 3H), 2.77 (q, 2H), 4.02 (q, 2H), 7.82-7.97
(m, 3H), 8.01 (m, 1H). 13C NMR: δ 188.09 (C=O), 165.70 (sydnone C=O), 162.69 (C=O),
134.80, 133.30, 132.09, 131.89, 129.83, 126.81, 107.40 (sydnone C-4), 62.02, 33.32, 13.89,
7.07.
Anal. Calcd. for C14H14N2O5: C, 57.93; N, 9.65; H, 4.86. Found: C, 57.71; N, 9.38;
H, 4.81.

368
Turnbull et al.
4-Butanoyl-3-[2-(carboethoxy)phenyl]sydnone (2k)
Reaction of 1c with butyric anhydride for 40 minutes according to the general procedure
yielded light tan crystals (27%) of 2k, mp. 59–60◦C. IR: 2966, 2935, 2876, 1770 (sydnone
C=O), 1731 (C=O), 1667 (C=O) cm−1. 1H NMR: δ 0.92 (t, 3H), 1.27 (t, 3H), 1.60 (sextet,
2H), 2.85 (t, 2H), 4.25 (q, 2H), 7.40 (m, 1H), 7.77 (m, 2H), 8.27 (m, 1H). 13C NMR: δ
187.64 (C=O), 165.69 (sydnone C=O), 162.71 (C=O), 134.85, 133.30, 132.08, 131.92,
126.83, 126.80, 107.54 (sydnone C-4), 62.02, 41.59, 16.80, 13.91, 13.54.
Anal. Calcd. for C15H16N2O5: C, 59.21; N, 9.21; H, 5.30. Found: C, 59.22; N, 9.11;
H, 5.34.
3-[2-(Carboethoxy)phenyl]-4-isobutanoylsydnone (2l)
Reaction of 1c with isobutyric anhydride for 40 minutes according to the general procedure
yielded light tan crystals (11%) of 2l, mp. 84–86◦C. IR: 1761 (sydnone C=O), 1720 (C=O),
1668 (C=O) cm−1. 1H NMR: δ 1.10 (d, 6H), 1.28 (t, 3H), 3.51 (septet, 1H), 4.25 (q, 2H),
7.41 (m, 1H), 7.77 (m, 2H), 8.27 (m, 1H). 13C NMR: δ 191.94 (C=O), 165.26 (sydnone
C=O), 162.70 (C=O), 134.99, 133.31, 132.03, 131.91, 126.76, 107.05 (sydnone C-4),
62.01, 36.70, 17.69, 13.93.
Anal. Calcd. for C15H16N2O5: C, 55.90; N, 8.69; H, 5.63. Found: C, 56.03; N, 8.91;
H, 5.77.
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