The chemistry of α,β-ditosyloxyketones: Novel routes for the synthesis of desoxybenzoins and α-aryl-β-ketoaldehyde dimethylacetals from α,β-chalcone ditosylates

Article abstract of DOI:10.1055/s-2007-984915

The reaction of α,β-chalcone ditosylates 3 with potassium hydroxide in suitable conditions leads to 1,2-aryl shift and carbon-carbon bond cleavage, thereby providing a novel route for the synthesis of 1,2-diarylethan-1-ones 4 and 1,2-diaryl-3,3-dimethoxy propan-1-ones 5. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-984915

LETTER
2189
The Chemistry of a,b-Ditosyloxyketones: Novel Routes for the Synthesis of
Desoxybenzoins and a-Aryl-b-ketoaldehyde Dimethylacetals from
a,b-Chalcone Ditosylates
Synthesis of
D
esox
m
ybenzoins and
a
-Aryl-
b
-
k
P
etoaldehyde
D
r
imethyl
a
acetals kash,* Rajesh Kumar, Deepak Sharma, Kamaljeet Pannu, Raj Kamal
Department of Chemistry, Kurukshetra University, Kurukshetra, Haryana 136119, India
Fax +91(1744)238277; E-mail: dromprakash50@rediffmail.com
Received 16 May 2007
Table 1 Physical Data of a,b-Chalcone Ditosylates 3a–3j Prepared
Abstract: The reaction of a,b-chalcone ditosylates 3 with potassi-
um hydroxide in suitable conditions leads to 1,2-aryl shift and car-
bon–carbon bond cleavage, thereby providing a novel route for the
synthesis of 1,2-diarylethan-1-ones 4 and 1,2-diaryl-3,3-dimethoxy
propan-1-ones 5.
According to Scheme 1
Com-
Ar
Ph
Ar¢
Mp (°C)
(Lit. mp)
Yieldb (%)
65
poundsa
3a
Ph
134–136
Key words: a,b-ditosyloxyketones, desoxybenzoins, a,b-chalcone
ditosylates
(136–138)
3b
3c
3d
3e
3f
Ph
4-MeC6H4
114–115
59
70
62
68
58
60
59
62
60
Ph
4-MeOC6H4 138–140
A great deal of work from our research group and others
has emphasized the advantages of a-tosyloxyketones over
a-haloketones in various chemical transformations.1,2 On
the other hand while chemistry of a,b-chalcone di-
bromides 2 is well explored,3 the study pertaining to reac-
tivity mode of a,b-chalcone ditosylates 3 has remained an
uncharted territory. These observations coupled with our
ongoing program on advantageous use of a-tosyloxy-
ketones over a-haloketones prompted us to investigate the
reactivity pattern of a,b-chalcone ditosylates 3 in compar-
ison with a,b-chalcone dibromides 2. As a consequence of
our initial efforts, we wish to report novel routes for the
synthesis of 1,2-diarylethan-1-ones 4 and 1,2-diaryl-3,3-
dimethoxy propan-1-ones 5 by the reaction of a,b-chal-
cone ditosylates 3 with potassium hydroxide in suitable
conditions.
Ph
4-ClC6H4
Ph
101–102
113–114
134–135
110–112
124–125
132–133
108–110
4-MeC6H4
4-BrC6H4
Ph
Ph
3g
3h
3i
4-BrC6H4
4-FC6H4
Ph
Ph
4-MeOC6H4
4-ClC6H4
3j
Ph
a Compounds 3b–3j are unknown and their structures were confirmed
by spectral (IR, NMR) and elemental analytical data.
b The yields (%) of the isolated pure products 3 were calculated with
respect to the corresponding chalcone ditosylates.
Thus, various derivatives of a,b-chalcone ditosylates
3a–3j were prepared by the treatment of respective chal-
cone 1 with [hydroxy(tosyloxy)iodo]benzene (HTIB)4
according to the method of Koser (Scheme 1, Table 1).5,6
KOH, MeOH
Ar
C
O
CH CH Ar'
Ar
C
O
C
CH Ar'
reflux
Br Br
Br
2
HTIB
Scheme 2
Ar
C
O
CH CH Ar'
Ar
C
O
CH CH Ar'
OTs OTs
3
CH2Cl2
Thus, 3a was treated with two equivalents of potassium
hydroxide in ethanol under reflux for about 2–3 hours.
The workup of the reaction did not afford any elimination
product. Instead, a 1,2-aryl shift, followed by carbon–car-
bon bond cleavage occurred with the formation of 1,2-
diphenylethan-1-one (4a) in 58% yield. Under the same
conditions, other derivatives 3b–3j also afforded 1,2-di-
arylethan-1-ones 4b–4j in 60–68% yields (Scheme 3,
Table 2).7
1
Scheme 1
We first examined the reaction of a,b-chalcone dito-
sylates 3 with potassium hydroxide according to the con-
ditions described for the elimination of a,b-chalcone
dibromides 2 (Scheme 2).3b
To study the effect of reaction conditions, solvents, etc., a
series of experiments was performed on the substrate 3a
with potassium hydroxide under different conditions.
These experiments showed that the conversion 3a → 4a
SYNLETT 2007, No. 14, pp 2189–2192
Advanced online publication: 20.07.2007
DOI: 10.1055/s-2007-984915; Art ID: G11707ST
© Georg Thieme Verlag Stuttgart · New York
0
3
.0
9
.2
0
0
7

2190
O. Prakash et al.
LETTER
Table 2 Physical Data of 1,2-Diarylethan-1-ones 4 Prepared According to Scheme 3
Compoundsa
Ar
Ar¢
Mp (°C)
Yieldb (%)
(Lit. mp)8–16
4a
4b
4c
4d
4e
4f
Ph
Ph
52–54 (55–56)8
58
60
68
64
62
60
62
57
60
58
Ph
4-MeC6H4
4-MeOC6H4
4-ClC6H4
Ph
94–96 (97–99)12
Ph
90–92 (94–95)13
Ph
132–134 (135–136)11
104–107 (108–109)14
106–108 (112–113)10
134–136 (136–138)9
104–106 (108–110)10
72–74 (77–78)16
4-MeC6H4
4-BrC6H4
Ph
Ph
4g
4h
4i
4-BrC6H4
4-FC6H4
Ph
Ph
4-MeOC6H4
4-ClC6H4
4j
Ph
103–105 (103–105)15
a Spectral data (IR, NMR and MS) of all the products were in full agreement with the reported data.
b The yields (%) of the isolated pure products 4 were calculated with respect to the corresponding chalcone ditosylates.
KOH, ROH
Table 3 Physical Data of 1,2-Diaryl-3,3-dimethoxypropan-1-ones 5
Prepared According to Scheme 4
Ar
C
O
CH CH Ar'
OTs OTs
Ar
C
O
CH2 Ar'
reflux
3
4
Yieldb
(%)
R = H, Me, Et
Com- Ar
poundsa
Ar¢
Mp (°C)
(Lit. mp)18
Scheme 3
5a
5b
5c
5d
5e
5f
Ph
Ph
Ph
Ph
Ph
91–92 (94.5–96.5)
58–59 (59.5–61.5)
51
56
59
58
4-MeC6H4
can be effected by stirring the mixture of 3a with two
equivalents of KOH at room temperature in any of the
following solvents: methanol, ethanol and THF–H2O.
4-MeOC6H4 79–81 (84–86)
4-ClC6H4 89–91 (93–93.5)
However, when the reaction was carried out by using
catalytic amount of KOH in methanol at room tempera-
ture, the rearranged product 1,2-diphenyl-3,3-dimethoxy-
propan-1-one (5a) was obtained in 51% yield without
isolating any carbon–carbon bond cleavage product
(Scheme 4, Table 3).17
4-MeC6H4 Ph
4-BrC6H4 Ph
108–110 (113–115) 61
78–80 (84–86) 54
a Spectral data (IR, NMR and MS) of all the products were in full
agreement with the reported data.
b The yields (%) of the isolated pure products 5 were calculated with
respect to the corresponding chalcone ditosylates.
KOH (cat. amount),
MeOH
Ar
C
O
CH CH Ar'
OTs OTs
3
Ar
C
O
CH CH(OMe)2
stirring, r.t.
Ar'
migration and carbon–carbon bond cleavage resulting in
5
the formation of 1,2-diarylethan-1-ones 4.
Scheme 4
It is evident from the results of the present study that the
reactivities of a,b-chalcone dibromides 2 and a,b-chal-
cone ditosylates 3 are quite different. The actual reason
for this difference in the reactivity is not known yet. De-
tailed investigations dealing with the comparison of the
reactions of a,b-chalcone dibromides 2 and a,b-chalcone
ditosylates 3 are under progress. The initial results follow
similar trends. For example, 1,4,5-triphenylpyrazole was
obtained by the treatment of a,b-chalcone ditosylate 3a
with phenylhydrazine in dimethylformamide in contrast
to the reported reaction of a,b-chalcone dibromide 2 with
phenylhydrazine giving the isomer 1,3,5-triphenyl-
pyrazole.3j
To determine that the conversion 3a → 4a can occur
through the intermediacy of 1,2-diphenyl-3,3-dimethoxy
propan-1-one (5a), the latter was treated with two equiva-
lents of potassium hydroxide in methanol at room temper-
ature. The reaction indeed afforded the desired carbon–
carbon bond cleavage product, 1,2-diphenylethan-1-one
(4a).
Although the mechanism for the conversion of 3 → 4 is
not clear, a plausible pathway has been outlined in
Scheme 5. The reaction may proceed through the sub-
stitution of OTs group by OR group, followed by an aryl
Synlett 2007, No. 14, 2189–2192 © Thieme Stuttgart · New York

LETTER
Synthesis of Desoxybenzoins and a-Aryl-b-ketoaldehyde Dimethylacetals
2191
KOH + ROH
: OR
O
O
OTs
CH
OTs
OTs
CH
Ar
C
CH
Ar'
Ar
C
CH
Ar
'
3
ROK + H2O
ROH
O
O
+
Ar
CH
Ar
CH
Ar
CH
Ar
CH(OR)2
C
OR
C
'
'
RO–
ArCOCH2Ar'
R = H, Et, Me
4
Scheme 5
3791. (g) Elba, M. E.; Darwish, A. I.; Hamada, N. M. Egypt.
J. Chem. 1997, 40, 81. (h) Elba, M. E.; Darwish, A. I.;
Hamada, N. M. J. Indian Chem. Soc. 1997, 74, 202.
(i) Elba, M. E. Phosphorus, Sulfur Silicon Relat. Elem. 2000,
160, 233. (j) Wislicennus, W.; Ruthing, A. Justus Liebigs
Ann. Chem. 1911, 379, 299.
Finally, the noteworthy features of the first report on the
reactivity of a,b-chalcone ditosylates and their dibromo
analogues are:
(a) It offers a novel and convenient route for the synthesis
of 1,2-diarylethan-1-ones 4 and 1,2-diarl-3,3-dimethoxy-
propan-1-ones 5.
(4) (a) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2002, 102,
2523. (b) Moriarty, R. M. J. Org. Chem. 2005, 70, 2893.
(5) Rebrovic, L.; Koser, G. F. J. Org. Chem. 1984, 49, 2462.
(6) Experimental Procedure for a,b-Chalcone Ditosylates 3:
To a solution of chalcone (1b, 1.11 g, 0.005 mol) in CH2Cl2
(40 mL) was added HTIB (3.92 g, 0.01 mol). The resulting
mixture was allowed to stir at 40–42 °C. HTIB was highly
insoluble in CH2Cl2, but gradually disappeared as the
reaction proceeded. The stirring was allowed to continue for
about 16–18 h. The solvent was evaporated in vacuo. The
gummy mass so obtained was triturated with PE (60–80 °C)
to remove iodobenzene. The colorless solid obtained was
thoroughly washed with H2O to remove p-toluenesulfonic
acid formed as byproduct. The solid was recrystallized from
MeCN to give the pure chalcone ditosylate 3b; yield: 1.66 g
(59%); mp 114–115 °C. IR (KBr): 1675 (CO stretch) cm–1.
1H NMR (300 MHz, CDCl3): d = 2.21 (s, 3 H, Me), 2.43 (s,
6 H, Me), 5.00 (d, J = 8.1 Hz, 1 H, CH), 6.97 (d, J = 8.1 Hz,
1 H, CH), 6.80–6.87 (m, 2 H, ArH), 7.10–7.21 (m, 4 H,
ArH), 7.32–7.35 (m, 3 H, ArH), 7.38–7.48 (m, 4 H, ArH),
7.71–7.79 (m, 4 H, ArH). Anal. Calcd for C30H28O7S2: C,
63.8; H, 4.9. Found: C, 62.7; H, 4.2.
(b) a,b-Chalcone ditosylates behave differently than their
a,b-dibromo analogues.
(c) There is a great scope of using a,b-chalcone ditosylate
derivatives to effect selective transformations which are
otherwise not possible through a,b-chalcone dibromides.
Acknowledgment
We are thankful to CSIR, New Delhi for the award of Senior
Research Fellowship to Rajesh Kumar.
References and Notes
(1) For reviews see: (a) Prakash, O.; Saini, N.; Sharma, P. K.
Heterocycles 1994, 38, 409. (b) Koser, G. F. Aldrichimica
Acta 2001, 34, 89.
(2) (a) Prakash, O.; Rani, N.; Goyal, S. J. Chem. Soc., Perkin
Trans 1 1992, 707. (b) Mohan, J.; Verma, P.; Singh, V.
Synth. Commun. 1992, 22, 1293. (c) Prakash, O.; Aggarwal,
R.; Saini, N.; Goyal, S.; Tomer, R. K.; Singh, S. P. Indian J.
Chem., Sect. B. 1994, 33, 116. (d) Mohan, J.; Singh, V.;
Kumar, V.; Kataria, S. J. Chem. Res., Synop. 1994, 38.
(e) Singh, S. P.; Batra, H.; Sharma, P. K.; Prakash, O. J.
Indian Chem. Soc. 1997, 74, 940. (f) Singh, S. P.; Naithani,
R.; Prakash, O. J. Indian Chem. Soc. 1998, 75, 770.
(g) Prakash, O.; Pundeer, R.; Chaudhri, V. J. Indian Chem.
Soc. 2004, 34, 2659. (h) Aggarwal, R.; Pundeer, R.; Kumar,
V.; Chaudhri, V.; Singh, S. P.; Prakash, O. Synth. Commun.
2004, 34, 2659.
(3) (a) House, H. O.; Ryerson, G. D. J. Am. Chem. Soc. 1961, 83,
979. (b) Sharma, T. C.; Patel, H.; Bokadia, M. M. Indian J.
Chem. 1973, 11, 703. (c) Weber, F. G.; Radeglia, R. J.
Prakt. Chem. 1989, 331, 212. (d) Holla, B. S.; Shridhara, K.
Chim. Acta Turc. 1992, 20, 161. (e) Saoudi, A.; Hamelin, J.;
Benhaoua, H. J. Chem. Res., Synop. 1996, 491.
Other derivatives 3a, 3c–3j were prepared in a similar
manner.
(7) Experimental Procedure for Desoxybenzoins 4: To a
solution of a,b-chalcone ditosylate 3a (0.550 g, 0.01 mol) in
EtOH (20 mL) was added KOH (0.112 g, 0.02 mol). The
mixture was heated under reflux for 2–3 h. The progress of
the reaction was monitored by TLC. When all of the starting
material had been consumed, the reaction mixture was
poured over crushed ice, extracted with CH2Cl2 and the
crude product 4a was purified by column chromatography
using EtOAc–PE as eluent; yield: 0.114 g (58%); mp 52–
54 °C (Lit. mp 55–56 °C). IR (KBr): 1685 (CO stretch)
cm–1. 1H NMR (300 MHz, CDCl3): d = 4.18 (s, 2 H, CH2),
7.12–7.13 (m, 2 H, ArH), 7.51–7.70 (m, 6 H, ArH), 7.99–
8.21 (m, 2 H, ArH).
Other derivatives 4b–j were prepared in a similar manner.
(f) Khurana, J. M.; Seghal, A. Synth. Commun. 1996, 26,
Synlett 2007, No. 14, 2189–2192 © Thieme Stuttgart · New York

2192
O. Prakash et al.
LETTER
(17) Experimental Procedure for a-Aryl-b-ketoaldehyde
(8) Allen, C. F. H.; Baker, W. E. Org. Synth., Coll. Vol. II;
Wiley: New York, 1943, 156.
(9) Blay, G.; Fernandez, I.; Monje, B.; Pedro, J. R. Molecules
2004, 9, 365.
Dimethylacetals 5: To a solution of a,b-chalcone ditosylate
3a (0.550 g, 0.01 mol) in EtOH (20 mL) was added KOH in
catalytic amount. The mixture was stirred at r.t. for about
2 h and was heated under reflux for 2–3 h. The reaction
mixture was poured over crushed ice. The crude product 5a
was purified by recrystallization using MeOH as a solvent;
yield: 0.138 g (51%); mp 93–94 °C (Lit.18 mp 94.5–96.5 °C).
IR (KBr): 1682 (CO stretch) cm–1. 1H NMR (300 MHz,
CDCl3): d = 3.28 (s, 3 H, OMe), 3.49 (s, 3 H, OMe), 4.92 (d,
J = 9.0 Hz, 1 H, CH), 5.16 (d, J = 9.0 Hz, 1 H, CH), 7.04–
7.05 (m, 2 H, ArH), 7.39–7.68 (m, 6 H, ArH), 7.97–8.08 (m,
2 H, ArH).
(10) Kim, S. H.; Rieke, R. D. J. Org. Chem. 2000, 65, 2322.
(11) Veno, Y.; Okawara, M. Synthesis 1975, 268.
(12) Miyashita, A.; Matsuoka, Y.; Suzuki, Y.; Iwamoto, K.;
Hgashino, T. Chem. Pharm. Bull. 1997, 45, 1235.
(13) Curtin, D. Y.; Crew, M. C. J. Am. Chem. Soc. 1954, 76,
3719.
(14) Mann, W. Ber. Dtsch. Chem. Ges. 1881, 14, 1646.
(15) Hauser, C. R.; Morris, G. F. J. Org. Chem. 1961, 26, 4740.
(16) Meisenheimer, J.; Jochelson, L. Justus Liebigs Ann. Chem.
1907, 355, 291.
Other derivatives 5b–5j were prepared in a similar manner.
(18) Taylor, E. C.; Conley, R. A.; Johnson, D. K.; McKillop, A.;
Ford, M. E. J. Org. Chem. 1980, 45, 3433.
Synlett 2007, No. 14, 2189–2192 © Thieme Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not
be copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for
individual use.