An unexpected formation of benzoyl benzoin from benzil during the attempted Knoevenagel type condensation with dimethylmalonate (or malononitrile)

Article abstract of DOI:10.1016/j.tetlet.2012.03.084

An unexpected product, 2-oxo-1,2-diphenylethyl benzoate (benzoyl benzoin), was isolated during the attempted Knoevenagel reaction of benzil and dimethylmalonate (or malononitrile) in the presence of potassium carbonate. The product was confirmed by spectral analysis as well as by single crystal studies and a mechanism is proposed to explain its formation.

Full text of DOI:10.1016/j.tetlet.2012.03.084

Tetrahedron Letters 53 (2012) 2745–2747
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An unexpected formation of benzoyl benzoin from benzil during the attempted
Knoevenagel type condensation with dimethylmalonate (or malononitrile)
⇑
M. Shyam Sundar, Ashutosh V. Bedekar
Department of Chemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara 390 002, India
a r t i c l e i n f o
a b s t r a c t
Article history:
An unexpected product, 2-oxo-1,2-diphenylethyl benzoate (benzoyl benzoin), was isolated during the
attempted Knoevenagel reaction of benzil and dimethylmalonate (or malononitrile) in the presence of
potassium carbonate. The product was confirmed by spectral analysis as well as by single crystal studies
and a mechanism is proposed to explain its formation.
Received 21 February 2012
Revised 20 March 2012
Accepted 22 March 2012
Available online 29 March 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Benzil
Benzoyl benzoin
Knoevenagel
Unexpected reaction
The classical Knoevenagel reaction of aldehydes and ketones
with molecules containing active methylene group, like Z-CH2-Z
where Z is electron withdrawing group, gives conjugated systems.1
As a part of our ongoing research project we were keen to carry out
Knoevenagel condensation on 1,2-diketo compounds like benzil 1
to prepare mono substituted conjugated system 2. Benzil is known
to react with various nucleophilic species like hydroxide to under-
go benzilic acid rearrangement,2 diphenyl acetone to give tetra-
phenyl cyclopentadienone,3 1° amines to form mono imines,4 etc.
Benzils are also known to form other heterocyclic compounds
when treated with nucleophilic reagents under specific condi-
tions.5 A bis-imine prepared from benzil with 2 equiv of chiral 1°
amines is used as a ligand for Mo-catalyzed reactions6 and another
one prepared from aminophenols is used in catalytic oxidation
reactions.7
However, a number of attempts in our laboratory to carry out
this conversion could not furnish the desired compound 2. Initially,
the reaction of benzil and dimethylmalonate was conducted in dry
acetonitrile in the presence of potassium carbonate to facilitate the
anion formation. Two new products were detected in the reaction
mixture, but on separation none of them was the expected
compound 2. One of the lesser polar products was isolated and
identified to be 2-oxo-1,2-diphenylethyl benzoate (benzoyl
benzoin), 3 by spectroscopic analysis and also by comparison of
R
O
O
O
Ph
R
Ph
R
OCOPh
Ph
Ph
Ph
K2CO3
CH3CN
reflux
H
Ph
O
1
R
2
3
R = COOMe or CN
expected
isolated
Scheme 1. Attempted Knoevenagel reaction of benzil.
⇑
Corresponding author. Tel.: +91 265 2795552.
E-mail address: avbedekar@yahoo.co.in (A.V. Bedekar).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.03.084

2746
M. Shyam Sundar, A. V. Bedekar / Tetrahedron Letters 53 (2012) 2745–2747
Figure 1. ORTEP diagram of the organic compound 3 with atom numbering scheme (50% probability factor for the thermal ellipsoids.9
Ph
CN
Ph
CN
Ph
H
Ph
NC
Ph
Ph
O
NC
O
HO
O
O
N
N
H
N
H
H
CN
6
5
4
ref. 10a
ref. 11
ref. 11
Scheme 2. Observed products from earlier literature.
R
Ph
O
O
O
Ph
O
R
Ph
Ph
Ph
Ph
O
O
7
R
R
OK
Ph
Ph
KO
Ph
O
OK
K O
O
R
Ph
+
Ph
Ph
R
R
11
R
O
O
O
O
R
O
R
Ph
Ph
Ph
COPh
9
10
8
Ph
O
Ph
H3O+
H3O+
R
3
11
10
Ph
work-up
or
work-up
or
R
SiO2 column
SiO2 column
12, R = COOMe
13, R = CN
Scheme 3. Suggested mechanism to explain formation of 3 from benzil 1.

M. Shyam Sundar, A. V. Bedekar / Tetrahedron Letters 53 (2012) 2745–2747
2747
melting point with that of the reported one8 (see Scheme 1). Inter-
estingly, the same product 3 was formed when reaction of benzil
was carried out with malononitrile. It was noteworthy to observe
the complete absence of this product when neither dimethylmalo-
nate nor malononitrile was used and 1 was heated only with K2CO3
in acetonitrile.
New Delhi [No. 01(2386)/10/EMR-II]. We are thankful to Professor
V.K.Singh (Department of Chemistry, IIT, Mumbai) and Dr. Trushar
Bagul (COMB Discovery Services, Vadodara) for their helpful
suggestions and Professor B.V. Kamath for his support and
encouragements.
The structure of 3 was also established by single crystal X-ray
Reference and notes
analysis as shown in Figure 1.9
1. Jones, G. Org. React. 1967, 15, 204.
2. Liebig, J. Ann. Chemie. 1838, 25, 1.
Reaction of benzil with malononitrile is first reported by Junek
et al.10 to observe the formation of 2-benzoyl-2-phenyl-ethylene-
1,1-dicarbonitrile (2; R@CN) and 2,5-dioxo-4,4-diphenyl-pyrroli-
dine-3-carbonitrile 4. This reaction was reinvestigated by Ducker
and Gunter11 and have proposed the formation of two other
heterocyclic products, 40-cyano-50-oxo-20,30-diphenyl-30-pyrrolin-
20-ylmalononitrile 5 and 5-hydroxy-2-oxo-4,5-diphenyl-3-pyrro-
lin-3-carbonitrile 6 (see Scheme 2).
The same product 3 is reported to have formed when benzil is
treated with cyanide ion in the presence of benzaldehyde and the
key step in the mechanism involves 1,2 C–O shift.8a Such a possibil-
ity can be ruled out in the present case as the reaction does not have
cyanide ion or benzaldehyde. Another reaction of benzil with
cyanide ion is reported to be following a different mechanistic
pathway.12
3. Johnson, J. R.; Grummitt, J. R. Org. Synth. Coll. 1943, Vol. 2, 805.
4. a) Garcia-Ruano, J. L.; Henao, M. A.; Molina, D.; Pérez-Ossorio, R.; Plumet, J.
Tetrahedron Lett. 1979, 33, 3123; b) Haro, R.; Jimenez-Tebar, A.; Pérez-Ossorio,
R.; Plumet, J. Tetrahedron Lett. 1979, 33, 1355; c) Nomura, K.; Oshima, K.;
Matsubara, S. Tetrahedron Lett. 2004, 45, 5957; d) Krishnan, G. R.; Sreekumar, K.
Eur. J. Org. Chem. 2008, 4763.
5. a) Singh, S. B.; Mehrotra, K. N. Can. J. Chem. 1901, 1982, 60; b) Mehrotra, K. N.;
Singh, I. S.; Roy, J. Bull. Chem. Soc. Jpn. 1985, 58, 2399; c) Charrier, J.-D.;
Landreau, C.; Deniaud, D.; Reliquet, F.; Reliquet, A.; Meslin, J. C. Tetrahedron
2001, 57, 4195.
6. Gago, S.; Rodríguez-Borges, J. E.; Teixeira, C.; Santos, A. M.; Zhao, J.; Pillinger,
M.; Nunes, C. D.; Petrovski, Z.; Santos, T. M.; Kühn, F. E.; Romão, C. C.;
Gonçalves, I. S. J. Mol. Catal. A: Chem. 2005, 236, 1.
7. Salavati-Niasari, M.; Mirsattari, S. N. J. Mol. Catal. A: Chem. 2007, 268, 50.
8. a) Kuebrich, J. P.; Schowen, R. L. J. Am. Chem. Soc. 1971, 93, 1220; b) Celebi, N.;
Yildiz, N.; Demir, A. S.; Calimli, A. J. Supercrit. Fluids 2007, 41, 386.
9. The single crystal data is deposited at Cambridge Crystallographic Data Centre
and it has been allocated the deposition number CCDC 867618.
10. a) Junek, H.; Hornischer, B.; Hambock, H. Monatsh. Chem. 1969, 100, 503; b)
Junek, H.; Hambock, H.; Hornischer, B. Monatsh. Chem. 1969, 100, 699.
11. Ducker, J. W.; Gunter, M. J. Aust. J. Chem. 1974, 27, 2229.
The proposed mechanism of the formation of product 3 from
benzil is outlined in Scheme 3. The fact that the reaction does
not proceed in the absence of either a base or dimethylmalonate
or malononitrile clearly indicate that the reaction starts by a
nucleophilic attack of the anion of active methylene to one of the
carbonyls of benzil. The intermediate 7 may further attach to an-
other benzil molecule to form intermediate 8, which can undergo
an intramolecular nucleophilic attack on the second carbonyl of
the second benzil molecule to give a tetrahydrofuran intermediate
9. Intramolecular ring opening of this highly substituted interme-
diate 9 is quite possible to give stabilized species 10 and 11, which
during work up can give 3 and 12/13 as products, respectively.
Product 12 was isolated (43% yield) and its structure was con-
firmed by spectral analysis (mass and 1H NMR) when dimethyl-
malonate was used with benzil.
Our attempts to carry out identical reaction with camphorqui-
none and phenanthraquinone with dimethylmalonate did not re-
sult in similar reaction and products from usual Knovenagel
condensation were detected.
In this short communication we have thus presented the unu-
sual observation when benzil was treated with dimethylmalonate
or malononitrile in the presence of a base.13
12. Trisler, J. C.; Frye, J. L. J. Org. Chem. 1965, 30, 306.
13. General reaction condition: Benzil (0.25 g, 1.19 mmol) was dissolved in
acetonitrile (10 mL) in a two neck r.b. flask attached with water condenser.
To this mixture K2CO3 (0.411 g, 2.98 mmol) was added and stirred for few
minutes at room temperature and dimethylmalonate (0.157 g, 1.19 mmol) was
added drop wise. The reaction mixture was stirred at reflux temperature for
72 h. The reaction mixture was cooled to room temperature and the solvent
was removed in vacuum, the residue was taken in saturated aqueous NH4Cl,
extracted with ethyl acetate (3 ꢀ 25 mL). The organic layer was washed with
dilute aqueous NaOH (2 ꢀ 25 mL) and the ethyl acetate layer was dried on
anhydrous sodium sulfate, evaporated in vacuum. The crude white solid was
purified over silica gel column (petroleum ether/ethyl acetate 95:5) to obtain
pure compound 3 (0.175 g, 47% Y) and further purified by recrystallization
from acetonitrile. The aqueous NaOH layer was combined and acidified with
cold dilute HCl, and extracted with ethyl acetate (3 ꢀ 25 mL), dried over
anhydrous sodium sulfate, concentrated in vacuum to obtain a pale yellow
liquid as crude product, purified over silica gel column (petroleum ether/ethyl
acetate 90:10) to obtain pure compound 12, as colorless liquid (0.12 g, 43% Y).
2-Oxo-1,2-diphenylethyl benzoate (benzoyl benzoin), 3: Mp = 130–132 °C. IR:
m
cmꢁ1(KBr): 3070 (C–H stretch aromatic), 2952 (C–H stretch aliphatic), 1714
(Ar–COO), 1695 (Ar–CO), 1597, 1451, 1353, 1314, 1281, 1247, 1174, 1118,
1068, 1029, 956, 853, 758, 702, 590. 1H NMR (400 MHz, CDCl3): d 8.17–8.14
(2H, m), 8.05–8.02 (2H, m), 7.62–7.54 (4H, m), 7.49–7.39 (7H, m), 7.12 (1H, s).
13C NMR (100 MHz CDCl3): d 193.7, 166.1, 134.66, 133.7, 133.6, 133.4, 130.0,
129.4, 129.2, 128.9, 128.7, 128.5, 77.9. Mass (EI+): m/z (%) 316.07, 211.02 (17%),
106.01 (9%), 104.96 (100%), 77.01 (36%). 2-Benzoyl dimethylmalonate, 12:
Colorless oil. 1H NMR (400 MHz, CDCl3): d 7.93–7.89 (2H, m), 7.65–7.60 (1H,
m), 7.52–7.46 (2H, m), 5.36 (1H, s), 3.81 (6H, s). Mass (EI+): m/z (%) 237.2
(M+1), 236.3 (46%), 235.4 (100%), 205.1 (24%), 175.8 (23%), 106.1 (49%), 105.3
(72%), 104.3 (87%), 77.3 (49%), 76.5 (66%), 78.1 (11%), 58.9 (13%).
Acknowledgements
This work was carried out as a part of an ongoing project sup-
ported by the Council of Scientific and Industrial Research (CSIR),