Synthesis of sterically hindered 1,3-diketones

Article abstract of DOI:10.1080/00397910701572803

An efficient and practical method for the synthesis of sterically hindered aliphatic/aromatic 1,3-diketones via coupling of ketones with esters using potassium tert-butoxide is described. The protocol requires milder operating conditions, and the products are obained in good to excellent yields. Copyright Taylor & Francis Group, LLC.

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Synthesis of Sterically Hindered
1,3‐Diketones
Nitin S. Nandurkar a , Mayur J. Bhanushali a , Dinkar S. Patil b & Bhalchandra
M. Bhanage a
a Department of Chemistry, Institute of Chemical Technology, Mumbai, India
b Laser and Plasma Technology Division, Bhabha Atomic Research Centre,
Mumbai, India
Published online: 10 Dec 2007.
To cite this article: Nitin S. Nandurkar , Mayur J. Bhanushali , Dinkar S. Patil & Bhalchandra M. Bhanage
(2007) Synthesis of Sterically Hindered 1,3‐Diketones, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 37:23, 4111-4115, DOI: 10.1080/00397910701572803
To link to this article: http://dx.doi.org/10.1080/00397910701572803
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Synthetic Communicationsw, 37: 4111–4115, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701572803
Synthesis of Sterically Hindered
1,3-Diketones
Nitin S. Nandurkar, and Mayur J. Bhanushali
Department of Chemistry, Institute of Chemical Technology,
Mumbai, India
Dinkar S. Patil
Laser and Plasma Technology Division, Bhabha Atomic Research
Centre, Mumbai, India
Bhalchandra M. Bhanage
Department of Chemistry, Institute of Chemical Technology,
Mumbai, India
Abstract: An efficient and practical method for the synthesis of sterically hindered
aliphatic/aromatic 1,3-diketones via coupling of ketones with esters using potassium
tert-butoxide is described. The protocol requires milder operating conditions, and the
products are obained in good to excellent yields.
Keywords: claisen condensation, 1,3-diketone, ester, potassium tert-butoxide
INTRODUCTION
The traditional route for the synthesis of 1,3-diketones is generally carried out
by Claisen condensation[1] using reagents such as SmI3,[2] LiHMDS,[3] NaH/
dibenzo 18-crown-6,[4] sodium hydride,[5] lithium amide,[2,6] and
sodamide.[7,8] Recently, the use of potassium tert butoxide has been
Received in India May 3, 2007
Address correspondence to Bhalchandra M. Bhanage, Department of Chemistry,
Institute of Chemical Technology, N. Parekh Marg, Matunga, Mumbai 40019, India.
E-mail: bhalchandra_bhanage@yahoo.com
4111

4112
N. S. Nandurkar et al.
reported for the Michael reaction followed by intramolecular Claisen cycliza-
tions to give cyclohexane-1,3-dione framework.[9]
RESULTS AND DISCUSSION
The present study reports a convenient, cost-effective, high-yielding protocol
for the synthesis of higher aliphatic and aromatic 1,3-diketones involving
sterically hindered substrates via coupling of ketones with esters using
potassium tert-butoxide (Scheme 1). The mechanism of the reaction is
outlined in Scheme 2.
A series of aliphatic/aromatic 1,3-diketones with different steric and elec-
tronic properties were synthesized as shown in Table 1. Initially, various
aliphatic ketones with bulky groups were condensed with sterically hindered
aliphatic esters (entries 1–4) to give the corresponding 1,3-diketone in good
to excellent yields. The protocol was also applicable for the synthesis of indust-
rially important 2,2,6,6-tetramethyl-3,5-heptanedione (dipivaloylmethane,
entry 2). In addition to its simplicity and milder reaction conditions, the
system also permits the condensation of ketones and esters with branching at
the alpha position, which difficult to synthesize because the complexity of
the substrates (entries 5–7). Successful condensation of acetyl ferrocene
with ethyl acetate was also carried out, providing 80% yield of the desired
product within 0.45 h. The protocol was also applicable for the condensation
of deactivated aromatic ketones such as 4-Cl-acetophenone, affording
excellent yield. The reaction of aromatic ketone with aliphatic ester and vice
Scheme 1.
Scheme 2.

Synthesis of Sterically Hindered 1,3-Diketones
4113
Table 1. Synthesis of aliphatic and aromatic 1,3-diketones
Time
Yieldb
(%)
Entry
1
Ketone
Ester
(h)
5
Product
70
2
5
64 (60)
3
4
5
5
5
5
65
66
46
6
6
6
34
40
82
7
8a
0.45
9a
0.45
80
75
10a
1
(continued)

4114
N. S. Nandurkar et al.
Table 1. Continued
Time
(h)
Yieldb
(%)
Entry
11a
Ketone
Ester
Product
1
70
12a
0.45
75
Notes. Reaction conditions: ketone (20 mmol), ester (30 mmol), KOtBu (50 mmol),
and DMF 27.5 ml at 508C.
aKOtBu (40 mmol).
bIsolated yield. Yields in parentheses represent purification by copper chelation.
versa was also studied (entries 11 and 12), and good yields were obtained
within 0.45–1 h, indicating the generality of the procedure.
The influence of various parameters such as temperature, solvent, base,
ketone–ester ratio, and ketone–base ratio on the reaction system was
studied. Table 1 describes conditions with optimal yields.
EXPERIMENTAL
General
All chemicals were obtained from commercial sources and used as received.
Optimization yields were based on gas chromographic (GC) analysis
(Chemito 8610). The isolated products were characterized by spectral
analysis such as FT-IR (Perkin-Elmer 100 spectrochem series) using KBr
1
and H NMR (Varian 400 MHz).
Typical Experimental Procedure (Table 1, Entry 2)
N,N-dimethylformamide (DMF) (25 ml) and potassium tert-butoxic (KOtBu)
(5.6 g, 50 mmol) were heated to 508C under nitrogen. Methyl pivalate (3.5 g,
30 mmol) was added dropwise, followed by a solution of pinacolone (2 g,
20 mmol) in DMF (2.5 ml). The progress of the reaction was monitored by
GC. After the completion of the reaction, the reaction mixture was allowed
to cool and slowly neutralized with 20% H2SO4 solution. Water (25 ml)
was further added to separate two layers. The layer containing the crude
diketone 2,2,6,6-tetramethyl-3,5-heptanedione(thd) was purified using

Synthesis of Sterically Hindered 1,3-Diketones
4115
column chromatography (silica gel, 60–120 mesh) with petroleum ether
(60/80) as an eluent (2.35 g, 64%).
Purification of 1,3-Diketone
A solution of Cu(OAc)2 (1.4 g) in methanol (7 ml), H2O (10 ml), and 2,2,6,6-
Tetramethyl-3,5-heptanedione (THD) (2.5 g) was stirred. The solid was filtered
and recrystallized from methanol. Pure THD was obtained after shaking the
diethylether solution of chelate with 10% HCl, followed by evaporation of
the solvent and distillation at 96–988C/20 mm. IR (KBr): 3180 cm21 (OH),
1
1608 cm21 (C55O, C55C). H NMR (CDCl3), d (ppm): 1.18 (18H, s, But),
5.73 (1H, s, CH), 16.18 (1H, s, OH).
ACKNOWLEDGMENTS
Financial assistance from Department of Atomic Energy/Board of Research in
Nuclear Sciences (DAE/BRNS) is acknowledged.
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