The synthesis of 3,3,4,4-tetraphenyl-2-butanone from 1,1-diphenylacetone

Article abstract of DOI:10.1016/S0040-4039(02)00861-4

The preparation of 3,3,4,4-tetraphenyl-2-butanone by treatment of 1,1-diphenylacetone(1,1-DPA) with potassium-t-butoxide or lithium diisopropyl amide in THF at 0°C followed by heating with a diphenylmethylhalide is described. A single crystal X-ray analys

Full text of DOI:10.1016/S0040-4039(02)00861-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 4845–4848
The synthesis of 3,3,4,4-tetraphenyl-2-butanone from
1,1-diphenylacetone
Herman E. Zieger,a,* Choi Han Tsang,a Mohammed Malika and Louis J. Todarob
aDepartment of Chemistry, Brooklyn College of CUNY, 2900 Bedford Avenue, Brooklyn, NY 11210, USA
bDepartment of Chemistry, Hunter College of CUNY, 695 Park Avenue, New York, NY 10021, USA
Received 1 May 2002; accepted 6 May 2002
Abstract—The preparation of 3,3,4,4-tetraphenyl-2-butanone by treatment of 1,1-diphenylacetone(1,1-DPA) with potassium-t-
butoxide or lithium diisopropyl amide in THF at 0°C followed by heating with a diphenylmethylhalide is described. A single
crystal X-ray analysis on the new ketone shows that the molecule crystallizes in a conformation in which the carbonyl group is
not eclipsed with the benzylic hydrogen, but has a torsional angle of +41° toward a gauche (120°) conformation. © 2002 Elsevier
Science Ltd. All rights reserved.
In previous work the coupling reactions of benzylic
organolithium reagents with benzylic halides were
found to form highly phenylated alkanes predomi-
nantly by SN2 displacement.1–3 In an extension of those
earlier synthetic efforts 1,1-diphenylacetone (1,1-DPA)
was treated with potassium t-butoxide in THF at tem-
peratures from 0–25°C and alkylated with diphenyl-
methylbromide by heating to afford 3,3,4,4-tetra-
phenyl-2-butanone, 1 (see Scheme 1 and literature
reviews).4–9
methanol. None of the isomeric 1,1,4,4-tetraphenyl-2-
butanone expected from the methylene enolate could be
found.12
A possible explanation for the failure to observe alkyla-
tion on the methyl carbon may be that it isomerizes
rapidly in the presence of excess starting ketone into the
diphenylmethylene enolate in a manner similar to
Rathke’s report on the isomerization of E- and Z-eno-
lates of 3-pentanone by a reversible aldol condensation
mechanism.13 Because LDA and 1,1-DPA in THF at
0°C did not undergo alkylation with diphenyl-
methylchloride, it might be possible that the methylene
enolate forms first but isomerizes completely into
diphenylmethylene enolate faster on heating than
diphenylmethyl halides can alkylate it.
No alkylation products from the methyl group enolate
or from oxygen alkylation of either enolate were iso-
lated. The greater acidity of the benzylic hydrogen in
1,1-DPA (pKaꢀ10.42) over the methyl hydrogens
(pKaꢀ18.27) can be estimated by comparison with
diphenylacetaldehyde10 and benzylmethyl ketone11
acidities.
Although the new ketone, 3,3,4,4-tetraphenyl-2-
butanone, 1, mp 155–156°C, had a properly integrated
proton NMR spectrum, 13C NMR peak at l=205.97
for CꢀO, a strong peak in the IR at 1700 cm−1, analyt-
ical data that matched for C28H24O, and a MS with a
molecular ion at m/z=376, its melting point did not
agree with the literature (117–118°C).14,15
When 1,1-DPA was treated with LDA at 0°C in THF
(2.0 h) followed by dropwise addition of diphenyl-
methyl-chloride and 2.0 h of heating, only 1 was
formed in 19–22% yields. 1,1-DPA was recovered (45%)
together with sym-tetraphenylethane and diphenyl-
Scheme 1.
* Corresponding author. Tel.: 1-718-951-5744; fax: 1-718-951-4607; e-mail: hzieger@brooklyn.cuny.edu
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00861-4

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H. E. Zieger et al. / Tetrahedron Letters 43 (2002) 4845–4848
The erroneous literature assignment was based on the
assumption16 that oxidation of 2-methyl-1,1,3,3-tetra-
phenylpropene, 2, with chromium trioxide in boiling
acetic acid produced an epoxide, 3, or a diol which
subsequently experienced pinacol rearrangement to give
1.
One of the more interesting aspects of the crystal
structure is the fact that in the Newman projection
formula of Fig. 2 where the bulky phenyl groups might
have been expected to be all anti to each other, the
acetyl group on C3 is found to be +syn clinal (30–90°)18
to the benzylic hydrogen. If we recall that the parent
compound for ketone 1 is 2-butanone, which is known
to have two conformations in which the C4 methyl
group or a C3 methylene hydrogen are eclipsed with the
carbonyl group (i.e. have an ꢀ of 0°), then the observed
dihedral angle of +41.0° displaced from ꢀ=0° for the
benzylic hydrogen to carbonyl group plane in solid 1 is
a measure of the degree to which the non-bonding
steric interactions of the four substituent phenyl groups
oppose the orbital interactions which stabilize eclipsed
conformations in 2-butanone.19,20
To verify the literature report a sample of 2 was
prepared by the literature procedure and was oxidized
with chromium trioxide in boiling acetic acid to give
epoxide 3 as shown in Scheme 2. An IR spectrum
showed that epoxide 3 had been mis-identified as
ketone 1 as judged by the absence of the carbonyl
signal and the presence of epoxide ring signals in the
13C NMR at l=70.05 and 71.64 ppm.
X-Ray analysis of the new ketone was undertaken not
only to verify its structure but also to indicate whether
1 would be a suitable precursor in polyphenylethane
syntheses. We thought that replacing a phenyl group of
pentaphenylethane with an acetyl moiety might lead to
a shorter central carbon–carbon bond. This goal was
achieved in that the rc value for pentaphenylethane17 is
In the packing diagram there are eight molecules in the
(
unit cell of space group P1. Because of the inversion
symmetry operation, one has four independent
molecules (A, B, C, and D) and their mirror images.
The values of the C2ꢁC3ꢁC4ꢁH torsion angles for A–D
in the 295° data are: −41.0, 48.0, −40.7, 44.7°.
,
1.606 A, while the new ketone has a C3ꢁC4 bond
,
distance of 1.587 A. See Figs. 1 and 2 for the atom
In Fig. 3 of one of the four independent molecules, A,
in the unit cell, it appears as if the ortho aromatic
hydrogen atom on C-46 is pointing toward the p cloud
numbering scheme and the torsion angles (ꢀ).
,
of ring two (C21–C26) at a distance of 2.4 A from the p
face. Such hydrogens are thought to provide an attrac-
tive edge-to-p-face interaction21 estimated to be ꢀ0.5
kcal/mol.22,23 Unfortunately in molecules B, C and D
the ring plane rotational angles vary widely so that the
distance between the ortho hydrogen atom on C-46 and
,
,
the face of ring two is increased to 3.82 A, 3.19 A and
3.27 A. Thus it does not appear that aromatic edge–
,
hydrogen to aromatic p-face interactions play any sig-
nificant role in the conformation in which ketone 1
crystallizes.21–23
Figure 1. The numbering scheme for ketone 1. C3ꢁC4=1.587
,
A.
Experimental
Crystallographic data (excluding structure factors) for
the title ketone have been deposited with the Cam-
bridge Crystallographic Data Centre as supplementary
publication number CCDC 182217. Copies of the data
can be obtained free of charge on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK
[fax: +44 (0) 1223-336033 or e-mail: deposit@
ccdc.cam.ac.uk].
(
Crystals of 1 are triclinic, space group P1, a=9.721(2)
Figure 2. Projection of ketone 1 down the C3ꢁC4 bond.
Torsion angles are shown.
, , ,
A, b=19.982(7) A, c=21.856(6) A, h=89.67(3)°, i=
Scheme 2.

H. E. Zieger et al. / Tetrahedron Letters 43 (2002) 4845–4848
4847
Figure 3. X-Ray structure of independent molecule A of 1 at 295 K.
3
,
81.87°, k=81.49(2)°, V=4155.7(21) A , and Dcalc
=
matrix least-squares methods. The final discrepancy
indices are R=0.0720 and Rw=0.0722 for the 1850
1.204 g/cm3 for Z=8 (C28H24O),=376.503. The crystal
used for data collection measured 0.16×0.20×0.40 mm.
Intensity data were measured on an Enraf–Nonius
CAD4 diffractometer with graphite monochromated
Mo Ka radiation, v–2u scans having v=0.771 cm−1.
Data were not corrected for absorption. Of 5710 inde-
pendent reflections for q<18°, 1850 were considered
observed [I>3.0|(I)].
observed reflections. The final difference map has no
−3
,
peaks greater than 0.24 e A . In the final refinement,
the oxygen atoms were refined anisotropically and the
carbon atoms were refined isotropically. The hydrogen
atoms were included in the structure factor calculations,
but their parameters were not refined.
The structure was solved at Bruker-AXS using
SHELXTL software by Dr. Charles Campana who col-
lected data on a second crystal at 110 K. The applica-
tion of low temperature parameters to room
temperature data produced a refined structure by full-
Acknowledgements
The CUNY Faculty research award program grant
number 669341 is gratefully acknowledged.

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H. E. Zieger et al. / Tetrahedron Letters 43 (2002) 4845–4848
12. Palucki, M.; Buchwald, S. L. J. Am. Chem. Soc. 1997,
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