4,4-Diphenylcyclohexa-2,5-dienylidene: Rearrangement via an Isobenzene Pathway

Article abstract of DOI:10.1021/jo982400z

Pyrolytic decompostition of the Li salt of the tosylhydrazone of 4,4-diphenyl-2,5-cyclohexadienone produces a mixture of products which includes biphenyl, p-terphenyl, the azine of 4,4-diphenyl-2,5-cyclohexadienone, and o-terphenyl. ¹³C labeling studies and computational results (semiempirical AM1 and density functional B3LYP/6-31G* molecular orbital calculations) elucidate the mechanistic pathway for the formation of o-terphenyl. A single mechanism is involved which proceeds through formation of an isobenzene species followed by subsequent phenyl and hydrogen migrations.

Full text of DOI:10.1021/jo982400z

J . Org. Chem. 1999, 64, 3947-3953
3947
4,4-Dip h en ylcycloh exa -2,5-d ien ylid en e: Rea r r a n gem en t via a n
Isoben zen e P a th w a y
Peter K. Freeman* and J ames K. Pugh
Department of Chemistry, Oregon State University, Corvallis, Oregon 97331
Received December 8, 1998
Pyrolytic decompostition of the Li salt of the tosylhydrazone of 4,4-diphenyl-2,5-cyclohexadienone
produces a mixture of products which includes biphenyl, p-terphenyl, the azine of 4,4-diphenyl-
2,5-cyclohexadienone, and o-terphenyl. 13C labeling studies and computational results (semiempirical
AM1 and density functional B3LYP/6-31G* molecular orbital calculations) elucidate the mechanistic
pathway for the formation of o-terphenyl. A single mechanism is involved which proceeds through
formation of an isobenzene species followed by subsequent phenyl and hydrogen migrations.
Sch em e 1
The photochemistry of the cyclohexadienone chro-
mophore has been known for some time.1 Early work
focused on the photochemical rearrangement of the
sesquiterpene R-santonin and its route to product forma-
tion.2 This led to a decade of intensive studies on the 2,5-
cyclohexadienone system during the 1960s that eluci-
dated the mechanistic pathway for rearrangement.3
Evidence has been developed for a sequence of steps that
is formally represented by a [π2a + 2a] reaction.4 The
during the tosylhydrazone degradation, a carbocation
could form to provide a route to o-terphenyl formation.
To test the sensitivity of the decomposition to protic
impurities, tosylhydrazone 8 was converted to its sodium
salt with sodium hydride and photolyzed in THF in the
presence of 1 equiv of deuterium oxide.5 No deuterium
was found to be incorporated into the o-terphenyl. This
provides evidence that the o-terphenyl is formed via a
carbene rearrangement and not through a carbocation
intermediate.
A first thought was to consider the formation of
o-terphenyl using monodeuterated diphenylcyclohexadi-
enylidene (14).5 Using this experimental approach, three
alternative mechanistic schemes were evaluated. Our
current investigation utilizes diphenylcyclohexadienyli-
dene with a 13C enhancement at C-1 (15). The following
σ
mechanism includes a zwitterionic intermediate as out-
lined in Scheme 1.
With this background, it was logical to investigate the
carbene analogue. If a singlet carbene were generated
that contained the electron pair in the σ orbital, then a
similar rearrangement might well occur. Carbene 4 could
undergo an allylcarbinyl-cyclopropylcarbinyl rearrange-
ment to generate zwitterion 5. A 1,4 sigmatropic shift
would then produce bicyclic bivalent 6 as in Scheme 2.
Previously we have investigated carbene rearrange-
ments of 4,4-diphenylcyclohexa-2,5-dienylidene (4).5 Ther-
mal degradation of the lithium salt of the tosylhydrazone
of ketone 7 gave seven products. Five of the products
could be identified and are shown in Scheme 3. The azine
(11) was formed in 51% yield, with the volatile monomeric
components (6.4%) present in a percent composition ratio
of 24.8 (9):9.2 (10):46.7 (12):5.8 (13); a fifth component
(13.4%) remains unidentified. This work focuses on the
mechanistic formation of o-terphenyl (12), the major
monomeric product. This product is unique to the diaryl-
substituted cyclohexadienylidene intermediates for no
ortho products were isolated from analogous 4,4-dialkyl-
cyclohexadienylidenes.6 It is known that the photochem-
istry of 4,4-diphenylcyclohexadienones can lead to similar
products via a carbocation intermediate followed by a
phenyl migration.7 If there were a proton source available
mechanistic schemes follow the path of both the deuter-
ium and the proposed 13C label. Scheme 4 starts with
the rearrangement of diphenylcyclohexadienylidene (4a )
to bicyclic carbene 6a (6b). A cyclopropylcarbinyl to allyl-
carbinyl ring cleavage produces 16a (16b). A 1,2-phenyl
shift generates carbene 17a (17b). Hydrogen (deuterium)
migration leads to o-terphenyl with equal proportions of
(1) Schuster, D. I. Acc. Chem. Res. 1978, 11, 65 and references
therein.
(2) Barton, D. H. R. J . Chem. Soc. 1958, 3314.
(3) (a) Zimmerman, H. E. Adv. Photochem. 1963, 1, 183. (b)
Zimmerman, H. E.; Schuster, D. I. J . Am. Chem. Soc. 1961, 83, 4486.
(c) Zimmerman, H. E.; Crumrine, D. S.; Dopp, D.; Huyfter, P. S. J .
Am. Chem. Soc. 1969, 91, 434. (d) Zimmerman, H. E.; Epling, G. A. J .
Am. Chem. Soc. 1972, 94, 7806. (e) Schuster, D. I.; Liu, K. C. J . Am.
Chem. Soc. 1971, 93, 6711.
(4) Woodward, R. B.; Hoffmann, R. The Conservation of Orbital
Symmetry; Verlag Chemie/Academic: Weinheim, 1970.
(5) Freeman, P. K.; Swenson, K. E. Tetrahedron 1982, 38, 3737.
(6) (a) Fry, A. J . J . Am. Chem. Soc. 1965, 87, 1816. (b) J ones, M.,
J r.; Harrison, M.; Rettig, K. R. J . Am. Chem. Soc. 1969, 91, 7462. (c)
Berdick, R. H.; Levin, R. H.; Wolf, A. D.; J ones, M., J r. J . Am. Chem.
Soc. 1973, 95, 5087. (d) Wolf, A. D.; Kane, V. V.; Levin, R. H.; J ones,
M. J . Am. Chem. Soc. 1973, 95, 1680. (e) Kane, V. V.; Wolf, A. D.;
J ones J r., M., J r. J . Am. Chem. Soc. 1974, 96, 2643. (f) J ones, M., J r.
Acc. Chem. Res. 1974, 7, 415.
(7) Zimmerman, H. E.; Schuster, D. I. J . Am. Chem. Soc. 1961, 83,
4486.
10.1021/jo982400z CCC: $18.00 © 1999 American Chemical Society
Published on Web 05/01/1999

3948 J . Org. Chem., Vol. 64, No. 11, 1999
Freeman and Pugh
Sch em e 2
Sch em e 4
Sch em e 3
Sch em e 5
12a and 12b. In this mechanistic scheme a 13C label
would be at position 3 of the central benzene ring.
Alternatively, bicyclic carbene 6a (6b) could undergo
a 1,4 suprafacial alkyl shift to produce 18a (18b).
Cyclopropylcarbinyl to allylcarbinyl cleavage would gen-
erate carbene 19a (19b) (Scheme 5). Phenyl migration
from either would result in o-terphenyl with the deuter-
ium label solely in the ortho position (12b). The 13C label
in this example would be located at position 1 of the
center ring. Both the alkyl shift (6 f 18) and the 1,2
phenyl migration have literature precedence.8
The third mechanistic pathway is analogous to that
suggested by Dannenberg and Gross to explain the
carbenoid decomposition of a steroidal cyclohexadienone
tosylhydrazone.9 Consecutive phenyl and hydrogen mi-
grations generate carbene 20a (20b) (Scheme 6). In the
final step, carbene 20a would be expected to exhibit more
facile migration of the hydrogen over deuterium based
upon the deuterium isotope effect (kH/kD should be in the
range of 1.0-1.5).10 Allowing for the isotope effect, this
mechanism would lead to a ratio of 12a to 12b of 70-
75:25-30. The 13C label would end up at position 4 of
the central ring. The experimental results from the
deuterated study gave a product ratio of 31 ( 8.8:69 (
8.8 of 12a to 12b. On the basis of these results none of
the proposed mechanistic schemes could alone account
for the observed product ratio. At best it could be a
combination of different pathways.5 There are, however,
some points of concern in the deuterium tracer experi-
ment. The low incorporation of deuterium in the experi-
mental sample (42%) clouds the issue. This left a large
amount of nondeuterated o-terphenyl that complicated
the deuterium analysis which was based on natural
abundance 13C NMR analysis and geminal (13CCD)
isotope effects.
A reassessment of the deuterium labeling experiment
reveals that only Scheme 5 can be ruled out completely.
(8) (a) Kirmse, W. Carbene Chemistry, 2nd ed.; Academic Press:
New York, 1971; pp 457-462. (b) Baron, W. J .; DeCamp, M. R.;
Hendrick, M. E.; J ones, M., J r.; Levin, R. H.; Sohn, M. B. Carbenes;
Wiley: New York, 1973; pp 32-40.
(10) (a) Freeman, P. K.; Hardy, T. A.; Balyeat, J . R.; Wescott, L. D.,
J r. J . Org. Chem. 1977, 42, 3356. (b) Nickon, A.; Huang, F.; Weglein,
R.; Matsuo, K.; Yogi, H. J . Am. Chem. Soc. 1979, 96, 5264. (c) Kirmse,
W.; von Schultz, H. D.; Arold, H. J ustus Liebigs Ann. Chem. 1968,
711, 22.
(9) Dannenberg, H.; Gross, H. J . Tetrahedron 1965, 21, 1611.

4,4-Diphenylcyclohexa-2,5-dienylidene
J . Org. Chem., Vol. 64, No. 11, 1999 3949
Sch em e 6
Sch em e 7
Sch em e 8
Both Schemes 4 and 6 could theoretically give natural
abundance 13C NMR spectra that are very similar. With
this in mind, a labeling study employing 13C enhance-
ment at C-1 was carried out to clear up the mechanistic
picture.
Resu lts a n d Discu ssion
Syn th esis of 13C-En h a n ced Dip h en ylcycloh exa -
d ien ylid en e. Our first route to incorporate the 13C label
was to utilize acetic-1-13C acid as the synthetic precursor,
convert this to an acid chloride and then use Stille
coupling11 with tetravinyltin to synthesize methyl vinyl
ketone. All attempts at this reaction sequence led to
extremely low or no yields of desired product. Other
methods also based on the acid chloride (cuprate addition,
MnI2 coupling, and Grignard reagent chemistry) were
unsuccessful. We next focused our attention on the use
of a Mannich base product from the reaction of diethyl-
amine hydrochloride, acetone, and paraformaldehyde. By
using acetone-2-13C diluted with reagent grade acetone,
diethylamino-2-butanone (21) was synthesized in 60%
yield with a calculated 6.63% 13C enhancement (vide
infra) at the carbonyl carbon (Scheme 7). Adding 1 equiv
of iodomethane yielded the methiodide of diethylamino-
2-butanone (22). Diphenylacetaldehyde, the methiodide,
and base were combined to form the Robinson annulation
product 4,4-diphenylcyclohex-2-enone (23) in 60% yield.
To introduce the second double bond, an R-phenylseleno
ketone was synthesized followed by hydrogen peroxide
elimination, but again low yields prevented us from using
this method. Instead, heating 23 at reflux in the presence
of isopropenyl acetate formed the enol acetate (24) in 44%
yield. Typical yields from this reaction are 60-80%, but
unfortunately a slight excess of heat upon workup caused
reversion to starting material and subsequent repetition
of the synthetic step. Bromine was added to the enol
acetate to give 6-bromo-4,4-diphenycyclohex-2-enone (25)
in 89% yield. Dehydrohalogenation followed to yield 4,4-
diphenyl-2,5-cyclohexadienone (26) which was converted
to the tosylhydrazone (27) by adding tosylhydrazine. FAB
mass spectral analysis shows 13C enhancement to 6.55
( 0.98%. The imine carbon exhibits a 3.98-fold 13C
enhancement. The yield was 65% for the two steps. 4,4-
Diphenylcyclohexadienylidene (4) was generated by first
converting to the lithium salt with methyllithium and
then heating to 180 °C. After the thermal degradation
of the tosylhydrazone, o-terphenyl was isolated by a
combination of silica gel chromatography and preparative
gas chromatography.
An a lysis of th e La belin g Stu d y. Semiempirical AM1
calculations were carried out on the key entities in the
competing rearrangement pathways, and density func-
tional B3LYP/6-31G(d) calculations were employed for
nonphenylated analogues for the purpose of comparison
(Scheme 8). Given in this scheme are the relative ∆H°f
values (AM1) and electronic energies plus zero point
energies (B3LYP/6-31G(d)), respectively, in kcal/mol. The
competition would be between a skeletal rearrangement
to a bicyclocarbenoid species (Schemes 4 and 5) and a
1,2 phenyl migration (Scheme 6). If one looks at the
thermodynamic picture, a clear pathway leading to 20
is supported. This intermediate lies 43.24 kcal/mol below
6 and 18.90 kcal/mol below initial carbene 4 and is, in
(11) Stille, J . K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508.

3950 J . Org. Chem., Vol. 64, No. 11, 1999
Freeman and Pugh
F igu r e 2. 13C NMR spectra of 13C-enriched o-terphenyl.
Ta ble 1. Rela tive In ten sities of 13C NMR P ea k s
F igu r e 1. 13C NMR spectra of o-terphenyl standard.
chemical
shifta
relative peak size for
relative peak size for
standard o-terphenylb
13C enhanced o-terphenylb
Sch em e 9
126.44
127.47
127.85
129.89
130.59
140.59
141.53
0.534 ( 0.032
0.496 ( 0.049
1.000
1.221 ( 0.149
0.551 ( 0.045
0.198 ( 0.050
0.211 ( 0.010
0.562
2.081
1.000
0.963
0.507
0.117
0.129
a
b
Measured in ppm relative to TMS. Relative to the peak at
127.85 ppm.
fact, an isobenzene species.12,13 The pathway from 4 to 6
is endothermic by 24.34 kcal/mol. The stabilities of the
intermediates in the analogous nonphenylated rear-
rangements, relative to 3-carbena-1,4-cyclohexadiene,
provide a similar picture (Scheme 8).
C4′ and C5′. If Scheme 4 were in effect, the 13C label
would be located at C3′ and C6′. To keep mechanistic
choices simple, we have not considered above in Scheme
4 a phenyl migration in the opposite direction (16a f
17c). At this point, however, it is clear that since 16a f
17a does not occur, it is unlikely that 16a f 17c would
be operative (eq 1). Likewise, Scheme 5 would have given
enhancement at C1′ and C2′. On the basis of these
results, the only pathway in operation is Scheme 6. This
also reflects the thermodynamic picture revealed in the
AM1 and B3LYP/6-31G(d) calculations. With these new
findings in hand, we have clear evidence to support the
mechanism of Scheme 6, free of the ambiguity of the
deuterium study.
These results strongly suggest that the favored product
would be that formed from an initial phenyl migration
as outlined in Scheme 6. These computational results are
also in agreement with the experimental analysis. The
13C NMR chemical shift assignments of product o-ter-
phenyl were made by using tabulated data for substitu-
ent effects on benzene14 and by the effect of deuterium
at known positions.5 Experimentally the incorporation of
the deuterium at C3′ and C4′ led to a splitting of the 13C
signals at 130.5 (C3′, C6′) and 127.4 (C4′, C5′) ppm,
leaving four signals at 130.5, 130.4, 127.4, and 127.3 ppm
(Scheme 9). Figures 1 and 2 show the 13C NMR of
standard o-terphenyl and our 13C-enriched o-terphenyl
formed in the pyrolysis of the lithium salt of 27. To gain
an idea of the normal relative peak size, the 13C spectra
of seven standard solutions of o-terphenyl (1 M soln in
CDCl3) were obtained. Table 1 shows the relative peak
size as measured against the peak at 127.85 ppm for both
normal and 13C-enriched o-terphenyl.
Com p u ta tion a l Deta ils
Geometry optimizations for the phenylated substrates were
obtained using AM1 semiempirical calculations15 in the Spar-
tan 4.1.1 suite of programs.16 The density functional theory
module included in the Gaussian 94 suite of programs17 was
used, employing Becke’s three-parameter hybrid functional18
As can be seen from the 13C spectra on partially labeled
o-terphenyl, only the peak at 127.47 ppm shows clear
enhancement of the signal. This corresponds to enriched
(12) (a) Bettinger, H. F.; Schreiner, P. R.; Schaefer, H. F., III;
Schleyer, P. v. R. J . Am. Chem. Soc. 1998, 120, 5741. (b) Hopf, H.;
Berger, H.; Zimmermann, G.; Nu¨chter, U.; J ones, P. G.; Dix, I. Angew.
Chem., Int. Ed. Engl. 1997, 36, 1187. (c) Roth, W.; Hopf, H.; Horn, C.
Chem. Ber. 1994, 127, 1765. (d) Christl, M.; Braun, M.; Mu¨ller, G.
Angew. Chem., Int. Ed. Engl. 1992, 31, 473. (d) J anoschek, R. Angew.
Chem., Int. Ed. Engl. 1992, 31, 476.
(13) The geometry reported in ref 12a for isobenzene at the B3LYP/
DZP level is in close agreement with that at the B3LYP/6-31G* level.
(14) Levy, G. C.; Lichter, R. L.; Nelson, G. L. Carbon-13 Nuclear
Magnetic Resonance Spectroscopy, 2nd ed.; Wiley-Interscience: New
York, 1980; pp 111-112. (b) Pretsch; Clerc; Seibl; Simon. Spectral Data
for Structure Determination of Organic Compounds, 2nd ed.; Springer-
Verlag: Berlin, 1989; pp C120-C125.
(15) Dewar, M. J .; Thiel, W. J . Am. Chem. Soc. 1977, 99, 4499.
(16) Spartan IBM version 4.1.1. Wavefunction, Inc., Irvine, CA,
1991-1997.
(17) Frisch, M. J .; Trucks, G. W.; Schlegel, H. B.; Gill, P. M. W.;
J ohnson, B. G.; Robb, M. A.; Cheeseman, J . R.; Keith, T.; Petersson,
G. A.; Montgomery, J . A.; Raghavachari, K.; Al-Laham, M. A.;
Zakrzewski, V. G.; Ortiz, J . V.; Foresman, J . B.; Cioslowski, J .;
Stefanov, B. B.; Nanayakkara, A.; Challacombe, M.; Peng, C. Y.; Ayala,
P. Y.; Chen, W.; Wong, M. W.; Andres, J . L.; Replogle, E. S.; Gomperts,
R.; Martin, R. L.; Fox, D. J .; Binkley, J . S.; Defrees, D. J .; Baker, J .;
Stewart, J . P.; Head-Gordon, M.; Gonzalez, C.; Pople, J . A. GAUSSIAN
94, Revision B.2, Gaussian, Inc., Pittsburgh, PA, 1995.
(18) Becke, A. D. J . Chem. Phys. 1993, 98, 5648.

4,4-Diphenylcyclohexa-2,5-dienylidene
J . Org. Chem., Vol. 64, No. 11, 1999 3951
with the gradient-corrected correlation functional of Lee, Yang,
and Parr19 for the nonphenylated analogues using the 6-31G*
basis set.20 Once structures had converged, frequency calcula-
tions at the same level of theory were carried out to ensure
each molecule was an energy minimum.
mL) was placed in the dropping funnel and added quickly to
the sodium methoxide solution. The dropping funnel was then
charged with the cold methiodide (22) prepared from dieth-
ylamino-2-butanone (17.06 g, 119.1 mmol) as described above.
The methiodide was added over a period of 120 min. Stirring
was continued for 2 h at ice bath temperatures. The ice bath
was replaced by an oil bath and the mixture heated at reflux
for 90 min. The resultant orange mixture was cooled to room
temperature and transferred to a separatory funnel. A 10%
HCl solution was added until the aqueous layer was no longer
basic to litmus paper. Cold H2O (50 mL) was added, and the
two layers were separated. The aqueous layer was extracted
with cold Et2O (3 × 90 mL). The combined organic layers were
extracted once with a saturated sodium chloride solution.
Finally, the combined aqueous layers were washed once with
ether (90 mL). The organic layers were combined and dried
over sodium sulfate. The solvent was removed by rotary
evaporation, and an orange oil was collected. Upon cooling to
room temperature, crystals started to form in the oil. Cold
EtOH was added and immediately light-yellow crystals started
to form. The solution was gently warmed and then cooled in a
0 °C refrigerator for 3 h. Crystals were collected by vacuum
filtration and dried in the open air for 24 h. Cyclohex-2-enone
23 (17.75 g, 60%) was obtained: mp 90-91 °C; 1H NMR (300
MHz, CDCl3) δ 7.29 (m, 11H), 6.21 (d, 1H, J ) 10.26 Hz), 2.71
(t, 2H, J ) 6.48 Hz.), 2.42 (t, 2H, J ) 6.36 Hz).
Exp er im en ta l Section
Gen er al Meth ods. Solvents were purchased from Mallinck-
rodt Chemical and Fischer Scientific and used without further
purification. Reagent grade chemicals were purchased from
Aldrich Chemical.
2-13C-4-Dieth yla m in o-2-bu ta n on e (21). The procedure of
Wilds, Nowak, and McCaleb was followed.21 Diethylamine
hydrochloride (22.00 g, 200 mmol), paraformaldehyde (8.400
g, 280 mmol), acetone (70 mL), methyl alcohol (10 mL), 35%
HCl (0.25 mL), and acetone-2-13C (99% 13C at C-2) (4.00 g,
67.72 mmol) were added to an oven-dried 250 mL round-
bottom flask fitted with a reflux condenser and magnetic stir
bar. The mixture was heated for 12 h in a 70 °C oil bath at
which time a light-yellow solution remained. The mixture was
allowed to cool to room temperature. Fresh sodium hydroxide
solution (8.2 g, 5.4 M in H2O, 205 mmol) was prepared and
cooled in a refrigerator. The yellow reaction solution was
transferred to a separatory funnel, and the cold base was
added. Et2O (25 mL) was added, and the two layers were
separated. The aqueous layer was extracted with Et2O (2 ×
25 mL). The combined ether extracts were washed with a
saturated sodium chloride solution (2 × 20 mL). The combined
aqueous layers were washed with Et2O (2 × 20 mL); then the
combined ether layers were dried for 1 h over sodium sulfate.
The final solution was filtered and concentrated using a rotary
evaporator. Final purification was done by reduced pressure
spinning band distillation (12.5 Torr, 18 in. × ∼3/8 in. column
with jacket heated to 50-60 °C). The product was collected as
a light yellow to colorless liquid that is calculated to be 6.6%
labeled at position 2 (which is in agreement with the analysis
of tosylhydrazone 27, vide infra) (17.06 g, 60%): bp 72-75 °C
at 12.5 Torr; n24D ) 1.4300; 1H NMR (300 MHz, CDCl3) δ 2.69
(t, 2H, J ) 7.45 Hz.), 2.52 (t, 2H, J ) 7.23 Hz.), 2.45 (q, 4H, J
) 7.15 Hz.), 2.11 (s, 3H), 0.96 (t, 6H, J ) 7.15 Hz.).
2-13C-5,5-Dip h en yl-2-a cetoxy-1,3-cycloh exa d ien e (24).
The procedure of Moffett and Weisblat was followed.23 1-13C-
4,4-Diphenylcyclohex-2-enone (23) (17.5 g, 70 mmol), p-tolu-
enesulfonic acid monohydrate (0.9 g, 4.73 mmol), and isopro-
penyl acetate (70 mL) were placed in a 500 mL round-bottom
flask. The flask was fitted with a single-piece distillation
apparatus and placed in an oil bath. The solution was slowly
distilled (oil bath temperature of 115 °C) for 10 h, with periodic
replacement of the isopropenyl acetate. The dark amber
solution left in the pot was allowed to cool to room temperature
and left overnight. Solid NaHCO3 (5.50 g, 66 mmol) was added
to the mixture with stirring; then the solution was transferred
to a separatory funnel. The flask was washed with Et2O and
ice water, both of which were added to the separatory funnel.
The two-phase mixture was separated, and the aqueous layer
was washed with Et2O. The combined Et2O extracts were then
washed with a saturated NaCl solution. The combined aqueous
layers were washed with Et2O. The combined organic layers
were then dried briefly over sodium sulfate, filtered by vacuum
filtration, and then concentrated by rotary evaporation (50 °C,
∼10 Torr). The solution was transferred to a beaker, the flask
was washed with EtOH, and the wash was added to the
beaker. The resultant amber mixture was allowed to cool to
room temperature, and more EtOH (∼ 50 mL) was added. The
material was placed in a refrigerator for 2 h. Crystallization
was induced by scratching with a glass stirring rod. The light
tan crystals were collected by vacuum filtration and dried in
a vacuum oven for 2 h (∼10 Torr, 50 °C). 1H NMR analysis
showed about a 50/50 mixture of starting material (23) to
product (24). At this time the crystals were collected and placed
in a round-bottom flask. The isopropenyl acetate reaction was
run a second time as above. The amber reaction mixture was
allowed to cool to room temperature and then concentrated in
vacuo (∼3 Torr) to a volume of about 50 mL. Excess isopro-
penyl acetate was then removed carefully in vacuo at temper-
atures not exceeding 30 °C until crystals started to form. The
mixture was then transferred to a beaker, and cold Et2O was
added. The final solution was placed in a refrigerator for 3 h
at which time the crystals were collected by vacuum filtration
and dried. 1H NMR showed complete conversion to product.
The enol acetate 24 was collected as off-white crystals (8.93
2-13C-4-Dieth ylam in o-2-bu tan on e Meth iodide (22).Fresh-
ly distilled 2-13C-4-diethylamino-2-butanone (17.06 g, 119.1
mmol) was placed in a 50 mL round-bottom flask. The flask
was fitted with a pressure equalizing dropping funnel and
nitrogen inlet and then cooled to 0 °C in an ice bath. Methyl
iodide (17.06 g, 120.2 mmol) was added to the dropping funnel
and dripped into the amine slowly over the course of 30 min.
CAUTION: this is an extremely exothermic reaction. The
methyl iodide should be added slowly. After complete addition,
the mixture was allowed to sit for 2 h in the ice bath and then
an additional 2 h in a 0 °C refrigerator. Upon removal, the
semicrystalline methiodide was washed with cold Et2O (10 mL)
and the Et2O decanted. The Et2O wash was repeated (2 × 10
mL). The methiodide was dissolved in MeOH (50 mL) and
stored under nitrogen. No further purification was attempted.
1-13C-4,4-Dip h en ylcycloh ex-2-en on e (23). The general
procedure of J ohnson, Szmuszkovicz, Rogier, Hadler, and
Wynberg was followed.22 A magnetic stir bar and MeOH (100
mL) were added to a 500 mL round-bottom flask. Sodium
metal (4.11 g, 178.7 mmol) was slowly added to the flask, after
which time the flask was fitted with a pressure-equalizing
dropping funnel and nitrogen bubbler and cooled in an ice
bath. CAUTION: addition of the sodium too fast can lead to
a very vigorous reaction. After the sodium was dissolved,
diphenylacetaldehyde (23.55 g, 120.0 mmol) in benzene (100
1
g, 44%): mp 102-105 °C; H NMR (300 MHz, CDCl3) δ 7.25
(19) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 785.
(20) Bettinger, H. F.; Schleyer, P. v. R.; Schreiner, P. R.; Schaefer,
H. F. In Modern Electronic Structure Theory and Applications in
Organic Chemistry; Davidson, E. R., Ed.; World Scientific: Singapore,
1997; pp 89-170.
(m, 11H), 6.34 (d, 1H, J ) 10.07 Hz.), 5.90 (dd, 1H, J ) 2.11,
10.18 Hz.), 5.50 (dt, 1H, J ) 1.99, 4.63 Hz.), 3.01 (d, 2H, J )
4.65 Hz.), 2.11 (s, 3H).
1-13C-6-Br om o-4,4-d ip h en ylcycloh ex-2-en on e (25). A
modified procedure of Zimmerman, Hackett, J uers, McCall,
(21) Wilds, A. L.; Nowak, R. M.; McCaleb, K. E. Organic Syntheses;
Wiley: New York, 1963; Collect. Vol. 4, p 281.
(22) J ohnson, W. S.; Szmuszkovicz, J .; Rogier, E. R.; Hadler, H. I.
Wynberg, H. J . Am. Chem. Soc. 1956, 78, 6285.
(23) Moffett, R. B.; Weisblat, D. I. J . Am. Chem. Soc. 1952, 74, 2183.

3952 J . Org. Chem., Vol. 64, No. 11, 1999
Freeman and Pugh
and Schro¨der was followed.24 5,5-Diphenyl-2-acetoxy-1,3-cy-
clohexadiene (24) (8.24 g, 29 mmol) was placed in a 250 mL
round-bottom flask. To this was added CCl4 (50 mL), and the
flask was fitted with a magnetic stirrer and pressure equal-
izing dropping funnel. The flask was then cooled in an ice bath.
Cold bromine (1.5 mL, 31 mmol) was added dropwise to the
mixture over the course of 60 min. The solution was stirred
at 0 °C for 3 h. Upon removal, the dark yellow mixture was
washed with a saturated sodium bicarbonate solution (60 mL).
The two layers were separated, and the aqueous layer was
washed with Et2O (2 × 50 mL). The combined organic layers
were dried over sodium sulfate for 30 min. The solution was
filtered by vacuum filtration and then concentrated by rotary
evaporation to a dark yellow oil. The oil was stirred with ether
and then placed in a 0 °C refrigerator. Crystallization was
induced by scratching the surface of the beaker with a glass
stir rod. The material was left in the refrigerator overnight.
Upon removal, the off-white crystals were collected via vacuum
filtration and dried. R-Bromo ketone 25 was obtained (8.33 g,
89%): mp 102-105 °C; 1H NMR (300 MHz, CDCl3) δ 7.27 (m,
10H); 6.32 (d, 1H, J ) 10.18 Hz), 4.71 (dd, 1H, J ) 13.52, 4.69
Hz), 3.26 (ddd, 1H, J ) 13.20, 4.70, 2.34 Hz), 3.17 (t, 1H, J )
13.46 Hz).
the stirring was turned on. Upon mixing, the tosylhydrazone
(27) dissolved, and a light yellow solution remained. The
solution allowed to stir for 30 min. A 5 cm3 Leur tip syringe
was flushed with dry nitrogen and used to transfer 2 mL of
methyllithium (1.4 M in Et2O, 2.8 mmol) to the round-bottom
flask. After about 1 min, the yellow solution became cloudy
and a white precipitate started to form. After 5 min of stirring,
additional methyllithium (0.2 mL) was added. A deep gold color
appeared at the top of the mixture, showing evidence of dianion
formation. The mixture was then stirred for 2 h. At that time
the flask was opened and the THF blown out with a stream of
dry nitrogen. The rest of the THF was removed by pumping
on the flask for 2 h at 0.8 Torr. A white solid coating was left
on the walls and bottom of the flask. This was gently scraped
off the sides with a microspatula and broken up into smaller
pieces. A glass decomposition apparatus was then set up
consisting of the original round-bottom flask fitted with a gas
outlet and two ground glass stoppers. The gas outlet was fitted
with a 8 in. length of Tygon tubing that was attached to a
glass trap cooled in dry ice/ethyl alcohol. Another 8 in. length
of Tygon tubing was attached from the first trap to a second.
An outlet tube from the second trap was attached to a mineral
oil bubbler. The round-bottom flask was placed in an oil bath,
and the lithium salt was heated to 175 °C. Nitrogen evolution
was observed at about 130 °C and was complete by 140 °C.
The material was heated at 175 °C for 10 min, and then the
oil bath was removed and the brown-orange residue was
allowed to cool to room temperature. Chloroform (50 mL) was
added first to the flask and then the contents were transferred
to a separatory funnel. The chloroform layer was washed with
water (3 × 60 mL). The aqueous layer was washed with
chloroform (1 × 50 mL). The combined chloroform layers were
washed with saturated NaCl (1 × 50 mL) and then dried
overnight over sodium sulfate. The dark orange solution was
then filtered by vacuum filtration and concentrated by rotary
evaporation. A dark orange oil (0.72 g) was collected.
Sep a r a tion a n d An a lysis of o-Ter p h en yl (12). The oil
from the tosylhydrazone decomposition was brought up in
dichloromethane (2 mL) and then chromatographed using flash
chromatography techniques25 on a 2.5 cm diameter × 20 cm
silica gel column (Aldrich chemical silica gel, Merck, grade 60,
70-230 mesh, 60 Å) eluting with straight dichloromethane
until 19 25 mL test tubes of solution had been collected. The
final polar band was eluted from the column with MeOH.
Analytical thin-layer chromatography (TLC) of each fraction
using Spectrum precoated silica gel 60 F254 and dichlo-
romethane solvent gave the appearance of four bands in
fractions 3, 4, and 5 (Rf values 0.20, 0.37, 0.49, and 0.80
respectively), one band in fractions 6-12 (Rf 0.20), and one
band in fractions 13-15 (Rf 0.00). The last four fractions
contained the polar residue from the MeOH wash. Capillary
gas chromatography (Varian instruments 3400 gas chromato-
graph fitted with a SE-54 30m capillary column; initial
temperature 140 °C for 1 min and then ramped at 10 °C/min
to 240 °C and held for 10 min, He carrier gas-head pressure
10 psi) was used to identify some of the products in the silica
gel fractions. o-Terphenyl, p-terphenyl, and biphenyl were
identified as three of the six major peaks in fractions 3-5 by
coinjection with known standards and comparison of retention
times (10.280, 13.940, and 4.774 min, respectively). o-Terphen-
yl was separated by preparative gas chromatography (Varian
3700 gas chromatograph fitted with a 3/8 in. 10% OV-17 +
10% SE-30 on Chromosorb W 45/60 mesh, 3 m column, He
carrier gas 40 mL/min) by collecting the peak at retention
time 7.30 min with a glass collection tube cooled in dry ice/
2-propanol. The o-terphenyl was washed from the collection
tube with a small amount of dichloromethane and then
analyzed via capillary GC as described above. The impurities
in each sample were held at 10% or below. If the amount was
greater, the mixture was separated via preparative GC again.
The separation was complicated by the fact that there was an
impurity that coeluted with almost exactly the same retention
time as o-terphenyl. This impurity was minimized by collecting
1-13C-4,4-Dip h en yl-2,5-cycloh exa d ien on e (26). The pro-
cedure of Zimmerman, Hackett, J uers, McCall, and Schro¨der
was followed.20 6-Bromo-4,4-diphenylcyclohex-2-enone (25)
(5.60 g, 17.1 mmol), lithium carbonate (4.36 g, 59 mmol),
lithium bromide (4.95 g, 57 mmol), and dimethylformamide
(50 mL) were placed in a 200 mL round-bottom flask. A
magnetic stir bar was added, and the flask fitted with a reflux
condensor and nitrogen bubbler. The solution was heated to
170 °C with an oil bath and stirred at reflux for 11 h under
nitrogen in a darkened hood. After the mixture cooled, a white
solid was observed in the bottom of the flask. The dark amber
solution was filtered by vacuum filtration to remove the
inorganic salts. It was heated with a warm water bath and
concentrated in vacuo. The thick amber residue was mixed
with Et2O. Immediately crystals formed. These were dissolved
by the addition of MeOH. The solution was transferred to a
separatory funnel, more Et2O was added, and the solution was
washed with H2O. The layers were separated, and the organic
layer was washed with saturated sodium chloride. The com-
bined aqueous layers were washed with Et2O and then with
benzene. The combined organic layers were dried over sodium
sulfate, concentrated by rotary evaporation, and crystallized
from EtOH. Dienone 26 was collected as light brown crystals
1
(3.20 g, 76%): mp 122-124 °C; H NMR (300 MHz, CDCl3) δ
7.30 (m, 12H), 6.34 (d, 2H, J ) 10.20 Hz.).
1-13C-4,4-Dip h en yl-2,5-cycloh exa d ien on e Tosylh yd r a -
zon e (27). p-Toluenesulfonhydrazide (2.23 g, 12 mmol), 1-13C-
4,4-diphenyl-2,5-cyclohexadienone (26) (2.95 g, 12 mmol), and
a magnetic stir bar were placed in a 100 mL round-bottom
flask. MeOH (50 mL) was added, and the solution was heated
at reflux (70 °C oil bath) for 4 h. The mixture was allowed to
cool to room temperature and then placed in a 0 °C refrigerator
overnight. Upon removal, light-yellow crystals had formed.
Tosylhydrazone 27 was obtained (4.24 g, 85%): mp 139-140
1
°C; H NMR (300 MHz, CDCl3) δ 7.87 (d, 2H, J ) 8.18 Hz.),
7.23 (m, 12H), 6.74 (dd, 1H, J ) 10.29, 2.26 Hz.), 6.54 (dd,
1H, J ) 10.29, 1.59 Hz.), 6.47 (dd, 1H, J ) 10.19, 2.29 Hz.),
6.39 (dd, 1H, J ) 10.18, 2.07 Hz.), 2.42 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 146.2, 144.2, 143.9, 140.6, 135.3, 129.7, 128.7,
128.1, 127.9, 127.1, 124.4, 113.4, 53.8, 21.6. The imine carbon
(146.2 ppm) is 3.98-fold enhanced relative to the normal signal.
FAB mass spectrometry: 13C enhancement is 6.55 ( 0.98%.
Decom p osition of th e Lith iu m Sa lt of 1-13C-4,4-Dip h en -
yl-2,5-cycloh exa d ien on e Tosylh yd r a zon e (27). The title
tosylhydrazone (27) (0.94 g, 2.27 mmol), THF (20 mL), and a
magnetic stir bar were placed in a 100 mL three-necked,
round-bottom flask. The flask was fitted with a nitrogen inlet,
septum, and glass stopper. The nitrogen flow was started, and
(24) Zimmerman, H. E.; Hackett, P.; J uers, D. F.; McCall, J . M.;
Schro¨der, B. J . Am. Chem. Soc. 1971, 93, 3653.
(25) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923.

4,4-Diphenylcyclohexa-2,5-dienylidene
J . Org. Chem., Vol. 64, No. 11, 1999 3953
only the front portion of the o-terphenyl peak. A final 13C NMR
(400 MHz, CDCl3) spectrum was gathered by a Bru¨ker am400
spectrometer fitted with a Nalorac 3 mm microprobe. 13C
NMR: δ 141.5, 140.6, 130.6, 129.9, 127.9, 127.5, 126.4. The
aromatic carbon 4 of the central ring (127.5 ppm) is 4.07-fold
enhanced relative to the normal signal.
Ack n ow led gm en t. Support from the Oregon State
University Research Council, the MRF fund, and NIE-
HS is gratefully acknowledged.
J O982400Z