Facile formation of benzene from a novel cyclohexane derivative

Article abstract of DOI:10.1016/S0040-4039(01)00745-6

Upon acidification, benzene forms at room temperature from the novel 1,3,5-cis-trisubstituted cyclohexane wherein the substituents are the azido phosphine cage moieties N₃P(MeNCH₂CH₂)₃N. The dominant reaction in the decomposition of this unusually thermally stable intermediate in the presence of HA is the formation of nitrogen and the salt [H₂N=P(MeNCH₂CH₂)₃N]A in addition to benzene. Evidence for a transannulated cage intermediate is presented.

Full text of DOI:10.1016/S0040-4039(01)00745-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 4449–4451
Facile formation of benzene from a novel cyclohexane derivative
Xiadong Liu,a Guangtao Zhanga,b and John G. Verkadeb,*
aDionex Corp., 1228-T Titan Way, PO Box 3603, Sunnyvale, CA 94088, USA
bDepartment of Chemistry, Iowa State University, Ames, IA 50011, USA
Received 6 September 2000; revised 1 May 2001; accepted 3 May 2001
Abstract—Upon acidification, benzene forms at room temperature from the novel 1,3,5-cis-trisubstituted cyclohexane wherein the
substituents are the azido phosphine cage moieties N3P(MeNCH2CH2)3N. The dominant reaction in the decomposition of this
unusually thermally stable intermediate in the presence of HA is the formation of nitrogen and the salt
[H2NꢀP(MeNCH2CH2)3N]A in addition to benzene. Evidence for a transannulated cage intermediate is presented. © 2001
Published by Elsevier Science Ltd.
The aromatization of cyclohexane derivatives at room
temperature is to our knowledge unknown in the litera-
ture. Such a transformation has been reported for
cyclohexanedione dioximes upon treatment with
polyphosphoric acid at 95–105°C1 and in the oxidative
aromatization of substituted cyclohexanes with
Pd(OAc)2 and Na2Cr2O7 in CF3CO2H at 90°C.2 Tem-
peratures well above this range are required for aroma-
tizations of cyclohexanes over bismuth phosphate,3
stannic oxide,3 a platinum complex,4 and zeolitic5 cata-
lysts. Here we report that 1 undergoes a novel reaction
with PhCO2H to form benzene (in 56% yield) within 1
h. Although a prohibitively expensive synthesis of ben-
zene, this transformation represents the first example of
PR3
N
R
N
R
Me
Ph
CH2Ph
Polymer
N
N
Me
Me
Me
Me
N
N
N
Me
PR3
Me
N
N
N
N
P
N
3
P
N
N
N
N
N
N
= PR3 = 2
1
R3P
PR3
H
N
N
PR3
N
P
R
R
R
N
PR3
5
4
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Published by Elsevier Science Ltd.
PII: S0040-4039(01)00745-6

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X. Liu et al. / Tetrahedron Letters 42 (2001) 4449–4451
the aromatization of a cyclohexane derivative under
very mild conditions.
stable 1:1 adducts in solution,8 while strong acids cleave
such compounds to the corresponding amine and phos-
phine oxide.9 There is, however, a report describing the
reaction of triphenylmethyl azido triphenylphosphine
with acetic acid that gives N2, Ph3CO2CH3 and
Ph3PꢀNH.10 In this reaction Ph3C+ was postulated to
be an intermediate, as we believe is similarly the case in
our reaction (D in Scheme 1). However, in this scheme
carbocation formation facilitates proton abstraction by
the product base 5 to form a CꢀC bond.
The reaction of
3 equiv. of 2 with cis-1,3,5-
triazidocyclohexane6 in MeCN at 0°C in MeCN gave
the triazido derivative 1 as an isolable thermally stable
Staudinger intermediate, rather than the expected
iminophosphine 4. Compound 1 is very stable to ther-
molytic decomposition to the corresponding tris-
iminophosphine derivative 4 even at 100°C/0.5 Torr for
10 h or in refluxing toluene for 24 h.
NMR studies showed that 1 does not undergo decom-
position in the presence of acid at −30°C at an observ-
able rate, although it does protonate. Thus, addition of
PhCO2H to a solution of 1 in CD3CN led to an initial
dramatic upfield shift of the 31P NMR resonance of the
reaction mixture from 37.2 ppm to an asymptotically
reached value of −11.0 ppm after 22.4 equiv. of
PhCO2H had been added. This upfield shift strongly
suggests that protonation in a rapidly established equi-
librium is accompanied by the formation of species
containing five-coordinated phosphorus arising from
transannulation in the cage moieties. That such
transannulation plays a role in the excellent leaving
group properties exhibited by the cage moieties in 1 is
strongly supported by the behavior in the presence of
acids of its acyclic analogue 4 (R=NMe2) which reacts
about ten times slower and is also more susceptible to
nitrogen evolution thermolytically when treated with
acids at room temperature.
The Staudinger reaction is a two-step process involving
the initial electrophilic addition of an alkyl or aryl azide
to a PIII center followed by N2 elimination from the
intermediate phosphazide A to give the iminophosphine
B in reaction l.7 Steric hindrance at the PIII center does
not interfere with the electrophilic addition step, but it
does suppress decomposition, since steric requirements
in the four-membered ring transition state are much
more rigorous than those in the addition transition
state.7 Donor character on the part of the PIII sub-
stituents stabilizes phosphazides,7 and this factor appar-
ently also operates in 1 to give it thermal stability. The
unusual resistance of 1 to thermolysis may be enhanced
by the rigidity of the cage structure, which by virtue of
the planar geometry around the MeN nitrogens, main-
tains a methyl group in close proximity to the phospho-
rus–azido linkage.
R3P
NR'
R3P=NR' + N2
R3PN3R'
R3P + N3R'
(1)
N
N
B
A
When 1 was treated with acids such as PhCO2H,
CH3CO2H, or CF3CO2H in CH3CN at room tempera-
ture, an exothermic reaction accompanied by the rapid
formation of N2 (confirmed by GC–MS) and benzene
To better understand the mechanism of benzene forma-
tion in our reaction, we followed it over time by ESI
mass spectroscopy. During the reaction of 1 with
PhCO2H, two intermediates [6H]+ (m/z=597) and
[7H]+ (m/z=338) were detected, which disappeared
upon reaction completion, while the product [5H]+ (m/
z=232) increased over time. Two additional species
[8H]+ (m/z=541) and [9H]+ (m/z=310) were observed
as minor products.
1
(confirmed by H NMR and GC mass spectroscopies)
took place. In the case of PhCO2H, benzene was
formed in 56% yield (using toluene as a reference in the
GC–MS experiment) within 1 h. Upon evaporation of
the reaction mixture to dryness, crude [5H]PhCO2 was
isolated. Upon deprotonation of this salt with KOtBu
in THF, the iminophosphine 5 was obtained.
These observations are consistent with the reaction
pathway shown in Scheme 1. The reaction begins with
protonation of the exocyclic PꢁN nitrogen atom, which
activates N2 elimination to give 5 and a carbocation.
In contrast to our observation with 1, weak acids have
been reported to combine with azido phosphines to give
+
H
D
+
H+
+
N
N
R3P NH2
+
N
+N
R3P NH
N
N
[5H]+
5
+
R3P
H
R3P
N2
C
Scheme 1.

X. Liu et al. / Tetrahedron Letters 42 (2001) 4449–4451
4451
+NH
NH+
C
N
+
N2
N
PR3
PR3
F
E
Scheme 2.
N
References
N N
PR3
N
N N
PR3
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N
N
6
7
N
R3P
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N
PR3
9
8
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Then 5 serves as a base that quickly extracts a proton
from the b carbon in the cyclohexane moiety to gener-
ate a new CꢀC bond. To gain further support for this
mechanism, the proposed intermediate 6 was synthe-
sized.11 As expected, treatment of 6 with PhCO2H gave
the same products as were observed with 1.
The formation of impurities [8H]+ and [9H]+ in the
reaction of 1 with PhCO2H may result from the com-
petitive side reaction shown in Scheme 2. After proto-
nation, a four-membered ring transition state E could
form by rearrangement, followed by evolution of N2 to
give the protonated iminophosphine F.
11. The formation of 3,5-cis-diazidocyclohexa-1-ene was
1
observed in the present work as a minor product by H
NMR spectroscopy during the synthesis of 1,3,5-cis-tri-
azidocyclohexane. This mixture, when subjected to silica
gel column chromatography, gave 3,5-cis-diazidocyclo-
hexa-1-ene in 10% yield. This product was combined with
2 in a 1:2 molar ratio in MeCN at 0°C, and then the
reaction mixture was stirred at ambient temperature for 3
h. After evaporating the solvent and washing the residue
with ether, compound 6 was obtained as a white solid in
85% yield.
Acknowledgements
This work was supported by the NSF and the Donors
of the PRF administered by the American Chemical
Society. The authors would like to thank Dr. N. Thiru-
pathi for experimental assistance.