Phototransposition reactions of methyl-substituted benzotrifluorides: Proof of the role of trifluoromethyl-substituted carbon

Article abstract of DOI:10.1021/jo0205715

Irradiation in acetonitrile of any one of the six isomers of dimethylbenzotrifluoride 8 resulted in efficient photoisomerization to the others. The dominant processes in these phototransposition reactions divides the isomers into two triads. The first consists of 8-2,6 (2,6-dimethylbenzotrifluoride), 8-2,3, and 8-3,4; the second consists of 8-3,5, 8-2,4, and 8-2,5. Moreover, irradiation of 2,6-dideuterio-4-methylbenzotrifluoride 5-d₂ resulted in formation of 5,6-dideuterio-3-methylbenzotrifluoride 6-d₂. These observations demonstrate that it is the trifluoromethyl-substituted carbon that is the migratory one in these reactions.

Full text of DOI:10.1021/jo0205715

SCHEME 1. P r op osed Mech a n ism for th e
P h ototr a n sp osition in Aceton itr ile a n d th e
P h otoa d d ition in TF E of th e Meth yben zon itr iles
P h ototr a n sp osition Rea ction s of
Meth yl-Su bstitu ted Ben zotr iflu or id es:
P r oof of th e Role of
Tr iflu or om eth yl-Su bstitu ted Ca r bon
Dayal DeCosta† and J ames Pincock*,‡
Department of Chemistry, University of Colombo,
Colombo, Sri Lanka, and Department of Chemistry,
Dalhousie University, Halifax,
Nova Scotia, Canada B3H 4J 3
james.pincock@dal.ca
Received August 28, 2002
Abstr a ct: Irradiation in acetonitrile of any one of the six
isomers of dimethylbenzotrifluoride 8 resulted in efficient
photoisomerization to the others. The dominant processes
in these phototransposition reactions divides the isomers
into two triads. The first consists of 8-2,6 (2,6-dimethylben-
zotrifluoride), 8-2,3, and 8-3,4; the second consists of 8-3,5,
8-2,4, and 8-2,5. Moreover, irradiation of 2,6-dideuterio-4-
methylbenzotrifluoride 5-d2 resulted in formation of 5,6-
dideuterio-3-methylbenzotrifluoride 6-d2. These observations
demonstrate that it is the trifluoromethyl-substituted carbon
that is the migratory one in these reactions.
Recently, we have published a set of papers1-4 on the
phototransposition reactions of substituted benzenes and
the photoaddition of 2,2,2-trifluoroethanol (TFE) to the
same isomers. The three methylbenzonitriles 1 (para), 2
(meta), and 3 (ortho) were examined the most exten-
sively.1 The results are summarized in Scheme 1.
the cyano and TFE groups endo. No phototransposition
was observed in TFE. Second, irradiation of 1-d2, which
has all the carbons labeled with a substitutent, resulted
in 2-d2 and 3-d2, specifically labeled as in eq 1.1 Other
Irradiation in acetonitrile of either 1, 2, or 3 results in
formation of the other two isomers, Scheme 1, although
with quite different efficiencies (relative reactivity para/
meta/ortho ) 32:4:1). The mechanism proposed for these
excited singlet-state reactions involved formation of
bicyclo[3.1.0]hex-3-ene-2,6-diyl singlet biradicals/zwitter-
ions, which allows the cyano-substituted carbon to mi-
grate around the periphery of the other five carbons and
collapse to any of the three isomers. The fact that the
cyano-subsituted carbon was the critical one in these
phototransposition reactions was demonstrated by two
different experiments. First, as also shown in Scheme 1,
irradiation of the para and meta isomers in TFE resulted
in alcohol addition. The products formed, 6-cyanobicyclo-
[3.1.0]hex-3-en-1-yl derivatives 4a and 4b, all resulted
from protonation by TFE on the cyano-substituted car-
bon. Six of the eight possible regio- and stereoisomers
were obtained, the missing ones being those with both
deuterated isomers would be obtained if carbons other
than the cyano-substituted one were involved in the
rearrangement. Because these reactions are providing
fundamental information about changes in charge dis-
tribution and geometry that occur on excitation of
substituted benzenes to S1, we completed a survey of
other substitutents.4 In general, electron-withdrawing
groups are required to make the phototransposition
efficient. The methylbenzotrifluorides 5, 6, and 7 are
particularly interesting for two reasons. First, all three
reach a photostationary state composition of ortho/meta/
para ) 7:32:61 that is essentially the reverse of that of
the methylbenzonitriles (ortho/meta/para ) 77:20:3).1
Second, they reach this photostationary state about
10 times faster than 4-methylbenzonitrile. We inferred
from these results that, by analogy to the nitrile substi-
* To whom correspondence should be addressed. Phone: 902-494-
3324. Fax: 902-494-1310.
† University of Colombo.
‡ Dalhousie University.
(1) MacLeod, P. J .; Pincock, A. L.; Pincock, J . A.; Thompson, K. A.
J . Am. Chem. Soc. 1998, 120, 6443-6450.
(2) Foster, J .; Pincock, A. L.; Pincock, J . A.; Thompson, K. A. J . Am.
Chem. Soc. 1998, 120, 13354-13361.
(3) Foster, J .; Pincock, A. L.; Pincock, J . A.; Rifai, S.; Thompson, K.
A. Can. J . Chem. 2000, 78, 1019-1029.
(4) Howell, N.; Pincock, J . A.; Stefanova, R. J . Org. Chem. 2000,
65, 6173-6178.
10.1021/jo0205715 CCC: $22.00 © 2002 American Chemical Society
Published on Web 11/23/2002
9484
J . Org. Chem. 2002, 67, 9484-9487

TABLE 1. P h otolysis of Dim eth ylben zotr iflu or id es 8 in
Aceton itr ile
major products
time for 10%
and their ratio
isomer
conversion (min)
at low conversion
leakage
8-2,6
8-2,3
8-3,4
8-3,5
8-2,4
8-2,5
80
20
665
130
30
8-2,3/8-3,4 ) 10
8-3,4/8-2,6 > 100
8-2,3/8-2,6 > 100
8-2,4/8-2,5 ) 12
8-3,5/8-2,5 ) 1.6
8-2,4/8-3.5 > 50
8-2,5 ) 8%
8-3,5 ) 8%
8-3,4 ) 6%
8-2,3 ) 18%
500
tuted cases, that the trifluoromethyl-substituted carbon
is the migratory one. However, although the two groups
are both electron withdrawing (σ ) 0.66 [4-CN]; σ ) 0.54
[4-CF3]), the former has a conjugative effect that the
latter does not.
F IGURE 1. Phototransposition of 2,4-dimethylbenzonitrile in
acetonitrile.
To prove whether the one carbon is critical for the
rearrangement of the methylbenzotrifluorides as in the
mechanism proposed in Scheme 1 for the methylbenzoni-
triles, we now report the results of two different experi-
mental tests. The first used the six isomeric dimethyl-
benzotrifluorides 8 and the second, deuterated 4-methyl-
benzotrifluoride 5-d2.
SCHEME 2. P h ototr a n sp osition Rea ction s of th e
Six Isom er ic Dim eth ylben zon itr iles 8 in
Aceton itr ilea
P h otoch em istr y of th e Six Isom er s of Dim eth yl-
ben zotr iflu or id e 8 in Aceton itr ile. The six compounds
were synthesized from the corresponding bromides by a
method described previously5 for 8-2,6; MS, 1H NMR, 13
C
NMR, 19F NMR, and HRMS are given in the Supporting
Information. Irradiation of each of the isomers in aceto-
nitrile using a low-pressure Hg lamp (254 nm) resulted
in conversion to the other isomers as followed by GC/
FID. The results are summarized in Table 1, and a
typical conversion plot is shown in Figure 1.
From the results in Table 1, the isomers react with
different efficiencies, the time for 10% conversion of the
starting material varying from 20 min (8-2,3) to 500 min
(8-2,5). Moreover, as Figure 1 indicates, the major
products for each of the substrates divide the six com-
pounds into two triads, Scheme 2. One traid consists of
8-2,6, 8-2,3, and 8-3,4; the other of 8-3,5, 8-2,4, and 8-2,5.
By measuring yields at very low conversion (<5%),
product ratios for each of the isomers could be obtained
(Table 1). For some cases, only lower limits for these
values could be estimated because overlapping peaks in
the GC traces prevented the reliable quantitation of the
a
Relative efficiencies for each process are given by the reaction
arrow.
very small peaks growing in beside the very large ones.
Using these product ratios and the times for 10% conver-
sion of each substrate, the relative efficiency of the twelve
possible conversions were estimated, arbitrarily scaled
to 4500 for the fastest process, conversion of 8-2,3 to 8-3,4.
These values are shown over each reaction arrow in
(5) Van der Boom, M.; Ben-David, Y.; Milstein, D. J . Am. Chem.
Soc. 1999, 121, 6652-6656.
J . Org. Chem, Vol. 67, No. 26, 2002 9485

Scheme 2. This very large range of reactivities means
that the less reactive compounds would likely be consid-
ered to be unreactive unless one were specifically looking
for phototranspositions.
The low efficiency of the leakage processes indicates that
the quantum yield of phototransposition for the methyl-
benzotrifluorides is 5-10 times more efficient than that
reported for m-xylene (0.01).9
The fact that the major photochemical process is
conversion within the triads shown in Scheme 2 indicates
that the mechanism does indeed proceed through two
triads of bicyclic diradicals that are trifluoromethyl-
substituted at C6. One triad 9a -c allows interconversion
of 8-2,6, 8-2,3, and 8-3,4; the other, 10a -c, allows
interconversion of 8-3,5, 8-2,5, and 8-2,4. The same
mechanistic proposal has been advanced by us previously
for the dimethylbenzonitriles4 where the cyano-substi-
tuted carbon is at C6 (as in Scheme 1 for the mono-
methylbenzonitriles) and in the gas-phase phototrans-
position reactions of the dimethylpyridines where the
nitrogen of the pyridine served the role of the migratory
atom.6
We have examined the phototransposition reactions of
the xylenes in acetonitrile as solvent3 in more detail than
previous reports.7,9 The relative reactivity of the three
isomers is 1:1.4:0.3 for ortho/meta/para and the primary
product ratios are meta/para ) 11:1 for ortho, ortho/para
) 6.0:1 for meta and meta/ortho > 25:1 for para. Thus
the most reactive isomer is the meta one with the ortho
one reacting somewhat more slowly. Therefore, as ex-
pected and indicated in Scheme 2, three of the leakage
processes involve reaction of a meta xylene isomer, i.e.,
8-2,6, 8-3,5, and 8-2,4; the fourth involves reaction of an
ortho xylene derivative, namely 8-3,4.
The efficiency of these reactions must be determined
by two quite different factors. The first is how efficiently
the excited-state undergoes the required geometric changes
to convert it to the bicyclic diradicals 9 and 10. If the
barrier for this process is high, then other nonproductive
excited-state processes (fluorescence, internal conversion,
intersystem crossing) likely dominate. The second re-
quired step is migration of the trifluoromethyl-substi-
tuted carbon around the periphery of the other five
allowing interconversion of the three isomeric intermedi-
ates in the two sets 9 and 10. If the barrier to the latter
steps is high then, even if the intermediates 9 and 10
are formed, no reaction will be observed. The process will
just be one mode of internal conversion. With the limited
evidence available, determining whether one or the other
of these two possibilities is the more important one is
not posssible. However, a tentative proposal is possible
on the basis of the results for photolysis of the isomers
of 8 in TFE.
All six of the isomers react in TFE to give products
that clearly result from alcohol addition (GC/MS, molec-
ular ion m/z ) 274). No phototranspositions were ob-
served. All gave complex mixtures, with 8-2,3 being
typical with four major products accounting for around
65% of the yield and more than a dozen others constitut-
ing the rest. Presumably, these addition products are
similar to those shown in Scheme 1 for the methylben-
zonitriles but we were unable to characterize them
further. Even simply evaporating the solvent gave samples
whose 1H NMR spectra showed no assignable signals but
rather broad bands extending over ranges of δ 1-3 and
δ 4.5-4.0 suggesting oligomers or polymers. We had
previously observed the same difficulties characterizing
TFE addition products for the three monomethylbenzo-
trifluorides and trifluoromethylbenzene itself.3
However, the photoreactions in TFE did provide evi-
dence on their relative reactivity. As in the phototrans-
position reactions, the least reactive isomers were again
8-3,4 and 8-2,5. This suggests that formation of the
bicyclic diradical intermediates 9 or 10 is slow in both
solvents. After this formation, they either isomerize
(acetonitrile) or are trapped (TFE).
Because of the symmetry of the intermediate/transition
state for the migration of two of the intermediates,
namely 9c and 10c, some phototranspositions will be
invisible. For instance, both 8-3,4 and 8-2,5 can undergo
transposition reactions that switch a trifluoromethyl-
substituted carbon with a neighboring hydrogen-sub-
situted carbon in a process that does not result in
formation of a new isomer. Therefore, the efficiency of
reactivity for the two compounds could be greatly under-
estimated.
As indicated in Table 1, “leakage” occurs from one triad
to the other. This is shown graphically in Figure 1 where
formation of 8-2,3 from 8-2,4 occurs with a yield of 18%
at low conversion. This is the highest yield of the leakage
process, the others being under 10%. Because 8-2,3 is the
most reactive isomer of the set of six, it very rapidly
undergoes its own photochemistry so that 8-3,4 is formed.
These leakage pathways, shown in Scheme 2, all involve
phototransposition of a methyl-substituted carbon. This
is not unexpected because the substrates 8 can be
regarded as trifluoromethyl-substituted xylenes and
historically, the xylenes were among the first substrates
where phototranspositions were observed.7 In fact, this
discovery lead to the proposal that substituted benz-
valenes were important intermediates in aromatic pho-
totransposition reactions and eventually to the photo-
chemical preparations of benzvalene from benzene itself.8
Th e P h otoch em istr y of 4-Meth ylben zotr iflu or id e-
d 2 (5-d 2). This compound was synthesized starting from
(6) Pavlik, J . W.; Kebede, N.; Thompson, M.; Day, A. C.; Barltrop,
J . A. J . Am. Chem. Soc. 1999, 121, 5666-5673.
(7) Wiltzbach, K. E.; Kaplan, L. J . Am. Chem. Soc. 1964, 86, 2307-
2308.
(8) Wilzbach, K. E.; Ritscher, J . S.; Kaplan, L. J . Am. Chem. Soc.
1967, 89, 1031-1032.
(9) Anderson, D. J . Phys. Chem. 1970, 74, 1686-1690.
9486 J . Org. Chem., Vol. 67, No. 26, 2002

4-methylanilinium hydrochloride, exchanging the protons
ortho to the ammonium group with D2O as described
previously,1 followed by diazotization and conversion to
the iodide with KI and finally conversion of the iodide to
a CF3 group. As with the deuterated 4-methylbenzonitrile
studied previously,1 all the chemically distinct carbons
are now labeled and their positions can be tracked during
phototranposition. The analytical method used is 13C
NMR of those aromatic ring carbons which are proton
(hydrogen or deuterium) substituted. Those with deute-
rium give very weak signals with the normal pulse delay
(1 s) acquisition because of their long relaxation times.
For instance, 4-methylbenzotrifluoride 5 gives two strong
signals at δ 130.8 and 126.2, the latter being assigned to
C2 by the coupling (3.7 Hz) to the CF3 group. In 5-d2,
this signal is essentially invisible appearing as a very
weak triplet at δ 125.9.
On irradiation in acetonitrile, 5-d2 (para) is converted
to 3-methylbenzotrifluoride 6-d2 (meta) by phototranpo-
sition. The meta isomer 6 has four proton-substituted
carbons appearing at δ 134.1, J < 1 Hz (C4), 130.2, J )
2.3 Hz (C5), 126.7, J ) 3.7 Hz (C2) and 123.3, J ) 3.7
Hz (C6). These assignments are also made on the basis
of coupling constants with the fluorines of the CF3 group
and by distinguishing C2 from C6 by simulation using
the ACD program.10 The 6-d2 produced in the mixture
by phototransposition11 has visible carbons at δ 134.3
(C4) and 126.6 (C2), as expected. A very weak signal
could be observed for C6 at δ 123.3 with an intensity ratio
of C2:C6 > 10:1; in the fully protonated sample this
intensity ratio is ∼1:1. Unfortunately, the region of the
spectrum for the signal corresponding to C5 was obscured
by other signals and a noisy baseline. However, 6-d2 most
probably is principally the isomer with the deuterium
distribution shown. Therefore, 5 is converted to 6 by
migration of the CF3-substituted carbon.
We are in the process of doing high level MO calcula-
tions to probe the potential energy surfaces for these
phototransposition reactions. The knowledge that the
CF3-substituted carbon is the migratory one is necessary
for this approach that may help to explain why the order
of reactivity (ortho/meta/para) is reversed on going from
a CN to CF3 group.
Ack n ow led gm en t. We thank NSERC of Canada for
financial support and Sepracor Canada Ltd., Windsor,
Nova Scotia, for donation of chemicals. D.D. also thanks
the University of Colombo for support during his visit
to Dalhousie University.
Su p p or tin g In for m a tion Ava ila ble: The Experimental
Section including spectral data for the five synthesized isomers
of dimethylbenzotrifluoride 8. This material is available free
of charge via the Internet at http://pubs.acs.org.
J O0205715
(11) The deuterium distribution in the ortho isomer 7 could not be
obtained because it reaches a yield of only 7% at complete photoequili-
bration.
(10) Advanced Chemistry Development, Inc., 90 Adelaide Street
West, Toronto, ON M5H 3V9, Canada.
J . Org. Chem, Vol. 67, No. 26, 2002 9487