Chlorofluorocarbene: First UV observation of a dihalocarbene in solution

Article abstract of DOI:10.1021/ol701804m

Chlorofluorocarbene (CICF), generated by laser flash photolysis of chlorofluorodiazirine, absorbs at 368 nm in pentane. Absolute rate constants are reported for CICF additions to several alkenes and pyridine. CICF is less reactive toward alkenes than CCI<

Full text of DOI:10.1021/ol701804m

ORGANIC
LETTERS
2007
Vol. 9, No. 20
4053-4056
Chlorofluorocarbene: First UV
Observation of a Dihalocarbene in
Solution
Robert A. Moss,* Jingzhi Tian, Ronald R. Sauers, Christopher Skalit, and
Karsten Krogh-Jespersen*
Department of Chemistry and Chemical Biology, Rutgers, The State UniVersity of
New Jersey, New Brunswick, New Jersey 08903
moss@rutchem.rutgers.edu; krogh@rutchem.rutgers.edu
Received July 27, 2007
ABSTRACT
Chlorofluorocarbene (ClCF), generated by laser flash photolysis of chlorofluorodiazirine, absorbs at 368 nm in pentane. Absolute rate constants
are reported for ClCF additions to several alkenes and pyridine. ClCF is less reactive toward alkenes than CCl2, and it does not react rapidly
with oxygen. Pertinent computational studies are included.
In the development of laser flash photolysis (LFP) for the
study of halocarbenes in solution, halodiazirines have been
the essential carbene precursors.1 Diazirine precursors for
ArCX, RCX, ArOCX, and ROCX, where X ) F, Cl, or Br,
are available via the Graham hypohalite oxidation of
amidines or isouronium salts,2 coupled (when X ) F) with
the diazirine exchange reaction.1,3 However, dihalodiazirines,
and thus dihalocarbenes, were unavailable by this methodol-
ogy until 2005, when we successfully prepared chlorofluo-
rodiazirine (1).4 A parallel preparation of dichlorodiazirine
(2) soon followed.5
heptane).6 No UV-vis signals were observed under nitrogen,
while a transient absorption observed at 465 nm in pentane
under air was assigned to dichlorocarbene carbonyl oxide
3.6 CCl2 and ClCF have been photoextruded from hydro-
carbon precursors 47 and 5,8 respectively, but LFP experi-
ments did not afford UV-vis spectra of the carbenes; only
spectra of their pyridinium ylides were obtained.
Here, we report an improved synthesis of chlorofluorodi-
azirine, the UV spectrum of ClCF in solution as obtained
by LFP of diazirine 1, absolute rate constants for the reactions
of ClCF with several olefins, the failure of ClCF to react
with oxygen, and a computational study of the latter reaction.
Diazirine 1 was first prepared by the reductive defluori-
nation-cyclization of a trifluoroamidine precursor,9,10 but
Photolyses of 1 and 2 generated ClCF and CCl2,4,5 but
LFP experiments with 2 did not reveal the absorption
signature of CCl2, calculated at 492 nm (in simulated
(1) Moss, R. A. Acc. Chem. Res. 2006, 39, 267.
(2) Graham, W. H. J. Am. Chem. Soc. 1965, 87, 4396.
(3) Moss, R. A. In Chemistry of Diazirines; Liu, M.T.H., Ed.; CRC
Press: Boca Raton, FL, 1987; Vol. 1, p 99f.
(4) Moss, R. A.; Chu, G.; Sauers, R. R. J. Am. Chem. Soc. 2005, 127,
2408.
(6) Moss, R. A.; Tian, J.; Sauers, R. R.; Ess, D. H.; Houk, K. N.; Krogh-
Jespersen, K. J. Am. Chem. Soc. 2007, 129, 5167.
(7) Chateauneuf, J. E.; Johnson, R. P.; Kirchoff, M. M. J. Am. Chem.
Soc. 1990, 112, 3217.
(5) Chu, G.; Moss, R. A.; Sauers, R. R. J. Am. Chem. Soc. 2005, 127,
14206.
(8) Tippmann, E. M.; Platz, M. S. J. Phys. Chem. A 2003, 107, 8547.
10.1021/ol701804m CCC: $37.00
© 2007 American Chemical Society
Published on Web 09/01/2007

that precursor was inconvenient and explosive. We reported
that the reaction of p-nitrophenoxychlorodiazirine (6) with
tetrabutylammonium (TBA) fluoride provided diazirine 1 and
diazirinone.4 Now we describe a related, but more efficient
and reproducible, preparation of 1 (cf. Scheme 1).
Chlorofluorodiazirine was identified by its UV spectrum
in pentane (see Supporting Information, Figure S-1) which
displayed absorption peaks at 356, 351, 344, 339, 334, 329,
324, and 320 nm, in excellent agreement with the published
(gas phase) spectrum.9 Diazirine 1 also afforded a 19F NMR
resonance at δ -104.8 (CFCl3, CDCl3).
LFP6 of diazirine 1 (A356 ) 0.5 in pentane) affords a weak
absorption at 368 nm (Figure 1) which we assign to ClCF.
Scheme 1
N-Methanesulfonyloxy-O-phenylisourea (7)11 was oxidized
to phenoxychlorodiazirine (8)12 by NaOCl in methanol. The
diazirine, purified by flash chromatography, was obtained
in 84% yield.13 Diazirine 8 was converted to phenoxyfluo-
rodiazirine (9) by exchange with “molten” TBAF,14 and the
fluorodiazirine was dinitrated to 2,4-dinitrophenoxyfluorodi-
azirine (10) with nitronium tetrafluoroborate in nitromethane.
Diazirine 10 was slowly added to a solution of 3-fold excess
anhydrous TBACl in HMPA under a vacuum at 25 °C.
Chlorofluorodiazirine 1 distilled out and was trapped in 1
mL of pentane or CDCl3 at 77 K. After dilution with an
additional 1 mL of solvent, we obtained solutions of 1 with
A ) 1.6-2.0 at 356 nm.
The diazirine exchange reaction which converts 10 to 1
most likely proceeds via a double SN2′ mechanism,1 in which
an initial SN2′ attack of Cl- at diazirine N leads to the loss
of 2,4-dinitrophenoxide and the generation of a N-chloro-
isodiazirine. The latter is then converted to 1 by a second
SN2′ attack of Cl- at carbon. (The process is analogous to
the conversion of 2,4-dinitrophenoxychlorodiazirine to dichlo-
rodiazirine by TBACl.6) A competitive ipso attack of Cl-
on the 2,4-dinitrophenoxy moiety of 10 presumably leads
to diazirinone (11), which subsequently fragments to nitrogen
and carbon monoxide (within 5 min at rt).4
Figure 1. LFP UV spectrum of ClCF under nitrogen. The spectrum
is unchanged under oxygen.
The spectrum is identical under nitrogen or oxygen. There
is no evidence for rapid reaction of ClCF with oxygen, in
contrast to the behavior of CCl2.6 The 368 nm absorption
accords with the reported UV specrum of ClCF at 340-390
nm obtained by photolysis of CH2ClF or CD2ClF in Ar
matrices at 14 K.15,16
The computed absorption of ClCF is at 365 nm (Table
1), in excellent agreement with experiment. For CCl2, ClCF,
and CF2, the percent contribution of the HOMO-LUMO
excitation to the lowest carbene excited state is nearly
constant at 75%. The doubly occupied in-plane σ lone pair
and the formally vacant 2p orbitals on C are the primary
contributors to these two molecular orbitals, so that a σ f
p designation for the excitation appears appropriate. Note
that the computed oscillator strength (f) of ClCF is 3 times
that of CCl2. Given that the observed absorbance of ClCF is
very weak (Figure 1), it is perhaps not surprising that we
were unable to observe the absorbance of CCl2 under
comparable LFP conditions.6
(9) Mitsch, R. A.; Neuvar, E. W.; Koshar, R. J.; Dybvig, D. H. J.
Heterocycl. Chem. 1965, 2, 371.
(10) Mitsch, R. A. J. Org. Chem. 1968, 33, 1847.
(15) Smith, C. E.; Milligan, D. E.; Jacox, M. E. J. Chem. Phys. 1971,
54, 2780.
(11) Fede´, J.-M.; Jockusch, S.; Lin, N.; Moss, R. A.; Turro, N. J. Org.
Lett. 2003, 5, 5027.
(12) Moss, R. A.; Perez, L. A.; Wlostowska, J.; Guo, W.; Krogh-
Jespersen, K. J. Org. Chem. 1982, 47, 4177.
(13) See the Supporting Information for experimental details.
(14) (a) Cox, D. P.; Moss, R. A.; Terpinski, J. J. Am. Chem. Soc. 1983,
105, 6513. (b) Moss, R. A.; Terpinski, J.; Cox, D. P.; Denney, D. Z.; Krogh-
Jespersen, K. J. Am. Chem. Soc. 1985, 107, 2743.
(16) A reviewer has noted that the ClCF absorption is surprisingly narrow
for a HOMO to LUMO carbene band. At its base, it spans ∼100 nm. In
comparison, the HOMO to LUMO absorption of MeCCl in pentane solution
spans ∼200 nm (Moss, R. A.; Tian, J.; Sauers, R. R.; Krogh-Jespersen, K.
J. Am. Chem. Soc. 2007, 129, 10019). There are very few HOMO-LUMO
bands of carbenes in solution to afford further comparisons. Note that we
do not observe diazirine bleaching in Figure 1; only about 0.1% of the
diazirine is destroyed per laser pulse.
4054
Org. Lett., Vol. 9, No. 20, 2007

Table 1. Computed Absorptions of Dihalocarbenesa
carbene
λ (nm)
f
CCl2
ClCF
CF2
491.9
365.0
267.4
0.004
0.012
0.040
a
Calculations are TD-PBEPBE/6-311+G(d)//PBEPBE/6-311+G(d) in
simulated heptane (pentane). For details, see the Supporting Information.
Tippmann and Platz did not detect the UV absorbance of
ClCF upon LFP extrusion of the carbene from precursor 5,8
although they did observe an extremely weak signal at ∼365
nm in Freon-113 (see the inset in Figure 1 of ref 8). This
was assigned to a triene valence isomer of 5 (with a
computed absorbance at 285 nm),8 although a better assign-
ment would now appear to be ClCF, which absorbs at 368
nm in pentane (Figure 1). In any event, diazirine 1 is clearly
a more efficient progenitor of ClCF than diene 5.
Figure 2. LFP determination of kadd for the addition of ClCF to
tetramethylethylene: kobs for the formation of 12 vs [TME].
LFP of 1 in the presence of 0.65 mM pyridine in pentane
led to pyridine ylide 12 with a maximum at 464 nm (see
Figure S-2 in the Supporting Information). A value of 406
nm (f ) 0.286) was computed for this absorption at the TD-
PBEPBE/6-311+G(d) level (details appear in the Supporting
Information). A comparable UV spectrum, though with a
less well-defined maximum, was obtained for 12 via LFP
of 5 with pyridine in Freon-113.8 From a correlation of kobs
for the formation of 12 vs the concentration of pyridine in
pentane, we obtain kf ) 2.0 × 1010 M-1s-1 for the capture
of ClCF by pyridine (Supporting Information, Figure S-3),17
in reasonable accord with kf ) 8.0 × 109 M-1s-1 reported
for this reaction in cyclohexane.8
In all cases, we maintained constant concentrations of
pyridine (0.12 mM) and diazirine (A356 ) 0.5) in pentane at
25 °C. Rate constants are collected in Table 2, and the
Table 2. Rate Constants for Additions of Carbenes to Alkenesa
b
c
d
alkene
kClCF (M-1s-1
)
kCCl2 (M-1s-1
)
kCCl2 (M-1s-1
)
Me2CdCMe2
Me2CdCHMe
cyclohexene
1.2 × 109
3.8 × 108
2.7 × 107
1.1 × 107
4.7 × 109
2.5 × 109
6.4 × 107
1.8 × 107
(3.8 × 109)
(2.2 × 109)
(3.5 × 107)
(1.1 × 107)
CH2dCHC4H9
a
b
In pentane, 25 °C, [pyridine] ) 0.12 mM; Adiazirine ) 0.5. LFP of
diazirine 1; see text and Figures 1 and Supporting Information Figures S-4-
c
S-6. LFP of dichlorodiazirine; see Supporting Information Figures S-7-
S-10. d Rate constants in parentheses are from LFP of precursor 4; see ref
7.
The UV absorbance of ClCF is too weak for accurate direct
kinetics studies. Therefore we used the pyridine ylide
method18 to determine absolute rate constants for addition
of ClCF to several alkenes. The rate of formation of ylide
12 in pentane is accelerated by the addition of an alkene at
a constant concentration of pyridine. A correlation of the
observed rate constants for the formation of 12 vs [alkene]
is linear, and its slope gives kadd for the addition of ClCF to
the alkene.
correlations from which they derive appear in Supporting
Information Figures S-4-S-6.21
For comparison, we measured kadd for additions of CCl2
to the same alkenes. The carbene was generated by LFP of
dichlorodiazirine6 under conditions identical to those em-
ployed for ClCF. The new CCl2 data appear in Table 2 (and
in Supporting Information Figures S-7-S-10).21 Also in-
cluded in Table 2 are analogous CCl2 rate constants obtained
from LFP experiments with precursor 4.7 The two sets of
CCl2 data are comparable, although the diazirine-derived rate
constants are slightly larger.
An example, the addition of ClCF to tetramethylethylene
(TME), appears in Figure 2, where kadd ) 1.2 × 109 M-1s-1,
about 10 times faster than the value obtained with precursor
5 in Freon-113.8,19 Similarly, we determined kadd for ClCF
additions to trimethylethylene, cyclohexene, and 1-hexene.
The absolute rate constants of Table 2 generally accord
7
with expectations.22 Thus, ClCF (like CCl2 ) reacts as an
(17) From the Y-intercept of this correlation, we derive a lifetime of ∼0.2
µs for ClCF in pentane under our reaction conditions.
electrophile with the four alkenes: alkene reactivity increases
with increasing alkyl substitution. Moreover, CCl2, less
(18) Jackson, J. E.; Soundararajan, N.; Platz, M. S.; Liu, M. T. H. J.
Am. Chem. Soc. 1988, 110, 5595.
(19) GC spiking experiments and 1H, 13C, and 19F NMR comparisons
with an authentic sample20 showed that the appropriate cyclopropane was
produced when diazirine 1 was photolyzed in tetramethylethylene.
(20) Dolbier, W. R., Jr.; Burkholder, C. R. J. Org. Chem. 1990, 55, 589.
(21) We estimate the errors in the rate constants at 10-15%. All of the
correlation constants (r), from which the rate constants derive, are g0.99.
Org. Lett., Vol. 9, No. 20, 2007
4055

stabilized than ClCF by its substituents,22 reacts more rapidly
than ClCF with each alkene. We defer more detailed scrutiny
of comparative ClCF-CCl2 selectivity, as that analysis is
preferably grounded in more precise alkene relative reactivity
data22 rather than in the absolute rate constants with wide
dynamic ranges collected in Table 2.
As indicated above, ClCF does not react rapidly with
oxygen, whereas CCl2 does.6 Computational studies provide
a rationale for this contrast. Calculations at the PBE/6-
311+G(d) level find no barrier to the formation of a triplet
CCl2-O2 complex in an energetically favorable reaction (∆H
) -15.1 kcal/mol, ∆G ) -7.0 kcal/mol). This complex can
subsequently undergo intersystem crossing to the singlet
dichlorocarbene carbonyl oxide 3 with a low activation
energy (∼1.8 kcal/mol), favorable geometric factors, and
significant spin-orbit coupling.6 Indeed, intermediate 3 may
well have been detected by LFP at 465 nm.6 However,
analogous PBE/6-311+G(d) calculations detect a small
kinetic barrier for the formation of a triplet ClCF-O2
complex (∆Hq ) 0.9 kcal/mol, ∆Gq ) 8.0 kcal/mol).
Moreover, the reaction is not very favorable (∆H ) -5.9
kcal/mol, ∆G ) 2.1 kcal/mol).23 Computational details
appear in the Supporting Information.
In conclusion, we have obtained the first UV spectrum of
a dihalocarbene (ClCF) in solution (368 nm) and measured
the absolute rate constants of its addition reactions with
several alkenes. ClCF is a moderately selective electrophilic
carbene, and as anticipated, it is less reactive toward alkenes
than CCl2. In contrast to CCl2, ClCF does not rapidly react
with oxygen. Computational studies rationalize this difference
and support our assignment of the carbene’s UV absorbance.
Acknowledgment. We are pleased to acknowledge help-
ful correspondence with Dr. Eric Tippmann (University of
Cardiff, U.K.) and Professor M.S. Platz (Ohio State Uni-
versity). We are grateful to the National Science Foundation
for financial support.
Supporting Information Available: Preparations of 1,
8, 9, and 10; Figures S-1-S-10; and computational details
(optimized ground state geometries, absolute energies, and
excited-state data). This material is available free of charge
via the Internet at http://pubs.acs.org.
(22) (a) Moss, R. A. In Carbene Chemistry From Fleeting Intermediates
to Powerful Reagents; Bertrand, G., Ed.; Dekker-Fontis: New York, 2002;
pp 57f. (b) Moss, R. A. Acc. Chem. Res. 1989, 22 15. (c) Moss, R. A. Acc.
Chem. Res. 1980, 13, 58.
(23) At the B3LYP/6-311+G(d) level, the barriers for the formation of
3
3
the ClCF-O2 and CCl2-O2 complexes are ∆Gq ) 15.8 and 11.7 kcal/
mol, respectively, whereas the respective free energies of reaction are ∆G
) 4.2 and -3.8 kcal/mol.
OL701804M
4056
Org. Lett., Vol. 9, No. 20, 2007