Δ3-1,3,4-oxadiazolines: Photochemical precursors to diazoalkanes and sec-alkanediazonium ions in acidic solution

Full text of DOI:10.1021/ja962550w

J. Am. Chem. Soc. 1997, 119, 1789-1790
1789
∆3-1,3,4-Oxadiazolines: Photochemical Precursors
to Diazoalkanes and sec-Alkanediazonium Ions in
Acidic Solution1
John Paul Pezacki,†,§ Brian D. Wagner,‡, Calvin S. Q. Lew,‡
John Warkentin,*,† and Janusz Lusztyk*,‡
Department of Chemistry, McMaster UniVersity
Hamilton, Ontario, Canada L8S 4M1
Steacie Institute for Molecular Sciences
National Research Council of Canada
Ottawa, Ontario, Canada K1A 0R6
Figure 1. Time-resolved IR absorption traces and spectrum (inset)
observed following 308-nm laser flash photolysis of 1a in acetonitrile
and in acetonitrile containing 3.0 mM TFA. Decay of absorption of 3a
ReceiVed July 24, 1996
monitored at 2037 cm-1
.
Diazoalkanes and their conjugate acids, diazonium ions, are
important reactive intermediates which have been implicated
in the carcinogenicity and mutagenicity of N-alkyl-N-nitroso
compounds.2 Alkanediazoates have been studied extensively
and have been shown to decompose via diazonium ion
intermediates.3 Nitrous acid deaminations of aliphatic amines
are known to involve the same diazonium ion intermediates.4,5
It has been postulated that N-alkyl-N-nitroso compounds may,
under certain conditions, lead to the formation of diazoalkanes
in biological systems,2,6 and their studies serve as models from
which inferences about the biological implications have been
made. Despite the considerable interest surrounding these
reactive intermediates, there is little quantitative information on
their reactivities. The only known bimolecular rate constant
for protonation of an unstabilized diazoalkane by acidic species,
such as hydronium ions, is that for protonation of diazomethane
The formation of the two products upon 308 nm LFP of 1a
in acetonitrile at 25 °C, is readily confirmed with use of time-
resolved infrared (TRIR) detection.10 Absorptions assigned to
the diazo band of 2-diazopropane, centered at 2036 ( 3 cm-1
,
and to the carbonyl band of methyl acetate, centered at 1744
cm-1 (not shown), were formed instantaneously (within the
response time of the instrument) from 1a, Figure 1. Both
absorptions were persistent under the experimental conditions.
Under identical conditions, 308 nm LFP (UV-vis detection)
of 1a resulted in an instantaneous bleaching of its absorption
at 322 nm and was accompanied by the instantaneous appear-
ance of a strong persistent band, centered at 250 nm, assigned
to 3a.11 Both the UV and the IR absorptions assigned to 3a
decayed with first-order kinetics (τ ) 30µs) when trifluoroacetic
acid (TFA, 3.0 mM) was present (Figure 1).
by hydronium ion at 25 °C, estimated as kH ≈ 4 × 108 M-1
+
s-1 7
. The laser flash photolysis (LFP, 308 nm, with either UV
or IR detection of transients) of alkoxy substituted ∆3-1,3,4-
oxadiazoline precursors (1) has allowed us to determine rate
constants for protonation of diazoalkanes in both aqueous and
nonaqueous solutions.
The mechanism for the photochemical decomposition of
alkoxy substituted ∆3-1,3,4-oxadiazolines 1 involves initial
R-scission of the excited state to form biradicals, 2, which
subsequently undergo efficient â-scission selectively, to give
primarily diazoalkanes, 3, and an ester or carbonate (if R1 )
alkoxy).8,9
Rate constants for protonation of 3a by carboxylic acids with
pKA’s ranging from 10 to 23 in acetonitrile,12 at 25 °C, µ ) 0
M, are listed in Table 1. They were obtained as the slopes of
linear plots of observed rate constants (determined from LFP
TRIR measurements) Vs acid concentration.14 The linear least-
squares analysis of log kHA Vs log KA of the acids (data adjusted
for statistics) by the Brønsted procedure gave R ≈ 0.25.15
The reaction between 3a and hydronium ion was also studied
by monitoring decay of the UV absorption of 3a in aqueous
perchloric acid solutions at 25 °C, µ ) 1.0 M (NaClO4), and
† McMaster University.
‡ National Research Council of Canada.
§ NSERC Scholar, 1996.
NRCC Research Associate 1993-1996.
(1) Issued as NRCC No. 39135.
(2) Lijinsky, W. In Chemistry and Biology of N-nitroso Compounds;
Cambridge University Press: Cambridge, 1992.
(3) (a) Finneman, J. I.; Fishbein, J. C. J. Am. Chem. Soc. 1995, 117,
4228. (b) Ho, J.; Fishbein, J. C. J. Am. Chem. Soc. 1994, 116, 6611. (c)
Finneman, J. I.; Ho, J.; Fishbein, J. C. J. Am. Chem. Soc. 1993, 115, 3016.
(d) Hovinen, J.; Finneman, J. I.; Satapathy, S. N.; Ho, J.; Fishbein, J. C. J.
Am. Chem. Soc. 1992, 114, 10321. (e) Gold, B.; Deshpande, A.; Linder,
W.; Hines, L. J. Am. Chem. Soc. 1984, 106, 2072. (f) Moss, R. A. Acc.
Chem. Res., 1974, 7, 421.
6
-1
+
the rate constants found were kH ) (2.46 ( 0.07) × 10 M
s-1 in H2O and kD ) (1.32 ( 0.04) × 106 M-1 s-1 in D2O
+
(8) Majchrzak, M.; Bekhazi, M.; Tse-Sheepy, I.; Warkentin, J. J. Org.
Chem. 1989, 54, 1842.
(4) For some recent examples, see: (a) Brosch, D.; Kirmse, W. J. Org.
Chem. 1993, 58, 1118. (b) Brosch, D.; Kirmse, W. J. Org. Chem. 1991,
56, 907 and references therein. (c) Bunse, M.; Kirmse, W. Chem. Ber. 1993,
126, 1499.
(9) Adam, W.; Finzel, R. Tetrahedron Lett. 1990, 31, 863.
(10) The LFP system included a Mutek MPS-1000 diode laser (output
1520-2314 cm-1) as the monitoring source. Full details of the present
system will be provided in a forthcoming publication, see: Wagner, B. D.;
Arnold, B. R.; Brown, G. S.; Lusztyk, J. Manuscript submitted.
(11) For a description of the LFP system with UV-vis detection, see:
Kazanis, S.; Azarani, A.; Johnston, L. J. J. Phys. Chem. 1991, 95, 4430.
(12) The pKA values of the various acids in acetonitrile were obtained
from The IUPAC Chemical Data Series No. 35, 1990, compiled by K.
Izutsu.
(5) For reviews of aliphatic diazonium ion chemistry, see: (a) Laali,
K.; Olah, G. A. ReV. Chem. Intermed. 1986, 6, 237. (b) Kirmse, W. Angew.
Chem., Int. Ed. Engl. 1976, 15, 251. (c) Collins, C. J. Acc. Chem. Res.
1971, 4, 315. (d) More O’Ferrall, R. A. AdV. Phys. Org. Chem. 1967, 5,
331. (e) Huisgen, R. Angew. Chem. 1955, 67, 273. (f) Zollinger, H. In Diazo
Chemistry; VCH Publ.: New York, 1995; Vol. 1-2. (g) Whittaker, D. In
The Chemistry of Diazonium and Diazo Compounds; Patai, S., Ed.; Wiley-
Interscience: Chichester, 1978; pp 617-639.
(13) Based on the proclivity of N2 loss from sec-alkanediazonium ions5
we assume that the protonation reaction is irreversible in all cases (kobs
k1[HA]).
)
(6) (a) Leung, K. H.; Archer, M. C. Chem. Biol. Interact. 1984, 48, 169.
(b) Lawson, T., Nagel, D. Carcinogenesis 1988, 9, 1007. (c) Liberato, D.;
Saavedra, J. E.; Farnsworth, D.; Lijinski, W. Chem. Res. Toxicol. 1989, 2,
307.
(14) Kinetic measurements were made by LFP largely for convenience.
The long lifetime of diazopropane and the magnitude of the rate constants
for its protonation should allow for these measurements to be made with
conventional spectroscopic techniques.
(7) McGarrity, J. F.; Smyth, T. J. Am. Chem. Soc. 1980, 102, 7303.
S0002-7863(96)02550-4 CCC: $14.00 © 1997 American Chemical Society

1790 J. Am. Chem. Soc., Vol. 119, No. 7, 1997
Communications to the Editor
the transition state by a change in hybridization, from sp2 to
sp3.
Table 1. Observed Proton Transfer Rate Constants (kHA) for the
Reaction of 3a with Carboxylic Acids in Acetonitrile at 25 °Ca
Our results are consistent with those of McGarrity and Smyth7
in that the bimolecular rate constants for proton transfer to the
diazo carbon by strong acids are large, although still 2-3 orders
of magnitude below the limit for diffusion control. A Brønsted
coefficient of ∼0.25 for the protonation of 3a suggests an early
transition state and may indicate that the reaction is exothermic.20
Another implication is that the pKA’s of carboxylic acids and
of 2-propyl diazonium ions are significantly different.18,21
It has been suggested that the carbon atom of diazomethane
is a good hydrogen-bond acceptor.7,22 Stabilization of carbon
bases by hydrogen bonding is expected to be most favorable
when negative charge is localized at carbon. Examples of such
bases are cyanide23 and acetylide24 ions and C-2 of the ylide
thiamin.25 However, Washabaugh and Jencks have shown that
hydrogen bonding is not important in proton transfer reactions
of C-2 thiazolium ions,26 and rate constants for protonation at
carbon can reach the diffusion controlled limit even when a
lone pair on carbon is delocalized, at least formally, as in phenyl
ynolate ions.27 Thus, the effects of hydrogen bonding in
formally neutral diazoalkanes, on rates of proton transfer, remain
unclear. Whatever the reasons, protonations of dialkyldiazo
compounds are intrinsically fast, as indicated by our estimate
of the intrinsic barrier to protonation of 2-diazopropane.15
Phenyldiazomethane is ca. 70-fold less reactive than 3a
toward H3O+, and R-diazocarbonyl compounds are slower yet
by several orders of magnitude.28 Such structural effects on
rate constants for protonation at the diazo carbon atom presum-
ably include effects from changes in the structure of the ground
states (conjugation, H-bonding as well as other solvation) and
in the structure of corresponding transition states.
acid
pKA
kHA, M-1‚s-1
trichloroacetic
trifluoroacetic
10.57
12.65
8.2 × 106
6.8 × 106 (TRIR)
6.9 × 106 (UV)
2.8 × 106
dichloroacetic
oxalic
malonic
2,3-dibromopropionic
cyanoacetic
acetic
13.20
14.50
15.3
17.1
18.04
22.30
2.9 × 106
4.3 × 105
6.7 × 105
5.1 × 105
8.5 × 103 b
a Measured by TRIR at 2037 cm-1
[acid].
.
b From quadratic fit of kobs vs
Figure 2. Plots of the change in kobs, for the decay of 3a, as a function
of H+ concentration (O), and as a function of D+ concentration (4), in
aqueous perchloric acid solutions, at 25 °C, ionic strength 1.0 M
(NaClO4).
Photochemical generation of diazoalkanes (3) from oxadia-
zolines (1) in a variety of media containing a proton source
represents an alternative and convenient method for determining
rate constants for diazoalkane protonation reactions. Fast
protonation of dialkyldiazo compounds leads to the efficient
and relatively indiscriminate formation of cation-counterion pairs
which can then collapse to form alkylation products.29 Further
investigations of the effects of structure on the properties of
diazo compounds, using oxadiazolines (1) as convenient pho-
tochemical precursors, are in progress.
(Figure 2). The primary kinetic isotope effect for the reaction
+
+
of hydronium ion with 3a is kH /kD ) 1.86. A Brønsted
correlation for the protonation of 3a with carboxylic acids in
aqueous solutions showed a slope (∼0.22) similar to that found
in acetonitrile solutions.
Rate constants for protonation of diazocyclohexane (3b),
diazocyclopentane (3c), and diazocyclobutane (3d) by TFA in
acetonitrile at 25 °C were determined from the decays of their
UV absorptions upon 308 nm LFP of 1b-d in acetonitrile. The
linear plots of kobsd Vs [HA] gave bimolecular rate constants
(kHA) equal to (9.17 ( 0.12) × 106, (1.19 ( 0.03) × 107, and
(4.28 ( 0.10) × 107 M-1 s-1 for the reaction of TFA with 3b-
d, respectively.
Acknowledgment. J.P.P. and J.W. thank the Natural Sciences and
Engineering Research Council of Canada for continued support through
an operating grant. We also thank an anonymous referee for his/her
thoughtful comments.
It is unlikely that the magnitudes of rate constants of proton
transfer are governed by diazonium ion stabilities, given that
the observed Brønsted coefficient is consistent with an early,
reactant-like, transition state.18 It also seems that torsional
effects are not dominant since larger eclipsing interactions for
the smaller rings are expected for hybridization changes at the
diazocarbon in the transition state, which would give a trend
opposite to that observed experimentally.19 Thus, we conclude
that the relative reactivities, 3d > 3c > 3b, of the cyclic diazo
compounds largely reflect differences in their ground-state
stabilities. They relate to the ring strain which is relieved at
JA962550W
(19) It has been shown that the relative reactivity of cycloalkyl systems,
toward nucleophilic addition, could result from a complex interplay of
numerous factors. As an example, BH4- additions to cycloalkanones show
the reactivity order kbutyl > khexyl > kpentyl, see: (a) Brown, H. C.; Wheeler,
O. H.; Ichikawa, K. Tetrahedron 1957, 1, 214. (b) Brown, H. C.; Ichikawa,
K. Tetrahedron 1957, 1, 221.
(20) It has been shown, however, that the slope of the Brønsted plot can
be influenced by pre-equilibrium desolvation. Thus, the magnitude of the
obtained coefficient alone may not always reflect the thermodynamics of
the reaction. See: Murray, C. J.; Jencks, W. P. J. Am. Chem. Soc. 1990,
112, 1880. Unfortunately, the lack of appropriate thermodynamic data
precludes an independent assessment of the thermochemistry of these proton
transfer reactions.
(21) Bell, R. P. The Proton in Chemistry, 2nd ed.; Cornell University
Press: Ithaca, NY, 1973.
(22) Young, J. C. Can. J. Chem. 1975, 53, 2530.
(23) Larson, J. W.; McMahon, T. B. J. Am. Chem. Soc. 1987, 109, 6230.
(24) Kresge, A. J.; Powell, M. F. J. Org. Chem. 1986, 51, 819 and 822.
(25) Washabaugh, M. W.; Jencks, W. P. Biochemistry 1988, 27, 5044.
(26) Washabaugh, M. W.; Jencks, W. P. J. Am. Chem. Soc. 1989, 111,
674.
(27) Chiang, Y.; Kresge, A. J.; Popik, V. V. J. Am. Chem. Soc. 1995,
117, 9165.
(15) Alternatively, least-squares fitting of the data to a quadratic
expression gave coefficients which yielded values of the Marcus theory
parameters16 for the work required to bring the reactants into a reaction
complex, wr ≈ 9 kcal mol-1, and for the intrinsic reaction barrier, ∆Gq ≈
7 kcal mol-1 17
. However, the resulting curve was statistically indistinguish-
able from a straight line, which best describes the reactivity of 3a toward
the carboxylic acids that were studied.
(16) Marcus, R. A. J. Phys. Chem. 1968, 72, 891.
(17) For examples of the use of quadratic Brønsted correlations to solve
for Marcus theory parameters, see: (a) Chiang, Y.; Grant, A. S.; Kresge,
A. J.; Paine, S. W. J. Am. Chem. Soc. 1996, 118, 4366. (b) Albery, W. J.;
Campbell-Crawford, A. J.; Curran, J. S. J. Chem. Soc., Perkin Trans. 2
1972, 2206. (c) Kresge, A. J. Chem. Soc. ReV. 1973, 4, 475.
(18) Kresge, A. J. In Proton Transfer Reactions; Caldin, E. F., Gold,
V., Eds.; Chapman and Hall: London, 1975; Chapter 7.
(28) For comparison with phenyl and diphenyldiazomethanes, see:
Finneman, J. I.; Fishbein, J. C. J. Org. Chem. 1994, 59, 6251 and references
therein. For comparison with R-diazocarbonyl compounds see ref 5b and
references therein.
(29) Short-lived diazonium ions which alkylate via carbocations are well
known. See: refs 3a and 5.