Carbenes as substrates: Bimolecular fragmentation of alkoxychlorocarbenes

Article abstract of DOI:10.1021/ja984418x

Fragmentation reactions of n-butoxychlorocarbene (9), isobutoxychlorocarbene (10), and benzyloxychlorocarbene (2) were studied by product analysis and by laser flash photolysis (LFP). The carbenes were generated photochemically from 3-alkyl-3-chlorodiazirines in (1) MeCN solution; (2) 5.77 M pyridine in MeCN; (3) 0.504 M tetrabutylammonium chloride (Bu₄NCl) in MeCN; or (4) 5.77 M pyridine + 0.504 M Bu₄NCl in MeCN. In MeCN, 9 gave mainly HCl-capture product, n-butyl dichloromethyl ether (45.1%), carbene dimer (9.8%), and azine (14.6%). Fragmentation products 1- butene (14,4%), 2-butyl chloride (6.0%), and 1-butyl chloride (10.2%) were limited. With added pyridine. HCl was scavenged, the dichloromethyl ether was suppressed, and 1-butene (42.1%), 2-butyl chloride (7.3%), and butyl chloride (24.1%) were dominant. With added Bu₄NCl, 1-butyl chloride increased to 46.4%. With both pyridine and Bu₄NCl, 1-butyl choride was 63% of the product, with 1-butene at 22.8%. A similar pattern was observed with carbene 10. Products in MeCN included isobutene (23%), 1- and 2-butene (8-9%), tert- butyl chloride (1, 7%), 2-butyl chloride (5.8%), isobutyl chloride (0.4%), isobutyl dichloromethyl ether (53%), and carbene dimer (8%). The isobutyl chloride fragmentation product increased from 0.4% in MeCN, to 7.3% with pyridine, to 32% with Bu₄NCl, and to 38% with both addends. With 2, benzyl chloride increased from 83% in MeCN to 91% with added pyridine and Bu₄NCl. The increase in chloride displacement products are attributed to bimolecular attacks of chloride ions at the α-carbon atoms of the carbenes, particularly 9 and 10. LFP kinetic studies show that the rate constants for fragmentation of these carbenes increase linearly with the concentration of added Bu₄NCl in pyridine-MeCN. Second-order rate constant (k₂) as a function of [Cl^-] (M^-1 s^-1, 24 °C) for the fragmentations are 8.2 x 10⁶ (9), 2.7 x 10⁶ (10), and 2.2 x 10⁶ (2). The decrease in k₂ as R in ROCCI changes from n- butyl to isobutyl to benzyl is in accord with a S(N)2-like mechanism for the carbene fragmentations in which the benzyl case involves the competitive incursion of S(N)1-like fragmentation.

Full text of DOI:10.1021/ja984418x

5940
J. Am. Chem. Soc. 1999, 121, 5940-5944
Carbenes as Substrates: Bimolecular Fragmentation of
Alkoxychlorocarbenes
Robert A. Moss,* Lauren A. Johnson, Dina C. Merrer, and George E. Lee, Jr.
Contribution from the Department of Chemistry, Rutgers, The State UniVersity of New Jersey,
New Brunswick, New Jersey 08903
ReceiVed December 28, 1998. ReVised Manuscript ReceiVed March 30, 1999
Abstract: Fragmentation reactions of n-butoxychlorocarbene (9), isobutoxychlorocarbene (10), and benzy-
loxychlorocarbene (2) were studied by product analysis and by laser flash photolysis (LFP). The carbenes
were generated photochemically from 3-alkyl-3-chlorodiazirines in (1) MeCN solution; (2) 5.77 M pyridine in
MeCN; (3) 0.504 M tetrabutylammonium chloride (Bu4NCl) in MeCN; or (4) 5.77 M pyridine + 0.504 M
Bu4NCl in MeCN. In MeCN, 9 gave mainly HCl-capture product, n-butyl dichloromethyl ether (45.1%), carbene
dimer (9.8%), and azine (14.6%). Fragmentation products 1-butene (14.4%), 2-butyl chloride (6.0%), and
1-butyl chloride (10.2%) were limited. With added pyridine, HCl was scavenged, the dichloromethyl ether
was suppressed, and 1-butene (42.1%), 2-butyl chloride (7.3%), and 1-butyl chloride (24.1%) were dominant.
With added Bu4NCl, 1-butyl chloride increased to 46.4%. With both pyridine and Bu4NCl, 1-butyl choride
was 63% of the product, with 1-butene at 22.8%. A similar pattern was observed with carbene 10. Products
in MeCN included isobutene (23%), 1- and 2-butene (8-9%), tert-butyl chloride (1.7%), 2-butyl chloride
(5.8%), isobutyl chloride (0.4%), isobutyl dichloromethyl ether (53%), and carbene dimer (8%). The isobutyl
chloride fragmentation product increased from 0.4% in MeCN, to 7.3% with pyridine, to 32% with Bu4NCl,
and to 38% with both addends. With 2, benzyl chloride increased from 83% in MeCN to 91% with added
pyridine and Bu4NCl. The increases in chloride displacement products are attributed to bimolecular attacks of
chloride ions at the R-carbon atoms of the carbenes, particularly 9 and 10. LFP kinetic studies show that the
rate constants for fragmentations of these carbenes increase linearly with the concentration of added Bu4NCl
in pyridine-MeCN. Second-order rate constants (k2) as a function of [Cl-] (M-1 s-1, 24 °C) for the
fragmentations are 8.2 × 106 (9), 2.7 × 106 (10), and 2.2 × 106 (2). The decrease in k2 as R in ROCCl
changes from n-butyl to isobutyl to benzyl is in accord with a SN2-like mechanism for the carbene fragmentations
in which the benzyl case involves the competitive incursion of SN1-like fragmentation.
Decades ago, Hine1 and Skell2 discovered that alkoxyhalo-
carbenes (1) formed upon reaction of dihalocarbenes with
alkoxide ions, and Skell observed that these “derived” carbenes
fragmented to alkyl cations with loss of halide and carbon
monoxide,2 eq 1. Unfortunately, the requirement for strong base
were most easily rationalized according to a mechanistic scheme
in which the alkoxychlorocarbenes fragmented to alkyl chlo-
rides, alkenes, and solvolysis products via ion pairs (5); eq 2.4-6
In particular, with R ) PhCHD, return of Cl- occurred with
in this “deoxideation”2 reaction limits its utility as a means of
generating carbocations. Subsequently, however, Smith and
Stevens found that 3-methoxy- and 3-isobutoxy-3-chlorodiaz-
irines afforded the corresponding alkoxychlorocarbenes upon
thermolysis; fragmentation of the carbenes could be studied
under neutral conditions.3
We extended this methodology to studies of benzyloxychlo-
rocarbene (2),4 cyclopropylmethoxychlorocarbene (3),5 and
2-butoxychlorocarbene (4).6 Product and stereochemical studies
60-80% net retention.4b When R ) 2-butyl, chloride return
involved 56% net retention, while solvolysis in 1-butanol
afforded 2-chlorobutane by chloride return (82% net retention)
and 2-butyl 1-butyl ether by solvolysis (71% net inversion).6
Finally, with R ) cyclopropylmethyl, typical cyclopropylmethyl
cation rearrangement products were formed in distributions
consistent with the intermediacy of ion pairs.5
More recently, we have been able to measure the absolute
kinetics of several carbene fragmentation reactions, eq 2, by
laser flash photolysis (LFP).7 For benzyloxychlorocarbene (2),
1-adamantylmethoxychlorocarbene (6), and neopentoxychloro-
carbene (7), fragmentation rate constants (kfrag, s-1) were 0.69
× 106 to 1.3 × 106, 2.8 × 106 to 5.2 × 106, and 0.3 × 106 to
(1) Hine, J.; Pollitzer, E. L.; Wagner, H. J. Am. Chem. Soc. 1953, 75,
5607.
(2) Skell, P. S.; Starer, I. J. Am. Chem. Soc. 1959, 81, 4117.
(3) (a) Smith, N. P.; Stevens, I. D. R. J. Chem. Soc., Perkin Trans. 2
1979, 1298. (b) Smith, N. P.; Stevens, I. D. R. J. Chem. Soc., Perkin Trans.
2 1979, 213.
(4) (a) Moss, R. A.; Wilk, B. K.; Hadel, L. M. Tetrahedron Lett. 1987,
28, 1969. (b) Moss, R. A.; Kim, H.-R. Tetrahedron Lett. 1990, 31, 4715.
(5) Moss, R. A.; Ho, G.-J.; Wilk, B. K. Tetrahedron Lett. 1989, 30, 2473.
(6) Moss, R. A.; Balcerzak, P. J. Am. Chem. Soc. 1992, 114, 9386.
(7) Moss, R. A.; Ge, C.-S.; Maksimovic, L. J. Am. Chem. Soc. 1996,
118, 9792.
10.1021/ja984418x CCC: $18.00 © 1999 American Chemical Society
Published on Web 06/10/1999

Bimolecular Fragmentation of Alkoxychlorocarbenes
J. Am. Chem. Soc., Vol. 121, No. 25, 1999 5941
Table 1. Fragmentations of n-Butoxychlorocarbene (9)a
In MeCN alone, unrearranged fragmentation substitution and
elimination products, 1-BuCl and 1-butene, account for only
25% of product, while H-shift product 2-BuCl contributes 6%.
However, with 0.5 M added chloride (as n-Bu4N+Cl-), there is
a 4-fold increase in 1-BuCl and a 5-fold decrease in HCl capture
of the carbene; fragmentation products 1-butene, 1-BuCl, and
2-BuCl total 75%. With 5.77 M added pyridine (mimicking LFP
conditions; see below), HCl is scavenged, product 4a is
suppressed, and fragmentation accounts for ∼74% of the
products. Here, primary “displacement” to 1-BuCl is twice that
in MeCN alone, while elimination (E2?) product 1-butene rises
to 42%. Finally, with both added Cl- and pyridine, 1-BuCl is
the major product (63%) and fragmentation (89%) is the
principal fate of carbene 1a. The sensitivity of the product
distributions to added Cl- suggests direct nucleophilic attack
on the carbene or possibly on an ion pair derived from it.
1.3 × 106, respectively.7,8 The unexpectedly rapid fragmenta-
tions of primary alkoxychlorocarbenes 6 and 7, coupled with
rearranged alkyl groups in their products, suggested that the
fragmentations could have been concerted with alkyl participa-
tion.7,9
Now we describe the unexpectedly facile fragmentation
reactions of n-butoxychlorocarbene and isobutoxychlorocarbene,
which we believe are novel examples of bimolecular carbene
fragmentation, i.e, SN2 reactions in which the carbenes are
substrates for nucleophilic chloride attack at their R-carbons,
rather than at their carbenic centers.
A similar pattern is observed with isobutoxychlorocarbene
(10) generated photochemically from 8 (R ) i-Bu) in MeCN.
Products include isobutene (23%), 1- and 2-butenes (8-9%),
t-BuCl (1.7%), 2-BuCl (5.8%), and i-BuCl (0.4%), dichlorom-
ethyl ether 12 (R ) i-Bu, 53%), and carbene dimer (8%).
Complete product distributions appear in Table 2, where the
salient observations are that i-BuCl increases from 0.4% in
MeCN to 7.3% in 5.77 M pyridine/MeCN, to 32% with 0.5 M
Bu4NCl/MeCN, and to 38% in Bu4NCl/pyridine/MeCN. The
accompanying yields of isobutene are 23, 47, 40, and 27%,
respectively, under these four conditions. Again, the unrear-
ranged “displacement” alkyl chloride fragmentation product (i-
BuCl) becomes dominant in the chloride/pyridine/MeCN me-
dium.
Results and Discussion
Reactions and Products. Diazirine precursors, 8, for car-
benes 9, 10, and 2 were prepared by hypochlorite oxidations10
of the appropriate O-alkylisouronium tosylates, 11.3,4 The latter
were prepared by reactions of n-butyl alcohol, isobutyl alcohol,
or benzyl alcohol with cyanamide and anhydrous p-toluene-
sulfonic acid in dry chloroform.3a,4a The diazirines were purified
Benzyloxychlorocarbene (2) displays less product sensitivity.
The yield of benzyl chloride, which is 83% in MeCN, increases
to 91% in Bu4NCl/pyr/MeCN. The balance of product, in both
cases, is N-acetylbenzylamine, the Ritter product derived from
attack of benzyl cation on MeCN.7
Kinetics. Absolute rate constants for the fragmentations of
carbenes 9, 10, and 27 were determined by LFP11 by using the
pyridine ylide method;7,12 carbene 9 is illustrative. LFP at 351
nm and 24 °C of diazirine 8 (R ) n-Bu) in MeCN (A356 ) 1.0)
in the presence of pyridine produced an absorption due to ylide
14 (R ) n-Bu) at 469 nm; note that the corresponding ylide
produced from MeOCCl absorbs at 472 nm.14,15
by column chromatography over silica gel with pentane, and
then “transferred” to MeCN solution (see Experimental), where
they exhibited λmax 356 nm.
Photolysis (λ > 320 nm) of 8 (R ) n-Bu) at 25 °C in MeCN
(A356 ) 1.0) gave 1-butene, 2-chlorobutane, dichloromethyl ether
12 (R ) Bu), carbene dimer, and azine 13 (R ) Bu). Product
A correlation of the apparent rate constants for ylide forma-
tion, kobs (2.6-4.5 × 106 s-1), vs pyridine concentration (1.65-
7.42 M) was linear (8 points, r ) 0.992) with a slope of 3.33
× 105 M-1 s-1, equivalent to the rate constant for ylide
distributions were obtained by capillary GC, while product
identities were confirmed by GC-MS or GC comparisons with
authentic materials; a summary appears in Table 1.
In MeCN, n-butoxychlorocarbene (9), generated photochemi-
cally from diazirine 8, affords mainly dichloride 12, carbene
dimer, and azine 13. The dichloride is at least partly an HCl
capture product,7 although not enough 1-butene is produced to
account for all of the dichloride. Conceivably, the 1-butene is
underanalyzed due to its volatility, and/or some HCl is generated
during uncharacterized “polymer formation”.
(11) A description of our upgraded LFP system appears in the Experi-
mental Section.
(12) (a) Jackson, J. E.; Soundararajan, N.; Platz, M. S.; Liu, M. T. H. J.
Am. Chem. Soc. 1988, 110, 5595. (b) Platz, M. S.; Modarelli, D. A.; Morgan,
S.; White, W. R.; Mullins, M.; Celebi, S.; Toscano, J. P. Prog. React. Kinet.
1994, 19, 93.
(13) Ylides formed from carbenes 10 and 2 were monitored at 432 and
463 nm, respectively.
(14) Ge, C.-S.; Jang, E. G.; Jefferson, E. A.; Liu, W.; Moss, R. A.;
Wlostowska, J.; Xue, S. Chem. Commun. 1994, 1479.
(15) Diazirines 8 in MeCN react with pyridine (but not Bu4NCl) at 25
°C, affording an unknown product with λmax ) 338 nm. However, diazirine
decay is not appreciable over the initial 30 min (HPLC). Accordingly, our
diazirine-pyridine LFP experiments were performed on freshly prepared
samples within 5 min of pyridine addition.
(8) The ranges cited for the rate constants reflect alternative methods of
data analysis.7
(9) Liggero, S. H.; Sustmann, R.; Schleyer, P. v. R. J. Am. Chem. Soc.
1969, 91, 4571. Sanderson, W. A.; Mosher, H. S. J. Am. Chem. Soc. 1966,
88, 4185.
(10) Graham, W. H. J. Am. Chem. Soc. 1965, 87, 4396.

5942 J. Am. Chem. Soc., Vol. 121, No. 25, 1999
Table 2. Fragmentations of Isobutoxychlorocarbene (10)a
Moss et al.
Figure 2. Arrhenius correlation for the fragmentation of i-C4H9OCCl
(10); ln kfrag (s-1) vs 1/T (K-1).
-40.5 to 24 °C; the quality of the data is illustrated by Figure
2 for i-BuOCCl (10).
Figure 1. Representative correlations of kobs for formation of ylide 14
vs [pyridine] for the fragmentations of n-C4H9OCCl (4) and i-C4H9-
OCCl (b).
The activation parameters were the following: (9) Ea ) 3.1
kcal/mol, log A ) 8.42 s-1, ∆Sq ) -21.8 eu; and (10) Ea )
4.5 kcal/mol, log A ) 9.55 s-1, ∆Sq ) -16.5 eu. The large
negative activation entropies are not in accord with na¨ıve
expectations for a fragmentation of 1 molecule to 3 products,
as in eq 2, but are in the typical range for SN1-SN2 reactions.17
Chloride Dependence. The unexpectedly high kfrag and low
∆Sq values for the fragmentation of carbenes 9 and 10, together
with the striking increases in 1-BuCl and i-BuCl product
formation elicited by added Cl-, suggest the intervention of
bimolecular SN2-like fragmentations, in which these carbenes
(or tight ion pairs derived from them, see below) are attacked
by Cl- at their R carbons, eq 3.18,19 This suggestion is strongly
formation, ky,16 and a Y intercept of 2.1 × 106 s-1; cf., Figure
1. The intercept represents the sum of rate constants for those
processes that destroy carbene 9 when the concentration of
pyridine is zero. At first glance, this appears to be the sum of
the rate constant for fragmentation (kfrag) and the rate constant
for the formation of dichloride 12, which is a major product in
the absence of pyridine (Table 1). However, the intercept is
extrapolated from reactions run in the presence of pyridine.
Under these conditions, HCl is scavenged, the formation of 12
is suppressed,7 and fragmentation (Table 1) or pyridine capture
become the principal modes of carbene decay. The extrapolated
Y intercept of the correlation in Figure 1 therefore is a good
estimate of kfrag for carbene 9.
Repetition of these experiments afforded a second value for
kfrag of 1.4 × 106 s-1, leading to an average value of (1.75 (
0.35) × 106 s-1. The average rate constant for ylide formation
supported by additional kinetic evidence. LFP of diazirines 8
in MeCN with a constant concentration (5.77 M) of pyridine
and varying quantities (0.042-0.504 M) of added Bu4NCl give
linear correlations of kobs for the formation of ylides 14 as a
function of [Cl-]; see Figure 3. The slopes of these correlations
can be taken as the second-order rate constants (k2) for
quenching (i.e., fragmentation of the carbenes induced by
chloride.)12,20,21
is ky ) (3.0 ( 0.3) × 105 M-1 s-1
.
In a similar manner, we determined kfrag for i-BuOCCl (10);
cf., Figure 1. Two LFP runs afforded kfrag ) (1.9 ( 0.1) × 106
s-1 and ky ) (1.7 ( 0.06) × 105 M-1 s-1. We note that kfrag is
experimentally the same for carbenes 9 and 10. For PhCH2-
OCCl (2), kfrag ) 6.9 × 105 to 1.3 × 106 s-1, depending on the
data analysis.7 These results are surprising in that the “unsta-
bilized” primary alkyl species, 9 and 10, appear to fragment as
rapidly as the benzylic oxacarbene, 2, which seems out of line
with rate-determining fragmentation to alkyl cations, eq 2.
The linear fits in Figure 3 are quite good; the calculated
standard deviations are <10% for the slopes and intercepts of
the constituent correlations of kobs vs [pyridine], and of kobs vs
(17) See Gordon, A. J.; Ford, R. A. The Chemist’s Companion; Wiley:
New York, 1972; p 138ff.
Arrhenius LFP studies of the fragmentation reactions of
carbenes 9 and 10 were conducted over the temperature range
(18) Additions of Cl- at the carbenic centers of 9, 10, or 2 would yield
RCH2OCCl2-, but these carbanions should rapidly revert to carbenes by
Cl- loss.19 Note (Tables 1 and 2) that ethers 12 are suppressed, not enhanced,
by added chloride.
(16) Alkoxychlorocarbenes are ambiphilic and react “slowly” with
pyridine.14
(19) Hine, J. DiValent Carbon; Ronald Press: New York, 1964; p 70.

Bimolecular Fragmentation of Alkoxychlorocarbenes
J. Am. Chem. Soc., Vol. 121, No. 25, 1999 5943
monoxide in the gas-separated ion pairs, 5; once formed, such
ion pairs might not readily revert to the parent carbene.
Differentiation of the “classical” SN2 attack of Cl- on carbenes
9 and 10 from a SN2-like attack of Cl- on very tight ion pairs
derived from 9 or 10 is, therefore, very difficult. We are hopeful
that ab intio calculations, now in progress, may shed further
light on this question.26
The evidence is strong that carbenes 9 and 10 fragment in
the presence of Cl- by an SN2-like process, but what is the
mechanism in the absence of added chloride? We speculate that
the SN2 mechanism persists, using Cl- generated during initial
ROCCl f RO+dC Cl- ionization27 and, subsequently, Cl- that
is liberated during alkene formation.28
Finally, LFP of diazirine 8 (R ) PhCH2) in 1,3,5-trimethoxy-
benzene (TMB)-MeCN affords a [TMB]-dependent transient
absorbing at 410-430 nm, consistent with the cyclohexadienyl
cation formed by the trapping of the benzyl cation from the
fragmentation of 2;29 a similar transient is not observed during
an analogous experiment with n-butoxychlorodiazirine, sug-
gesting that the primary butyl cation is not liberated during the
fragmentation of carbene 9, either because the fragmentation
follows the SN2 mechanism or because the ion pair (5) formed
from 9 is much too tight or evanescent. Details of these
experiments and of computational studies26 will be published
in due course.
Figure 3. Examples of correlations of kobs for the formation of ylides
14 (106 s-1) from carbenes 9, 10, and 2 as a function of added Bu4NCl
(M) in 5.77 M pyridine-MeCN solutions at 24 °C: (2) 9, (+) 10,
and (b) 2.
[Cl-]. At [Cl-] ) 0, the Y intercepts of the correlations should
equal kobs for ylide formation at 5.77 M pyridine. This agreement
is observed: for carbene 9, the intercept is (3.89 ( 0.173) ×
106 s-1, whereas kobs(5.77 M pyridine) ) (3.52 ( 0.512) × 106
s-1, while for carbene 10, the analogous values are (3.06 (
0.042) × 106 and (2.86 ( 0.122) × 106 s-1
.
The values of k2 (M-1s-1) for the ROCCl/Cl- reactions
(Figure 3) are (8.2 ( 0.23) × 106, (2.7 ( 1.43) × 106, and (2.2
× 106) for carbenes 9, 10, and 2, in accord with expectations
for the SN2 mechanism depicted in eq 3. Thus, k2 is highest for
the straight-chain, primary n-BuOCCl, and is lowest for the
benzylic PhCH2OCCl, where “unimolecular” decomposition via
ion pair 54b will compete with chloride attack. We should not
be surprised that 9 and 10 fragment in a bimolecular fashion.
Their [CtO Cl-] leaving group is isoelectronic to the [NtN X-]
leaving group of the chiral R-D-substituted n-butyl- and
isobutyldiazonium ions which decompose in water with 96%
inversion, indicative of SN2-like solvolysis.22
Experimental Section
Solvents. Acetonitrile (Fisher, Certified A.C.S.) and pyridine (Fisher,
Certified A.C.S.) were dried by reflux over CaH2, followed by
distillation and storage over 5A molecular sieves. Pentane (Fisher,
HPLC grade) was also stored over 5A molecular sieves.
O-(Isobutoxy)isouronium p-Toluenesulfonate (11, R ) i-C4H9).
This material was prepared by the method of Smith and Stevens.3a
Anhydrous p-toluenesulfonic acid was obtained by heating the com-
mercially available monohydrate (30 g, 0.16 mol) under high vacuum
at 80-90 °C for 10 h. A mixture of isobutyl alcohol (18 mL, 0.2 mol),
cyanamide (5.0 g, 0.12 mol), and 21 g of anhydrous p-TsOH in 100
mL of dry chloroform was stirred under a nitrogen atmosphere for 5
days. Precipitate isourea tosylate was filtered off, the filtrate was reduced
on the rotary evaporator to ∼15 mL, and ∼ 200 mL of ether was added.
The precipitate of 11 was washed with ether and dried in air to afford
21 g (0.073 mol, 61%) of 11 (R ) i-C4H9), mp 92-94 °C (lit.3a mp
39-45 °C “indefinite”). 1H NMR (200 MHz, DMSO-d6): δ 0.95 (d, J
) 6.7 Hz, 6 H, 2 Me), 1.92-2.06 (m, 1 H, CH), 2.30 (s, 3 H, Ar-
CH3), 4.03 (d, J ) 6.6 Hz, 2 H, CH2O), 7.11-7.15, 7.47-7.51 (A2B2,
2 H + 2 H, Ar), 8.41 (br s, 4 H, 2 NH2).
O-(n-Butoxy)isouronium p-Toluenesulfonate (11, R ) n-C4H9).
The above procedure was followed with 18 mL (0.20 mol) of n-butyl
alcohol to afford 24.2 g (0.084 mol, 70%) of 11 (R ) n-C4H9), mp
89-91 °C. 1H NMR (as above): δ 0.93 (t, J ) 7.0 Hz, 3 H, CH2CH3),
1.33-1.44 (m, 2 H, CH2CH3), 1.63-1.71 (m, 2 H, OCH2CH2), 2.31
(s, 3 H, Ar-CH3), 4.23 (t, J ) 6.4 Hz, 2 H, OCH2), 7.11-7.15, 7.47-
7.51 (A2B2, 2 H + 2 H, Ar), 8.40 (br s, 4 H, NH2).
A referee has suggested that postulation of the SN2 mecha-
nism for 9 and 10 is not essential, and that the kinetic and
product dependence on chloride concentration could also be
explained by an extension of the ion pair mechanism [eq 2], in
which “tight” ion pair formation is reversible, and [ROCCl] >
[ion pair] with d[ion pair]/dt ∼ 0. This suggestion is formally
correct, and is reminiscent of Sneen’s idea that “SN2” reactions
of primary substrates can similarly be understood in terms of
reversibly formed ion pairs and the associated rate constants
for ion pair return and separation.23
Nevertheless, we prefer the SN2 mechanism for the reactions
of 9 or 10 with chloride ion. Thus, the lifetime of the benzyl
cation in 50/50 trifluoroethanol/water is ∼3 × 10-12 s-1 24
, and
those of n-butyl or isobutyl cations would be even shorter. These
systems thus approach the limiting enforced concerted or
“preassociation” (SN2) mechanism.25 A complication in the
fragmentations of ROCCl, however, is the presence of carbon
Anal. Calcd for C12H20N2O4S (288.24): C, 50.0; H, 6.99; N, 9.72.
Found: C, 50.0; H, 6.75; N, 9.63.
3-Chloro-3-isobutoxydiazirine (8, R ) i-C4H9).3a The general
method of Graham was followed.10 To 3.5 g of LiCl in DMSO was
(20) For parallel pseudo-first-order reactions, such as the reactions of
ROCCl with pyridine or Cl-, the rise time of any product (e.g., ylide 14)
equals the sum of the individual rate constants. Thus, at constant [pyridine],
the slope of the kobs(14) vs [Cl-] correlation gives the rate constant for the
reaction of ROCCl with Cl-. See ref 12 for analogous cases and references.
(21) These correlations do not represent salt effects on unimolecular
(26) Sauers, R. R.; Yan, S.; Moss, R. A. Work in progress.
(27) This ionization resembles the ROSOCl f ROSO+Cl- process
believed to occur in “SNi” reactions of primary alkylchlorosulfites:
Schreiner, P. R.; Schleyer, P. v. R.; Hill, R. K. J. Org. Chem. 1993, 58,
2822.
carbene fragmentations; there is essentially no dependence of kobs on 0.05-
0.5 M added Bu4N+BF4
.
-
(22) Brosch, D.; Kirmse, W. J. Org. Chem. 1991, 56, 907.
(23) Sneen, R. A.; Larson, J. W. J. Am. Chem. Soc. 1969, 91, 6031.
Sneen, R. A.; Larson, J. W. J. Am. Chem. Soc. 1969, 91, 362.
(24) Amyes, T. L.; Richard, J. P. J. Am. Chem. Soc. 1990, 112, 9507.
See also: Finnemann, J. I.; Fishbein, J. C. J. Am. Chem. Soc. 1995, 117,
4228.
(28) Indeed, the substantial (>40%) alkene yields attending the decom-
positions of 9 and 10 in pyridine/MeCN may reflect E2-like fragmentations
with pyridine acting as a base.
(29) This methodology was developed by: Pezacki, J. P.; Shukla, D.;
Lusztyk, J.; Warkentin, J. J. Am. Chem. Soc. In press. See also: Steenken,
S.; Ashokkumar, M.; Maruthamuthu, P.; McClelland, R. A. J. Am. Chem.
Soc. 1998, 120, 11925.
(25) Jencks, W. P. Acc. Chem. Res. 1980, 13, 161.

5944 J. Am. Chem. Soc., Vol. 121, No. 25, 1999
Moss et al.
added 2.0 g (0.007 mol) of isouronium salt 11 (R ) i-C4H9) and 15
mL of pentane. The mixture was cooled to 20 °C and stirred
magnetically. Then, 100 mL of 12% commercial aqueous sodium
hypochlorite solution (“pool chlorine”) saturated with NaCl was slowly
added. The reaction temperature was kept below 25 °C during the
addition. After the addition was complete, stirring was continued for
15 min at 15 °C. The reaction mixture was transferred to a separatory
funnel containing 150 mL of ice water, the aqueous phase was removed,
and the pentane phase was washed twice with ∼75 mL portions of ice
water, and then dried for 2 h over CaCl2 at 0 °C. The pentane/diazirine
solution was purified by chromatography over Aldrich 200-400 mesh,
60 Å, silica gel, eluted with cold pentane. All fractions were kept at 0
°C. Pentane was reduced by rotary evaporation (behind a shield)30 and
replaced by acetonitrile. The remaining pentane was then removed by
rotary evaporation at 0 °C. We thus obtained ∼30 mL of an acetonitrile
solution of diazirine 8 (R ) i-C4H9); UV (λmax) 352 (pentane), 356 nm
and the system was evacuated to 1-2 Torr. A shield was placed in
front of the traps during the reaction.30 The hypochlorite was then added
slowly with stirring over 15 min. After the addition, stirring was
continued for 10 min. At the end of the reaction, the diazirine had
collected in the fourth trap. The trap was equilibrated with the
atmosphere and the contents were allowed to slowly warm to room
temperature. Next, the diazirine-MeCN solution was dried over CaCl2
for 2 h. The chromatographic method was the same as described above,
but dry MeCN was used as the eluent. The chromatography afforded
∼25 mL of diazirine in MeCN (A356 ) 3.0).
Photolysis of Diazirines. Solutions of diazirines 8 in MeCN (3 mL)
with or without added 0.504 M Bu4NCl or 5.77 M pyridine were
photolyzed at 25 °C for 20 min with a focused Oriel lamp, λ > 320
nm (uranium glass filter). The products were analyzed by capillary GC
and by GC-MS. For the i-BuOCCl products, we used a 30 m × 0.25
mm (o.d.) × 0.25 µm (i.d.) HPInnowax (cross-linked poly(ethylene
glycol)) column at 25 °C (3 min), programmed to 200 °C at 30 deg/
min. For low boiling products, we used a SPB-20 (20% diphenyl, 80%
dimethylsiloxane) column at -15 °C (4 min), programmed to 200 °C
at 30 deg/min. For the n-BuOCCl products, we employed a CPSil-
5CB (poly(dimethylsiloxane)) column at 25 °C (3 min), programmed
to 200 °C at 30 deg/min. Lower boiling products were analyzed as
above. For the products of PhCH2OCCl, we used the Innowax column
(see above) at 150 °C, programmed to 200 °C at 30 deg/min. Products
are described above; see Tables 1 and 2 and text. Product identities
were confirmed by GC and GC-MS comparisons to authentic samples
(Aldrich), while dichloride 12 and azine 13 were identified by GC-
MS.
1
(MeCN); A356 ) 3.0. H NMR (CDCl3): δ 0.89 (d, J ) 6.8 Hz, 6 H,
2 Me), 1.83-2.01 (m, 1 H, CH), 3.67 (d, J ) 6.6 Hz, 2 H, CH2).
3-Chloro-3-n-butoxydiazirine (8, R ) n-C4H9). This material was
prepared in the same manner as the isobutoxy analogue (above). We
obtained ∼30 mL of an acetonitrile solution of diazirine 8 (R ) n-C4H9);
UV (λmax) 353 (pentane), 356 nm (MeCN); A356 ) 3.0. 1H NMR
(CDCl3): δ 0.88 (t, J ) 6.8 Hz, 3 H, CH3), 1.20-1.21 (m, 2 H,
CH3CH2), 1.53-1.69 (m, 2 H, CH2CH2O), 3.91 (t, J ) 6.4 Hz, 2 H,
CH2O).
Alternative Diazirine Preparation. The foregoing preparation10
affords MeCN solutions of diazirine that contain traces of pentane.
These solutions are adequate for LFP experiments, but the pentane
interferes with GC product analysis. For product studies, we therefore
used an alternative diazirine preparation adapted from Smith and
Stevens.3a
Isouronium salts 11 (R ) i-C4H9 and n-C4H9, 1 g, 0.0006 mol),
lithium chloride (3.5 g), and 100 mL of DMSO were placed in a three-
necked flask equipped with a dropping funnel and magnetic stirrer.
The flask was connected to a train of 4 traps, the last one containing
∼7 mL of dry MeCN. A glass U tube containing KOH pellets was
placed between the first and second traps. The first trap attached to the
reaction flask was kept between -10 and -20 °C throughout the
reaction, while the second, third, and fourth traps were kept at -30,
-40, and -196 (liquid N2) °C, respectively. After the salts had been
dissolved in the DMSO, sodium hypochlorite (12%) saturated with NaCl
was placed in the dropping funnel, the mixture was cooled to 0 °C,
Laser Flash Photolysis. These experiments were performed with a
Lambda Physik COMPex model 120 excimer laser using a Spectra
Gases fill of 0.1875% F2, 0.468% Xe, and 99.334% Ne. The laser
emitted 10 ns pulses at 351 nm and 80 mJ. The detection unit comprised
a 1000 W Oriel xenon arc lamp, a 1 in. Uniblitz shutter, Instruments
SA grating monochromator, and a RCA 4840 photomultiplier tube wired
in a 5-dynode configuration. The data collection and analysis system
included a Stanford Research Systems model DG535 4-channel digital
delay/pulse generator and a Tektronix TDS 320 2-channel oscilloscope.
Data analysis used the Igor Pro 2.00 program (Wave Metrics, Inc.).
Acknowledgment. We are grateful to Dr. John Pezacki and
Professor John Warkentin for helpful discussions. We thank the
National Science Foundation for financial support.
(30) All diazirine preparations were carried out behind shields. No
explosions were encountered, but these compounds are explosive, and neat
diazirines must be avoided.
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