Fragmentation of menthyl- and neomenthyloxychlorocarbenes: Elimination and substitution reactions of alicyclic oxychlorocarbenes

Article abstract of DOI:10.1021/jo030100y

Fragmentations of menthyloxychlorocarbene (5) and neomenthyloxychlorocarbene (6) follow distinct pathways to (largely) stereochemically retained substitution products from 5 and elimination products from 6, closely resembling the product distributions from deaminations of the corresponding menthyl- and neomenthylamines.

Full text of DOI:10.1021/jo030100y

F r a gm en ta tion of Men th yl- a n d Neom en th yloxych lor oca r ben es:
Elim in a tion a n d Su bstitu tion Rea ction s of Alicyclic
Oxych lor oca r ben es
Robert A. Moss,* Lauren A. J ohnson, Monica Kacprzynski, and Ronald R. Sauers
Department of Chemistry and Chemical Biology, Rutgers, The State University of New J ersey,
New Brunswick, New J ersey 08903
moss@rutchem.rutgers.edu
Received March 17, 2003
Fragmentations of menthyloxychlorocarbene (5) and neomenthyloxychlorocarbene (6) follow distinct
pathways to (largely) stereochemically retained substitution products from 5 and elimination
products from 6, closely resembling the product distributions from deaminations of the corresponding
menthyl- and neomenthylamines.
In tr od u ction
TABLE 1. P r od u ct Distr ibu tion s fr om
Cycloh exyloxych lor oca r ben e (4)a
The fragmentation of alkoxychlorocarbenes (1) consti-
tutes an intersection of carbene, carbocation, elimination,
and substitution chemistry. In polar solvents, the frag-
additive
cyclohexyl chloride cyclohexene
1
none
69.7
73.6
67.4
73.3
30.3
25.4
32.6
26.7
5
0
0
.77 M pyridine
.504 M Cl
.504 M Cl and 5.77 M pyr
mentations proceed through tight, short-lived ion pairs;
-
eq 1.1 When R is chiral, RCl is formed by anion return
-3
-
a
In DCE at 25 °C; distributions in percent.
NaOCl furnished alkoxychlorodiazirines 3, which were
with substantial but incomplete stereochemical retention,
purified by column chromatography (silica gel, pentane)
4
e.g., for R ) PhCHD, 60-80% net retention in MeCN,
and characterized by NMR and UV spectroscopy.
9
5
and for R ) 2-butyl, 56% net retention in MeCN. When
loss of a â-proton is feasible, net elimination of HCl
produces alkenes, in addition to RCl, e.g., in the frag-
mentations of exo- and endo-2-norbornyloxychlorocar-
benes.6
Alicyclic systems are well suited to a simultaneous
study of the stereoselectivity of fragmentation-initiated
substitution reactions, coupled with an evaluation of the
competing elimination reactions. Here, we report instruc-
tive results from the fragmentations of cyclohexyl-,
menthyl-, and neomenthyloxychlorocarbenes.
Photolysis of 3 (R ) cyclohexyl) in MeCN or 1,2-
dichloroethane (DCE) afforded cyclohexyloxychlorocar-
bene (4) and thence cyclohexyl chloride (62 or 70%) and
10,11
cyclohexene (32 or 30%),
representing the fragmenta-
tion of 4, followed either by the collapse of the ion pair
or loss of HCl; eq 2.
Resu lts a n d Discu ssion
Cyclohexanol, menthol, and neomenthol were each
converted to the corresponding isouronium methane-
sulfonate salts, 2, with cyanamide and methanesulfonic
7
8
Table 1 summarizes the product distributions from 4
in DCE. Experiments were also conducted with added
pyridine to mimic our laser flash photolytic kinetics
experiments (see below) and with added chloride ion
acid in THF. Graham oxidation of 2 with 12% aqueous
(
1) Moss, R. A. Acc. Chem. Res. 1999, 32, 969.
(2) Moss, R. A.; Ma, Y.; Zeng, F.; Sauers, R. R.; Bally, T.; Maltsev,
A.; Toscano, J . P.; Showalter, B. M. J . Phys. Chem. A. 2002, 106, 12280.
3) Moss, R. A.; Zeng, F.; Fed e´ , J .-M.; Sauers, R. R. Org. Lett. 2002,
, 2341.
(0.504 M tetrabutylammonium chloride) to determine if
(
4
(
(
(
4) Moss, R. A.; Kim, H. R. Tetrahedron Lett. 1990, 31, 4715.
5) Moss, R. A.; Balcerzak, P. J . Am. Chem. Soc. 1992, 114, 9386.
6) Moss, R. A.; Zeng, F.; Sauers, R. R.; Toscano, J . P. J . Am. Chem.
(9) λmax (nm) for all three diazirines: 354 (pentane), 356 (MeCN),
359 (dichloroethane).
(10) All products were identified by capillary GC spiking experi-
ments with authentic materials and by GC-MS.
(11) In MeCN, 6% of N-cyclohexylacetamide (Ritter product) was
formed by carbene attack on the solvent, followed by hydrolysis by
traces of water.
Soc. 2001, 123, 8109.
7) Moss, R. A.; Kaczmarczyk, G. M.; J ohnson, L. A. Synth. Commun.
000, 30, 3233.
8) Graham, W. H. J . Am. Chem. Soc. 1965, 87, 4396.
(
2
(
1
0.1021/jo030100y CCC: $25.00 © 2003 American Chemical Society
Published on Web 06/03/2003
5
114
J . Org. Chem. 2003, 68, 5114-5118

Fragmentation of Menthyl- and Neomenthyloxychlorocarbenes
SCHEME 1a
TABLE 2. P r od u ct Distr ibu tion s (%) fr om
a
Men th yloxych lor oca r ben e (5)
solvent
DCEc
additive
7
8
9
10 menthyl formateb
59.0 16.5 11.1 2.4
2.6
1.7
3.1
5.7
tr
d
TBACe 46.9 16.3 24.5 4.9
56.0 25.7 8.1 2.7
DCE
MeCNf
g
TBACe 40.1 11.1 24.2 4.0
54.9 15.9 14.1 2.8
MeCN
1
,4-Dioxaneh
a
At 25 °C. b See ref 13. c Four unknown products totaling 8.4%
d
were formed. Four unknown products totaling 5.7% were also
formed. 2.52 M tetrabutylammonium chloride. Three unknown
products totaling 4.4% were also formed. Three unknown prod-
ucts totaling 14.9% were also formed. Five unknown products
e
f
g
h
totaling 12.3% were also formed.
TABLE 3. P r od u ct Distr ibu tion s (%) fr om
a
Neom en th yloxych lor oca r ben e (6)
a
Product distributions are in percent, as determined by GC;10,13
neomenthyl
the menthyl-OCCl (5) distribution appears first.
solvent
DCEc
additive
7
8
9
10
formateb
5.4
Similar overall patterns are found in MeCN and
dioxane solvents. In MeCN, 7/8 is 56.0/25.7, correspond-
ing to 37% net retention in chloride return, somewhat
less than the 56% net retention observed in DCE. This
may be due to the greater polarity of MeCN (dielectric
constant of 36.6 at 20 °C) relative to DCE (dielectric
constant, 10.4), with attendant greater loss of stereo-
chemical “memory” in a longer lived ion pair in the more
polar solvent. In dioxane (dielectric constant 2.2), the
stereochemical result is 55% net retention, very similar
to the outcome in DCE. The dominance of 3-menthene
2.9
2.3
tr
1.8
tr
7.8 58.7 16.2
1.5 69.5 21.6
6.9 61.5 13.7
1.5 73.3 20.0
15.5 51.1 20.0
d
TBACe
DCE
MeCNf
9.4
1.0
g
TBACe
MeCN
1
,4-dioxaneh
a
5 °C. b See ref 13. Three unknown products totaling 9.0%
were also formed. Two unknown products totaling 5.1% were also
formed. 2.52 M tetrabutylammonium chloride. Two unknown
products totaling 8.5% were also formed. One unknown product
c
2
d
e
f
g
h
(
3.4%) was present. Four unknown products totaling 12.3% were
also formed.
(
9) over 2-menthene (10) persists in all three solvents,
chloride-induced S
N
2 fragmentation12 of carbene 4 was
and the overall ratio of substitution (return) to elimina-
tion is 7.6 in MeCN and 4.2 in dioxane, compared to 5.6
in DCE.
The effect of added chloride ion in DCE or MeCN is
mainly to increase elimination, especially to 3-menthene,
at the expense of the substitution products. The chloride
an important process. Cyclohexyl chloride increases very
slightly in the presence of 5.77 M pyridine, but not in
the presence of chloride ion. There is no evidence for an
N
S 2 component to the fragmentation of 4, which, we
conclude, follows the unimolecular pathway of eq 1, with
ion pair return to cyclohexyl chloride somewhat more
than twice as efficient as HCl elimination to cyclohexene.
We next examined the fragmentations of the confor-
mationally “locked” menthyl- (5) and neomenthyloxy-
chlorocarbene (6), generated by the photolysis (λ ∼ 350
+
functions mainly as a base to accept H , rather than as
a nucleophile to afford substitution product 8, by S 2
N
attack12 on carbene 5. As a base, the added chloride ion
can divert the ion pair toward alkene by accepting a
â-proton. The tertiary axial proton at C-4, removal of
which leads to the more highly substituted alkene isomer
(3-menthene), is a particularly attractive target.
In contrast, neomenthyloxychlorocarbene (6), with an
axial carbene moiety (6′), affords mainly elimination
products 9 (58.7%) and 10 (16.2%) in DCE, distantly
followed by chloride return products 8 (7.8%) and 7
(2.9%); see Table 3. The return products are again formed
with net retention (46%), but the striking difference
between the fragmentations of 6 and 5 is the dominance
of elimination pathways in the former case. For carbene
6, substitution/elimination ) 0.14, whereas this ratio is
5.6 for carbene 5.
nm) of the appropriate diazirines (3) in MeCN, DCE, or
,4-dioxane. The products1 and their distributions from
0,13
1
5
are shown in Table 2, while those from carbene 6
appear in Table 3. Scheme 1 illustrates the products,
together with the representative DCE distributions.
From the fragmentation of menthyloxychlorocarbene
(5), where the carbene moiety is equatorial (5′), we obtain
5
9% of the return (substitution) product, menthyl chlo-
ride (7), formed with retention, along with 16.5% of the
inverted return product, neomenthyl chloride (8); see
Table 2. The 7/8 distribution corresponds to 56% net
retention in the return process. There is also 13.5% of
elimination, with the expected dominance of the more
highly substituted 3-menthene (9, 11.1%) over 2-men-
thene (10, 2.4%). Note that 3-menthene formation here
constitutes “cis” elimination. The overall ratio of substi-
tution (return) to elimination is 5.6.
(
12) Moss, R. A.; J ohnson, L. A.; Merrer, D. C.; Lee, G. E., J r. J .
Am. Chem. Soc. 1999, 121, 5940.
13) In addition to the fragmentation products shown in Scheme 1,
Again, these trends are maintained in MeCN and
dioxane solvents, with minor variations, and as with
carbene 5, addition of chloride ions in DCE or MeCN
solvents leads to enhanced elimination, rather than to
an increase of inverting substitution.
(
1
-10% of menthyl formate (from 5) and neomenthyl formate (from 6)
were formed through trapping of the carbenes by adventitious water.
The formates were identified by GC and GC-MS comparisons with
authentic materials prepared from menthol or neomenthol.
J . Org. Chem, Vol. 68, No. 13, 2003 5115

Moss et al.
SCHEME 2a
a
Deamination of menthyl- and neomenthylamine with NaNO2, HOAc, and H2O at 60 °C; cf. ref 16. Product distributions are in percent,
1
0,13
as determined by GC;
the menthylamine (11) distribution appears first.
We have previously noted the parallel between carbene
fragmentation, in which CO is lost, and deaminative
observations extend to the deaminations of cis- and trans-
4-tert-butylcyclohexylamine.17 Indeed, the fragmentations
of cis- and trans-4-methylcyclohexyloxychlorocarbenes
1
,14
processes in which N
2
is the leaving group.
This
analogy was first proposed by Skell and Starer,1 but not
until the present instance has it been subjected to really
detailed stereochemical and substitution/elimination scru-
tiny. For comparison to Scheme 1, deaminations of
menthylamine (11) and neomenthylamine (12) with
aqueous nitrous and acetic acids provide the substitution
5
follow a similar pattern.
18
Clearly, deaminations of 11 and 12 do not pass through
equilibrated 3-menthyl cations; the product manifolds
remain distinct. Diazonium ions 16 and 17 may be paired
with anions, possibly H-bonded to water molecules, thus
1
7
leading to net retention in substitution processes. When
the diazonium leaving group is axial, loss of a â axial
proton (to an anion or water) is stereoelectronically
facilitated, and elimination dominates. For the fragmen-
tations of 5 and 6, short-lived ion pairs provide analogous
product-forming pathways. These ion pairs do not equili-
brate within their short lifetimes; “memory” of their
origin persists. The very close analogies between the
menthyl and neomenthyl product distributions for the
fragmentations of alkyldiazonium ions 16 and 17 and
alkoxychlorocarbenes 5′ and 6′ supports the contention
that the carbene fragmentations, like the diazonium ion
decompositions,17 are ionic.
(
13, 14), elimination (9, 10), and hydride-shift (15)
1
6
products illustrated in Scheme 2.
1
6
The deamination product distributions of Feltkamp
are remarkably similar to those of the corresponding
carbene fragmentations (Scheme 1). From menthylamine,
where nitrous acid deamination proceeds via equatorial
diazonium ion 16, one obtains 63.8% of substitution
(solvolysis) product menthol (13), formed with retention,
accompanied by 11.5% of inverted solvolysis product
neomenthol (14). There is 69% net retention in the
solvolysis of 16, compared to 56% net retention in the
fragmentation of carbene 5′ (see above). Elimination
(
5.4%) is a minor process, with 3-menthene (9) the
dominant olefin. The substitution/elimination ratio is
3.9.
We also measured absolute rate constants for the
fragmentations of cyclohexyloxychlorocarbene (4) and
1
12,19
carbenes 5 and 6 by laser flash photolysis (LFP)
of
diazirines 3 at 351 nm using UV detection and pyridine
ylide visualization.20 Thus, LFP at 351 nm and 25 °C in
DCE of diazirine precursors 3 (A350 ) 1.0) in the presence
of pyridine produced absorptions at 430-432 nm due to
the formation of ylides 18. Correlations of the apparent
rate constants for ylide formation vs pyridine concentra-
tion were linear, with slopes representing the rate
constants for ylide formation (k
y
) and Y-intercepts rep-
From neomenthylamine (12), one obtains via axial
resenting the rate constants for carbene fragmentation,
diazonium ion 17, 56.5% of 3-menthene and 2-menthene
in a distribution of ∼ 7.1:1, accompanied by solvolysis
products 14 (10.4%) and 13 (6.4%). Again, solvolysis
proceeds with net retention (24%). As with carbene
fragmentation, elimination is dominant for the neomen-
thyl substrate: in the deamination of 12, elimination/
substitution ∼ 3.4.
1
9,20
k
frag
.
The rate constants are collected in Table 4.
The axial leaving group f elimination, equatorial
leaving group f substitution pattern is paradigmatic for
the decomposition of alicyclic diazonium ions; similar
These rate constants are “normal” for sec-alkyloxychlo-
rocarbenes. For example, kfrag for cyclopentyloxychloro-
4
-1 6
carbene in DCE is 8.7 × 10 s . We do note that kfrag
(14) Moss, RA.; Ma, Y. Tetrahedron Lett. 2001, 42, 6045.
(15) Skell, P. S.; Starer, I. J . Am. Chem. Soc. 1959, 81, 4117.
(16) Feltkamp, H.; Koch, F.; Thanh, T. N. Annalen 1967, 707, 95.
(17) See the discussion in Zollinger, H. Diazo Chemistry II; VCH
Publishers: New York, 1995; p 278ff and references therein.
5
116 J . Org. Chem., Vol. 68, No. 13, 2003

Fragmentation of Menthyl- and Neomenthyloxychlorocarbenes
TABLE 4. Ra te Con sta n ts for Ca r ben e F r a gm en ta tion a
P r ep a r a tion of 3-Ch lor o-3-cycloh exyloxyd ia zir in e. Cy-
cloh exyl Isou r on iu m Meth a n esu lfon a te. Into a 100 mL
7
carbene
kfrag (s-1)
ky (M-1s-1
)
round-bottom flask fitted with a CaCl
2
drying tube and
4
5
4
3
4
4
5
6
3.3 ( (0.02) × 10
3.0 ( (0.4) × 10
7.5 ( (0.7) × 10
4.3 ( (0.3) × 10
magnetic stirring bar were placed 2.0 g (47.6 mmol) of
cyanamide and 57.0 g (0.57 mol) of cyclohexanol. To this
solution was added 4.6 g (47.6 mmol) of methanesulfonic acid.
The reaction mixture was stirred at room temperature for 24
h. The mixture was then diluted with 300 mL of ether,
whereupon a white precipitate formed. This solid was filtered,
washed with 3 × 50 mL of ether, and then dried under high
vacuum at room temperature, affording 10.6 g (44.9 mmol,
4
6.1 ( (0.4) × 10
1.2 ( (0.06) × 10
a
At 25 °C in DCE. Errors are average deviations of two
experiments.
for 6 (axial carbene) is about twice that of 5 (equatorial
carbene).
1
95%) of 2 (R ) cyclohexyl). Mp: 77-79 °C. H NMR (200 MHz,
DMSO-d ): δ 1.22-1.95 (m, 10H), 2.39 (s, 3H), 4.60-4.72 (br
6
13
m, 1H), 8.46 (br s, 4H). C NMR (100 MHz, DMSO-d
4.3, 38.9, 39.7, 78.9, 160.7.
2
Anal. Calcd for C S‚0.4 H O: C, 39.1; H, 7.7; N, 11.4
6
): δ 22.7,
Con clu sion
2
8
H
18
N
2
O
4
The fragmentations of menthyloxychlorocarbene (5)
and neomenthyloxychlorocarbene (6) follow distinct path-
ways to (largely) stereochemically retained substitution
products from 5 and elimination products from 6, closely
resembling the product distributions from deaminations
of the corresponding menthyl- and neomenthylamines.
These carbene fragmentations, like the decompositions
of the alkyldiazonium ion intermediates of the amine
deaminations, are readily understood in terms of short-
lived ion pair intermediates in polar solvents.
Found: C, 38.7; H, 7.3; N, 11.8. (The solid salt was hygro-
scopic.)
3
-Ch lor o-3-cycloh exyloxyd ia zir in e.8 Into a three-neck
round-bottom flask fitted with a dropping funnel, magnetic
stirring bar, and a thermometer were placed 4 g of LiCl, 2.0 g
of the isouronium salt, 100 mL of DMSO, and 50 mL of
pentane. Aqueous NaOCl solution (200 mL; “pool chlorine”,
-
1
2.5% OCl) was saturated with NaCl and added to the
reaction solution with stirring, maintaining the temperature
below 30 °C. After this addition, stirring was continued for
another 15 min at room temperature. The reaction solution
was poured into a separatory funnel containing 200 mL of ice-
water, and the pentane layer was separated, washed with ice-
Exp er im en ta l Section
water (2 × 200 mL), and dried over CaCl
2
. The pentane
solution was passed through a silica gel column (pentane
Gen er a l Meth od s. Melting points are uncorrected. Proton
NMR spectra were determined at 200, 300, or 400 MHz. 13
C
eluent), affording diazirine 3 (R ) cyclohexyl). We obtained
NMR spectra were measured at 75 or 100 MHz. Chemical
shifts are reported in ppm (δ) relative to TMS. GC-MS data
were obtained using a 5% phenyldimethylpolysiloxane column
attached to a mass selective detector. Photolyses were con-
ducted with a photochemical reactor equipped with RPR-3500
bulbs (λ ) 350 nm) or with a UV lamp with a uranium glass
filter (λ > 330 nm). UV spectra were determined on a diode
array spectrophotometer.
Acetonitrile and pyridine were dried by distillation from
2
CaH and stored over molecular sieves. 1,4-Dioxane was dried
over KOH and distilled from sodium benzophenone under N
prior to use. All other chemicals were used as received.
MeCN or DCE solutions of the diazirine: UV λmax 352 nm
1
(
pentane), 356 nm (MeCN), 359 nm (DCE); A356 ) 1.0. H NMR
(
400 MHz, CD
3
CN): δ 1.20-2.10 (m, 10 H), 4.10-4.20 (m, 1H).
C NMR (100 MHz, DMSO-d ): δ 23.3, 25.2, 31.9, 70.2, 77.9.
P r epar ation of 3-Ch lor o-3-m en th yloxydiazir in e. 3-Men -
th ylisou r on iu m Meth a n esu lfon a te a n d Tr ifla te. Into a
00 mL round-bottom flask fitted with a CaCl drying tube
13
6
1
2
and magnetic stirring bar were placed 22.3 g (0.143 mol) of
menthol, 2.0 g (47.6 mmol) of cyanamide, and 20 mL of
anhydrous THF. To this solution was slowly added 4.21 mL
2
(
3 3
47.6 mmol) of CH SO H. The mixture was stirred at room
temperature for 24 h, and then 300 mL of ether was added.
Upon addition of the ether, an oil formed at the bottom of the
flask. This oil was washed twice with 100 mL of ether, and
then the residual ether was removed by rotary evaporation
giving isouronium salt 2 (R-3-menthyl) as an oil. Although this
oil was used in most experiments, it was difficult to obtain as
a completely pure compound suitable for elemental analysis.
LFP experiments utilized a Lambda Physik COMPex 120
XeF excimer laser. The xenon fluoride laser produced pulses
at 351 nm with 14-ns durations and an average power of 35-
5
0 mJ /pulse. The laser beam was focused by a plano-convex
lens to irradiate the sample cell at a 90° angle to the
monitoring beam. The detection light source was an Oriel
1
000-W HG(Xe) arc lamp; exposure of the sample to the lamp
A similar salt was prepared with the triflate counterion,
was controlled by a fast, 1-in. Uniblitz shutter. Light was
transmitted through the sample into an ISA H-10 grating
monochromator, followed by an RCA 4840 photomultiplier tube
-
CF
3
SO
3
. Both salts react to form the same diazirine through
Graham oxidation. The triflate salt was prepared in exactly
the same manner as the mesylate salt, but CF SO H (7.14 g,
7.6 mmol) was used instead of CH SO H. After 24 h, the
3
3
(PMT) wired in a five dynode configuration. The output of the
4
3
3
PMT was transmitted to a Tektronix TDS 520A or 320 two
channel oscilloscope. The sequencing of the experiments was
controlled by a Stanford Research Systems DG535 four chan-
nel digital delay/pulse generator. Data were processed with
Igor Pro 2.0 software (Wavemetrics, Inc.) on a Macintosh IIsi
computer. Suprasil quartz cuvettes (1 × 1 cm) were used to
hold the samples.
reaction mixture was diluted with 300 mL of pentane and an
oil formed. This oil was washed with 2 × 100 mL of pentane.
The residual pentane was then removed by rotary evaporation,
and then 100 mL of chloroform was added. The solid precipi-
tate was filtered off and discarded, and the chloroform was
removed by rotary evaporation from the filtrate. The isouro-
nium salt (orange oil) which remained was formed in 43% yield
1
(
7.08 g, 20.5 mmol). H NMR (300 MHz, DMSO-d
6
): δ 0.90,
(18) From trans-4-methylcyclohexyloxychlorocarbene (e,e) we obtain
0.88, and 0.76 (3 H, each d, J ) 6.8, 7.2, and 6.8 Hz,
trans-4-methylcyclohexyl chloride (59%), cis-4-methylcyclohexyl chlo-
ride (17%), and 4-methylcyclohexene (16%). From the cis carbene
respectively), 0.70-2.10 (m, 9H), 4.50 (m, 1 H), 8.4 (br m, 4
H). 13C NMR (75 MHz, DMSO-d
): δ 15.9, 20.0, 21.4, 22.6,
6
(
ae,ea), these products are formed in yields of 32, 8, and 47%,
2
5.6, 30.2, 32.9, 39.4, 46.5, 80.6, 120.3, 160.5.
respectively. J ohnson, L. A. Ph.D. Dissertation, Rutgers University,
2
001.
Anal. Calcd for C12
Found: C, 41.13; H, 6.66; N, 7.83.
H
N
O
SF
: C, 41.37; H, 6.65; N, 8.04.
23
2
4
3
(19) Moss, R. A.; Ge, C.-S.; Maksimovic, L. J . Am. Chem. Soc. 1996,
1
18, 9792. Moss, R. A.; J ohnson, L. A.; Yan, S.; Toscano, J . P.;
8
3
-Ch lor o-3-(3-m en th yloxy)d ia zir in e. This material was
Showalter, B. M. J . Am. Chem. Soc. 2000, 122, 11256.
20) J ackson, J . E.; Soundararajan, N.; Platz, M. S.; Liu, M. T. H.
J . Am. Chem. Soc. 1988, 110, 5595.
(
prepared from the foregoing isouronium salt by Graham
8
oxidation in the same manner as 3-chloro-3-cyclohexyloxydi-
J . Org. Chem, Vol. 68, No. 13, 2003 5117

Moss et al.
azirine (see above). The diazirine (3, R ) 3-menthyloxy) had
siloxane)) GC column was utilized. Products included cyclo-
1
1
UV (λmax) 354 nm (pentane), 356 mn (MeCN), 359 nm (DCE),
hexene, cyclohexyl chloride, and N-cyclohexylacetamide. The
identity of cyclohexene was confirmed by a GC spiking
experiment with an authentic sample. GC-MS: m/e 82 (base
1
3
56 nm (1,4-dioxane); A356 ) 1.0. H NMR (200 MHz, CDCl
3
):
δ 0.75-2.40 (m, 9H), 0.77 (d, J ) 6 Hz, 3H), 0.86, 0.96 (2 d, J
1
3
+
)
6 Hz, 6 H), 3.90-4.05 (m, J ) 4 Hz, 1H). C NMR (75 MHz,
CDCl ): δ 15.7, 20.7, 22.1, 23.0, 25.4, 31.5, 34.0, 41.2, 47.1,
0.4, 80.0.
peak, M ).The identity of cyclohexyl chloride was confirmed
3
by a GC spiking experiment with an authentic sample. GC-
MS: m/e 118/120 (M /M + 2), 83 (base peak, M+ - 35). The
+
+
7
P r ep a r a t ion of 3-Ch lor o-3-n eom en t h yloxyd ia zir in e.
identity of N-cyclohexylacetamide was confirmed by a GC
2
1
3
-Neom en th ylisou r on iu m Tr ifla te. Into a 100 mL round-
spiking experiment with an authentic sample. GC-MS: m/e
+
+
bottom flask fitted with a CaCl
2
drying tube and magnetic
141 (M ), 83 (base peak, M - 58).
stirring bar were placed 22.3 g (0.143 mol) of neomenthol, 2.0
g (47.6 mmol) of cyanamide, and 20 mL of anhydrous THF.
From carbenes 5 and 6, products were analyzed by capillary
GC using a HP-5 Trace (5% Ph Me Siloxane) column: The
identity of 2-menthene (10) was confirmed by a GC-spiking
experiment with an authentic sample. The identity of 3-men-
thene (9) was confirmed by a GC spiking experiment with an
authentic sample and by NMR comparison to the literature
To this solution was slowly added 7.14 mL (47.6 mmol) of CF
3
-
SO H. The mixture was stirred at room temperature for 24 h,
3
and then 300 mL of pentane was added. Upon addition of the
pentane, an oil formed at the bottom of the flask. This oil was
washed twice with 100 mL of pentane, and residual pentane
was then removed by rotary evaporation leaving a mixture of
the desired neomenthyl isouronium salt and a byproduct,
isouronium trifluoromethanesulfonate, in a ratio of 0.2/1 as
determined by 1H NMR. (When more isouronium trifluo-
romethanesulfonate was added to this mixture, the NMR peak
for the byproduct increased.) Many unsuccessful attempts were
made to separate the byproduct. However, it is lost during
Graham oxidation to the diazirine, and the NMR spectra of
22
spectrum. The identity of menthyl chloride (7) was confirmed
by a GC-spiking experiment with an authentic sample and by
23
NMR comparison to the literature spectrum. Neomenthyl
chloride (8) was prepared from neomenthol, thionyl chloride
and pyridine (reflux, 2 h), purified by chromatography, and
1
identified by comparison of its H NMR spectrum with the
23
literature spectrum. The product 8 formed from carbenes 5
or 6 was identified by a GC-spiking experiment with the
authentic material and by NMR analysis of product mixtures.
the latter are free of impurities (see below).
1
LF P Stu d ies. Solutions of diazirines 3 in DCE (A356 ) 1.0)
containing 1.65-8.25 M pyridine (1.5 mL total solution) were
irradiated with an XeF excimer laser at 351 nm at 25 °C.
Further description of the methodology and the observed rate
constants (Table 4) can be found in the Results and Discussion.
H NMR (400 MHz, DMSO-d ) for 3 (R ) 3-neomenthyl): δ
6
0
9
(
.74, 0.82, and 0.86 (3 d, J ) 6.4, 6.4, and 7.2 Hz, respectively,
H), 0.70-2.10 (m, 9H), 4.48 (m, 1H), 8.3 (br m, 4H). 13C NMR
6
100 MHz, DMSO-d ): δ 16.3, 20.4, 21.7, 23.0, 26.0, 30.6, 33.3,
3
9.8, 46.9, 81.1, 120.9, 161.2.
-Ch lor o-3-(3-n eom en th yloxy)d ia zir in e. This material
8
3
was prepared from the foregoing isouronium salt by Graham
oxidation in the same manner as 3-chloro-3-cyclohexyloxydi-
Ack n ow led gm en t. We are grateful to the National
Science Foundation for financial support. We thank Dr.
Xiaolin Fu for several additional experiments.
8
azirine (see above). Diazirine 3 (R ) 3-neomenthyl) had UV
(λmax) 354 nm (pentane), 356 nm (MeCN), 359 nm (DCE), 356
1
nm (1,4-dioxane); A356 ) 1.0. H NMR (400 MHz, CDCl
3
): δ
J O030100Y
0
9
.64, 0.92, 1.02, (3 d, J ) 6.4, 6.8, and 7.2 Hz, respectively,
1
3
H), 0.75-2.44 (m, 9H), 4.03 (m, 1 H). C NMR (100 MHz,
): δ 15.8, 20.7, 22.1, 23.0, 25.4, 31.6, 34.0, 41.2, 47.1,
0.4, 80.4.
P r od u ct Stu d ies. From carbene 4, products were analyzed
by capillary GC and GC-MS. A CPSil-5CB (poly(dimethyl-
(
21) Hoeg-J ensen, T.; Olsen, C. E.; Holm, A. J . Org. Chem. 1994,
CDCl
3
5
9, 1257.
7
(22) McCormick, J . P.; Barton, D. L. Tetrahedron 1978, 34, 325.
(23) Drabowicz, J .; Luczak, J .; Mikolajczyk, M. J . Org. Chem. 1998,
63, 9565.
5
118 J . Org. Chem., Vol. 68, No. 13, 2003