Synthesis of bridgehead nitrogen heterocycles via cyclization of α- ammonio 5-hexenyl radicals

Article abstract of DOI:10.1021/jo9813538

Ring-closure of the 2,2-dimethyl-2-azonia-5-hexenyl radical (4) proceeds smoothly and efficiently to give the 5-exo isomer essentially quantitatively, in accordance with predictions based on MP4SDTQ/6-31G* ab initio calculations on the thermodynamic stability of α-ammonio radicals. The corresponding 5-hexynyl radical species 15 and its 6-phenyl derivative 19 display similar behavior affording the analogous 5-exo-3- methylenepyrrolidinium salts in high yield. In none of these cases were the products of reduction were detected. All of the radical intermediates were generated conveniently by treatment of the iodomethyl and/or phenylselenomethyl salts with tributyltin hydride. Application of this procedure to monocyclic precursors such as 1-methyl-1-iodomethyl-4-methylene- 1-azoniacyclohexyl iodide (31) provided an attractive entry into quaternary derivatives of the 1-azabicyclo[2.2.1]heptyl system in good yield via a three-step sequence from 1-methylpiperidone. Dequaternization of the bicyclic salts so obtained unexpectedly leads to rupture of one of the rings rather than loss of the N-methyl group. The 1-azabicyclo[2.2.1]heptane could be accessed readily via tin hydride-induced cyclization of the corresponding N- phenylethylammonium salt 54, followed by Hofmann elimination with potassium tert-butoxide.

Full text of DOI:10.1021/jo9813538

1798
J . Org. Chem. 1999, 64, 1798-1806
Syn th esis of Br id geh ea d Nitr ogen Heter ocycles via Cycliza tion of
r-Am m on io 5-Hexen yl Ra d ica ls
Ernest W. Della* and Paul A. Smith
Department of Chemistry, Flinders University, Bedford Park, South Australia 5042, Australia
Received J uly 13, 1998
Ring-closure of the 2,2-dimethyl-2-azonia-5-hexenyl radical (4) proceeds smoothly and efficiently
to give the 5-exo isomer essentially quantitatively, in accordance with predictions based on
MP4SDTQ/6-31G* ab initio calculations on the thermodynamic stability of R-ammonio radicals.
The corresponding 5-hexynyl radical species 15 and its 6-phenyl derivative 19 display similar
behavior affording the analogous 5-exo-3-methylenepyrrolidinium salts in high yield. In none of
these cases were the products of reduction were detected. All of the radical intermediates were
generated conveniently by treatment of the iodomethyl and/or phenylselenomethyl salts with
tributyltin hydride. Application of this procedure to monocyclic precursors such as 1-methyl-1-
iodomethyl-4-methylene-1-azoniacyclohexyl iodide (31) provided an attractive entry into quaternary
derivatives of the 1-azabicyclo[2.2.1]heptyl system in good yield via a three-step sequence from
1-methylpiperidone. Dequaternization of the bicyclic salts so obtained unexpectedly leads to rupture
of one of the rings rather than loss of the N-methyl group. The 1-azabicyclo[2.2.1]heptane could be
accessed readily via tin hydride-induced cyclization of the corresponding N-phenylethylammonium
salt 54, followed by Hofmann elimination with potassium tert-butoxide.
In tr od u ction
in synthesis, the failure of 3 to ring close seemingly
precludes access to nitrogen-based heterocycles via 2-aza
5-hexenyl radicals.
Substitution of the R-methylene group in the 5-hexenyl
radical by a group incorporating a first row heteroatom,
in particular O or NR, has been found1-4 to exert a
profound influence on the facility for ring closure of the
modified radical relative to the parent species. On one
hand, Rawal and associates1 observed that the oxo radical
1 undergoes smooth exo-trig cyclization to give the
mixture of diastereomeric tetrahydrofurans 2 in high
yield. By contrast, Padwa and associates4 found that the
corresponding 2-aza-2-benzylhexenyl radical 3 failed to
cyclize, and only the product of reduction, 2-aza-2-benzyl-
5-hexene, was isolated. These observations are consistent
with ab initio calculated data5 on radicals with R-het-
eroatom substitution, which demonstrate that radical
stabilization afforded by the presence of R-nitrogen is
significantly greater than that by R-oxygen. The reluc-
tance of the nitrogeneous species 3 compared with the
ability of 1 to undergo cyclization, therefore, can be
ascribed to a significantly higher activation barrier in the
case of the former as a result of its greater thermody-
namic stability. Accordingly, despite the fact that 5-hex-
enyl radical cyclizations have been employed extensively6
Intuitively, one would anticipate that the stabilizing
influence of the lone pair on the nitrogen atom in 3 would
be eliminated if the electrons were otherwise involved
in bond formation, a premise for which we have provided7
theoretical support by an ab initio study at the MP4SDTQ/
6-31G* level as described by Coolidge and Borden.5e Thus,
our calculations of the energies associated with the
isodesmic reaction depicted in eq 1 predict that, whereas
the reaction involving the species with X ) NH2 is highly
endothermic, in agreement with data obtained by Coolidge
and Borden, it becomes significantly exothermic when X
) NH3+. The attachment the of quaternary nitrogen to
the electron-deficient center in the ammoniomethyl radi-
cal is found to exert such a powerful destabilizing effect
(1) Rawal, V. H.; Singh, S. P.; Dufour, C.; Michoud, C. J . Org. Chem.
1993, 58, 7718 and references therein.
(2) J ournet, M., Malacria, M. J . Org. Chem. 1992, 57, 3085. Agnel,
G.; Malacria, M. Synthesis 1989, 687.
(3) Baban, J . A.; Marti, V. P. J .; Roberts, B. P. J . Chem. Soc., Perkin
Trans. 2 1985, 1723.
(4) Nimmesgern, H.; Padwa, A.; Wong, G. K. S. Tetrahedron Lett.
1985, 26, 957. Nimmesgern, H.; Padwa, A.; Wong, G. K. S. J . Org.
Chem. 1985, 50, 5620.
(5) For leading references, see: (a) Brocks, J . J .; Beckhaus, H.-D.;
Beckwith, A. L. J .; Ru¨chardt, C. J . Org. Chem. 1998, 63, 1935. (b)
J urisic, B. S.; Timberlake, J . W.; Engel, P. S. Tetrahedron Lett. 1996,
37, 6473. (c) Gauld, J . W.; Radom, L. J . Phys. Chem. 1994, 98, 777. (d)
Bordwell, F. G.; Zhang, X.-M.; Alnajjar, M. S. J . Am. Chem. Soc. 1992,
114, 7623. (e) Coolidge, M. B.; Borden, W. T. J . Am. Chem. Soc. 1988,
110, 2298. (f) Pasto, D. J .; Krasnansky, R.; Zercher, C. J . Org. Chem.
1987, 52, 3062.
(6) (a) Giese, B.; Kopping, B.; Gobel, T.; Dickhaut, J .; Thoma, G.;
Kulicke, K. J .; Trach, F. In Organic Reactions; Paquette, L. A., Ed.;
Wiley: New York, 1996; Vol. 48, p 301, Chapter 2, 1996. (b) For an
extensive review on radicals in natural product synthesis, see: Curran,
D. P.; Fevig, T. L.; J asperse, C. P. Chem. Rev. 1991, 91, 1237. (c)
Curran, D. P. Synlett 1991, 63. (d) Radikale, C. In Methoden der
Organischen Chimie; Regitz, M., Giese, B., Eds.; Houben-Weyl: Stut-
tgart, 1989; Band E 19a. (e) Curran, D. P. Synthesis 1988, 417 (Part
1), 489 (Part 2). (f) Newman, W. P. Synthesis 1987, 665. (g) Ramaiah,
M. Tetrahedron 1987, 43, 3541. (h) Giese, B. In Radicals in Organic
Synthesis: Formation of Carbon Carbon Bonds; Baldwin, J . E., Ed.;
Pergamon: New York, 1986. (i) Hart, D. J . Science 1984, 223, 883. (j)
Beckwith, A. L. J .; Ingold, K. U. In Rearrangements in Ground and
Excited States; de Mayo, P., Ed.; Academic Press: New York, 1980;
Vol. 1, p 162.
(7) Della, E. W.; Elsey, G. M. Unpublished observations.
10.1021/jo9813538 CCC: $18.00 © 1999 American Chemical Society
Published on Web 02/26/1999

Cyclization of R-Ammonio 5-Hexenyl Radicals
J . Org. Chem., Vol. 64, No. 6, 1999 1799
Sch em e 1
ternary salt 5. Exposure of the latter to tributyltin
hydride gave the salt 7 in quantitative yield in a process
that is presumed to involve the intermediacy and sub-
sequent trapping of the corresponding R-ammonio radical
6 by the reagent. For solubility reasons, reaction of these
salts with Bu3SnH requires a different solvent to the
typical hydrocarbon medium generally employed for
cyclization reactions of this kind. We discovered15 that
the protic solvent, 2-methyl-2-butanol, obviates the major
problem of insolubility and it also possesses the added
advantage that its boiling point (105 °C) provides favor-
able conditions for those cyclizations having a high
activation barrier.
Nevertheless, as described below, some of the iodom-
ethyl salts related to 5 were found to have limited
solubility in 2-methyl-2-butanol, which led to poorer
yields of product because a significant amount of starting
material was always recovered. We have recently ob-
served that the corresponding selenides 8, obtained in
excellent yields from reaction of tertiary amines (R3N)
with bromomethyl phenyl selenide, function as excellent
alternatives to the iodides 5 as precursors to the R-am-
monio radicals, a factor enhanced by their increased
solubility over the iodomethyl salts. It is noteworthy that
Beckwith and Pigou16 report that the reaction of PhSeCH2-
Cl with alkoxide ions gives very poor yields of substitu-
tion and the predominant product is diphenyldiselenom-
ethane. Formation of PhSeCH2SePh was attributed to the
occurrence of a reaction pathway promoted by the strong
basic character of RO- ions. Clearly, the lower basicity
of the amine is a distinct advantage in the synthesis of
the selenide salts 8 because the unwanted side reactions
that accompany the alkoxide substitutions are sup-
pressed. Thus, the reaction of triethylamine with bro-
momethyl phenyl selenide gives an 82:18 mixture of 8 to
triethylammonium bromide, from which the latter could
be removed by chromatography on alumina. Fortunately,
such purification was not required in the case of the
amines used in this work because they gave the product
of substitution only, presumably reflecting their less
hindered nature compared with triethylamine.
on the species that it possesses considerably higher
ground-state energy than either the ethyl or aminoethyl
radical. When translated to the 2,2-dimethyl-2-azonia-
5-hexenyl radical 4, these data suggest that the barrier
to cyclization of 4 should be lower than that of radical 3.
CH3CH3 + XCH2• f CH3CH2• + XCH3
calcd7 ∆H (kcal/mol)
X ) NH2+
+8.2
(1)
X ) NH3
-6.5
In a recent communication paper,8 we reported experi-
mental verification of the validity of these predictions and
showed that, unlike the neutral radicals 3, R-ammonio
radicals 4 undergo facile ring closure. We now wish to
disclose the results of this work in full and to describe
additional applications of this transformation as a valu-
able synthetic strategy. Since our original paper, two
reports have appeared9,10 describing the use of radical
cyclization of nitrogenous distonic radicals in synthesis.
Resu lts a n d Discu ssion
Gen er a tion of r-Am m on io Ra d ica ls. Generation of
radicals adjacent to a positive nitrogen atom has been
described in the literature, and the existence of these so-
called distonic radicals has been accepted for more than
two decades. Although a number of ESR and molecular
orbital studies have been conducted on R-ammonio
radicals,11-14 to our knowledge there was no precedence
at the commencement of this investigation for the use of
these intermediates in synthetic organic chemistry.
Generation of those species above for characterization
purposes was generally achieved via hydrogen abstrac-
tion by reagents such as the tert-butoxy radical, but a
more convenient precursor and practical technique for
its conversion into the radical were required for the
synthetic pathways we had envisaged.
Cycliza tion of Acyclic r-Am m on io Ra d ica ls
Th e 2,2-Dim eth yl-2-a zon ia -5-h exen yl Ra d ica l. As
illustrated in Scheme 2, the salt 10 leading to the
ammonio-5-hexenyl radical 4 was synthesized by treat-
ment at room temperature of N,N-dimethyl-3-buteny-
lamine 9 with excess diiodomethane overnight. Addition
of ether to the reaction mixture caused the precipitation
of 10 in high yield. A solution of tributyltin hydride (1.1
equiv) and a catalytic quantity of AIBN in 2-methyl-2-
butanol was added to a stirred solution (0.025 M) of 10
in 2-methyl-2-butanol held at 80 °C and irradiated with
a 300 W incandescent lamp. After 30 min, the mixture
was cooled, the solvent evaporated, and the residue
washed with ether to remove neutral material. The crude
We have shown that the process depicted in Scheme 1
represents a viable method of accessing the type of
distonic radical exemplified by 4. Thus, treatment of a
typical tertiary amine, such as triethylamine (or N-
ethylpiperidine), with diiodomethane leads to the qua-
1
product was assayed by H and 13C NMR analysis and
(8) Della, E. W.; Knill, A. M.; Smith, P. A. J . Chem. Soc., Chem.
Commun., 1996, 1637.
found to consist of essentially pure 1,1,3-trimethylpyr-
rolidinium iodide 11 (96% yield; 51%, in the overall step
sequence from 3-butenol). NMR signals associated with
either the reduced product trimethyl-3-butenylammo-
nium iodide 12 or the 6-endo-trig product were not
(9) Bertrand, M. P.; Gastaldi, S.; Nouguier, R. Synlett 1997, 1420.
(10) Rios, L. A.; Dolbier, W. R.; Paredes, R.; Lusztyk, J .; Ingold, K.
U.; J onsson, M. J . Am. Chem. Soc. 1996, 118, 11313.
(11) Anderson, N. H.; Norman, R. O. C. J . Chem. Soc. B 1971, 993.
(12) Bonazzola, L.; Iacona, C.; Michaut, J . P.; Roncin, J . J . Chem.
Phys. 1980, 73, 4175.
(13) Bonazzola, L.; LeRay, N.; Ellinger, Y. Chem. Phys. 1982, 73,
145.
(14) Bouma, W. J .; Dawes, J .; M. Radom, L. Org. Mass. Spectrom.
1983, 18, 12.
(15) Della, E. W.; Knill, A. M. J . Org. Chem. 1996, 61, 7529.
(16) Beckwith, A. L. J .; Pigou, P. E. Aust. J . Chem. 1986, 39, 77.

1800 J . Org. Chem., Vol. 64, No. 6, 1999
Della and Smith
Sch em e 2
Sch em e 3
detected under the spectroscopic conditions employed.
The structure of the cyclic salt 11 was established by
consideration of its NMR spectral properties and by
demethylation with DABCO in DMF17 to give 1,3-
dimethyl-1-azacyclopentane; the identity of the latter was
established by comparison of its physical properties with
those of an authentic specimen.18 This result contrasts
strongly with the observed4 reluctance of radical 3 toward
ring closure and is in accord with the predictions made
above of the relative kinetic reactivity of the intermediate
ammonio radical 4.
The 2,2-dimethyl-2-azonia-5-hexynyl radical. One of
our principal objectives was to extend this transformation
to the synthesis of pyrrolidines containing an exocyclic
methylene group in the expectation that these alkenes
could be further elaborated into modified 5-hexenyl
radical precursors. Accordingly, we investigated the
facility for cyclization of the hexynyl radical species 15
and 19. Access to the required precursors 14 and 18 was
achieved from the (substituted) 3-butynol as depicted in
Scheme 3.
The behavior of the parent alkyne 14 upon exposure
to Bu3SnH was disappointing, however, largely because
it proved to be quite insoluble in hot (80 °C) solvent, and
at the boiling point (105 °C) it began to decompose fairly
rapidly. Although the target salt 16 was found to be the
only detectable product, the optimum yield obtained for
the conversion 14f16 was only 40% (23% overall from
3-butynol). Despite the fact that this transformation is
not very efficient, it served to demonstrate that, aside
from solubility problems, the actual cyclization proceeds
very well. The intermediate 2-azonia-5-hexynyl radical
15 behaves in the same manner as its olefinic analogue
4 and yields only the 1,5 exo cyclization product; the
product of reduction, 17, was not detected.
More recently, we have observed that the solubility
problem associated with these iodides could be circum-
vented by employing the corresponding R-phenylseleno
substituted compound 20, which proved to be a superior
precursor to the radical cation 15. This occurs principally
because the salt 20 is much more soluble than 14 in
2-methyl-2-butanol, and when treated with Bu3SnH
under the standard conditions established it furnished
excellent yields of cyclized material 21, uncontaminated
with the product of reduction. Both 20 and the phenyl-
substituted derivative 24 were available in excellent yield
by treatment of the corresponding amine 13 (R ) H/Ph)
with PhSeCH2Br. Unlike triethylamine, the alkyny-
lamines 13 gave only substitution product.
The alkynyl salt 18 was found to be readily soluble in
2-methyl-2-butanol, and when treated with Bu3SnH at
80 °C, it afforded the target salt 22 smoothly and in high
yield as a mixture of diastereomers (88%; 55% from
4-phenyl-3-butynol). Again, neither the product of reduc-
tion 23, nor that arising from 6-endo-trig ring closure,
was detected. The selenide 24 also proved to be an
excellent source of cyclized material 25 via the radical
19.
Syn th esis of Bicyclic Heter ocycles. Having dem-
onstrated the viability of acyclic R-ammonio radical
cyclization as a route to monocyclic heterocycles, we
turned our attention to investigating whether this pro-
cedure could be extended to the synthesis of bridge-
head nitrogen bicyclic heterocycles incorporating the
1-azabicyclo[2.2.1]heptyl system. Our interest in this
study was aroused by the knowledge that compounds
containing this structure, such as the ester 26, have been
shown19 to possess powerful physiological properties and
their potential in the treatment of conditions involving
choline uptake including dementia caused by Alzheimer’s
(19) For leading references, see: Boelsterli, J .; Eggnauer, U.; Pombo-
Villar, E.; Weber, H.-P.; Walkinshaw, M.; Gould, R. O. Helv. Chim.
Acta 1992, 75, 507-512 and ref 2a-k cited therein. Cottrell, I. F.;
Hands, D.; Kennedy, D. J .; Paul, K. J .; Wright, S. H. B.; Hoogsteen,
K. J . Chem. Soc., Perkin Trans. 1 1991, 1091-1097 and refs 1-3 cited
therein.
(17) Ho, T. L. Synthesis, 1972, 702.
(18) Hawthorne, D. G.; J ohns, S. R.; Willing, R. I. Aust. J . Chem.
1976, 29, 315.

Cyclization of R-Ammonio 5-Hexenyl Radicals
J . Org. Chem., Vol. 64, No. 6, 1999 1801
Sch em e 4
perceptible decomposition at higher temperatures. Al-
though the phenyl-substituted compound 37 proved to
be rather less soluble than the ester 38 and it was
therefore necessary to maintain the temperature of the
reaction at reflux, the conditions were found not to be
deterimental in this case.
Dequ a ter n iza tion of th e Der ived Bicyclic Het-
er ocyclic Sa lts. Ultimately, our objective was to syn-
thesize the parent amines as well as their quaternary
salts, and it was therefore essential to be able to dem-
ethylate the bicyclic salts so obtained. A number of
procedures have been devised for the generation of free
amines from quaternary ammonium salts, and reagents
such as 1,4-diazobicyclo[2.2.2]octane (DABCO),17 triph-
enylphosphine,22 and the phenylselenide23 and phe-
nylthio24 anions have been shown to be very effective,
particularly in those cases where demethylation is in-
volved. In view of its simplicity, dequaternization with
DABCO/DMF was attempted on several of the hetero-
cyclic salts, viz., 11, 16, 33, and 39 prepared in this work.
Under typical conditions,17 both the monocyclic salts 11
and 16 were converted readily and in good yield into the
corresponding amines 43 and 44. However, DABCO
proved to be ineffective for the demethylation of the
bicyclic salts 33 and 39, both of which were recovered
unchanged under the most forcing conditions practicable.
disease has been recognized. A viable entry to heterocy-
clic compounds such as 26 could reasonably be expected
to arise from combining the cyclization of R-ammonio
radicals above with the observation20 that derivatives of
the 4-methylenecyclohexylmethyl radical 27 undergo ring
closure to bicyclo[2.2.1]heptanes 28.
The proposed route (Scheme 4) commences with N-
methylpiperidone (29), available commercially or by
synthesis from 4-piperidinol,21 which was smoothly trans-
formed via alkene 30 into the salt 31 as described earlier.
Treatment of a solution of the latter in refluxing 2-meth-
yl-2-butanol with Bu3SnH was performed under more
forcing conditions (105 °C) than those employed for the
acyclic salts 10, 14, and 18, to assist the more difficult
cyclization of the intermediate 32 (R ) H). An excellent
yield (88%) of the target bicyclic salt 33 was thereby
obtained, matching the high-yielding analogous all-
carbon isomerization (27 f 27′). The identity of the
product was established unambiguously by analysis of
its 1H and 13C NMR spectra, careful scrutiny of which
confirmed that 33 was obtained uncontaminated by the
product of reduction, N,N-dimethyl-4-methylenepiperi-
dinium iodide 34. An authentic sample of the latter was
prepared in order to facilitate the NMR analyses.
Encouraged by the efficiency with which the ammonio
radical 32 underwent cyclization, we sought to extend
the technique to allow introduction of more useful
functionality at the carbon bridgehead. This could be
achieved by the simple expedient of selecting the ap-
propriate Wittig reagent for reaction with N-methylpip-
eridone, and in this work, we chose to synthesize the
alkenes 35 and 36 (Scheme 4). Treatment of the derived
salts, 37 and 38, with Bu3SnH led to the formation of
the 4-substituted 1-azonia-1,1-dimethylbicyclo[2.2.1]-
heptane iodides 39 and 40 in excellent yields. The
isomeric products of reduction, 41 and 42, were not
detected. In practice, the high solubility of the ester 38
in 2-methyl-2-butanol allowed the reaction to be per-
formed at 80 °C, a desirable feature whenever possible
because, as noted above, some of these salts show
We decided, therefore, to use the more powerfully
nucleophilic phenyselenide anion. A solution of this
reagent in HMPA, generated conveniently by treatment
of phenylselenol with 1 equiv of sodium hydride, was
treated with a solution of the salt 39 in a small quantity
of DMSO and the mixture then heated at 100 °C for 4 h.
Under these conditions, dequaternization was found to
be effective, but surprisingly, the product consisted
entirely of ring opened material 45; the 1-azabicyclo-
(22) Pietraszkiewicz, M.; Salanski, P.; J urczak, J . J . Chem. Soc.
Chem. Commun. 1983, 1184.
(23) (a) Reich, H. J .; Cohen, M. L. J . Org. Chem. 1979, 44, 3148. (b)
Simanek, V.; Klasek, A. Tetrahedron Lett. 1969, 35, 3039.
(24) (a) Shamma, M.; Deno, N. C.; Remar, J . F. Tetrahedron Lett.
1966, 1375. (b) Kametani, T., Kigasawa, K.; Hiiragi, M.; Wagatsuma,
N.; Wakisaka, K. Tetrahedron Lett. 1969, 635.
(20) Della, E. W.; Knill, A. M. Aust. J . Chem. 1994, 47, 1833.
(21) McElvain, S. M.; McMahon, R. E. J . Org. Chem. 1949, 14, 1.

1802 J . Org. Chem., Vol. 64, No. 6, 1999
Della and Smith
Sch em e 5
chromatography on alumina, this represents an unac-
ceptable complication in the synthetic procedure. Use of
the corresponding selenide 54, which was prepared by
treatment of the amine 50 with PhSeCH2Br as discussed
above, proved to be more successful. The salt 54 had a
much improved solubility in the reaction medium, and
subsequent treatment with tributyltin hydride afforded
the bicyclic salt 55 in excellent yield and, importantly,
without contamination by reduced product 56.
When Hofmann elimination of the bicyclic heterocyclic
salt 55 was attempted using potassium tert-butoxide,
styrene was obtained accompanied by the amine 57. It
was found necessary to use t-BuOK as reagent over the
commonly used base diisopropylethylamine (DIEA)25
because, although DIEA promotes smooth Hofmann
elimination in â-ammonio substituted esters, it was found
to be ineffective in the case of the salt 55. In view of the
ease of preparation of the corresponding â-amino esters
58 via Michael addition, we had considered employing
the corresponding salts 59, incorporating the carbethoxy-
ethyl instead of the phenylethyl substituent, as precur-
sors to the radicals. Another advantage is that the
derived bicyclic esters can be converted readily into the
parent amines by DIEA. In practice, however, this did
not represent a viable alternative, because it has been
shown25a that â-N-carbethoxyethylammonium halide salts
are very labile under the kind of conditions required in
this work to promote the cyclization reactions.
[2.2.1]heptane 46 was not detected by NMR spectral
analysis. This result was unexpected because we had
observed that similar treatment of the piperidinium salt
47 affords N-ethylpiperidine 48 exclusively, demonstrat-
ing in this case that demethylation is the preferred course
of reaction and that the ring remains intact.
Exp er im en ta l Section
P r ep a r a tion of th e N-Iod om eth yl Qu a ter n a r y Am -
m on iu m Sa lts. Two general procedures were used for prepa-
ration of N-iodomethyl quaternary ammonium salts. Both
methods gave high yields, although method B is usually
quicker and better yielding. All salts were purified by recrys-
tallization prior to cyclization.
Method A. The precursor amine was stirred with di-
iodomethane (3-5 equiv) for periods of up to 1 week, depending
on the reactivity of the amine. The reaction progress was
followed by NMR. The salt was isolated either by stirring the
reaction mixture with dry diethyl ether or by dissolving it in
methanol or acetone prior to adding ether.
Method B. The precursor amine was stirred with di-
iodomethane (3-5 equiv) in refluxing dry diethyl ether until
no more solid appeared (ca. 3 days). Stirring the cooled mixture
with excess dry ether afforded complete precipitation of the
salt.
We believe that N-C2 rather than N-CH3 bond fission
in 39 occurs as a consequence of two factors; one, that
the increased s character of the nitrogen exocyclic orbital
used to bond nitrogen to the methyl carbon is associated
with an enhanced N-CH3 bond strength, which in turn
leads to an increase in the activation barrier for substitu-
tion at the methyl carbon. Second, nucleophilic substitu-
tion at the ring carbon is facilitated because this process
is associated with relief of strain, a feature that presum-
ably shows up in the transition state for reaction.
Evidently, the combined effect of these factors is sufficient
to ensure that nucleophilic attack at the methylene
carbon (C2) is favored.
Failure to demethylate the bicyclic salt 39 has impor-
tant ramifications because, if ultimately unsuccessful, it
necessitates the use of a much less convenient N-alkyl
substituent than methyl. The benzyl group is an attrac-
tive alternative because it can be removed readily by
hydrogenolysis with Pd/C. However, we were discouraged
from using it since attempts to iodomethylate N-ben-
zylpiperidine gave a complex mixture of unidentified
products. To circumvent this problem, we chose to carry
out the sequence of reactions depicted in Scheme 5,
commencing with commercially available N-phenyleth-
ylpiperidone 49. This was converted via the alkene 50
into the salt 51, treatment of which with Bu3SnH
afforded cyclized material 52, which was contaminated
with a significant amount (12%) of the reduced product
53. A major difficulty associated with the iodide 51 is its
poor solubility in 2-methyl-2-butanol, and the formation
of 53 was ascribed to the effect of the reduced solubility
of starting material and the consequence difficulty of
maintaining the chain. Although the isomeric mixture
of products 52 and 53 could be separated readily by
P r ep a r a tion of P h en ylselen om eth yl Qu a ter n a r y P r e-
cu r sor s. The amine was dissolved in acetonitrile (1 g/5 mL)
and stirred with bromomethyl phenylselenide (1.2 equiv)
overnight, after which the solvent was removed and the
product washed with ether and recrystallized.
P r ep a r a tion of Au th en tic Sa m p les of th e P r od u cts of
Bu 3Sn H Red u ction of th e N-Iod om eth yl Qu a ter n a r y
Am m on iu m Sa lts. These compounds were prepared by stir-
ring the precursor amine with iodomethane (1.5 equiv) in ether
(10 mL/g of amine) for 1 h. The reaction mixture was washed
with excess diethyl ether and then filtered to give an es-
sentially quantitative yield of the salts. Purification of the
latter was effected by recrystallization.
Iod om et h ylt r iet h yla m m on iu m Iod id e (5). Triethy-
lamine (0.27 g, 2.7 mmol) was treated with diiodomethane
(method A). The product was recrystallized from ethanol/ether
to give iodomethyltriethylammonium iodide (5) as off-white
crystals (0.92 g, 92%): mp 174-176 °C; 1H NMR (CDCl3/
DMSO-d6) δ 5.12 (s, 2H), 3.52 (q, J ) 7.2 Hz, 6H), 1.39 (t, J )
(25) (a) Brown, A. R.; Rees, D. C.; Rankovic, Z.; Morphy, J . R. J .
Am. Chem. Soc. 1997, 119, 3288. (b) Ouyang, X.; Armstrong, R. W.;
Murphy, M. M. J . Org. Chem. 1998, 63, 1027.

Cyclization of R-Ammonio 5-Hexenyl Radicals
J . Org. Chem., Vol. 64, No. 6, 1999 1803
7.2 Hz, 9H); 13C NMR (CDCl3/DMSO-d6) δ 54.6, 27.5, 8.1. Anal.
Calcd for C7H17NI2: C, 22.78, H, 4.64, N, 3.8. Found: C, 23.26,
H, 4.66, N, 3.76.
5 mL) to yield the iodide 11 as white crystals (0.13 g, 96%):
mp 180-182 °C; H NMR (CDCl3/DMSO-d6) δ 3.65 (m, 1H),
1
3.52 (m, 2H), 3.16 (s, 3H), 3.06 (s, 3H), 3.06 (m, 1H), 2.6 (m,
1H) 2.3 (m, 1H), 1.7 (m, 1H), 1.08 (d, J ) 6.8 Hz, 3H); 13C
NMR (CDCl3/DMSO-d6) δ 70.87, 65.1, 52.7, 51.6, 30.4, 30.2,
17.7. These data were in agreement with literature values.15
2,2-Dim eth yl-2-a zon ia -5-h exen yl Iod id e (12). This salt
was prepared from 2-methyl-2-aza-5-hexene (9) as described
and crystallized from 2-methyl-2-butanol: mp 239-240 °C; 1H
NMR (DMSO-d6) δ 5.75 (m, 1H), 5.2 (m, 2H), 3.4 (m, 2H), 3.1
(s, 9H), 2.5 (m, 2H); 13C NMR (DMSO-d6) δ 132.9, 118.2, 63.8,
52.2, 26.6.
Meth yltr ieth yla m m on iu m Iod id e (7). A 0.025 M solution
of iodomethyltriethylammonium iodide (5) (0.30 g, 0.81 mmol)
in 2-methyl-2-butanol was deoxygenated and then brought to
100 °C using a tungsten lamp before a solution of tributyltin
hydride (0.28 g, 0.98 mmol) in 2-methyl-2-butanol (1 mL)
containing a catalytic amount of AIBN was added at once. The
reaction mixture was refluxed under irradiation for 15 min,
when the solution had clarified, after which an additional
catalytic amount of AIBN in 2-methyl-2-butanol (1 mL) was
added and the mixture heated for a further 10 min. The solvent
was removed, and the resulting white solid was washed with
dry diethyl ether (3 × 5 mL). The product (7) (0.19 g, 96%),
2-Meth yl-2-a za -5-h exyn e (13, R ) H). 3-Butyn-1-ol (2.0
g, 28 mmol) was converted27 into its mesylate, which, without
purification, was stirred with 33% dimethylamine in ethanol
(18.0 g, 135 mmol) overnight. Dichloromethane (250 mL) was
added to the reaction mixture and the solution washed with
saturated NaCl solution (2 × 100 mL) and then dried (Na2-
SO4). Evaporation of the solvent and distillation of the residue
afforded the amine 13 (R ) H) (1.1 g, 82%) with bp (107 °C
(760 mm)) identical to that reported:29 1H NMR (CDCl3) δ 2.5
(t, J ) 7.0 Hz, 2H), 2.36 (m, 2H), 2.27, (s, 6H), 1.99 (t, J ) 2.5
Hz, 1H); 13C NMR (CDCl3) δ 82.7, 68.9, 58.1, 45.2, 17.4.
1-Iodo-2,2-dim eth yl-2-azon ia-5-h exyn yl Iodide (14). This
compound was prepared according to method A from 2-methyl-
2-azahex-5-yne 13 (R ) H) (1.0 g, 10 mmol) and crystallized
from methanol/2-methyl-2-butanol as fine orange needles (2.89
1
mp 298-298 °C, had identical mp and H and 13C NMR spectra
with those of an authentic sample prepared as described in
the general procedure.
P h en ylselen om eth yltr ieth yla m m on iu m Br om id e (8).
Phenylselenomethyltriethylammonium bromide (8) was pre-
pared from triethylamine (60 mg, 0.56 mmol) by the general
procedure. The product was shown (1H and 13C NMR) to consist
of an 82:18 mixture of 8 and triethylammonium bromide.
Chromatography (alumina, 10% methanol/dichloromethane)
gave title compound 8 (0.14 g, 70%) isolated as hygroscopic
white crystals: 1H NMR (CDCl3) δ 7.77-7.8 (m, 2H), 7.37-
7.4 (m, 3H), 5.12 (s, 2H), 3.58 (q, J ) 7.2 Hz, 6H), 1.18 (t, J )
7.2 Hz, 9H); 13C NMR (CDCl3) δ 134.8, 129.9, 129.5, 126.4,
58.1, 53.2, 7.8.
1
g, 77%): mp 150-152 °C; H NMR (DMSO-d6) δ 5.2 (s, 2H),
3.2 (s, 6H), 3.65 (t, J ) 6.3 Hz, 2H), 2.8 (m, 2H), 3.15 (t, J )
2.1 Hz, 1H); 13C NMR (DMSO-d6) δ 78.9, 74.2, 61.9, 51.3, 33.6,
13.3. Anal. Calcd for C7H13NI2: C, 23.04; H, 3.59; N, 3.84.
Found: C, 23.05; H, 3.5; N, 3.81.
Meth yltr ieth yla m m on iu m Br om id e. A 0.025 M solution
of phenylselenomethyltriethylammonium bromide (8) (0.20 g,
0.56 mmol) in 2-methyl-2-butanol was deoxygenated and then
treated as described above with a solution of tributyltin
hydride (0.20 g, 0.67 mmol) and a catalytic amount of AIBN
in 2-methyl-2-butanol (1 mL). Workup gave a crystalline
1,1-Dim eth yl-3-m eth ylen e-1-a zon ia cyclop en tyl Iod id e
(16). A 0.01 M solution of 1-iodo-2,2-dimethyl-2-azonia-5-
hexynyl iodide (14) (0.30 g, 0.82 mmol) in 2-methyl-2-butanol
was deoxygenated and treated at reflux with a solution of
tributyltin hydride (0.29 g, 0.98 mmol) and AIBN in 2-methyl-
2-butanol (1 mL) as described above to yield fine, colorless
crystals (80 mg, 40%) of the salt (16). Crystallized from
1
product (0.1 g, 94%) that had mp and H and 13C NMR spectra
identical to that reported for methyltriethylammonium bro-
mide.
2-Meth yl-2-a za -5-h exen e (9). 3-Buten-1-ol26 was converted
into the corresponding mesylate by reaction with mesyl
chloride as described.27 Without further purification, the
mesylate (2.0 g, 14 mmol) was stirred with 33% dimethylamine
in ethanol (18.0 g, 135 mmol) overnight. The reaction mixture
was dissolved in dichloromethane (250 mL) and the solution
washed with saturated NaCl solution (2 × 100 mL), dried (Na2-
SO4), and evaporated to give the title compound 9 as an amber
oil. Distillation afforded the pure amine (1.13 g, 86%), which
had a bp (86 °C (760 mm)) identical with that reported.28
1-Iod o-2,2-d im et h yl-2-a zon ia -5-h exen yl Iod id e (10).
Treatment of 2-methyl-2-aza-5-hexene (9) (0.5 g, 5 mmol) as
described in method A and recrystallization of the crude
product from methanol/2-methyl-2-butanol gave the salt 10 as
1
ethanol/ether as fine, colorless crystals: mp 176-178 °C; H
NMR (CDCl3/DMSO-d6) δ 5.35 (d, J ) 19.8 Hz, 2H), 4.35 (s,
2H), 3.95 (t, J ) 7.8 Hz, 2H), 3.35 (s, 6H), 2.95 (t, J ) 7.8 Hz,
2H); 13C NMR (CDCl3/DMSO-d6) δ 138.6, 112.1, 68.9, 64.3,
50.8, 27.3. Anal. Calcd for C7H14NI: C, 35.16; H, 5.90; N, 5.86.
Found: C, 35.22; H, 5.73; N, 5.91.
Note: Spectral analysis of the solution of 1-iodo-2,2-dim-
ethyl-2-azonia-5-hexynyl iodide (14) after being heated to
reflux in 2-methyl-2-butanol in the absence of tributyltin
hydride showed that extensive decomposition had occurred.
2,2-Dim eth yl-2-a zon ia -5-h exyn yl Iod id e (17). This salt,
prepared from 13 (R ) H) as described in the general
procedure above, crystallized from ethanol as white needles:
1
1
mp 218-220 °C; H NMR (CDCl3/DMSO-d6) δ 3.49 (t, J ) 7
fine yellow needles (1.25 g, 68%): mp 144-146 °C; H NMR
Hz, 2H), 3.09 (s, 9H), 2.99 (dt, J ) 2.7 Hz, 6.9 Hz, 2H), 2.73 (t,
J ) 2.4 Hz, 1H); 13C NMR (CDCl3/DMSO-d6) δ 79.8, 74.3, 63.4,
53.0, 13.6.
(CDCl3/DMSO-d6) δ 5.77 (m, 1H), 5.28 (s, 2H), 5.2 (m, 2H),
3.52 (m, 2H), 3.22 (s, 6H), 2.53 (m, 2H); 13C NMR (CDCl3/
DMSO-d6) δ 130.3, 116.8, 61.3, 49.5, 31.4, 24.9. Anal. Calcd
for C7H15NI2: C, 22.91; H, 4.12; N, 3.82. Found: C, 23.01; H,
4.15; N, 3.71.
2-Meth yl-6-p h en yl-2-a za -5-h exyn e (13, R ) P h ). 4-Phe-
nylbut-3-ynol30 (2 g, 13.7 mmol) was converted into the
corresponding mesylate as described27 and the ester (2.93 g,
13 mmol) stirred with 33% dimethylamine in ethanol (17.6 g,
130 mmol) overnight. The mixture was worked up as above
and the product distilled to give the amine 13 (R ) H) (2.16 g,
96%): bp 148 °C (15 mm); 1H NMR (CDCl3) δ 7.2-7.4 (m, 5H),
2.52 (s, 4H), 2.23 (s, 6H); 13C NMR (CDCl3) δ 131.4, 128.0,
127.5, 123.7, 88.2, 81.0, 58.3, 45.1,18.2; HRMS calcd for
1,1,3-Tr im eth yl-1-azon iacyclopen tyl Iodide (11). A 0.025
M solution of 1-iodo-2,2-dimethyl-2-azonia-5-hexenyl iodide
(10) (0.20 g, 0.55 mmol) in 2-methyl-2-butanol was deoxygen-
ated before being heated to 60 °C using a tungsten lamp and
then treated with a solution of tributyltin hydride (0.30 g, 1.0
mmol) in 2-methyl-2-butanol (1 mL) containing a catalytic
amount of AIBN. The reaction mixture was heated with
irradiation for 15 min and a further catalytic amount of AIBN
added with 2-methyl-2-butanol (1 mL) and heated with ir-
radiation for a further 10 min. The solvent was evaporated,
and the resulting white solid was washed with dry ether (3 ×
C
12H15N 173.1204, found 173.1198.
1-Iod o-2,2-d im et h yl-6-p h en yl-2-a zon ia -5-h exyn yl Io-
d id e (18). 2-Methyl-6-phenyl-2-aza-5-hexyne (13 R ) H) (1.0
g, 5.8 mmol) was transformed into 1-iodo-2,2-dimethyl-6-
phenyl-2-azonia-5-hexynyl iodide (18) via method A. The salt
(26) Kinnel, R. B.; Molloy, B. B.; Graham, D. W.; Harding, K. E.
Org. Prep. Proced. Int. 1972, 4, 27.
(27) Crossland, R. K.; Servis, K. L. J . Org. Chem. 1970, 35, 3195.
(28) Clark, R. J . H.; Stockwell, J . A. J . Chem. Soc., Dalton Trans.
1975, 468.
(29) Campbell, K. N.; Fatora, F. C.; Campbell, B. K. J . Org. Chem.
1952, 17, 1141.
(30) Collins, C. J .; Hanack, M.; Stutz, H.; Auchter, G.; Schoberth
W. J . Org. Chem. 1983, 48, 5265.

1804 J . Org. Chem., Vol. 64, No. 6, 1999
Della and Smith
crystallized from methanol as fine orange needles (1.76 g,
69%): mp 139-140 °C; H NMR (CDCl3/DMSO-d6) δ 7.4 (m,
5H), 5.55 (s, 2H), 3.95 (t, J ) 6.6 Hz, 2H), 3.42 (s, 6H), 3.1 (t,
J ) 6.6 Hz, 2H); 13C NMR (CDCl3/DMSO-d6) δ 129.3, 126.6,
126.4, 120.2, 82.3, 81.0, 60.4, 49.7, 32.9, 12.8. Anal. Calcd for
C13H17NI2: C, 35.39; H, 3.88; N, 3.17. Found: C, 35.31; H, 3.95;
N, 3.17.
g, 0.56 mmol) and AIBN (cat.) as described above. Workup
yielded fine hygroscopic white crystals (0.11 g, 89%) of 25, the
1H and 13C NMR spectral data of which corresponded with
those of the iodo analogue 22 synthesized previously. When
25 was dissolved in DMSO-d6, the 13C NMR signals for the
two diastereomers were now separated: 1H NMR (CDCl3) δ
7.18-7.45 (m, 5H), 6.66 (s, 1H), 4.67 (s, 2H), 4.18 (t, J ) 7.2
Hz, 2H), 3.51 (s, 6H), 3.11 (t, J ) 7.2 Hz, 2H); 13C NMR (CDCl3)
δ 135.5, 130.0, 128.8, 128.7, 128.5, 128.1, 128.0, 127.6, 71.2,
68.2, 65.3, 63.5, 51.8, 51.3, 29.5, 27.0.
1-Meth yl-4-m eth ylen e-1-a za cycloh exa n e (30). A solu-
tion of 1.5 M butyllithium in hexane (7.0 mL, 11 mmol) was
added dropwise to a stirred mixture of methyltriphenylphos-
phonium iodide (4.5 g, 11 mmol) in dry ether (55 mL) at room
temperature. The mixture was allowed to stir for 2 h, after
which a solution of 1-methyl-4-piperidone (29) (1.0 g, 8.9 mmol)
in dry ether (45 mL) was added dropwise and the mixture was
allowed to stir for a further 2 h. Triphenylphosphine oxide was
removed by vacuum filtration and the volume of the filtrate
reduced to 50 mL and then washed with H2O (2 × 50 mL)
and extracted with 5% HCl (2 × 50 mL). The aqueous layer
was washed with ether (25 mL) and then basified (pH10) with
3 M NaOH before being extracted with dichloromethane (2 ×
50 mL). The organic extracts were washed with H2O (50 mL)
and then dried (Na2SO4), and the solvent was evaporated to
yield the amine 30 (0.51 g, 51%), which was used without
further purification: 1H NMR (CDCl3) δ 4.63 (s, 2H), 2.65 (m,
4H), 2.5 (m, 4H), 2.25 (s, 3H); 13C NMR (CDCl3) δ 145.5, 107.7,
56.8, 45.8, 34.3; HRMS calcd for C7H13N 111.1048, found
111.1041.
1-Iod om eth yl-1-m eth yl-4-m eth ylen e-1-a zon ia cycloh ex-
yl Iod id e (31). 1-Methyl-4-methylene-1-azacyclohexane (30)
(0.50 g, 4.5 mmol) was treated according to the conditions
specified in method A to give the salt 31 (1.23 g, 72%) as fine
white crystals from methanol: mp 178-179 °C; 1H NMR
(CDCl3/DMSO-d6) δ 5.35 (s, 2H), 4.95 (s, 2H), 3.2-3.4 (m, 7H),
2.45 (m, 4H); 13C NMR (CDCl3/DMSO-d6) δ 136.26, 110.29,
59.44, 47.47, 30.99, 25.98. Anal. Calcd for C8H15NI2: C, 25.35,
H, 3.99, N, 3.69. Found: C, 25.29, H, 3.83, N, 3.63.
1,4-Dim eth yl-1-a zon ia bicyclo[2.2.1]h ep tyl Iod id e (33).
A solution of 1-iodomethyl-1-methyl-4-methylene-1-azoniacy-
clohexyl iodide (31) (0.20 g, 0.53 mmol) in 2-methyl-2-butanol
was deoxygenated and then heated to 90 °C with a tungsten
lamp before being treated with Bu3SnH (0.30 g, 0.53 mmol)
as described above. Workup yielded the bicyclic salt 33 as
hygroscopic orange crystals (0.12 g, 88%): mp 178-180 °C; 1H
NMR (CDCl3/acetone-d6) δ 4.05 (m, 4H), 3.72 (s, 2H), 3.51 (s,
3H), 2.15 (m, 4H), 1.4 (s, 3H); 13C NMR (CDCl3/acetone-d6) δ
70.4, 62.5, 44.0, 43.6, 34.1, 15.4.
1
2,2-Dim eth yl-1-p h en yselen o-2-a zon ia -5-h exyn yl Br o-
m id e (20). 2-Methyl-2-aza-5-hexyne (13, R ) H) (0.1 g, 1
mmol) was treated with PhSeCH2Br as in the general proce-
dure above to yield 1-phenylseleno-2,2-dimethyl-2-azonia-5-
hexynyl bromide (20), which crystallized from ethanol/ether
as white crystals (0.3 g, 87%): mp 120-121 °C; 1H NMR
(CDCl3) δ 7.74-7.77 (m, 2H), 7.36-7.39 (m, 3H), 5.59 (s, 2H),
3.93 (t, J ) 6.9 Hz, 2H), 3.46 (s, 6H), 2.72 (dt, J ) 2.7 Hz, 6.9
Hz, 2H), 2.17 (t, J ) 2.4 Hz, 1H); 13C NMR (CDCl3) δ 133.9,
130.4, 129.4, 127.1, 78.1, 73.1, 64.8, 61.4, 51.2, 14.3. Anal.
Calcd for C13H18NSeBr: C, 44.98, H, 5.23, N, 4.03. Found: C,
45.08, H, 5.35, N, 4.07.
1,1-Dim et h yl-3-m et h ylen e-1-a zon ia cyclop en t yl Br o-
m id e (21). A 0.025 M solution of 2,2-dimethyl-1-phenylsele-
nomethyl-2-azonia-5-hexynyl bromide (20) (0.65 g, 1.9 mmol)
in 2-methyl-2-butanol was deoxygenated. The stirred solution
was heated to 100 °C using a tungsten lamp, and tributyltin
hydride (0.65 g, 2.3 mmol) in 2-methyl-2-butanol (1 mL)
containing a catalytic amount of AIBN was added over 5 min.
The reaction mixture was heated for 10 min, and then a
further catalytic amount of AIBN was added and the mixture
stirred for a further 30 min. The solvent was removed, and
the resulting solid was washed with diethyl ether several times
to furnish the title compound 21 as fine hygroscopic white
crystals (0.33 g, 92%): 1H NMR (CDCl3) δ 5.3 (d, J ) 23.7 Hz,
2H), 4.34 (s, 2H), 3.94 (t, J ) 7.8 Hz, 2H), 3.34 (s, 6H), 2.91 (t,
J ) 7.8 Hz, 2H); 13C NMR (CDCl3) δ 138.8, 112.3, 68.9, 64.3,
50.8, 27.7.
1,1-Dim et h yl-3-p h en ylm et h ylen e-1-a zon ia cyclop en -
tyl Iod id e (22). A 0.025 M solution of 1-iodo-2,2-dimethyl-6-
phenyl-2-azonia-5-hexynyl iodide (18) (0.23 g, 0.52 mmol) in
2-methyl-2-butanol was deoxygenated and then heated to 80
°C using a tungsten lamp before being treated with tributyltin
hydride (0.23 g, 0.78 mmol) as described above. After 15 min
the reaction mixture was worked up to yield fine white crystals
(0.14 g, 88%) shown by NMR analysis to be a mixture of the
two diastereomers of the title compound 22: mp 198-200 °C;
1H NMR (CDCl3/DMSO-d6) δ 7.2-7.37 (m, 5H), 6.68 (s, 1H),
4.65 (s, 1H), 4.48 (s, 1H), 3.94 (t, J ) 7.2 Hz, 1H), 3.84 (t, J )
7.2 Hz, 1H), 3.23 (d, J ) 9 Hz, 6H), 3.1 (m, 2H); 13C NMR
(CDCl3/DMSO-d6) δ 133.9, 133.7, 129.8, 129.7, 126.6, 126.5,
126.3, 126.0, 125.5, 125.4, 124.7, 123.6, 68.4, 65.4, 62.7, 61.0,
49.2, 48.7, 27.7, 25.2. Anal. Calcd for C13H18NI: C, 49.54; H,
5.76; N, 4.44. Found: C, 49.60; H, 5.65; N, 4.46.
2,2-Dim eth yl-6-p h en yl-2-a zon ia -5-h exyn yl Iod id e (23).
This substance, prepared according to the general procedure
from 13 (R ) H), crystallized from ethanol/ether as colorless
crystals: mp 218-220 °C; 1H NMR (CDCl3/DMSO-d6) δ 7.35-
7.45 (m, 5H), 3.85 (t, J ) 7.2 Hz, 2H), 3.40 (s, 9H), 3.10 (t, J
) 7.2 Hz, 2H); 13C NMR (CDCl3/DMSO-d6) δ 130.3, 127.5,
127.3, 121.2, 82.8, 82.4, 62.9, 52.2, 13.7.
1,1-Dim eth yl-4-m eth ylen e-1-a zon ia cyclop en tyl Iod id e
(34). The product obtained from reaction of the amine 30 with
iodomethane as described in the general procedure was
recrystallized from ethanol, furnishing the salt 34 as white
1
crystals: mp 270-272 °C; H NMR (CDCl3/DMSO-d6) δ 4.95
(s, 2H), 3.47 (m, 4H), 3.23 (s, 6H), 2.58 (m, 4H); 13C NMR
(CDCl3/DMSO-d6) δ 138.5, 112.8, 62.5, 51.3, 28.3.
1-Meth yl-4-p h en ylm eth ylen e-1-a za cycloh exa n e (35). A
60% suspension of NaH in paraffin oil (0.21 g, 5.3 mmol) was
washed with hexane (2 × 3 mL) and then treated with a
solution of diethyl benzylphosphonate (1.1 g, 4.9 mmol),
prepared from triethyl phosphite and benzyl chloride as
reported.31 1-Methyl-4-piperidone (29) (0.50 g, 4.4 mmol) in
DME (10 mL) was added all at once and the stirred mixture
heated slowly to 85 °C and then refluxed for 1 h. The reaction
mixture was added to water (50 mL) and extracted with ether
(3 × 40 mL). The combined ether extracts were washed with
saturated NaCl solution (2 × 25 mL) and dried (Na2SO4), and
the solvent was removed. Distillation yielded the amine 35
2,2-Dim eth yl-6-p h en yl-1-p h en ylselen o-2-a zon ia -5-h ex-
yn yl Br om id e (24). Treatment of 2-methyl-6-phenyl-2-aza-
5-hexyne (13, R ) H) (0.23 g, 1.3 mmol) with PhSeCH2Br
according to the general procedure above and recrystallization
of the product from ethanol/ether afforded 1-phenylseleno-2,2-
dimethyl-6-phenyl-2-azonia-5-hexynyl bromide (24) as white
crystals (0.51 g, 90%): mp 86-88 °C: 1H NMR (CDCl3) δ 7.72-
7.74 (m, 2H), 7.28-7.35 (m, 8H), 5.64 (s, 2H), 3.98 (t, J ) 6.6
Hz, 2H), 3.51 (s, 6H), 2.93 (t, J ) 6.6 Hz, 2H); 13C NMR (CDCl3)
δ 133.9, 131.7, 130.3, 129.3, 128.7, 128.5, 127.1, 122.2, 84.5,
83.2, 64.6, 61.5, 51.3, 15.2. Anal. Calcd for C19H22NSeBr‚H2O:
C, 51.72, H, 5.48, N, 3.17. Found: C, 51.48, H, 5.37, N, 3.17.
1,1-Dim et h yl-3-p h en ylm et h ylen e-1-a zon ia cyclop en -
tyl Br om id e (25). A 0.025 M solution of 2,2-dimethyl-6-
phenyl-1-phenylselenomethyl-2-azonia-5-hexynyl bromide (24)
(0.20 g, 0.48 mmol) in 2-methyl-2-butanol was deoxygenated
and then treated with a solution of tributyltin hydride (0.16
1
(0.58 g, 70%): bp 86 °C (0.8 mm); H NMR (CDCl3) δ 7.27-
7.4 (m, 5H), 6.38 (s, 1H), 2.6 (m, 4H), 2.4 (m, 4H), 2.37 (s, 3H);
13C NMR (CDCl3) δ 138.7, 137.8, 128.8, 127.9, 125.9, 123.3,
57.1, 56.4, 46.0, 36.4, 29.0; HRMS calcd for C13H17N 187.1361,
found 187.1364.
(31) Kosolapoff, G. M. J . Org. Chem. 1946, 11, 3.

Cyclization of R-Ammonio 5-Hexenyl Radicals
J . Org. Chem., Vol. 64, No. 6, 1999 1805
4-Ca r b et h oxym et h ylen e-1-m et h yl-1-a za cycloh exa n e
(36). A suspension of 60% NaH in paraffin oil (0.41 g, 10 mmol)
was washed with hexane (2 × 3 mL), a solution of trieth-
ylphosphonoacetate31 (2.2 g, 9.7 mmol) in DME (10 mL) was
then added, and the reaction mixture was stirred for 1 h. A
solution of 1-methyl-4-piperidone (29) (1.0 g, 8.9 mmol) in DME
(1 mL) was added to the vigorously stirred mixture at such a
rate as to maintain the temperature below 10 °C. After being
stirred for 0.5 h, the reaction mixture was added to water (50
mL) and extracted with ether (3 × 50 mL). The ether extracts
were washed with saturated NaCl (2 × 25 mL) and dried (Na2-
SO4), and the solvent was removed. Distillation of the residue
yielded the ester 36 as a colorless oil (1.5 g, 92%): bp 65 °C
(0.1 mm); 1H NMR (CDCl3) δ 5.65 (s, 1H), 4.15 (q, J ) 7.1 Hz,
2H), 3.0 (m, 2H), 2.48 (m, 4H), 2.36 (m, 2H), 2.29 (s, 3H), 1.28
(t, J ) 7.1 Hz, 3H); 13C NMR (CDCl3) δ 166.3, 158.5, 114.1,
4-Ca r b et h oxym et h ylen e-1,1-d im et h yl-1-a zon ia cyclo-
h exyl iod id e (42) was prepared according to the general
procedure and recrystallized from ethanol as fine white
crystals: mp 129-131 °C; 1H NMR (CDCl3) δ 5.90 (s, 1H), 4.15
(q, J ) 7.2 Hz, 2H), 3.90 (t, J ) 6.3 Hz, 2H), 3.78 (t, J ) 6.3
Hz, 2H), 3.66 (s, 6H), 3.40 (t, J ) 5.7 Hz, 2H), 2.81 (t, J ) 5.7
Hz, 2H), 1.27 (t, J ) 7.2 Hz, 3H); 13C NMR (CDCl3/DMSO-d6)
δ 163.6, 147.7, 116.0, 115.9, 60.2, 59.9, 58.2, 28.3, 21.7, 12.5.
Dequ a t er n iza t ion of 1,1,3-Tr im et h yl-1-a zon ia cyclo-
p en tyl Iod id e (11). A solution of 11 (0.20 g, 0.83 mmol) and
1,4-diazabicyclo[2.2.2]octane (0.19 g, 1.6 mmol) in DMF (4 mL)
was added to a thick wall glass reaction vessel that was sealed
and then was stirred for 4 h at 170 °C. The cooled reaction
mixture was added to water (10 mL) and extracted with
benzene (2 × 10 mL). The organic layer was extracted with a
solution of 5% HCl (20 mL) and the aqueous layer basified
(pH 10) with 3 M NaOH and then extracted with dichlo-
romethane (2 × 15 mL). The solvent was evaporated to give
1,3-dimethyl-1-azacyclopentane (43) (0.06 g, 77%), which had
physical properties identical with those reported:29 13C NMR
(CDCl3) δ 64.3, 56.2, 42.5, 33.5, 32.7, 20.5.
Dequ a ter n iza tion of 1,1-Dim eth yl-3-p h en ylm eth ylen e-
1-a zon ia cyclop en tyl Iod id e (16). The diastereomeric mix-
ture of salts 16 (0.20 g, 0.64 mmol) was treated with 1,4-
diazabicyclo[2.2.2]octane (0.14 g, 1.3 mmol) as outlined above
for the salt 11. Workup gave 1-methyl-3-phenylmethylene-1-
azacyclopentane (44) (0.08 g, 72%) as a mixture of diastere-
oisomers: 1H NMR (CDCl3) δ 7.1-7.3 (m, 5H), 6.35 (s, 1H),
3.4 (m, 1H), 3.28 (m, 1H), 2.65 (m, 1H), 2.58 (m, 1H), 2.37 (s)
and 2.4 (s, total ) 3H), 2.29 (s, 2H); 13C NMR (CDCl3) δ 142.1,
137.8, 128.0, 127.9, 127.5, 127.6, 125.8, 125.8, 120.9, 120.1,
59.2, 56.4, 55.8, 45.4, 36.4, 28.9,13.9; HRMS calcd for C10H17
NO2 183.1259, found 183.1263.
-
1-Iod om et h yl-1-m et h yl-4-p h en ylm et h ylen e-1-a zon ia -
cycloh exyl Iod id e (37). Treatment of 1-methyl-4-phenylm-
ethylene-1-azacyclohexane (35) (1.0 g, 5.4 mmol) with CH2I2
as outlined under method B gave the salt 37 as fine off-white
crystals (2.2 g, 91%) from methanol: mp 188-189 °C; 1H NMR
(CDCl3/DMSO-d6) δ 7.24-7.38 (m, 5H), 6.55 (s, 1H), 5.4 (s, 2H),
3.6 (m, 4H), 3.2 (s, 3H), 2.82 (m, 2H), 2.72 (m, 2H); 13C NMR
(CDCl3/DMSO-d6) δ 134.3, 129.4, 126.9, 126.6, 125.1, 124.7,
59.7, 59.0, 47.8, 30.9, 26.7, 21.5. Anal. Calcd for C14H19NI2:
C, 36.95, H, 4.21, N, 3.08. Found: C, 36.78, H, 4.31, N, 3.02.
4-Ca r beth oxym eth ylen e-1-iod om eth yl-1-m eth yl-1-a zo-
n ia cycloh exyl Iod id e (38). Treatment of 4-carbethoxymeth-
ylene-1-methyl-1-azacyclohexane (36) (1.0 g, 5.4 mmol) under
method A conditions and recrystallization of the crude product
from methanol gave the salt 38 as fine white crystals (1.74 g,
71%): mp 155-156 °C; 1H NMR (CDCl3/DMSO-d6) δ 5.9 (s,
1H), 5.58 (s, 2H), 5.14 (q, J ) 7.1 Hz, 2H), 3.8 (m, 4H), 3.4 (s,
3H), 3.3 (m, 2H), 2.79 (s, 2H), 1.25 (t, J ) 7.1 Hz, 3H); 13C
NMR (CDCl3/DMSO-d6) δ 163.7, 147.4, 116.2, 59.5, 59.3, 58.4,
48.5, 32.1, 28.4, 12.7. Anal. Calcd for C11H19NO2I2: C, 27.36,
H, 4.36, N, 3.19. Found: C, 27.35, H, 4.36, N, 3.07.
63.0, 59.7, 56.7, 55.1,42.2, 42.0, 34.2; HRMS calcd for C12H15
173.1204, found 173.1199.
N
Dequ a ter n iza tion of 1-Eth yl-1-m eth yl-1-a zon ia cyclo-
h exyl Iod id e (47). (a ) With DABCO. When 1-ethyl-1-methyl-
1-azoniacyclohexyl iodide was treated with DABCO under the
conditions specified above, it was converted in high yield to
1-ethyl-1-azacyclohexane (48), which was identified by com-
parison of its physical properties with those of an authentic
specimen prepared as described above.
4-Ben zyl-1-m eth yl-1-a zon ia bicyclo[2.2.1]h ep tyl Iod id e
(39). A 0.02 M solution of 1-iodomethyl-1-methyl-4-phenylm-
ethylene-1-azoniacyclohexyl iodide (37) (0.2 0 g, 0.44 mmol)
in 2-methyl-2-butanol was deoxygenated and then, after being
heated to reflux, was treated with a solution of tributyltin
hydride (0.18 g, 0.66 mmol) in 2-methyl-2-butanol (1 mL) as
described above. After workup, the product was washed with
dry ether (3 × 5 mL) to yield 39 as white crystals (0.13 g, 93%):
mp 164-166 °C; 1H NMR (CDCl3) δ 7.16-7.32 (m, 5H), 3.74-
3.88 (m, 4H), 3.55 (s, 2H), 3.37 (s, 3H), 3.04 (s, 2H), 2.21 (m,
2H), 1.85 (m, 2H); 13C NMR (CDCl3) δ 135.5, 128.2, 127.4,
(b) With P h Se-. HMPA (1.5 mL) was added to NaH (0.15
g, 3.7 mmol) prepared from a hexane-washed 60% dispersion
in paraffin oil. Phenylselenol (0.42 mL, 3.9 mmol) was added
to the stirred mixture followed by a solution of 1-ethyl-1-
methyl-1-azoniacyclohexyl iodide (0.50 g, 1.9 mmol) in DMSO
(0.5 mL) The resultant mixture was heated at 110 °C. The
progress of the reaction was monitored by 13C NMR and found
to be complete after 4 h. Water (10 mL) was added to the cooled
reaction mixture, which was then extracted with ether (3 × 5
mL). The combined organic extracts were washed several times
with saturated NaCl solution and extracted with 5% HCl. The
aqueous layer was basified (pH 10) and extracted with dichlo-
romethane, and the combined extracts was dried (Na2SO4) and
evaporated. The 1H and 13C NMR spectra of the resulting
brown oil (0.19 g, 85%) were identical with those of authentic
1-ethyl-1-azacyclohexane.
125.7, 68.7, 61.9, 48.0, 43.8, 36.2, 31.8. Anal. Calcd for C14H20
-
NI: C, 51.08; H, 6.12; N, 4.25. Found: C, 50.82; H, 5.82; N,
3.98.
4-Ca r beth oxym eth yl-1-m eth yl-1-a zon ia bicyclo[2.2.1]-
h ep tyl Iod id e (40). A 0.025 M solution of 4-carbethoxymeth-
ylene-1-iodomethyl-1-methyl-1-azoniacyclohexyl iodide (38)
(0.20 g, 0.44 mmol) in 2-methyl-2-butanol was deoxygenated,
heated to 90 °C and then treated with a solution of tributyltin
hydride (0.19 g, 0.66 mmol) in 2-methyl-2-butanol (1 mL) under
irradiation as above. Workup yielded the salt 40 as orange
crystals (0.12 g, 87%) which crystallized from ethanol/ether:
Dequ ater n ization of 4-Ben zyl-1-m eth yl-1-azon iabicyclo-
[2.2.1]h ep tyl Iod id e (39). (a ) With DABCO. The salt 39 was
recovered unchanged when treated with DABCO under the
conditions specified above.
(b) With P h Se-. Generation of a slurry of sodium benzen-
eselenide in HMPA was performed as described above from a
60% dispersion of NaH in paraffin oil (0.02 g, 0.5 mmol),
HMPA (0.4 mL), and benzeneselenol (0.56 mL, 0.26 mmol). A
solution of 1-methyl-4-benzyl-1-azoniabicyclo[2.2.1]heptyl io-
dide (39) (0.10 g, 0.26 mmol) in DMSO (0.1 mL) was added
and the reaction mixture heated at 110 °C and worked up as
above. The oily product (0.04 g, 42%) was identified by NMR
spectral analysis as 3-benzyl-1-methyl-3-(2-phenylselenoethyl)-
azacyclopentane (45): 1H NMR (CDCl3/DMSO-d6) δ 7.05-7.5
(m, 10H), 2.9-3.0 (m, 2H), 2.73 (d, 2H), 2.5-2.6 (m, 4H), 2.31
(s, 3H), 2.29 (m, 2H), 1.74-1.84 (m, 2H); 13C NMR (CDCl3/
DMSO-d6) δ 138.6, 133.0, 130.3, 129.1, 128.1, 128.0, 126.9,
126.2, 66.9, 56.0, 46.9, 44.3, 42.5, 39.3, 36.4, 23.4; HRMS calcd
for C20H25NSe 359.1152, found 359.1140.
1
mp 112-114 °C; H NMR (CDCl3) δ 4.12 (q, J ) 7.1 Hz, 2H),
3.75 (m, 2H), 3.63 (m, 2H), 3.55 (s, 2H), 3.28 (s, 3H), 2.78 (s,
2H), 1.96-2.08 (m, 4H), 1.23 (t, J ) 7.1 Hz, 3H); 13C NMR
(CDCl3) δ 170.1, 70.3, 63.5, 61.2, 45.7, 45.6, 35.8, 35.6, 33.4,
14.3. Anal. Calcd for C11H20NO2I: C, 38.35, H, 6.44, N, 4.47.
Found: C, 38.69, H, 6.31, N, 4.19.
1,1-Dim et h yl-4-p h en ylm et h ylen e-1-a zon ia cycloh exyl
iod id e (41) was prepared from 35 as described in the general
procedure and recrystallized from ethanol as fine white
crystals: mp 219-220 °C; 1H NMR (CDCl3/DMSO-d6) δ 7.19-
7.36 (m, 5H), 6.56 (s, 1H), 3.73 (m, 2H), 3.59 (m, 2H), 3.48 (s,
6H), 2.85 (m, 2H), 2.77 (m, 2H); 13C NMR (CDCl3/DMSO-d6)
δ_134.3, 129.1, 126.9, 126.6, 125.2, 60.5, 59.8, 49.3, 27.9, 21.5.

1806 J . Org. Chem., Vol. 64, No. 6, 1999
Della and Smith
1-(2-P h en yleth yl)-4-p h en ylm eth ylen e-1-a za cycloh ex-
a n e (50). NaH (60%) in paraffin oil (0.24 g, 5.9 mmol) was
washed with hexane (2 × 3 mL) and the hexane removed
carefully. A solution of diethyl benzylphosphonate (1.1 g, 4.8
mmol) and 1-(2-phenylethyl)-4-piperidone (49) (1 g, 4.9 mmol)
in DME (10 mL) was added all at once and the stirred mixture
heated slowly to 85 °C and then refluxed for 1 h. The reaction
mixture was added to water (50 mL) and then extracted with
diethyl ether (3 × 40 mL). The combined ether extracts were
washed with saturated NaCl solution (2 × 25 mL) and dried
(Na2SO4), and the solvent was evaporated. Chromatography
on alumina (20% dichloromethane/hexane) yielded the amine
50 as an amber oil (0.88 g, 65%): bp 170 °C (0.3 mm); 1H NMR
(CDCl3) δ 7.15-7.27 (m, 10H), 6.27 (s, 1H), 2.8 (dt, J ) 3 Hz,
8.4 Hz, 2H), 2.53-2.6 (m, 6H), 2.46 (t, J ) 4.8 Hz, 2H), 2.4 (t,
J ) 4.8 Hz, 2H); 13C NMR (CDCl3/DMSO-d6) δ 140.4, 139.4,
137.7, 128.9, 128.6, 128.3, 128.0, 126.0, 125.9, 123.2, 60.3, 55.0,
54.3, 36.2, 33.6, 28.9; HRMS calcd for C20H23N 277.1830, found
277.1842.
64.1, 61.5, 60.9, 47.9, 29.5, 28.6, 23.2. Anal. Calcd for C21H26
NI: C, 60.15, H, 6.25, N, 3.34. Found: C, 60.18, H, 6.49, N,
3.34.
-
1-(2-P h en yleth yl)-4-ph en ylm eth ylen e-1-ph en ylselen om -
eth yl-1-a zon ia cycloh exyl Br om id e (54). Treatment of 1-(2-
phenylethyl)-4-phenylmethylene-1-azacyclohexane (50) (1.0 g,
3.8 mmol) with PhSeCH2Br as outlined above converted it into
the title salt 54, which crystallized from ethanol/ether as
colorless crystals (1.7 g, 86%): mp 201-202 °C; 1H NMR
(CDCl3) δ 7.79 (d, 2H), 7.07-7.4 (m, 13H), 6.4 (s, 1H), 5.69 (s,
2H), 3.7-4.0 (m, 6H), 3.01 (m, 2H), 2.67 (s, 2H), 2.54 (s, 2H);
13C NMR (CDCl3) δ 135.5, 134.8, 134.0, 130.0, 129.1, 128.8,
128.7, 128.6, 128.1, 127.0, 126.9, 126.6, 125.5, 59.4, 59.2, 59.0,
58.4, 29.1, 28.1, 22.9. Anal. Calcd for C27H30NSeBr: C, 61.49,
H, 5.73, N, 2.66. Found: C, 61.44, H, 5.64, N, 2.74.
4-Be n zyl-1-(2-p h e n yle t h yl)-1-a zon ia b icyclo[2.2.1]-
h ep tyl Br om id e (55). A 0.025 M solution of 1-(2-phenylethyl)-
1-phenylselenomethyl-4-phenylmethylene-1-azoniacyclohex-
yl bromide (54) (0.4 g, 0.76 mmol) in 2-methyl-2-butanol was
deoxygenated and treated with a solution of tributyltin hydride
(0.33 g, 1.1 mmol) and AIBN (cat.) in 2-methyl-2-butanol (1
mL) under irradiation at reflux as discussed earlier. Workup
and recrystallization of the product from ethanol/ether yielded
the title compound 55 as white crystals (0.26 g, 92%): mp 198-
1-Iod om eth yl-1-(2-p h en yleth yl)-4-p h en ylm eth ylen e-1-
a zon ia cycloh exyl Iod id e (51). This compound was prepared
via method A and purified by column chromatography on
alumina (dichloromethane/methanol): 1H NMR (CDCl3) δ
7.15-7.32 (m, 10H), 6.48 (s, 1H), 5.26 (s, 2H), 3.72 (t, J ) 5.7
Hz, 2H), 3.49-3.55 (m, 4H), 2.98-3.04 (m, 2H), 2.74 (t, J )
5.7 Hz, 2H), 2.84-2.75 (m, 2H); 13C NMR (CDCl3/DMSO-d6) δ
135.6, 134.7, 129.5, 129.0, 128.8, 128.5, 128.3, 127.7, 127.3,
127.0, 62.1, 60.1, 59.4, 29.2, 28.7, 27.8, 23.0.
1
200 °C; H NMR (CDCl3) δ 7.08-7.34 (m, 10H), 3.8-4.0 (m,
6H), 3.6 (s, 2H), 3.08 (t, J ) 8.1 Hz, 2H), 2.95 (s, 2H), 2.19 (s,
2H), 1.75 (s, 2H); 13C NMR (CDCl3) δ 136.2, 135.1, 128.9, 128.5,
128.4, 128.2, 126.8, 126.5, 68.8, 60.4, 58.0, 47.7, 36.9, 32.0, 30.1.
Anal. Calcd for C21H26NBr: C, 67.74, H, 7.04, N, 3.76. Found:
C, 67.75, H, 7.00, N, 3.80.
4-Ben zyl-1-azabicyclo[2.2.1]h eptan e (57). Potassium tert-
butoxide (0.60 g, 5.6 mmol) was added to a solution of 4-benzyl-
1-(2-phenylethyl)-1-azoniabicyclo[2.2.1]heptyl bromide (55) (0.20
g, 0.56 mmol) in DMF (4 mL) and the solution stirred for 12
h. Diethyl ether (10 mL) was added and the mixture washed
with water (3 × 10 mL). The ether extracts were then extracted
with 5% HCl, which was basified (pH 10) with NaOH (3 M),
and then extracted with dichloromethane. After being dried
(Na2SO4), the solvent was evaporated yielding the title amine
57 (60 mg, 60%) as an amber solid: 1H NMR (CDCl3) δ 7.13-
7.31 (m, 5H), 2.97 (s, 2H), 2.88 (m, 2H), 2.55 (m, 2H), 2.28 (s,
2H), 1.54 (m, 2H), 1.18 (m, 2H); 13C NMR (CDCl3) δ 140.0,
129.7, 128.2, 126.0, 63.8, 55.4, 50.5, 38.9, 35.3; HRMS calcd
for C13H17N 187.1361, found 187.1363.
Attem p ted Syn th esis of 4-Ben zyl-1-(2-p h en yleth yl)-1-
a zon ia bicyclo[2.2.1]h ep tyl Iod id e (52). The salt 51 exhib-
ited very low solubility in 2-methyl-2-butanol; treatment of the
resulting mixture with tributyltin hydride and AIBN (cat.) at
reflux under irradiation as discussed followed by workup of
the reaction mixture yielded a complex mixture of products
containing starting material (51), cyclized product, and re-
duced product (53).
1-Meth yl-1-(2-p h en yleth yl)-4-p h en ylm eth ylen e-1-a zo-
n ia cycloh exyl Iod id e (53). 1-(2-Phenylethyl)-4-phenylmeth-
ylene-1-azacyclohexane (50) was converted into the salt 53 as
described in the general procedure above. The latter crystal-
lized from ethanol/ether as white crystals: mp 165-167 °C;
1H NMR (CDCl3) δ 7.15-7.43 (m, 10H), 6.5 (s, 1H), 3.95 (t,
2H), 3.82 (m, 1H), 3.7 (m, 2H), 3.55 (m, 1H), 3.5 (s, 3H), 3.17
(m, 2H), 2.77(m, 3H), 2.66 (m, 1H); 13C NMR (CDCl3) δ 135.7,
134.9, 129.4, 129.0, 128.8, 128.8, 128.6, 128.5, 127.5, 127.3,
Su p p or tin g In for m a tion Ava ila ble: NMR data for ob-
tained compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
J O9813538