Radical cations of trialkylamines: ESR spectra and structures

Article abstract of DOI:10.1021/jo990458n

Novel syntheses of cyclopropyldiisopropylamine (15), di-tert- butylcyclopropylamine (16), dicyclopropylisopropylamine (17), and tricyclopropylamine (18) are described. Hyperfine data were determined by ESR spectroscopy for the radical cations of these trialkylamines, as well as for those of ethyldiisopropylamine (10), diisopropyl-n-propylamine (11), dicyclohexylethylamine (12), diisopropyl-3-pentylamine (14), and 1- azabicyclo[3.3.3]undecane (manxine; 27). The radical cation of triisopropylamine (13) was reexamined under conditions of improved spectral resolution. Coupling constants of the ¹⁴N nucleus and the β-protons in the radical cations of 18 trialkylamines provide reliable information about the geometries of these species, which are confirmed by theoretical calculations. With the exception of a few oligocyclic amines, for which flattening is impaired by the rigid molecular framework, all of the radical cations should be planar. Correlation between the observed coupling constants of the β- protons and the calculated 2 θ> values of the dihedral angle θ, defining the conformation of the alkyl substituent or the azacycloalkane, is verified. Upon oxidation, striking changes occur for those amines that have cyclopropyl substituents, because of the tendency of these groups to assume a perpendicular conformation in the neutral amines and a bisected orientation in the corresponding radical cations.

Full text of DOI:10.1021/jo990458n

J . Org. Chem. 1999, 64, 6951-6959
6951
Ra d ica l Ca tion s of Tr ia lk yla m in es: ESR Sp ectr a a n d Str u ctu r es
Armin de Meijere,*,† Vladimir Chaplinski,† Fabian Gerson,*,‡ Pascal Merstetter,‡ and
Edwin Haselbach§
Institut fu¨r Organische Chemie der Georg-August Universita¨t Go¨ttingen, Tammannstrasse 2,
D-37077 Go¨ttingen, Germany, Institut fu¨r Physikalische Chemie der Universita¨t Basel,
Klingelbergstrasse 80, CH-4056 Basel, Switzerland, and Institut de Chimie Physique,
Universite´ de Fribourg, Pe´rolles, CH-1700 Fribourg, Switzerland
Received March 12, 1999
Novel syntheses of cyclopropyldiisopropylamine (15), di-tert-butylcyclopropylamine (16), dicyclo-
propylisopropylamine (17), and tricyclopropylamine (18) are described. Hyperfine data were
determined by ESR spectroscopy for the radical cations of these trialkylamines, as well as for those
of ethyldiisopropylamine (10), diisopropyl-n-propylamine (11), dicyclohexylethylamine (12), diiso-
propyl-3-pentylamine (14), and 1-azabicyclo[3.3.3]undecane (manxine; 27). The radical cation of
triisopropylamine (13) was reexamined under conditions of improved spectral resolution. Coupling
constants of the 14N nucleus and the â-protons in the radical cations of 18 trialkylamines provide
reliable information about the geometries of these species, which are confirmed by theoretical
calculations. With the exception of a few oligocyclic amines, for which flattening is impaired by the
rigid molecular framework, all of the radical cations should be planar. Correlation between the
observed coupling constants of the â-protons and the calculated <cos2 θ> values of the dihedral
angle θ, defining the conformation of the alkyl substituent or the azacycloalkane, is verified. Upon
oxidation, striking changes occur for those amines that have cyclopropyl substituents, because of
the tendency of these groups to assume a perpendicular conformation in the neutral amines and a
bisected orientation in the corresponding radical cations.
In tr od u ction
and enhances the persistence of the corresponding radical
cation, so that the radical cations of diverse acyclic and
oligocyclic amines could be studied by ESR spectroscopy
in fluid solution or Freon matrices. In the following, a
brief account of these studies is presented without
claiming comprehensiveness.12
Ammonia (1) is the simplest neutral molecule of
pyramidal geometry and of C3v symmetry.1 Ionization of
its N-lone pair requires an energy IEv of 10.88 eV.2,3 The
radical cation 1•+ thus generated is planar and of D3h
symmetry, according to ESR-spectroscopic evidence4,5 and
theoretical calculations.6 Because of the relatively high
IEv value of 1 and the poor persistence of 1•+, conversion
of ammonia into its radical cation was performed in the
solid state by γ-irradiation of a single crystal4 or a
polycrystalline powder5 of NH4ClO4. Later on, an isotropic
ESR spectrum of 1•+, generated by photoionization of 1
in a neon matrix at 4 K, was observed.7
The majority of the radical cations in question were
generated by UV-photolysis in strongly acidic solutions.
This procedure was used for dimethylamine (3), diethyl-
amine (4), di-n-propylamine (5), diisopropylamine (6), and
tert-butylmethylamine (7) in 90% H2SO4,13 for 3 and
2,2,6,6-tetramethylpiperidine (22) in CF3COOH,14 and for
trimethylamine (8), 1-azabicyclo[2.2.1]heptane (1-aza-
norbornane, 24), 1-azabicyclo[2.2.2]octane (quinuclidine,
25), and 1-azatricyclo[3.3.1.13,7]decane (1-azaadaman-
tane, 26) in CF3SO3H.15 Radical cations of 3 and 8 were
also produced by steady-state radiolysis of the corre-
sponding amines in aqueous HClO4.16 Generation of more
persistent radical cations, such as those of triisopropyl-
amine (13)17 and 9-tert-butylazabicyclo[3.3.1]nonane (23),18
Alkyl substitution on 1 and/or incorporation of am-
monia into a cycle lowers the ionization energy of 13,8-11
* To whom correspondence should be addressed. E-mail: (A.d.M.)
ameijer1@uni-goettingen.de; (F.G.) gerson@ubaclu.unibas.ch.
† Institut fu¨r Organische Chemie der Georg-August Universita¨t
Go¨ttingen.
‡ Institut fu¨r Physikalische Chemie der Universita¨t Basel.
§ Universite´ de Fribourg.
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10.1021/jo990458n CCC: $18.00 © 1999 American Chemical Society
Published on Web 08/25/1999

6952 J . Org. Chem., Vol. 64, No. 19, 1999
de Meijere et al.
Sch em e 1. Syn th eses of
required less rigorous methods. These amines were
oxidized in dichloromethane with SbF5 and (p-BrC6H4)3N•+-
SbCl6-, respectively.
Cyclop r op yld iisop r op yla m in e (15) a n d
Di-ter t-bu tylcyclop r op yla m in e (16)a
With the advent of γ-irradiation of organic compounds
in Freon matrices at 77 K as a method of generating
radical cations,19 this treatment was applied to several
amines in frozen CFCl3, namely to methylamine (2),20 8,21
and triethylamine (9),21 as well to azetidine (19),22
N-methylpyrrolidine (20),21 and N-methylpiperidine (21).21
Recently, the radical cations were also produced from
tricyclopropylamine (18)23 and 10-azatricyclo[5.2.1.04,10]-
decane (azatriquinane; 28)24 by γ-rays in a CF2ClCFCl2
matrix.
aKey: (a) CHCl3, 36% NaOH, cat. NBu4Cl, CH2Cl2, reflux, 4 h;
(b) 6 equiv of EtMgBr, 3 equiv of Ti(O-i-Pr)4, THF, reflux, 3 d; (c)
same as (b) but 10 d.
amine (16), dicyclopropylisopropylamine (17), and 1-azabi-
cyclo[3.3.3]undecane (manxine, 27). The ESR spectrum
of the radical cation of triisopropylamine (13) has been
reexamined. The interest is focused on the geometry of
the radical cations, in particular on the planarity and
on the conformation of alkyl substituents.
Resu lts
Sou r ce of Com p ou n d s. The acyclic trialkylamines
10-12 and 14 are commercially available (Aldrich, Gold
Label); they were purified before use. The tertiary amine
1317,25 and the bicyclic amine 2726 were prepared accord-
ing to literature procedures.
The syntheses of the new tertiary cyclopropylamines
15-18 were achieved by appropriate adaptations of the
previously developed,27 titanium-mediated cyclopropa-
nation of carboxylic acid dialkylamides. Diisopropylform-
amide (30), which is easily available from commercial
diisopropylamine (29) by formylation with dichlorocar-
bene,28 afforded cyclopropyldiisopropylamine (15) in good
yield (76%) by treatment with the ethylmagnesium
bromide/titanium tetraisopropoxide reagent at reflux
temperature. On the other hand, the cyclopropanation
of the more sterically congested di-tert-butylformamide
(31)29 with the same reagent was achieved only upon
heating to give di-tert-butylcyclopropylamine (16), yet in
low yield (20%) (Scheme 1). Thus, the success of this
reaction, unlike any other one, demonstrates the high
versatility of this titanium-mediated cyclopropanation of
acid dialkylamides and its potential for the synthesis of
even the most sterically congested and, not otherwise
accessible, tertiary cyclopropylamines such as 16.
In the present work, we have extended the ESR studies
to the radical cations of further acyclic and oligocyclic
trialkylamines, i.e., those amines that contain three C-N
single bonds. These compounds are ethyldiisopropyl-
amine (10), diisopropyl-n-propylamine (11), dicyclohexyl-
ethylamine (12), diisopropyl-3-pentylamine (14), cyclo-
propyldiisopropylamine (15), di-tert-butylcyclopropyl-
A similar formylation-cyclopropanation sequence as
for 15 was used to convert cyclopropylisopropylamine (33)
to dicyclopropylisopropylamine (17) (Scheme 2). The
secondary amine 33 was prepared in excellent yield by
reductive amination of acetone with cyclopropylamine
(32), applying as reducing agent sodium cyanoborohy-
(19) Shida, T.; Haselbach, E.; Bally, T. Acc. Chem. Res. 1984, 17,
180. Symons, M. C. R. Chem. Soc. Rev. 1984, 13, 393.
(20) Khisidman, M. B.; Vyatkin, V. P.; Grigor’eva, N. V.; Dobychin,
S. L. Zh. Prikl. Khim. (Leningrad) 1983, 56, 222; Chem. Abstr. 1983,
98, 160106r.
(21) Eastland, G. W.; Rao, D. N. R.; Symons, M. C. R. J . Chem. Soc.,
Perkin Trans. 2 1984, 1551.
(22) Qin, X.-Z.; Williams, F. J . Phys. Chem. 1986, 90, 2292.
(23) de Meijere, A.; Chaplinski, V.; Kusnetsov, M. A.; Rademacher,
P.; Boese, R.; Haumann, T.; Schleyer, P. v. R.; Zywietz, T.; J iao, H.;
Merstetter, P.; Gerson, F. Angew. Chem. 1999, 111, 2582; Angew.
Chem., Int. Ed. Engl. 1999, 38, 2430.
(25) Coll, J . C.; Crist, D. R.; Barrio, M. C. G.; Leonard, N. J . J . Am.
Chem. Soc. 1972, 94, 7092.
(26) Kuffner, F.; Koechlin, W. Monatsh. Chem. 1962, 93, 476.
(27) Chaplinski, V.; de Meijere, A. Angew. Chem. 1996, 108, 491;
Angew. Chem., Int. Ed. Engl. 1996, 35, 413. Chaplinski, V.; Winsel,
H.; Kordes, M.; de Meijere, A. Synlett 1997, 111.
(28) Graefe, J .; Fro¨hlich, I.; Mu¨hlsta¨dt, M. Z. Chem. 1974, 14, 434.
(29) Audeh, C. A.; Fuller, S. E.; Hutchinson, R. J .; Smith, J . R. L.
J . Chem. Res., Synop. 1979, 270; J . Chem. Res., Miniprint 1979, 2984.
(24) Gerson, F.; Merstetter, P.; Mascal, M.; Next, N. M. Helv. Chim.
Acta 1998, 81, 1749.

Radical Cations of Trialkylamines
J . Org. Chem., Vol. 64, No. 19, 1999 6953
Sch em e 2. Syn th esis of
Sch em e 3. Syn th esis of th e Tr icyclop r op yla m in e
(18) via Dicyclop r op yla m in e (38)a
Dicyclop r op ylisop r op yla m in e (17)a
aKey: (a) Me2CO, NaBH3CN, HCl, CH3OH, rt, 2 h; (b) CHCl3,
NaOH, H2O, CH2Cl2, 40 °C, 4 h; (c) 2.3 equiv of EtMgBr, 1.3 equiv
of Ti(O-i-Pr)4, THF, rt, 3 d.
dride30 rather than catalytic hydrogenation over platinum
as previously reported (65% yield).31 The crude hydro-
chloride of 33 was pure enough to be used for the
formylation in the next step without purification. The
cyclopropanation of the formyl group in 34 was achieved
in 48% yield.
aKey: (a) BnBr, NaH, benzene, 40 °C, 10 h; (b) 2.3 equiv of
EtMgBr, 1.3 equiv of Ti(O-i-Pr)4, THF, rt, 24 h; (c) Pd/C, H2,
MeOH; (d) CHCl3, NaOH, cat. NBu4Cl, CH2Cl2, 40 °C, 4 h; (e) same
as (b) but 10 h.
The preparation of tricyclopropylamine (18) required
more steps, yet followed the same sequence of formylation
of a secondary amine with dichlorocarbene and titanium-
mediated cyclopropanation of the formyl group. A suit-
able starting material, benzylcyclopropylformamide (36),
was prepared by benzylation of cyclopropylformamide
(35)32 with benzyl bromide after deprotonation with
sodium hydride. Cyclopropanation of 36 by treatment
with the ethylmagnesium bromide/titanium tetraisoprop-
oxide reagent at ambient temperature produced the
benzyldicyclopropylamine (37) (83%). Performing this
reaction at elevated temperature led to the formation of
significant quantities of the interesting byproduct, ben-
zylcyclopropyl(3-pentyl)amine, apparently by transfer of
two ethyl groups from the Grignard reagent onto the
formyl group of 36 (probably mediated by the titanium
tetraisopropoxide).33 Removal of the benzyl group by
catalytic hydrogenation over Pd/C gave dicyclopropyl-
amine (38),34 which was formylated again to dicyclopro-
pylformamide (39); this compound, in turn, was cyclo-
propanated to give 1835 (overall yield from 35: 28%) along
with 38 (Scheme 3).
Gen er a tion of Ra d ica l Ca tion s. The amines 10-16
and 27 were oxidized to their radical cations by SbF5 in
fluid dichloromethane solutions at 195 K, whereas for 17,
as for 1823 and 28,24 γ-irradiation with a 60Co source in
the “mobile” CF2ClCFCl2 matrix at 77 K was required to
produce the corresponding radical cations. The slightly
temperature-dependent ESR spectra of the fairly persist-
ent radical cations 10•+-16•+ and 27•+ in dichloromethane
were recorded in the range 200-300 K, with the resolu-
tion generally improving upon warming. The tempera-
ture dependence is mainly due to changes of the coupling
constants of â-protons;36 for example, that for 13•+
increased from 0.13 to 0.16 mT on going from 230 to 300
23
K. For 17•+ in a CF2ClCFCl2 matrix, as for 18•+ and
28•+,24 the resolution was strongly affected by the residual
hyperfine anisotropy, but the spectra became quasi-
isotropic at the softening point of the glass (ca. 125 K).
Analyses of hyperfine patterns were carried out with the
aid of a computer program.37 An 1H-ENDOR spectrum
could be observed only for 13•+. The g factors of the acyclic
radical cations 10•+-18•+ are all 2.0037 ( 0.0001; that
of the bicyclic 27•+ is slightly higher, 2.0041 ( 0.0001.
Eth yld iisop r op yla m in e (10), Diisop r op yl-n -p r o-
p yla m in e (11), a n d Dicycloh exyleth yla m in e (12).
Figure 1 shows the ESR spectra of the radical cations
11•+ and 12•+ at 300 K. As the major coupling constants
are almost equal for 10•+ and 11•+, their spectra closely
resemble each other; that of 10•+ is, therefore, not
reproduced here. With the values for 10•+ preceding those
for 11•+, the 14N-coupling constants amount to |aN| ) 2.02
( 0.02 and 2.00 ( 0.02 mT, while the two methylene
â-protons36 in the ethyl or n-propyl substituent give rise
â
to the coupling constants |aHâ(Et)| ) 1.85 ( 0.02 and |aH
-
(n-Pr)| ) 1.88 ( 0.02 mT. The corresponding values of
the methine â-protons in the two isopropyl substituents
are |aHâ(i-Pr)| ) 0.45 ( 0.01 and 0.44 ( 0.01 mT. The
smallest resolved splittings in the spectra of both 10•+
and 11•+, |aHγ(i-Pr)| ) 0.06 ( 0.01 mT, are due to the 12
methyl γ-protons in these substituents. Those from the
three methyl γ-protons in the ethyl substituent of 10•+
(30) Borch, R. F.; Bernstein, M. D.; Durst, H. D. J . Am. Chem. Soc.
1971, 93, 2897.
(31) Freifelder, M.; Horrom, B. W. J . Pharm. Sci. 1963, 52, 1191.
(32) Gate, E. N.; Threadgill, M. D.; Stevens, M. F. G.; Chubb, D.;
Vickers, L. M.; Langdon, S. P.; Hickman, J . A.; Gescher, A. J . Med.
Chem. 1986, 29, 1046.
(33) Under appropriate conditions, this transfer of two alkyl groups
onto any diorganylformamide occurs as the sole reaction. Welz-
Biermann, U.; Buchholz, H. A.; de Meijere, A. To be published.
(34) Maeda, Y.; Ingold, K. U. J . Am. Chem. Soc. 1980, 102, 328.
(35) This synthesis of tricyclopropylamine (18) was presented by one
of us (A.d.M.) at the Gordon Conference on Physical Organic Chem-
istry, J uly 2-7, 1995, in Plymouth, NH. Four months later, an
alternative synthesis of tricyclopropylamine (18) was reported: Gillaspy,
M. L.; Lefker, B. A.; Hada, W. A.; Hoover, D. J . Tetrahedron Lett. 1995,
36, 7399.
(36) In ESR spectroscopy, protons separated from the spin-bearing
π-center by 0, 1, 2, 3, and 4 sp3-hybridized C atoms are denoted R, â,
γ, δ, and ꢀ. The π-center in amines is the N atom. Trialkylamines
contain no R-protons. The following notation holds for the substituents
at the N atom in 8-18, 20, 21, and 23: â-Protons are CH3 in Me; CH2
in Et and n-Pr; CH in i-Pr, 3Pn, c-Hx, and c-Pr. γ-Protons are CH3 in
Et, i-Pr, and t-Bu; CH2 in n-Pr, 3Pn, c-Hx, and c-Pr. δ-Protons are
CH3 in 3Pn; CH2 in c-Hx. ꢀ-Protons are CH2 in c-Hx. For the azacycles,
the corresponding notation is as follows: â-Protons are CH2 in 20, 21,
and 24-27; CH in 23 and 28. γ-Protons are CH3 in Me of 22; CH2 in
20-25, 27, and 28; CH in 26. δ-Protons are CH2 in 21-23, 26 and 27;
CH in 24 and 25. ꢀ-Proton is CH in 27.
(37) Duling, D. WinSim, Public EPR Software Tools, Institute of
Environmental Health Sciences: Research Triangle Park, NC, 1996.

6954 J . Org. Chem., Vol. 64, No. 19, 1999
de Meijere et al.
F igu r e 2. ESR spectrum of 13•+. Solvent: CH2Cl2. Temper-
ature: 270 K.
F igu r e 1. ESR spectra of 11•+ (top) and 12•+ (bottom).
Solvent: CH2Cl2. Temperature: 300 K.
F igu r e 3. ESR spectra of 14•+ (top) and 17•+ (bottom).
Solvent: CH2Cl2 (14•+) and CF2ClCFCl2 (17•+, matrix). Tem-
perature: 300 K (14•+) and 125 K (17•+). The dashed part of
the spectrum of 17•+ is affected by an absorption from the
γ-irradiated quartz sample tube.
and from the two methylene γ-protons and the three
methyl δ-protons36 in the propyl substituent of 11•+ were
unresolved, |aHγ(Et)|, |aHγ(n-Pr)|, |aHδ(n-Pr)| < 0.03 mT.
The two largest coupling constants for 12•+, |aN| ) 1.93
( 0.01 mT and |aHâ(Et)| ) 1.70 ( 0.01 mT, of the two
methylene â-protons in the ethyl substituent, do not
greatly differ from the corresponding values in the
spectrum of 10•+ and 11•+. Analysis of the remaining
complex hyperfine pattern yielded 0.38 ( 0.01, 0.24 (
0.01, and 0.12 ( 0.01 mT for two, eight, and eight
protons, respectively, in the two cyclohexyl substituents.
Guided by theoretical calculations (see Discussion), the
largest value was assigned to the two methine â-protons,
|aHâ(c-Hx)|, the middle-size one to the eight methylene
δ-protons, |aHδ(c-Hx)|, and the smallest one to the eight
methylene γ-protons, |aHγ(c-Hx)|. The hyperfine splittings
from the three methyl γ-protons in the ethyl substituent
and the four methylene ꢀ-protons36 in the cyclohexyl rings
were not resolved, |aHγ(Et)|, |aHꢀ(c-Hx)| < 0.03 mT.
Tr iisop r op yla m in e (13) a n d Diisop r op yl-3-p en tyl-
a m in e (14). The radical cation 13•+ enjoys an unusual
thermodynamic and kinetic stability. In a previous
study,17 only the coupling constant |aN| ) 1.95 mT was
derived from the ESR spectrum of 13•+ consisting of three
broad 14N-hyperfine components. The splittings from the
protons of the three isopropyl substituents were con-
cealed by the large line width. In the ESR spectrum of
13•+, taken at 270 K and presented in Figure 2, these
splittings are fully resolved. Apart from |aN| ) 2.02 (
0.01 mT, the spectrum exhibits the coupling constants,
|aHâ(i-Pr)| ) 0.148 ( 0.002 mT, of the three methine
â-protons and, |aHγ(i-Pr)| ) 0.060 ( 0.002 mT, of the 12
methyl γ-protons. Owing to the persistence and the high
symmetry of 13•+, 13C satellites were also readily observ-
able. Their relative intensities indicate that they arise
from the 13C isotopes in the six methyl groups with |aC|
) 1.38 ( 0.02 mT.
1
The resolution of the H-hyperfine splittings was lost
in the ESR spectrum of 14•+, as the replacement of the
two γ-protons in one isopropyl substituent of 13•+ by
methyl groups lowers the symmetry of the radical cation.
Disregarding the poor resolution, the spectrum of 14•+
,
shown in Figure 3, is congruent with that of 13•+, as the
broad 14N-hyperfine components in 14•+ are spaced by
|aN| ) 2.00 ( 0.02 mT and their width is comparable to
the sum of the 1H-coupling constants for 13•+. It is,
therefore, reasonable to assume that these coupling
constants are similar for both radical cations, in particu-
lar the |aHâ(i-Pr)| values.

Radical Cations of Trialkylamines
J . Org. Chem., Vol. 64, No. 19, 1999 6955
Cyclop r op yld iisop r op yla m in e (15) a n d Di-ter t-
bu tylcyclop r op yla m in e (16). In contrast to 14•+, re-
placement of one isopropyl by a cyclopropyl substituent
did not substantially affect the resolution of the ESR
spectrum on going from 13•+ to 15•+. The coupling
constants for 15•+ strongly resemble those for 13•+; at 240
K, they are |aN| ) 2.02 ( 0.01 mT, |aHâ(c-Pr)| ≈ |aHâ(i-
Pr)| ) 0.13 ( 0.01 mT, and |aHγ(c-Pr)| ≈ |aHγ(i-Pr)| ) 0.06
( 0.01 mT. Thus, within the limits of experimental
resolution, the single methine â-proton in the cyclopropyl
substituent has the same coupling constant as in its two
isopropyl counterparts, and an analogous statement holds
for the four methylene and the 12 methyl γ-protons in
the cyclopropyl and the two isopropyl substituents,
respectively.
Resolution of 1H-hyperfine splittings is retained in the
ESR spectrum of 16•+ when the two isopropyl substitu-
ents in 15•+ are replaced by tert-butyl groups. The
coupling constants observed for 16•+ at 210 K are |aN| )
2.01 ( 0.02 and |aHâ(c-Pr)| ) 0.11 ( 0.01 of the single
â-proton in the cyclopropyl substituent, and |aHγ(c-Pr)|
≈ |aHγ(t-Bu)| ) 0.07 ( 0.01 of the four methylene
γ-protons in the cyclopropyl substituent and the 18
methyl γ-protons in the two tert-butyl groups.
F igu r e 4. ESR spectrum of 27•+. Solvent: CH2Cl2. Temper-
ature: 240 K.
Discu ssion
Ion iza tion En er gies. Table 1 lists the vertical ioniza-
tion energies, IEv, determined by photoelectron spectro-
scopy for those trialkylamines, of which radical cations
were characterized by their hyperfine data (see Introduc-
tion). A relation exists between these gas-phase values
and the method required for generation of the radical
cations. In our present and recent work,23,24 the border-
line ionization energy IEv appears to be about 8 eV. Thus,
the acyclic trialkylamines 10-16, with none or one
cyclopropyl substituents could be oxidized to persistent
radical cations by SbF5 in fluid solution, whereas for 17
and 18 with two or three cyclopropyl substituents, as for
azatriquinane (28),24 γ-irradiation in a Freon matrix had
to be used to this aim. The tricyclic amine 28 represents
an exception insofar, as its IEv value is somewhat lower
than 8 eV.
P la n a r ity. In general, alkyl-substituted amines are
expected to share the pyramidal structure of the parent
ammonia (1).1 The geometry at the N atom is reflected
by the sum, Σæ, of the three CNC angles, æ, and by the
distance, d, of this atom from the plane of its C neighbors.
Such Σæ and d values, listed in Table 1, were calculated
by AM138 and, in part, by other quantum theoretical
methods39-41 (see footnotes to Table 1). Planarity implies
Σæ ) 360° and d ) 0, while a decrease in the former and
an increase in the latter indicate a progressive pyrami-
dalization. The predicted pyramidal geometry at the N
atom was experimentally confirmed for trimethylamine
(8)42 and triethylamine (9).43 Trialkylamines with at least
Dicyclop r op ylisop r op yla m in e (17) a n d Tr icyclo-
p r op yla m in e (18). As stated in the section on genera-
tion of radical cations, the ESR spectrum of 17•+, like that
of 18•+ 23
was taken in a CF2ClCFCl2 matrix at 125 K.
,
The resolution was greatly affected by the residual
hyperfine anisotropy, so that the splittings from the
protons remained unresolved in both spectra. The coup-
ling constants, |aN| ) 2.00 ( 0.01 mT for 17•+ and |aN| )
2.01 ( 0.01 mT for 18•+, are close to the corresponding
values for 10•+-16•+. A striking characteristic is the
narrowing of the 14N-hyperfine components, as illustrated
in Figure 3 by comparison of the ESR spectra of 14•+ and
17•+; on going from the former to the latter, the peak-
to-peak distance diminishes from 0.45 to 0.15 mT. This
finding points to a strong reduction in the coupling
constant of the methine â-protons. As stated above, such
â
|aH | values decrease on lowering the temperature, which
is the case when using Freon matrices. In addition, with
the successive replacement of isopropyl or 3-pentyl by
cyclopropyl substituents, the coupling constants of the
methine â-protons may be reduced, because the “bisected”
orientation of cyclopropyl groups becomes increasingly
favored (see below). For the three methine â-protons in
the radical cation 18•+, an |aHâ(c-Pr)| value of 0.06-0.08
mT was estimated in the previous communication.23
1-Aza b icyclo[3.3.3]u n d eca n e (Ma n xin e, 27). A
prominent feature of the ESR spectrum of 27•+, displayed
in Figure 4, is the large coupling constant of the three
methylene â-protons, which are equatorial with respect
to the ring and in a favorable position for hyperconjuga-
tion with the p-orbital at the spin-bearing N atom (see
below); the value, |aHâ(eq)| ) 3.85 ( 0.03 mT, of this
coupling constant is twice |aN| ) 1.92 ( 0.02 mT. Analysis
of the smaller hyperfine splittings reveals a coupling
(38) Dewar, M. J . S.; Zoebisch, E. G.; Healy, E. F.; Stewart, J . J . P.
J . Am. Chem. Soc. 1985, 107, 3902. MOPAC 60 package (Seiler, F. J .
Res. Lab., U. S. Air Force Academy: Colorado Springs, 1994) was used.
(39) For SCF-STO-G calculations on 8 and 13, see: Ko¨lmel, C.;
Ochsenfeld, C.; Ahlrichs, R. Theor. Chim. Acta 1991, 82, 271.
(40) 3-21G* and DFT calculations were performed with GAUSSIAN
94.41 The latter involve B3LYP hybrid functionals: Becke, A. D. Phys.
Rev. A 1988, 38, 3098; J . Chem. Phys. 1993, 98, 1372.
(41) Frisch, M. J .; Trucks, G. W.; Schlegel, H. B.; Gill, P. M. W.;
J ohnson, B. G.; Robb, M. A.; Cheeseman, J . R.; Keith, T.; Peterson, G.
A.; Montgomery, J . A.; Raghavachari, K.; Al-Laham, M. A.; Zakrzewski,
V. G.; Oritz, J . V.; Foresman, J . B.; Cioslowski, J .; Stefanov, B. B.;
Nanayakkara, A.; Challacombe, M.; Peng, C. Y.; Ayala, P. Y.; Chen,
W.; Wong, M. W.; Andres, J . L.; Peplogle, E. S.; Gomperts, R.; Martin,
R. L.; Fox, D. J .; Binkley, J . S.; DeFrees, D. J .; Baker, J .; Stewart, J .
P.; Head-Gordon, M.; Gonzalez, C.; Pople, J . A. Gaussian 94, Revision
B.3; Gaussian, Inc.: Pittsburgh, PA, 1995.
ꢀ
constant |aH | ) 0.60 ( 0.01 mT, due to the single
methine ꢀ-proton36 in the bridgehead position (through-
space, long-range interaction15), as well as three smaller
|aH| values, 0.23, 0.18, and 0.16, each arising from three
protons. Candidates therefore are the sets of the axial
methylene â-protons, |aHâ(ax)|, and those of the axial and/
or equatorial methylene γ- and δ-protons.
(42) Blake, A. J .; Ebsworth, E. A. V.; Welch, A. J . Acta Crystallogr.,
Sect. C 1984, 40, 413.
(43) Boese, R.; Bla¨ser, D.; Antipin, M. Y.; Chaplinski, V.; de Meijere,
A. J . Chem. Soc., Chem. Commun. 1998, 781.

6956 J . Org. Chem., Vol. 64, No. 19, 1999
Ta ble 1. Obser ved a n d Ca lcu la ted Da ta for Tr ia lk yla m in es a n d Th eir Ra d ica l Ca tion a
de Meijere et al.
observed
AM1-calculated
θ (deg)
observed
IEv [eV] ref Σæ (deg) d (pm)
aN (mT)
aHâ (mT)
ref
NMe3
8
8.53
8.08
7.7
3
3
339b
360
337c
360
349e
360
349
360
349g
360
349h
360
350i
360
343k
360
342l
360
338m
360
335n
360o
336
360
338
360
360
360
308
325
325
340
327
342
349
359q
326r
343s
39b
0
45
45
8•+
9
+2.07
+2.08d
+2.02
+2.00
+1.93
+2.02
+2.00
+2.02
+2.01
+2.00
+2.01
p
+2.85
+1.9
16
21
NEt3
41c
0
52/68
57/57
41/74(Et)/82(i-Pr)
36/84(Et)/82(i-Pr)
41/74(n-Pr)/86(i-Pr)
41/80(n-Pr)/83(i-Pr)
39/84(Et)/83(c-Hx)
40/80(Et)/85(c-Hx)
88(i-Pr)
89(i-Pr)
80(3Pn)/88(i-Pr)
85(3Pn)/84(i-Pr)
174(c-Pr)/80(i-Pr)
90(c-Pr)/89(i-Pr)
174
84
177(c-Pr)/68(i-Pr)
90(c-Pr)/90(i-Pr)
179
90
178(ax)/64(eq)/45(Me)
151/34(“ax/eq”)/45(Me)
178(ax)/64(eq)/45(Me)
178(ax)/66(eq)/45(Me)
9•+
NEt(i-Pr)2
10
11
29e
<1
28
<1
28g
<1
28h
<1
27i
0
10•+
11
+1.85(Et)/+0.45(i-Pr)
this work
N(n-Pr)(i-Pr)2
NEt(c-Hx)2
N(i-Pr)3
f
11•+
12
+1.88(n-Pr)/+0.44(i-Pr) this work
7.35
7.18
7.2
11
17
11
23
49
23
23
9
12•+
13
+1.70(Et)/+0.38(c-Hx)
this work
this work
this work
13•+
14
+0.15
<0.2j
N(3Pn)(i-Pr)2
N(c-Pr)(i-Pr)2
N(c-Pr)(t-Bu)2
N(c-Pr)2(i-Pr)
N(c-Pr)3
14•+
15
7.79
7.76
8.14
8.44
8.41
8.29
f
36k
<1
36l
0
15•+
16
+0.13(c-Pr)/+0.13(i-Pr) this work
16•+
17
+0.11(c-Pr)
<0.1j
this work
40m
<1
43n
0o
17•+
18
this work
18•+
20
+0.06 to +0.08
+5.7(ax)/+2.8(eq;Me)
+3.8(ax)/+2.9(Me)
f
23
21
21
18
NMe-pyrrolidine
NMe-piperidine
42
<1
40
2
0
0
20•+
21
9
21•+
p
N(t-Bu)bicyclononane 23
0
0
23•+
+1.95
+3.02
+2.51
+2.16
+1.92
+2.50
azanorbornane
quinuclidine
azaadamantane
manxine
24
f
65
52
52
39
50
36
28
5q
44(exo)/75(endo)
47(exo)/75(endo)
58
60
59
61
32(ax)/83(eq)
34(eq)/84(ax)
0
0
24•+
25
+1.51(exo)/+0.30(endo) 15
8.05
7.94
7.13
7.80
3
50
11
45
25•+
26
+0.94
15
26•+
27
+0.87
15
27•+
28
+3.85(eq)
this work
azatriquinane
52r
36s
28•+
+4.00
24
a
b
See text for the meaning of Σæ, d, and θ. SCF-STO-G: Σæ ) 335°, d ) 42 pm (ref 39); exptl: Σæ ) 331°, d ) 46 pm (ref 42). c Exptl:
Σæ ) 330°, d ) 47 pm (ref 43). This more reliable value is taken from ref 48. e 3-21G*: Σæ ) 353°, d ) 23 pm. f Not reported. 3-21G*:
d
g
h
i
Σæ ) 354°, d ) 20 pm. SCF-STO-G: Σæ ) 357°, d ) 15 pm (ref 39); exptl: Σæ ) 350°, d ) 28 pm (ref 43). 3-21G*: Σæ ) 360°, d ) 0
j
k
l
m
pm. Not resolved. 3-21G*: Σæ ) 349°, d ) 29 pm; exptl: Σæ ) 340°, d ) 39 (ref 44). 3-21G*: Σæ ) 346°, d ) 33 pm. 3-21G*: Σæ )
342°, d ) 37 pm. RB3LYP/6-31G**: Σæ ) 333°, d ) 44 pm (ref 23); exptl: Σæ ) 330°, d ) 47 pm (ref 23). o UB3LYP/6-31G**: Σæ )
n
p
q
r
360°, d ) 0 pm (ref 23). Only a rough estimate is reported. UB3LYP/6-31G**: Σæ ) 360°, d ) 0 pm. 6-31G*: Σæ ) 326°, d ) 51 pm
s
(ref 45). UB3LYP/6-31G**: Σæ ) 346°, d ) 24 pm (ref 24).
two isopropyl substituents, such as 10, 11, and 13-15,
should be closer to planarity. On the other hand, intro-
duction of cyclopropyl groups, to yield successively 15 (or
16), 17, and 18, is expected to increase pyramidalization.
These predictions were confirmed by X-ray crystal-
structure analyses for 13,43 15,44 and 1823 with Σæ ) 350,
340, and 330°, respectively. The monocyclic N-methylpyr-
rolidine (20) and N-methylpiperidine (21) are predicted
to be pyramidal as are certainly the bicyclic 1-azanor-
bornane (24) and quinuclidine (25), as well as the tricyclic
1-azaadamantane (26) and azatriquinane (28),45 while
the bicyclic N-tert-butylbicyclononane (23) and manxine
(27) should be planar or nearly planar.
On passing to their radical cations, all alkyl-substi-
tuted amines tend to flatten at the N atom, as does
ammonia (1) on its conversion to 1•+. However, planarity
cannot be achieved for the radical cations of the oligocy-
clic amines 24-26 and 28, because it is impaired by their
rigid molecular frameworks. Inspection of the observed
14N-coupling constants with a positive sign, required by
theory46 (see Table 1), reveals that those aN values that
markedly exceed +2.0 mT belong to these four radical
cations. The sequence of increasing aN, 26•+ < 25•+ ≈ 28•+
< 24•+, indicates that the pyramidalization becomes more
pronounced in this order, as expected from the Σæ and d
values. On the other hand, the 14N-coupling constants of
the radical cations of the remaining acyclic and bicyclic
amines are +2.0 mT with a deviation of less than 0.1 mT;
this finding is also in accord with the prediction.
The increase in the aN values upon pyramidalization
is due to a growing s-contribution by the spin-bearing
orbital at the N atom. Such an s-contribution arises from
p,s-spin delocalization, while in planar radical cations
this orbital has a “pure p-character” with the 14N-coupling
constants brought about solely by p,s-spin polarization.46
Con for m a tion s. Apart from Σæ and d values, calcula-
tions by the AM1 procedure yielded the dihedral angles,
θ, between the axis of the spin-bearing p-orbital at the
N atom and the direction of the C-Hâ bond. These angles
are also listed in Table 1 for the trialkylamines and their
(44) Boese, R.; Bla¨ser, D.; Winsel, H.; de Meijere, A. To be published.
(45) Galasso, V.; Hansen, J .; J ones, D.; Mascal, M. THEOCHEM
1997, 392, 21.
(46) See, e.g.: Gerson, F. High-Resolution ESR Spectroscopy; Wiley
and Verlag Chemie: New York and Weinheim, Germany, 1970;
Chapter 1.5.

Radical Cations of Trialkylamines
J . Org. Chem., Vol. 64, No. 19, 1999 6957
radical cations, along with the observed coupling con-
stants aHâ, for which theory requires a positive sign.46 In
general, the θ values vary only slightly on going from
the neutral amines to their radical cations. Striking
exceptions are those with cyclopropyl substituents, in
which θ changes from ca. 180° in 15-18 to ca. 90° in
15•+-18•+. Such a change occurs because these rings
assume a “bisected” orientation with θ ) 90° in the
radical cations instead of a “perpendicular” conformation
in the corresponding neutral compounds where they are
vertical to the orbital axis at the N atom, i.e., have θ )
180°.23
â
The coupling constants aH should be proportional to
<cos2 θ>,47
aHâ ) B<cos2 θ>
(1)
as they are due to p,s-spin delocalization from the
p-orbital at the N atom to a pseudo-p-MO formed by the
1s-AO’s of the Hâ atoms (hyperconjugation). Thus, θ )
0° or 180° and <cos2θ> ) 1 imply eclipsing of the p-axis
at the N atom by the C-Hâ bond (hyperconjugation at
its optimum), while θ ) 90° and <cos2 θ> ) 0 point to a
position of this bond in the nodal plane of the p-orbital
(no hyperconjugation). For a freely rotating methyl
substituent, <cos2 θ> ) 0.5, which corresponds to θ )
45°, so that the proportionality factor B in eq 1 should
â
F igu r e 5. Observed coupling constants of â-protons, aH in
mT, vs <cos2θ> values of AM1-calculated dihedral angles θ
for radical cations of trialkylamines. Filled and open circles
refer to planar and nonplanar species, respectively.
â
be equal to 2aHâ. With aH ) +2.85 mT for the nine
methyl â-protons in the radical cation, 8•+, of trimethyl-
amine,16 B thus becomes +5.7 mT. It is evident from
â
Figure 5, in which the observed coupling constants aH
expressed in ppm downfield from tetramethylsilane used as
an internal standard (δ value). Coupling constants J are given
in Hz. Assignments of 13C signals were made with the aid of
DEPT (distortionless enhancement by polarization transfer)
experiments, and multiplicities are indicated by the usual
symbols, i.e., + for primary and tertiary, - for secondary, and
Cquat for quaternary carbons (no signal in the DEPT spectrum).
Mass spectra were measured with Varian MAT CH 7, MAT
731 mass spectrometers. Silica gel TLC was performed on 60F-
254 precoated sheets (E. Merck), and column chromatography
was carried out using Merck Kieselgel 60 (200-400 mesh).
Elemental analyses were performed in the Microanalytical
Laboratory of the Institut fu¨r Organische Chemie, Universita¨t
Go¨ttingen.
Gen er a l P r oced u r e (GP 1) for th e F or m yla tion of
Dia lk yla m in es w ith Dich lor oca r ben e. To a mixture of 30
mL of dichloromethane, 7.0 mL (87 mmol) of chloroform, 10.0
mmol of dialkylamine or its hydrochloride, and 23 mL of 36%
NaOH solution was added 0.5 g of Et3BnNCl (TEBACl), and
the mixture was heated under reflux for 4 h. After being cooled,
the mixture was diluted with 30 mL of water, the organic
phase was separated, and the water phase was extracted with
three portions of 20 mL each of dichloromethane. The com-
bined organic extracts were washed with 20 mL of 0.5 N HCl
solution and then with 20 mL of saturated sodium bicarbonate
solution, dried over MgSO4, filtered, and concentrated under
reduced pressure. The crude product was then purified by
column chromatography on silica gel (34 and 39) or by
distillation (30).
are plotted vs the AM1-calculated angles θ, that eq 1 with
B ) 5.7 mT holds for planar radical cations, such as 8•+-
15•+, 17•+, 18•+, and 27•+. However, for the nonplanar
24•+-26•+ and 28•+, eq 1 with a much smaller B value of
ca. 4 mT appears to be more appropriate.
In the case of methylene â-protons of ethyl or n-propyl
substituents in 9•+-12•+, the coupling constants aHâ(Et)
and aHâ(n-Pr) cluster at about +1.7 to +1.9 mT. The value
for 9•+ correlates with <cos2 θ> ) 0.30, where θ ) 57°,
1
and those for 10•+-12•+ with an average /2(<cos2 θ1> +
<cos2 θ2>) ≈ 0.30, where θ1 ≈ 40 and θ2 ≈ 80° stand for
two interchanging conformations. Clustering also occurs
for methine â-protons of isopropyl or cyclohexyl substitu-
ents in 10•+-12•+ with aHâ(i-Pr), aHâ(c-Hx) ≈ +0.4 mT,
and for those of isopropyl or cyclopropyl substituents in
13•+, 15•+, 17•+, and 18•+ with aHâ(i-Pr), aHâ(c-Pr) ≈ +0.1
mT; the corresponding <cos2 θ> values are 0-0.03 where
θ ) 90-80°. Not included in Figure 5 are the pertinent
points for the radical cations, 20•+ and 21•+, of the
monocyclic N-methylamines, because the AM1 calcula-
tions failed to yield results compatible with the reported
coupling constants of the methylene â-protons in the ring.
Exp er im en ta l Section
Gen er a l Meth od s. Melting points are uncorrected. IR
Diisop r op ylfor m a m id e (30). The large-scale formylation
of 14.0 mL (0.10 mol) of diisopropylamine according to GP 1
gave a brown mixture of crude products. The distillation
afforded 7.35 g (57%) of 30 as a colorless liquid.
1
spectra were recorded for neat films. H NMR and 13C NMR
spectra were taken at 250 and 62.9 MHz. Chemical shifts are
Gen er a l P r oced u r e (GP 2) for th e Cyclop r op a n a tion
of Dia lk ylfor m a m id es. A solution of ethylmagnesium bro-
mide in diethyl ether was added via cannula to 200 mL of
anhydrous THF kept in a dry ice bath to form a suspension,
to which was added at -78 °C a solution of titanium tetra-
isopropoxide in 20 mL of anhydrous THF via cannula over 2
min. After the mixture had been stirred for an additional 2
(47) Heller, H. C.; McConnell, H. M. J . Chem. Phys. 1960, 32, 1535.
Horsfield, A.; Morton, J . R.; Whiffen, D. H. Mol. Phys. 1961, 4, 425.
(48) Lefkowitz, S. M.; Trifunac, A. J . Phys. Chem. 1984, 88, 77.
(49) Rademacher, P. In The chemistry of amino, nitroso, nitro, and
related groups; Patai, S., Ed.; Wiley: New York, 1996; Supplement
F2.
(50) Worrell, C.; Verhoeven, J . W.; Speckamp, W. N. Tetrahedron
1974, 30, 3525.

6958 J . Org. Chem., Vol. 64, No. 19, 1999
de Meijere et al.
min, a solution of the respective dialkylformamide in 10 mL
of anhydrous THF was added during 1 min via cannula.
Stirring was continued at -78 °C for 5 min, the cooling was
stopped, and the mixture was allowed to warm to room
temperature and stirred at this temperature or heated under
reflux for the stated time. The mixture was then hydrolyzed
by addition of 150 mL of concentrated NH4Cl solution, followed
by 50 mL of water and stirring for 1-3 h until it became
colorless (yellow). The precipitate was filtered off and washed
twice with 30 mL of diethyl ether. The filtrate was made
alkaline (pH > 11) by addition of 15% NaOH until Mg(OH)2
started to precipitate, and extracted with three portions of 50
mL each of diethyl ether. The combined organic extracts were
washed with brine, dried over K2CO3, and filtered. The high-
boiling amine 37 was then purified by distillation after
evaporation of the solvent. Low-boiling amines were converted
into hydrochlorides by addition of ethereal HCl to the extracts.
The solvent was then evaporated under reduced pressure at
0 °C, the residue was taken up with 50 mL of chloroform, and
the solvent was evaporated again. This procedure was repeated
two more times to remove traces of 2-propanol and water. Most
of the amines were released from hydrochlorides by addition
of a 40% aqueous solution of K2CO3 and subsequent extraction
with three portions of 10 mL each of pentane. The combined
pentane solutions were dried over K2CO3, the solvent was
removed under reduced pressure, and the products were
purified by means of preparative GC (Intersmat 131, 2 m 15%
SE 30) after “bulb-to-bulb” distillation in vacuo.
and filtered, and the solvent was removed under reduced
pressure with cooling. Purification by means of preparative
GC (Intersmat 131, 2 m 15% SE 30, 150 °C) gave 1.24 g (8%)
1
of 16 as a colorless oil (tR 11.2 min): IR (film) 2970 cm-1; H
NMR (250 MHz, CDCl3) δ 0.52-0.75 (m, 4 H, c-Pr-H), 1.32 [s,
18 H, C(CH3)3], 1.89 (mc, 1 H, c-Pr-H); 13C NMR (62.9 MHz,
CDCl3) δ 11.11 (-, C-2 and C-3), 31.16 (+, C-1), 32.59 [+,
C(CH3)3], 59.44 [Cquat, C(CH3)3]; MS m/z 169 [M+] (1); HRMS
calcd for C11H23N 169.1830, found 169.1830.
Cyclop r op ylisop r op yla m in e Hyd r och lor id e (33‚HCl).31
To a solution of 1.0 mL (14.2 mmol) of cyclopropylamine in 10
mL of anhydrous methanol were successively added 12.5 mL
(50 mmol) of a 0.4 N methanolic solution of HCl and 2.2 mL
(30 mmol) of anhydrous acetone. The solution was allowed to
cool to room temperature, and 1.15 g (18 mmol) of NaBH3CN
was added at a rate so as to keep the gas evolution from
becoming too fast. After 2 h of stirring at room temperature,
the solvent was removed under reduced pressure (50 °C), and
the solid residue was dissolved with cooling in 30 mL of a 10%
NaOH solution. The product was extracted with three portions
of 20 mL each of diethyl ether, and the combined extracts were
dried over K2CO3, filtered, and acidified with ethereal HCl.
Evaporation of the solvent in vacuo gave 1.89 g (98%) of the
colorless hydrochloride 33‚HCl: 1H NMR (250 MHz, CDCl3)
δ 0.74 (mc, 2 H, c-Pr-H), 1.19 (mc, 2 H, c-Pr-H), 1.43 [d, 6 H, 3J
3
6.5, (CH3)2CH], 2.46 (mc, 1 H, c-Pr-H), 3.33 [sept, 1 H, J 6.4,
(CH3)2CH], 9.33 (bs, 2 H, NH2+); 13C NMR (62.9 MHz, CDCl3)
δ 3.40 (-, C-2 and C-3), 19.03 (+, CH3), 27.57 (+, C-1), 51.87
(+, CH).
Cyclop r op yld iisop r op yla m in e (15). According to GP 2,
1.29 g (10.0 mmol) of diisopropylformamide (30) was treated
with 8.53 g (30.0 mmol) of titanium tetraisopropoxide and 60.0
mmol of ethylmagnesium bromide. The reaction mixture was
heated under reflux for 3 d, after which time 30 could not be
found any more in a hydrolyzed aliquot of the reaction mixture.
The product was purified by preparative GC (Intersmat 131,
2 m 15% SE 30, 95 °C), which afforded 1.07 g (76%) of 15 as
a colorless oil (tR 12.3 min): 1H NMR (250 MHz, CDCl3) δ 0.42
Cyclop r op ylisop r op ylfor m a m id e (34). The title com-
pound was prepared from 1.35 g (10.0 mmol) of cyclopropyl-
isopropylamine hydrochloride (33‚HCl) according to GP 1.
Column chromatography on 20 g of silica gel with diethyl ether
gave 1.00 g of 34 as a pale brown oil (Rf 0.59), which was
almost pure according to its 1H NMR spectrum. Additional
purification via “bulb-to-bulb” distillation afforded 914 mg
(72%) of 34 as a colorless oil: IR (film) 3030, 2872 (HCO), 1674
(CdO) cm-1. The 1H and 13C NMR spectra indicated a mixture
of syn and anti diastereomers in a ratio of 1:9: 1H NMR (250
MHz, CDCl3) δ 0.52-0.65 (m, 2 H, c-Pr-H), 0.65-0.78 (m, 2
H, c-Pr-H), 1.15 [d, 5.4 H, 3J ) 8.4, (CH3)2CH anti], 1.21 [d,
3
3
(d, 4 H, J 5.6, c-Pr-H), 1.08 [d, 12 H, J 6.5, (CH3)2CH], 1.92
[quint, 1 H, 3J 5.6, (CH2)2CH], 3.05 [sept, 2 H, 3J 6.5,
(CH3)2CH]; 13C NMR (62.9 MHz, CDCl3) δ 6.67 (-, C-2 and
C-3), 21.21 [+, CH(CH3)2], 28.64 (+, C-1), 50.49 [+, CH(CH3)2].
Anal. Calcd for C9H20ClN: C, 60.83; H, 11.34. Found: C, 60.63;
H, 11.26. Hydrochloride 15‚HCl: mp 154 °C (CHCl3/Et2O).
Di-ter t-bu tylcyclop r op yla m in e (16). The title compound
was prepared according to GP 2 from 19.2 mmol of ethylmag-
nesium bromide, 2.85 mL (9.6 mmol) of titanium tetraisoprop-
oxide, and 0.50 g (3.2 mmol) of di-tert-butylformamide28 (31)
in 100 mL of anhydrous THF. The reaction mixture was heated
under reflux for 10 d, after which time the crude hydrochloride,
containing large quantities of side products, was obtained as
a brown oil. Column chromatography of the residue after
workup on 50 g of silica gel with dichloromethane-methanol
(10:1) gave fraction I: 73 mg (23%) of tert-butylformamide
(mixture of syn and anti isomers) as a colorless oil (Rf 0.71).
Fraction II: 16‚HCl (Rf 0.60), pale brown oil (135 mg, 20%),
most of which slowly crystallized as colorless needles which
decomposed with gas evolution (isobutene?) at 104 °C to leave
3
0.6 H, J 8.4, (CH3)2CH syn], 2.31 [mc, 0.1 H, (CH2)2CH syn],
2.41 [mc, 0.9 H, (CH2)2CH anti], 3.57 [sept, 0.1 H, (CH3)2CH
syn], 4.38 [sept, 0.9 H, (CH3)2CH anti], 8.14 (s, 1 H, HCdO);
13C NMR (62.9 MHz, CDCl3) δ 5.03 (-, C-2 and C-3), 20.10
(+, CH3), 25.75 (+, C-1), 45.21 (+, CH), 163.88 (+, CHdO)
[anti]; 6.07 (-, C-2 and C-3), 22.43 (+, CH3), 24.66 (+, C-1),
50.95 (+, CH), 163.28 (+, CHdO) [syn]; MS m/z 127 [M+] (18);
HRMS calcd for C7H13NO 127.0997, found 127.0997.
Dicyclop r op ylisop r op yla m in e (17). The title compound
was prepared according to GP 2 from 1.40 g (11.0 mmol) of
cyclopropylisopropylformamide (34), 4.05 g (14.3 mmol) of
titanium tetraisopropoxide, and 25.4 mmol of ethylmagnesium
bromide. The reaction mixture was stirred for 3 d at room
temperature and worked up as normal, which afforded 1.16 g
of a mixture of hydrochlorides of 17 and cyclopropylisopropyl-
1
amine (33) in a ratio of 7:1 (according to H NMR analysis).
1
a solid which melted at 195 °C; H NMR (250 MHz, CDCl3) δ
The free amines obtained from these hydrochlorides were
separated by means of preparative GC (Intersmat 131, 2 m
15% SE 30, 111 °C) to give pure 730 mg (48%) of 17 as a
colorless liquid (tR 12.4 min): 1H NMR (250 MHz, CDCl3) δ
0.35-0.51 (m, 8 H, c-Pr-H), 1.11 [d, 6 H, 3J 6.4, (CH3)2CH],
0.68-0.79 (m, 2 H, c-Pr-H), 1.52-1.65 (m, 2 H, c-Pr-H), 1.45
[s, 18 H, C(CH3)3], 2.23-2.36 (m, 1 H, c-Pr-H), 9.56 (bs, 1 H,
NH+); 13C NMR (62.9 MHz, CDCl3) δ 8.11 (-, C-2 and C-3),
29.88 [+, C(CH3)3], 33.71 [Cquat, C(CH3)3], 72.00 (+, C-1). Anal.
Calcd for C11H24ClN: C, 64.21; H, 11.76. Found: C, 64.61; H,
11.89.
3
1.95 (mc, 2 H, c-Pr-H), 3.08 [sept, 1 H, J 6.4, (CH3)2CH]; 13C
NMR (62.9 MHz, CDCl3) δ 5.86 (-, c-Pr-C), 19.04 (+, CH3),
33.14 (+, C-1), 54.61 (+, CH). Anal. Calcd for C9H18ClN: C,
61.53; H, 10.33. Found: C, 60.68; H, 10.42. Hydrochloride 17‚
HCl: mp 166 °C (MeOH/Et2O).
Ben zylcyclop r op ylfor m a m id e (36). A 9.0 g (0.22 mol)
portion of a 60% sodium hydride suspension in mineral oil was
washed with three portions of 40 mL of anhydrous toluene
each and the residue suspended in 200 mL of anhydrous
benzene. The suspension was warmed to 70 °C, and 15.2 g
(0.18 mol) of cyclopropylformamide (35) was added over 20
min. After being heated under reflux for 10 min, the mixture
was allowed to cool to 40 °C, and 29.7 mL (0.25 mol) of benzyl
Fraction III: 50 mg of mixture of di-tert-butylamine hydro-
chloride (29‚HCl) and tert-butylcyclopropylamine hydrochlo-
ride (1:1) as a colorless, slowly crystallizing oil (Rf 0.42).
Fraction IV: 108 mg (31%) of tert-butylamine hydrochloride
(Rf 0.14).
The experiment was repeated on a larger scale, starting
from 14.50 g (92.2 mmol) of 31, to give the hydrochloride 16‚
HCl after column chromatography. The latter was treated
under cooling (ice-water) with 10 mL of saturated K2CO3
solution, and the amine was extracted with three portions of
5 mL each of pentane. The extracts were dried over K2CO3

Radical Cations of Trialkylamines
J . Org. Chem., Vol. 64, No. 19, 1999 6959
bromide in 30 mL of anhydrous benzene was added. The
mixture was stirred at this temperature for 10 h and then
allowed to cool to room temperature. Sodium bromide was
removed by filtration and the filtrate distilled through a 20
cm Vigreux column to give 30.1 g (96%) of 36 as a colorless
oil: bp 104 °C (0.2 mbar); IR (film) 2977, 2878 (HCO), 1675
(CdO) cm-1; 1H NMR (250 MHz, CDCl3) δ 0.65-0.80 (m, 4 H,
c-Pr-H), 2.50 (mc, 1 H, c-Pr-H), 5.00 (s, 2 H, CH2Ph), 7.22-
7.40 (m, 5 H, Ph-H), 8.39 (s, 1 H, HCdO); 13C NMR (62.9 MHz,
CDCl3) δ 5.51 (-, C-2 and C-3), 28.78 (+, C-1), 47.79 (-, CH2-
Ph), 127.19 (+, Ph-C), 128.11 (+, Ph-C), 128.30 (+, Ph-C),
136.75 (Cquat, Ph-C), 163.99 (+, CHdO); MS m/z 175 [M+] (36);
HRMS calcd for C11H13NO 175.0997, found 175.0997.
crude hydrochloride 38‚HCl (1.15 g, 93%) thus obtained was
formylated according to GP 1 without further purification to
give dicyclopropylformamide (39).
Dicyclop r op yla m in e (38).34 The free base 38 was obtained
from 1.00 g (7.5 mmol) of crude hydrochloride 38‚HCl as
described for amine 17. Purification by preparative GC (In-
tersmat 131, 2 m 15% SE 30, 110 °C) gave 630 mg (87%) based
on crude hydrochloride) of 38 as a colorless oil (tR 4.0 min)
with cyclopropylamine smell: 1H NMR (250 MHz, CDCl3) δ
0.28-0.39 (m, 4 H, c-Pr-H), 0.39-0.51 (m, 4 H, c-Pr-H), 1.75-
1.98 (bs, 1 H, NH), 2.24 (mc, 2 H, c-Pr-H); 13C NMR (62.9 MHz,
CDCl3) δ 5.78 (-, C-2 and C-3), 30.30 (+, C-1); MS m/z 97 [M+]
(23). Hydrochloride 38‚HCl: Anal. Calcd for C6H12ClN: C,
53.93; H, 9.05. Found: C, 54.08; H, 8.96.
Ben zyld icyclop r op yla m in e (37). The title compound was
prepared according to GP 2 from 5.0 g (28.5 mmol) of
benzylcyclopropylformamide (36), 10.5 g (36.9 mmol) of tita-
nium tetraisopropoxide, and 65.6 mmol of ethylmagnesium
bromide. The reaction mixture was stirred for 24 h at room
temperature and hydrolyzed and the product distilled in vacuo
to give 4.43 g (83%) of 37 as a colorless oil: bp 48 °C (0.2 mbar);
Dicyclop r op ylfor m a m id e (39). The title compound was
prepared from 1.33 g (10.0 mmol) of dicyclopropylamine
hydrochloride (38‚HCl) according to GP 1. Column chroma-
tography on 20 g of silica gel eluting with diethyl ether gave
922 mg of 39 as a pale brown oil (Rf 0.31) that was almost
pure according to its 1H NMR spectrum. Additional purifica-
tion via “bulb-to-bulb” distillation afforded 860 mg (69%) of
pure 39 as a colorless oil: IR (film) 3093, 3014, 2875 (HCO),
1680 (CdO) cm-1; 1H NMR (250 MHz, CDCl3) δ 0.48-0.59 (m,
2 H, c-Pr-H), 0.59-0.78 (m, 6 H, c-Pr-H), 2.37 (mc, 1 H, c-Pr-
H), 2.50 (mc, 1 H, c-Pr-H), 8.11 (s, 1 H, HCdO); 13C NMR (62.9
MHz, CDCl3) δ 5.03 (-, c-Pr-C), 5.58 (-, c-Pr-C), 27.14 (+, c-Pr-
C), 28.64 (+, c-Pr-C), 165.44 (+, CHdO); MS m/z 125 [M+] (4);
HRMS calcd for C7H11NO 125.0840, found 125.0840.
IR (film) 3087, 3063, 3011, 2922, 2851 cm-1 1H NMR (250
;
MHz, CDCl3) δ 0.40-0.57 (m, 8 H, c-Pr-H), 1.84-1.96 (mc, 2
H, c-Pr-H), 3.91 (s, 2 H, CH2Ph), 7.27-7.42 (m, 5 H, Ph-H);
13C NMR (62.9 MHz, CDCl3) δ 6.22 (-, c-Pr-C), 35.92 (+, c-Pr-
C), 60.57 (-, CH2Ph), 126.80 (+, Ph-C), 127.82 (+, Ph-C),
129.93 (+, Ph-C), 137.82 (Cquat, Ph-C); MS m/z 187 [M+] (21);
HRMS calcd for C13H17N 187.1360, found 187.1360. Hydro-
chloride: mp 166 °C dec (MeOH/Et2O).
In another run, the reaction mixture was heated under
reflux for 3 h. The usual workup gave a crude product
containing considerable amounts of the side product benzyl-
cyclopropyl(3-pentyl)amine, which could not be separated from
37 by distillation. Column chromatography on 150 g of silica
gel eluting with pentane-diethyl ether (40:1) gave fraction I,
2.20 g (35%) of benzylcyclopropyl(3-pentyl)amine as a colorless
oil (Rf 0.92): 1H NMR (250 MHz, CDCl3) δ 0.33-0.42 (m, 2 H,
Tr icyclop r op yla m in e (18).23 The title compound was
prepared according to GP 2 from 4.00 g (32.0 mmol) of
dicyclopropylformamide (39), 11.8 g (41.5 mmol) of titanium
tetraisopropoxide, and 73.6 mmol of ethylmagnesium bromide.
The reaction mixture was stirred for 10 h at room temperature
and worked up as usual to afford 5.11 g of a mixture of the
1
hydrochlorides of 18 and 38 in a ratio of 2:1 (according to H
3
NMR analysis). The free amines obtained from this hydro-
chloride mixture were separated by means of preparative GC
(Intersmat 131, 2 m 15% SE 30, 111 °C) to give 2.54 g (58%)
of pure 18 as a colorless oil (tR 16.1 min): IR (film) 3093, 3014,
2925, 2865 cm-1; 1H NMR (250 MHz, CDCl3) δ 0.39-0.42 (m,
6 H, c-Pr-H), 0.42-0.45 (m, 6 H, c-Pr-H), 1.92-2.03 (mc, 3 H,
c-Pr-H); 13C NMR (62.9 MHz, CDCl3) δ 4.55 (-, C-2 and C-3),
37.90 (+, C-1); Hydrochloride 18‚HCl: mp (dec and sublima-
tion) 181 °C (MeOH/Et2O).
c-Pr-H), 0.42-0.54 (m, 2 H, c-Pr-H), 1.08 (t, 6 H, J 7.4, CH3-
CH2), 1.52 (m, 2 H, CH3CHH), 1.76 (m, 2 H, CH3CHH), 2.19
(mc, 1 H, c-Pr-H), 2.56 [mc, 1 H, (CH3CH2)2CH], 3.87 (s, 2 H,
CH2Ph), 7.28-7.49 (m, 5 H, Ph-H); 13C NMR (62.9 MHz,
CDCl3) δ 7.17 (-, c-Pr-C), 12.20 (+, CH3), 23.30 (-, CH2), 33.81
(+, C-1), 55.83 (-, CH2Ph), 65.56 (+, CH), 126.37 (+, Ph-C),
128.36 (+, Ph-C), 129.07 (+, Ph-C), 141.76 (Cquat, Ph-C).
Fraction II: 2.72 g (51%) of 37 (Rf 0.38).
Dicyclop r op yla m in e Hyd r och lor id e (38‚HCl). A solu-
tion of 1.73 g (9.2 mmol) of benzyldicyclopropylamine (37) in
40 mL of anhydrous methanol was hydrogenated over 100 mg
of 10% Pd on charcoal at atmospheric pressure. After the
calculated volume of hydrogen (210 mL) had been consumed,
the mixture was flushed with nitrogen to remove dissolved
hydrogen, and filtered from the catalyst through a 1 cm layer
of silica gel. The catalyst was washed with 20 mL of methanol
and the combined methanolic solutions were acidified with
ethereal HCl. The solvent was removed under reduced pres-
sure, and the solid residue was treated with 20 mL of
chloroform, the solvent evaporated to dryness, and this treat-
ment with 20 mL of chloroform and evaporation was repeated
two more times to remove traces of 2-propanol and water. The
Ack n ow led gm en t. This work was supported by the
Fonds der Chemischen Industrie as well as by Bayer,
BASF, Degussa AG, and Chemetall GmbH (chemicals).
V.C. is indebted to the Gottlieb-Daimler-und-Carl-Benz-
Stiftung for a graduate student fellowship. The authors
are grateful to Dr. B. Knieriem for his careful proof-
reading of the manuscript. E.H. acknowledges support
by the Swiss National Science Foundation (Project No.
20-53568.98).
J O990458N