Rigid core vinamidinium salts and their N,N′-rotamers

Article abstract of DOI:10.1021/jo020654l

The power of proton magnetic resonance spectroscopy to unravel stereochemical details is amply demonstrated. O-Methylation of 3-methylamino-5,5-dimethyl-2-cylohexen-1-one (1a) produces stable diastereomers, (Z)- and (E)-N-(3-methoxy-5,5-dimethyl-2-cyclohexen-1-ylidine)-N-methylaminium iodide (2a). As predicted by computation and confirmed by spectroscopy, the (Z)-vinylogous imidate salt predominates. Reaction of 2a with primary and secondary amines furnished a number of vinamidinium salts, including N-(3-methylamino-5,5-dimethyl-2-cyclohexen-1-ylidene)-N-methylaminium iodide (3a). Two rotamers of 3a were identified and characterized. A substantial number of additional compounds 2 and 3 are included in the study.

Full text of DOI:10.1021/jo020654l

Rigid Cor e Vin a m id in iu m Sa lts a n d Th eir N,N′-Rota m er s
Daryl L. Ostercamp,* Yen Dinh, David Graff, and Sarah Wiles
Department of Chemistry, Concordia College, Moorhead, Minnesota 56562
ostercam@cord.edu
Received October 15, 2002
The power of proton magnetic resonance spectroscopy to unravel stereochemical details is amply
demonstrated. O-Methylation of 3-methylamino-5,5-dimethyl-2-cylohexen-1-one (1a ) produces stable
diastereomers, (Z)- and (E)-N-(3-methoxy-5,5-dimethyl-2-cyclohexen-1-ylidine)-N-methylaminium
iodide (2a ). As predicted by computation and confirmed by spectroscopy, the (Z)-vinylogous imidate
salt predominates. Reaction of 2a with primary and secondary amines furnished a number of
vinamidinium salts, including N-(3-methylamino-5,5-dimethyl-2-cyclohexen-1-ylidene)-N-methyl-
aminium iodide (3a ). Two rotamers of 3a were identified and characterized. A substantial number
of additional compounds 2 and 3 are included in the study.
In tr od u ction
More recently, a fluorescent, heterocyclic vinamidinium
cation has been strongly implicated in the natural process
of postmitotic cell degeneration, the charged species being
formed as a result of the pathological cross-linking of
lipoprotein. The fluorescence of the pigments lipofuchsin
(formed in aging) and ceroid (found in artherosclerotic
plaque) is used to detect and monitor oxidative degrada-
tion in living systems.10
A versatile method for generating the vinamidinium
cation framework (3 in Scheme 1) involves the reaction
of its vinylogous imidate counterpart (2 in Scheme 1) with
ammonia, a primary amine, or a secondary amine.11-13
In the present work, enaminones 1a -d (Scheme 1)
derived from dimedone were used as starting materials,
the six-membered carbocyclic ring ensuring a rigid “W”-
shaped core structure. In the course of characterizing
products 2a -g and 3a -n (Scheme 1) via 1H NMR, the
presence of diastereomeric vinylogous imidate salts as
well as rotameric vinamidinium salts was observed.
Electronic interactions between p-donor atoms and
π-acceptor groups permeate the chemistry of conjugated
organic systems. Considerable evidence exists that viny-
logous conjugation is much more efficient than its con-
tiguous correlate. For example, vinylogous amides (com-
monly known as enaminones) are much stronger bases
than ordinary amides,1 and carbonyl frequencies are
noticeably lower for the extended system.2 This general
phenomenon extends to many other functional groups
wherein p-π conjugation is relayed through an interven-
ing carbon-to-carbon double bond.3
The vinamidines, with saturated nitrogen as the p-
donor and the imino group as the π-acceptor, are of
particular interest to us.4a No systemic investigation of
either their electronic or vibrational spectra has, to our
knowledge, been undertaken. Published solution pKa
values are rare;4 Taft has suggested that the neutral
conjugate bases of our salts would be highly effective gas-
phase proton acceptors.5 It is in this context that a
number of model vinamidinium salts were prepared
recently in our laboratory, each compound sharing the
same rigid, conjugated core.
Resu lts a n d Discu ssion
The O-alkylation of enaminones has been little studied
in its own right. All classes (primary, secondary, and
Vinamidinum salts have long found practical use as
versatile three-carbon building blocks in the synthesis
of benzenoid, nonbenzenoid, and heterocyclic aromatic
rings, from cyclic and acyclic precursors alike.6-8 Spiroket-
al-linked vinamidinium salts are under active investiga-
tion as potential muscle relaxants in surgical procedures.9
(6) J utz, J . C. Top. Curr. Chem. 1978, 73, 125-230.
(7) Yamamaka, H.; Kazuma, H.; Kase, J .; Ishihara, T.; Gupton, J .
T. Tetrahedron Lett. 1998, 39, 4355-4358 and references therein.
(8) Marcoux, J . F.; Marcotte, F.-A.; Wu, J .; Dormer, P. G.; Davies,
I. W.; Hughes, D.; Reider, P. J . J . Org. Chem. 2001, 66, 4194-4199
and references therein.
(9) Cholli, A. L.; Lau, M. L.; Gala, K. J . Pharm. Sci. 1993, 82, 1275-
1280.
(1) Greenhill, J . V. Chem. Soc. Rev. 1977, 6, 277-294.
(2) Smith, D.; Taylor, P. J . Spectrochim. Acta, Part A 1976, 32,
1477-1488 and references therein.
(10) Xu, G.; Liu, Y.; Sayre, L. M. J . Org. Chem. 1999, 64, 5732-
5745.
(11) (a) McGeachin, S. G. Can. J . Chem. 1968, 46, 1903-1912. (b)
Wagner, R. M.; J utz, C. Chem. Ber. 1971, 104, 2975-2983. (c) Kuhn,
N.; Lanfermann, H.; Schmitz, P. Liebigs Ann. Chem. 1987, 727-728.
(d) Drees, D.; Magull, J . Z. Anorg. Allg. Chem. 1995, 621, 948-952.
(12) (a) Arnold, Z.; Holy, A. Collect. Czech. Chem. Commun. 1963,
28, 2040-2046. (b) Bredereck, H.; Effenberger, D.; Zeyfang, D.; Hirsch,
K. A. Chem. Ber. 1968, 101, 4036-4047.
(13) (a) Leonard, N. J .; Adamcik, J . A. J . Am. Chem. Soc. 1959, 80,
595-602. (b) Meyers, A. I.; Reine, A. H.; Gault, R. J . Org. Chem. 1969,
34, 698-705.
(3) Bruneau, P.; Taylor, P. J .; Wilkinson, A. J . J . Chem. Soc., Perkin
Trans. 2 1996, 2263-2269.
(4) (a) Ostercamp, D. L.; Preston, L. M.; Onan, K. D. Z. Naturforsch.
1993, 48B, 1138-1142. (b) Schwarzenbach, G.; Lutz, K. Helv. Chim.
Acta 1940, 23, 1162-1190. (c) Brown, R. F. C.; Clark, V. M.; Suther-
land, I. O.; Todd, A. J . Chem. Soc. 1959, 2109-2122. (d) Lloyd, D.;
McGoughall, R. H.; Marshall, D. R. J . Chem. Soc. C 1966, 780-782.
(5) Taft, R. W.; Gal, J .-F.; Geribaldi, S.; Maria, P.-C. J . Am. Chem.
Soc. 1986, 108, 861-863.
10.1021/jo020654l CCC: $25.00 © 2003 American Chemical Society
Published on Web 03/12/2003
J . Org. Chem. 2003, 68, 3099-3105
3099

Ostercamp et al.
SCHEME 1a
a
Compounds 2a -e form stable diastereomers. Chloride, rather than iodide, is the counterion in compound 3n , which was prepared
directly from 1c. See the Experimental Section.
TABLE 1. Dia gn ostic H-2 Ch em ica l Sh ift Va lu es for
Vin ylogou s Im id a te Sa lts 2
tertiary) of vinylogous amides appear to react smoothly
and efficiently with triethyloxonium fluoroborate.11 O-
Methylation of acyclic tertiary enaminones with dimethyl
sulfate has been successful as well.12 Use of refluxing
methyl or ethyl iodide, neat or with additional solvent,
is an efficient method for transforming 3-amino-2-cyclo-
hexen-1-ones (fixed trans configuration) into their viny-
logous imidate salts.13,14 Results with the cyclic cis-
enamin-one 4 were mixed, aprotic solvents giving mixtures
of C-alkyl and O-alkyl salts and protic solvents mixtures
of O-alkyl and O-protonated salts.13b
compd
R1
R2
R3
δ (H-2)
(E)-2a
(Z)-2a
(E)-2b
(Z)-2b
(E)-2c
(Z)-2c
(E)-2d
(Z)-2d
(E)-2e
(Z)-2e
2f
H
Me
H
Me
H
Me
H
t-Bu
H
Bn
Me
H
Me
H
Me
H
t-Bu
H
Me
Me
Et
Et
Pr
Pr
Et
Et
Et
Et
Me
Et
7.02
5.82
6.80
5.80
6.81
5.75
7.47
5.85
6.90
5.75
5.86
5.80
Bn
H
-(CH2)4-
-(CH2)4-
2g
Preparation of intermediates 2a -e in gram quantities
was straightforward. It was immediately evident from
1H NMR spectral data that each reaction led to a pair of
diastereomers. When the vinyl hydrogen (H-2, IUPAC)
is flanked by an sp3 carbon, this being the case for 2f-g
and (Z)-2a -e, its δ value lies between 5.75 and 5.86
(Table 1). NOE difference confirms the stereochemical
assignment of (Z)-2a , with H-2 showing NOE not only
with N-CH3, but also with O-CH3 (vide infra). In (E)-2a -c
and 2e, the corresponding one-proton singlet is found
about 1 ppm further downfield; (E)-2d is exceptional. We
were not able to isolate pure (E)-crystals. However, (E/
Z) mixtures of crystalline 2b-d and oily 2e were used
to prepare three of the vinamidinium salts, without
(14) Greenhill, J . V. J . Chem Soc. B 1969, 299-300.
3100 J . Org. Chem., Vol. 68, No. 8, 2003

Rigid Core Vinamidinium Salts and Their N,N′-Rotamers
TABLE 2. Dia gn ostic H-2 Ch em ica l Sh ift Va lu es for
Rota m er s of Selected Vin a m id in iu m Sa lts 3
apparent penalty. Enaminone 1e is recovered unchanged
under our alkylation conditions, its behavior reflecting
the deactivating effect of the N-phenyl group.
Available information regarding the rotational energy
barrier about the imino double bond in a vinylogous
imidate or a salt thereof is anecdotal. Passing mention
has been made in the literature of two neutral camphor
derivatives with diastereotopic ethoxy groups (1H NMR).15
No noticeable changes were observed in the 1H NMR
spectrum16 of salt 5 in DMSO-d6 between 297 and 400
K, leading the authors to conclude that “the barrier to
rotation about the CN bond is very high and is probably
a full double bond.”9
Theoretical calculations17 of potential energy differ-
ences were carried out on cation 2a . Rotation about the
partial C-N double bond involves these incremental
changes (kcal/mol) relative to the Z-form: energy barrier,
21.2 (PM3), 30.8 (HF/STO-3G), and 31.6 (HF/3-21G*);
E-form, 0.0 (PM3), 0.4 (HF/STO-3G), and 1.2 (HF/
3-21G*). The preceding HF/3-21G* values are compat-
ible with our observations: stable imidate salt diaster-
eomers and a Z/E diastereomeric ratio 90:10 for 2a .
Independent movement of the other methyl [O-CH3,
(“O-Z”) f (“O-E”)] away from the vinyl hydrogen affords
the following relative values (kcal/mol): energy bar-
rier, 7.5 (PM3), 10.8 (HF/STO-3G), and 9.8 (HF/3-21G*);
(“O-E”)-form, 0.5 (PM3), 2.2 (HF/STO-3G), and 2.9 (HF/
3-21G*). The much lower barrier to rotation and rela-
tively high potential energy of the “O-E” form means the
methoxy methyl is synperiplanar to C-2 (IUPAC) in both
diastereomeric salts. This bias is attributable to steric
and stereoelectronic factors, the latter being amply noted
in the literature.18
rotamer
R1
R2
R4
Me
Me
R5
δ (H-2)
3a A
3a B
3e
3fA
3fB
3j
Me
H
H
Me
H
H
Me
H
H
Me
H
H
5.01
5.98
6.15
5.01
6.23
5.07
5.53
6.56
-(CH2)4-
-(CH2)4-
-(CH2)4-
-(CH2)4-
-(CH2)4-
t-Bu
H
3k A
3k B
H
t-Bu
t-Bu
t-Bu
H
H
[1.324(5) Å] and C(6)-N(2) [1.310(6) Å] are consonant
with literature values.19
Three unique forms, differing only in the orientation
of the N-methyls, are possible and may be described
popularly as “up,up” (3a A), “up,down” (3a B), and “down,-
down” (3a C). Although 1H NMR evidence for rotamer
3a C is problematic, equilibrium between the three in
CDCl3 solution at room temperature is quickly estab-
lished. [This behavior is consistent with reported9 rota-
tional energy barriers about CN bonds (1H NMR, tem-
perature-dependent peak coalescence20 in DMSO-d6) in
salts 6, ∆Gq ) 17.8 kcal/mol, and 7, ∆Gq ) 17.4 kcal/mol.]
In every instance, the dominant rotamer in solution (com-
monly CDCl3, less commonly DMSO-d6) is the “up,up”
form 3A.21 Data in Table 2 follow the same pattern we
Target vinamidinium salts 3a -m (Scheme 1) were
obtained without incident and generally in high yield.
At present, we regard the poorer results with compounds
3b, 3e, and particularly 3h to be anomalous, with no
readily apparent explanation. In principle, there are two
complementary pathways to unsymmetrical salts, i.e., 3b.
Both possible electrophile/nucleophile pairs were used
successfully to prepare 3b, 3f, and 3g. The synthesis of
symmetrical compound 3n is exceptional, this salt being
formed directly from enaminone 1c and benzylamine
hydrochloride in AcOH solution at elevated temperature.
The X-ray crystal structure of compound 3a (see the
Supporting Information) reveals a cation with a single
plane of symmetry (point group Cs), the vinyl hydrogen
being flanked by both N-methyls.
Ignoring remote sp3 carbons C(4), C(7), and C(8), the
largest deviation from planarity shown by the atomic
skeleton is evidenced by a C(6)-C(1)-C(2)-N(1) dihedral
angle of 177.4(4)°. π electron delocalization and ac-
companying bond equalization are well documented for
vinamidinium cations. Pivotal bond lengths C(1)-C(2)
[1.377(6) Å] and C(1)-C(6) [1.382(6) Å] and C(2)-N(1)
found for the vinylogous imidate salts 2 of Table 1. The
more encumbered vinyl hydrogen H-2 (IUPAC), as in
3a A, 3fA, 3j, and 3k A, is relatively shielded, its singlet
being found about 1 ppm upfield from that for the less
encumbered vinyl hydrogen, as in 3a B, 3e, 3f, and 3k B.
Symmetry permits only one “up,down” isomer in most
(19) (a) Matthews, B. W.; Stenkamp, R. E.; Colman, P. M. Acta
Crystallogr., Sect. B 1973, 29, 449-454. (b) Brownstein, S.; Gabe, E.
J .; Prasad, L. Can. J . Chem. 1983, 61, 1410-1413. (c) Ferguson, G.;
Marsh, W. C.; Lloyd, D.; Marshall, D. R. J . Chem Soc., Perkin Trans
2 1979, 74-76. (d) Ferguson, G.; Ruhl, B.; Wieckowski, T.; Lloyd, D.;
McNab, H. Acta Crystallog., Sect. C 1984, 40, 1740-1742.
(20) (a) Breitmaier, E. Structure Elucidation by NMR in Organic
Chemistry; Wiley: New York, 1993; p 62. (b) Using the same procedure
and solvent, we find ∆Gq ) 19.4 kcal/mol for symmetrical salt 3n . (c)
Rabiller, C.; Ricolleau, G.; Martin, M. L.; Martin, G. J . Nouv. J . Chem.
1980, 4, 35-42 report ∆Gq ) 20.7 kcal/mol for a rigid cyclobutene
cyanine in TCE.
(15) Knorr, R.; Ruf, F. Chem. Ber. 1985, 118, 4486-4495.
(16) A pair of closely spaced singlets is centered at 6.0 ppm (vinyl
protons). Intensities are comparable and the diastereomeric ratio is
close to one.
(17) PC SPARTAN PRO, version 1.0.6, Wavefunction, Inc., 18401
Von Karman Avenue, Suite 370, Irvine, CA, 92715.
(18) (a) Larson, J . R.; Epiotis, N. D.; Bernardi, F. J . Am. Chem. Soc.
1978, 100, 5713-5716. (b) Kirby, A. J . Stereoelectric Effects; Oxford
University Press: New York, 1996; Chapter 3.
(21) This is confirmed for 3a by NOE solution measurements.
J . Org. Chem, Vol. 68, No. 8, 2003 3101

Ostercamp et al.
TABLE 3. Equ ilibr iu m Rota m er P op u la tion s (%) for
Vin a m id in iu m Sa lts 3a
Chemical shifts are reported in ppm relative to tetramethyl-
silane or the solvent signal, and J values are in Hz.
Ma ter ia ls. Commercial reagent-grade solvents and chemi-
cals were used as received unless otherwise noted. Liquid
amines were distilled prior to use. Ammonia and methylamine
were purchased as 2.0 M solutions in ethanol and methanol,
respectively. Alternatively, methylamine was generated by
heating a mixture of methylaminium chloride, calcium hy-
droxide, and water.22 The following known compounds were
prepared via condensation23 of dimedone and the appropriate
primary or secondary amine: 3-methylamino-5,5-dimethyl-2-
cyclohexen-1-one (1a ),24 3-tert-butylamino-5,5-dimethyl-2-cy-
clohexen-1-one (1b),25 3-benzylamino-5,5-dimethyl-2-cyclohexen-
1-one (1c),23 3-(1′-pyrrolidino)-5,5-dimethyl-2-cyclohexen-1-one
(1d ),13a and 3-anilino-5,5-dimethyl-2-cyclohexen-1-one (1e).26
Conversion of enaminone 1d to salts 2f and 2g is also
known.13a
(Z)-N-(3-Meth oxy-5,5-dim eth yl-2-cycloh exen -1-yliden e)-
N-m eth yla m in iu m Iod id e (2a ). A suspension of enaminone
1a (1.53 g, 10.0 mmol) in methyl iodide (10 mL) was stirred
under gentle reflux overnight, dissolution being complete
within 2 h. Evaporation of excess methyl iodide under reduced
pressure left a thick oil that solidified (2.91 g) when triturated
with ether.
compd
rotamer A
rotamer B
rotamer B′
3a
3b
3c
3d
3f
3g
3h
3i
3k
3l
3m
3n
88
85
70
88
93
88
75
89
89
66
86
86
12
10
18
8
5b
12b
4b
7
12
25
11
11
17
14
14
17
a
NMR solvent was DMSO-d6 for 3c and 3l-n . Otherwise it was
b
CDCl3. Rotamer B′ has the smaller methyl substituent “up,” and
the other, larger group “down.”
cases. Two such forms are present with salts 3b-d and
3l, however, and were detected. Characteristically, one
finds a major H-2 signal near 5 ppm (rotamer A) and
two closely spaced minor signals near 6 ppm (rotamers
B and B′), each of which finds its necessary counterparts
1H NMR analysis of the crude product indicated the major
component to be the Z-diastereomer (∼90%) along with a small
amount of the E-form (∼10%) and possibly starting material.
Crystallization from MeOH/EtOAc afforded pale yellow
crystals of (Z)-2a (1.60 g, 54%): mp 119-120 °C; 1H NMR (Z)
δ 1.12 (s, 6H), 2.45 (s, 2H), 2.91 (s, 2H), 3.31 (d, J ) 4.8, 3H),
4.09 (s, 3H), 5.82 (s, 1H), 10.98 (br s, 1H); 1H NMR (E) δ 1.16
(s, 6H), 2.39 (s, 2H), 2.52 (s, 2H), 3.27 (d, J ) 4.8, 3H), 3.98 (s,
3H), 7.02 (s, 1H), 11.50 (br s, 1H); 13C NMR (Z), δ 27.9, 33.2,
1
in the rest of the H NMR spectrum. Estimated rotamer
abundances are given in Table 3. Within experimental
error, rotamer ratios A/B are the same for the sym-
metrical N,N′-dialkylated compounds 3a ,k ,m -n , albeit
the first two are in CDCl3 and the latter two in DMSO-
d6. With trisubstituted pyrrolidinium salts 3f-i, the
proportion of the less stable “up,down” rotamer B in-
creases thusly: Me < Bn, t-Bu< Ph. This order carries
over into the unsymmetrical N,N′-disubstituted salts
3b-d as well, rotamer 3cA being less abundant at
equilibrium than either 3bA or 3d A.
Theoretical calculations of potential energy differences
were fruitful here also, with rotamer 3a A being assigned
a relative potential energy of 0.0 kcal/mol. For the process
3a A f 3a B, the energy barrier (kcal/mol) is 15.4 (PM3),
22.8 (HF/STO-3G), and 25.7 (HF/3-21G*); rotamer 3a B,
0.7 (PM3), 0.7 (HF/STO-3G), 1.6 (HF/3-21G*); rotamer
3a C, 2.8 (HF/3-21G*). The associated entropy and en-
thalpy changes (see the Supporting Information) indicate
an equilibrium ratio of 94% 3a A and 6% 3a B at 298 K,
values that are consistent with 1H NMR results (Table
3). The calculated abundance of rotamer 3a C is <1%.
Rotational energy barriers for 3 compared to 2 are
definitely smaller, consonant with the change from stable
diastereomers to observable rotamers.
33.4, 43.3. 43.9, 59.4, 91.6, 177.2, 185.1. Anal. Calcd for C10H18
-
INO: C, 40.69; H, 6.15; N, 4.75. Found: C, 40.74; H, 6.09; N,
4.70.
(Z)-N-(3-Eth oxy-5,5-d im eth yl-2-cycloh exen -1-ylid en e)-
N-m eth yla m in iu m Iod id e (2b). Reaction of enaminone 1a
(1.53 g) and ethyl iodide (10 mL) as above led to three crops
of [1.87 g (mp 119-120 °C), 0.65 g (mp 113-119 °C), 0.21 g
(mp 111-118 °C); 88% overall yield] pale yellow crystals of
2b, the Z-form being quite dominant in the first crop, but less
so thereafter. Fractional crystallization provided the pure
Z-diastereoisomer: mp 120-121 °C (2-butanone/EtOAc); 1H
NMR (Z) δ 1.12 (s, 6H), 1.47 (t, J ) 6.9, 3H), 2.45 (s, 2H), 2.90
(s, 2H), 3.28 (d, J ) 5.4, 3H), 4.35 (q, J ) 6.9, 2H) 5.72 (s, 1H),
1
10.9 (br s, 1H); H NMR (E) δ 1.18 (s, 6H), 1.42 (t, J ) 6.9,
3H), 2.39 (s, 2H), 2.62 (s, 2H), 3.26 (d, J ) 5.4, 3H), 4.19 (q, J
) 6.9, 2H), 6.80 (s, 1H), 11.4 (br s, 1H); 13C NMR (Z) δ 14.3,
27.9, 32.0, 33.4, 43.4, 44.2, 68.3, 91.7, 177.1, 184.4. Anal. Calcd
for C11H20INO: C, 42.73; H, 6.52; N, 4.53. Found: C, 42.13;
H, 6.33; N, 4.55.27
(Z)-N-(3-P r opoxy-5,5-dim eth yl-2-cycloh exen -1-yliden e)-
N-m eth yla m in iu m Iod id e (2c). Results with propyl iodide
(10 mL) and starting material 1a (1.53 g) paralleled those for
the preceding ethoxy derivative [i.e., three crops of 2c, first
crop richest in the (Z)-form; 2.68 g in all, 84%]. Fractional
crystallization provided pale yellow needles of (Z)-2c: mp 134-
136 °C (2-butanone); 1H NMR (Z) δ 1.05 (t, J ) 7.5, 3H), 1.12
(s, 6H); 1.86 (m, 2H), 2.45 (s, 2H), 2.90 (s, 2H), 3.27 (d, J )
5.1, 3H), 4.21 (t, J ) 6.3, 2H), 5.75 (s, 1H), 10.95 (br s, 1H); 1H
NMR (E) δ 1.00 (t, J ) 7.5, 3H), 1.16 (s, 6H), 1.81 (m, 2H),
2.40 (s, 2H), 2.49 (s, 2H), 3.25 (d, J ) 5.1, 3H), 4.08 (t, J ) 6.3,
In summary, a number of novel vinylogous imidate and
viamidinium cations have been prepared and their ster-
eochemical properties examined. Anchoring the hetero-
atoms to a rigid cyclohexene platform allows the detection
and chacterization of stable vinylogous imidate diaster-
1
eomers and vinamidinium rotamers by H NMR. Com-
putation of potential energy differences provides addi-
tional support to conclusions based upon spectroscopic
evidence.
(22) Shakhashiri, B. Z. Chemical Demonstrations: A Handbook for
Teachers of Chemistry; University of Wisconsin: Madison, WI, 1986;
Vol. 2, p 202.
Exp er im en ta l Section
(23) J irkovsky, I. Can. J . Chem. 1974, 52, 55-65.
(24) Goerdeler, J .; Keuser, U. Chem. Ber. 1964, 97, 2209-2217.
(25) Greenhill, J . V. J . Chem. Soc. C 1970, 1002-1004.
(26) Haas, P. J . Chem. Soc. 1903, 89, 187-205.
Gen er a l P r oced u r es. Melting points are uncorrected and
were obtained in capillary tubes (oil bath); evacuated tubes
(metal block) were employed for samples with melting points
>200 °C. Unless otherwise stated, 1H NMR (300 MHz) and
13C NMR (75 MHz) spectra were recorded as CDCl3 solutions.
(27) One of three combustion elemental analytical values is unsat-
isfactory. Nevertheless, the compound was used successfully to prepare
daughter vinamidinium salts of acceptable purity.
3102 J . Org. Chem., Vol. 68, No. 8, 2003

Rigid Core Vinamidinium Salts and Their N,N′-Rotamers
2H), 6.86 (s, 1H), 11.34 (br s, 1 H); 13C NMR (Z) δ 10.7, 22.1,
27.9, 31.8, 33.4, 43.2, 44.2, 73.5, 91.5, 171.1, 184.5. Anal. Calcd
for C12H22INO: C, 44.59; H, 6.86; N, 4.33. Found: C, 44.61;
H, 6.47; N, 4.44.
N -(3-t er t -Bu t yla m in o-5,5-d im e t h yl-2-cycloh e xe n -1-
ylid en e)-N-m eth yla m in iu m Iod id e (3b). A solution of
ethoxy salt 2b (3.09 g, 10.0 mmol) and tert-butylamine (731
mg, 10.0 mmol) in EtOH (20 mL) was refluxed (drying tube)
for 42 h. Evaporation of solvent and crystallization of the
residual golden syrup gave faintly yellow crystals (2.53 g,
75%): mp 164-165 °C (2-butanone/EtOAc); 1H NMR, rotamers
A/B/B′, 15/2/1, δ 1.06 (s, major, 5H), 1.10 (s, minor, 0.33H),
1.12 (s, minor, 0.67H), 1.50-1.56 (m, 9H), 2.31(s, minor,
0.22H), 2.52 (s, minor, 0.33H), 2.55 (s, minor, 0.11H), 2.60 (s,
major, 1.67H), 2.69 (s, major, 1.67H), 2.96-3.01 (overlapping
doublets, major and minor, 2.67H), 3.04 (d, J ) 5.1, minor,
0.33H), 5.29 (s, major, 0.83H), 6.35 (s, minor, 0.11H), 6.40 (s,
minor, 0.06H), 6.80 (br s, minor, 0.11H), 7.60 (s, major, 0.83H),
8.10 (br s, minor, 0.06H), 8.47 (br s, minor, 0.06H), 8.77 (br q,
major, 0.83H), 9.45 (br s, minor, 0.11H); 13C NMR, rotamers,
δ 27.8, 29.5, 29.6, 29.7, 30.0, 32.9, 43.0, 44.9, 55.4, 86.3, 168.6,
170.0. Anal. Calcd for C13H25IN2: C, 46.43; H, 7.49; N, 8.33.
Found: C, 46.48; H, 7.30; N, 8.59.
N-(3-An ilin o-5,5-d im eth yl-2-cycloh exen -1-ylid en e)-N-
m eth yla m in iu m Iod id e (3c). A solution of methoxy salt 2a
(1.56 g, 5.29 mmol) and aniline (0.99 g, 10.6 mmol) in EtOH
(5 mL) was allowed to stand at room temperature for 5 d.
Seeding with authentic product, suction filtration, evaporation
of filtrate, and crystallization of the residual oil from EtOH/
EtOAc gave 3c as pale yellow crystals (two crops, 1.77 g in
all, 94%): mp 218-219 °C; 1H NMR (DMSO-d6) rotamers A/B/
B′, 12/3/2, δ 0.95-1.11 (3 overlapping s, 6H), 2.46-2.65 (4
overlapping s, 4H), 2.80-3.00 (3 overlapping d, 3H), 5.53 (s,
major, 0.70H), 5.72 (2 overlapping s, minor, 0.30H), 7.2-7.6
(m, 5H), 9.27 (br s, minor, 0.12H), 9.43 (s, major, 0.70H), 9.69
(s, minor, 0.18H), 10.20 (s, minor, 0.18H), 10.61 (s, major,
0.70H), 11.17 (br s, minor 0.12H); 13C NMR (DMSO-d6),
rotamers, δ 27.9, 28.4, 30.6, 32.9, 42.8, 43.1, 85.8, 125.2, 128.0,
130.7, 137.6, 168.3, 172.3. Anal. Calcd for C15H21IN2: C, 50.57;
H, 5.94; N, 7.86. Found: C, 50.72; H, 5.74; N, 8.09.
N-(3-Ben zylam in o-5,5-dim eth yl-2-cycloh exen -1-yliden e)-
N-m eth yla m in iu m Iod id e (3d ). Compound 3d was isolated
in almost quantitative yield from the reaction of benzylamine
(1.50 g, 14.0 mmol) and ethoxy salt 2b (4.33 g, 14.0 mmol) in
EtOH (40 mL) at room temperature for 4 d. Subsequent
evaporation of EtOH left a viscous colorless gel which depos-
ited white crystals of 3d quite slowly (three crops over a 2-week
period) from mixed solvent (2-butanone/EtOAc, 5.14 g in all,
99%): mp 99-102 °C; 1H NMR, rotamers A/B/B′, 22/2/1, δ 0.96
(s, minor, 0.48H), 1.02 (s, major, 5.28H), 1.08 (s, minor, 0.24H),
2.24 (s, minor, 0.16H), 2.28 (s, minor, 0.08H), 2.46 (s, minor,
0.16 H) 2.50 (s, minor, 0.08H), 2.54 (s, major, 1.76H), 2.62 (s,
major, 1.76H), 2.79 (d, J ) 4.5, major, 2.64H), 2.94(d, J ) 4.5,
minor, 0.24H), 3.04 (d, J ) 4.5, 0.12H), 4.43 (d, J ) 5.7, minor,
0.08H), 4.53 (d, J ) 5.7, major and minor, 1.92H), 4.97 (s,
major, 0.88H), 6.06 (s, minor, 0.04H), 6.10 (s, minor, 0.08H),
7.25-7.34 (m, 5H), 7.8 (v br s, minor, 0,04H), 8.1 (br s, minor,
0.08H), 8.63 (m, major, 0.88 HI), 8.95 (m, major, 0.88H), 9.1
(br s, minor, 0.04H), 9.4 (m, minor, 0.08H); 13C NMR, rotamers,
δ 27.8, 30.0, 33.1, 43.2, 43.5, 47.3, 85.2, 127.8, 128.4, 129.3,
135.9, 169.7, 170.5. Anal. Calcd for C16H23IN2: C, 51.90; H,
6.26; N, 7.57. Found: C, 51.43; H, 6.18; N, 7.74.28
(Z)-N-(3-Eth oxy-5,5-d im eth yl-2-cycloh exen -1-ylid en e)-
N-ter t-bu tyla m in iu m Iod id e (2d ). The overnight reaction
of enaminone 1b (0.88 g, 4.5 mmol) and ethyl iodide (10 mL)
under gentle reflux led to a single crop (1.15 g, 73%) of pale
yellow crystals of 2d (mp 135-139 °C, E/Z ) 2/3) when the
crude product was crystallized from 2-butanone/EtOAc. Simi-
lar yields were obtained in additional runs, although diaste-
reomer ratios varied substantially. Fractional crystallization
ultimately provided pure (Z)-2d : mp 141-143 °C (2-butanone/
EtOAc); 1H NMR (Z) δ 1.13 (s, 6H), 1.49 (t, J ) 6.9, 3H), 1.66
(s, 9H), 2.41 (s, 2H), 3.18 (s, 2H), 4.21 (q, J ) 6.9, 2H), 5.85 (s,
1
1H), 10.42 (br s, 1H); H NMR (E) δ 1.16 (s, 6H), 1.41 (t, J )
6.9, 3H), 1.64 (s, 9H), 2.35 (s, 2H), 2.67 (s, 2H), 4.24 (q, J )
6.9, 2H), 7.47 (s, 1H), 10.81 (br s, 1H); 13C NMR (Z) δ 14.4,
27.8, 30.2, 33.3, 43.9, 44.2, 58.5, 67.5, 93.3, 177.0, 183.6. Anal.
Calcd for C14H26INO: C, 47.87; H, 7.46; N, 3.99. Found: C,
47.77; H, 7.16; N, 3.97.
(Z)-N-(3-Eth oxy-5,5-d im eth yl-2-cycloh exen -1-ylid en e)-
N-ben zyla m in iu m Iod id e (2e). A solution of enaminone 1c
(2.29 g, 10.0 mmol) in ethyl iodide (10.0 mL) was heated at 64
°C for 3 d. Removal of excess ethyl iodide left a thick golden
syrup, which solidified when triturated with EtOAc. A sig-
nificant partition of the two stereoisomers occurred, the crude
solid (2.65 g, suction filtration) being largely Z and the oil (1.33
g, 3.45 mmol if pure) isolated from the filtrate being largely
E. Reaction of this oil with benzylamine (374 mg, 3.45 mmol)
in methanol solution led to the symmetrical vinamidinium salt
3m (vide infra, 1.23 g, 2.76 mmol). Crystallization of the crude
solid portion from MeOH/EtOAc yielded the desired product
2e [2.52 g in two crops, 6.88 mmol, the overall yield of 2e being
96% (2.76 mmol + 6.88 mmol)] in the Z-form: mp 139-140
1
°C; H NMR (Z) δ 1.08 (s, 6H), 1.36 (t, J ) 6.9, 3H), 2.36 (s,
2H), 2.95 (s, 2H), 4.14 (q, J ) 6.9, 2H), 4.86 (d, J ) 6.3, 2H),
1
5.75 (s, 1H), 7.3-7.5 (m, 5H), 11.50 (br s, 1H); H NMR (E) δ
1.04 (s, 6H), 1.40 (t, J ) 6.9, 3H), 2.35 (s, 2H), 2.56 (s, 2H),
4.18 (q, J ) 6.9, 2H), 4.78 (d, J ) 6.3, 2H), 6.90 (s, 1H), 7.3-
7.5 (m, 5H), 11.78 (br s, 1H); 13C NMR (Z) δ 14.2, 27.9, 33,6,
43.3, 44.1, 48.0, 68.0, 92.6, 128.3, 128.7, 129.5, 135.0, 177.3,
184.5. Anal. Calcd for C17H24INO: C, 53.00; H, 6.28; N, 3.64.
Found: C, 52.92; H, 5.51; N, 3.82.27
N-(3-Met h oxy-5,5-d im et h yl-2-cycloh exen -1-ylid en e)-
p yr r olid in iu m iod id e (2f):13a 1H NMR (CDCl3), δ 1.16 (s, 6H),
2.12 (m, 4H), 2.41 (s, 2H), 2.81 (s, 2H), 4.01 (m, 2H), 4.06 (s +
1
m, 5H), 5.86 (s, 1H); H NMR (DMSO-d6) δ 1.06 (s, 6H), 2.02
(m, 4H), 2.43 (s, 2H), 2.72 (s, 2H), 3.86 (m, 4H), 3.97 (s, 3H),
5.90 (s, 1H); 13C NMR (DMSO-d6) δ 24.8, 25.0, 28.2, 33.1, 42.4,
58.8, 94.8, 173.2, 182.4.
N-(3-Eth oxy-5,5-d im eth yl-2-cycloh exen -1-ylid en e)p yr -
r olid in iu m iod id e (2g):13a 1H NMR δ 1.16 (s, 6H), 1.44 (t, J
) 7.2, 3H), 2.10 (m, 4H), 2.41 (s, 2H), 2.81 (s, 2H), 3.99 (m,
4H), 4.31 (q, J ) 7.2, 2H), 5.80 (s, 1H).
N -(3-Me t h yla m in o-5,5-d im e t h yl-2-cycloh e xe n -1-yli-
d en e)-N-m eth yla m in iu m Iod id e (3a ). Methanolic methyl-
amine (2 M, 9.0 mL, 18 mmol) was added to a solution of
ethoxy salt 2b (4.33 g, 14.0 mmol) in ethanol (40 mL). After 6
d at room temperature, the solvent was evaporated and the
residual oil taken up in hot 2-butanone. Cooling gave the
symmetrical vinamidinium salt 3a as white crystals (3.83 g,
93%): mp 159-161 °C; 1H NMR, rotamers A/B, 7/1, δ 1.08 (s,
major, 5.25H), 1.11 (s, minor, 0.75H), 2.35 (s, minor, 0.25H),
2.54 (s, minor, 0.25H), 2.61 (s, major, 3.50H), 2.97(d, J ) 5.1,
minor, 0.37H), 3.01 (d, J ) 5.1, major, 5.25H), 3.05 (d, J )
5.1, minor, 0.37H), 5.01 (s, major, 0.88H), 5.98 (s, minor,
0.12H), 8.01 (br s, minor, 0.12 H), 8.56 (br s, 1.75 H), 8.88
(br s, 0.12H); 13C NMR, rotamers, δ 27.8, 28.4, 30.2, 30.5,
32.4, 32.9, 34.2, 43.3, 83.7, 170.2, 172.4. Anal. Calcd for
N-(3-Am in o-5,5-d im eth yl-2-cycloh exen -1-ylid en e)p yr -
r olid in iu m Iod id e (3e). Ethanolic ammonia (2 M, 2.2 mL,
4.4 mmol) was added to a solution of methoxy salt 2f (1.34 g,
4.00 mmol) in MeOH (10 mL). After 4 d at room temperature,
the alcohol solvent was gradually replaced by ethyl acetate in
the boiling solution. Cooling and seeding produced fine white
crystals (0.96 g, 3.0 mmol, 75%) of vinamidinium salt 3e: mp
1
219-222 °C (MeOH/EtOAc); H NMR (CDCl3) δ 1.10 (s, 6H),
2.04 (m, 4H), 2.42 (s, 2H), 2.57 (s, 2H), 3.58 (m, 4H), 6.15 (s,
1H), 7.72, (s, 1H), 8.30 (s, 1H); 1H NMR (DMSO-d6) δ 1.04 (s,
6H), 1.94 (m, 4H), 2.34 (s, 2H), 2.52 (s, 2H), 3.42 (m, 2H), 3.63
C
10H19IN2: C, 40.81; H, 6.51; N, 9.56. Found: C, 40.77; H, 6.29;
(28) Elemental analytical value for carbon is equivocal; NMR data
fully support the assigned structure.
N, 9.46.
J . Org. Chem, Vol. 68, No. 8, 2003 3103

Ostercamp et al.
(m, 2H), 5.35 (s, 1H), 8.45 (s, 1H), 8.69 (s, 1H); 13C NMR
(DMSO-d6) δ 25.1, 25.4, 28.3, 32.5, 50.0, 50.2, 89.5, 167.1,
172.2. Anal. Calcd for C12H21IN2: C, 44.99; H, 6.61; N, 8.78.
Found: C, 44.76; H, 6.28; N, 8.58.
9.42 (br s, major, 0.9H), 9.81 (br s, minor, 0.1H); 13C NMR,
rotamers, δ 24.9, 25.4, 28.4, 32.7, 42.3, 42.9, 47.0, 50.3, 50.6,
88.3, 128.0 129.2, 136.4, 166.7, 168.6. Anal. Calcd for
C19H27IN2: C, 55.61; H, 6.63; N, 6.83. Found: C, 55.65; H, 6.56;
N, 6.97.
N -(3-Me t h yla m in o-5,5-d im e t h yl-2-cycloh e xe n -1-yli-
d en e)p yr r olid in iu m Iod id e (3f). The unsymmetrical salt 3f
was readily prepared at room temperature from equimolar
quantities of (a) methoxy salt 2f and methanolic methylamine
(MeOH solvent, overnight, 94%), (b) ethoxy salt 2b (E/Z
mixture) and pyrrolidine (EtOH solvent, 6 d, 96%), or (c)
propoxy salt 2c (E/Z mixture) and pyrrolidine (EtOH solvent,
6 d, 95%). Compound 3f forms white crystals: mp 176-178
°C (MeOH/EtOAc); 1H NMR, rotamers A/B, 13/1, δ 1.08 (s,
major, 5.58H), 1.14 (s, minor, 0.42H), 2.06-2.15 (m, 4H), 2.36
(s, minor, 0.14H), 2.46 (s, minor, 0.14H), 2.50 (s, major, 1.86H),
2.64 (s, major, 1.86H), 2.98 (d, J ) 5.1, major, 2.79H), 3.04 (d,
J ) 5.1, minor, 0.21H), 3.57 (m, 2H), 3.69 (m, 2H), 5.01 (s,
major, 0.93H), 6.23 (s, minor, 0.07H), 8.94 (br s, major, 0.93H),
9.26 (br s, minor, 0.07H); 13C NMR, rotamers, δ 25.0, 25.5,
28.4, 30.2, 32.6, 42.3, 43.0, 50.5, 50.6, 86.7, 166.6, 169.1. Anal.
Calcd for C13H23IN2: C, 46.71; H, 6.94; N, 8.38. Found: C,
46.79; H, 6.81; N, 8.54.
N -(3-t er t -Bu t yla m in o-5,5-d im e t h yl-2-cycloh e xe n -1-
ylid en e)p yr r olid in iu m Iod id e (3g). A solution of ethoxy salt
2d (E/Z mixture, 1.13 g, 3.22 mmol) and pyrrolidine (0.299 g,
3.22 mmol) in methanol (10 mL) was allowed to stand at room
temperature for 1 week. Evaporation of solvent and crystal-
lization provided the white vinamidinium salt 3g (1.15 g,
95%): mp 162-165 °C (2-butanone/EtOAc); 1H NMR, rotamers
A/B, 7/1, δ 1.12 (s, major, 5.25H), 1.15 (s, minor, 0.75H), 1.52
(s, minor, 1.12H), 1.54 (s, major, 7.88H), 2.03 (m, minor,
0.50H), 2.10 (m, major, 3.50H), 2.37 (s, minor, 0.25H), 2.44 (s,
major, 1.75H), 2.49 (s, minor, 0.25H), 2.78 (s, major, 1.75H),
3.51 (m, major, 1.75H), 3.60 (m, minor, 0.50H), 3.67 (m, major,
1.75H), 5.30 (s, major, 0.88H), 6.64 (s, minor, 0.12H), 8.09 (s,
major, 0.88H), 8.88 (s, minor, 0.12H); 13C NMR, rotamers, δ
25.0, 25.5, 28.3, 28.7, 29.6, 31.4, 32.6, 42.4, 43.6, 50.2, 50.6,
55.4, 89.4, 166.4, 168.0. Anal. Calcd for C16H29IN2: C, 51.05;
H, 7.76; N, 7.47. Found: C, 51.41; H, 7.46; N, 7.45.
N-[3-(1′-P yr r olid in o)-5,5-d im eth yl-2-cycloh exen -1-yli-
d en e]p yr r olid in iu m iod id e (3j):13a 1H NMR δ 1.16 (s, 6H),
2.10 (m, 8H), 2.54 (s, 4H), 3.58 (t, J ) 6.3, 4H), 3.70 (t, J )
6.3, 4H), 5.07 (s, 1H).
N -(3-t er t -Bu t yla m in o-5,5-d im e t h yl-2-cycloh e xe n -1-
ylid en e)-N-ter t-bu tyla m in iu m Iod id e (3k ). Reaction of
ethoxy salt 2d (2.11 g, 6.00 mmol) with tert-butylamine (0.66
g, 9.0 mmol) in ethanol (20 mL) solution at room temperature
for 4 d, followed by the usual workup, gave white crystals of
the symmetrical vinamidinium salt 3k (2.09 g, 92%): mp 199-
202 °C (2-butanone/EtOAc); 1H NMR, rotamers A/B, 8/1, δ 1.07
(s, major, 5.33H), 1.11 (s, minor, 0.67H), 1.54 (s, major, 16H),
1.55 (sh, minor, 2H), 2.49 (s, minor, 0.22H), 2.54 (s, minor,
0.22H), 2.70 (s, major, 3.56H), 5.53 (s, major, 0.89H), 6.56 (s,
minor, 0.11H), 6.68 (br s, minor, 0.11H), 7.77 (s, major, 1.78H),
9.01 (br s, minor, 0.11H); 13C NMR, rotamers, δ 28.0, 29.7,
29.9, 30.0, 31.5, 32.8, 44.4, 55.1, 89.0, 168.4. Anal. Calcd for
C16H31IN2: C, 50.79; H, 8.26; N, 7.40. Found: C, 50.91; H, 8.28;
N, 7.53.
N-(3-An ilin o-5,5-d im eth yl-2-cycloh exen -1-ylid en e)-N-
ben zyla m in iu m Iod id e (3l). The desired product precipi-
tated overnight at room temperature from a solution of salt
2e (1.50 g, 3.91 mmol) and aniline (0.728 g, 7.8 mmol) in EtOH
(8 mL). Compound 3l (1.65 g, two crops, 98%) forms pale yellow
crystals: mp 249-251 °C (EtOH/EtOAc); 1H NMR (DMSO-
d6), rotamers A/B/B′, 4/1/1, δ 1.07 (m, 6H), 2.58 (m, 4H), 4.45
(s, major, 1.34H), 4.59 (s, minor, 0.33H), 4.65 (s, minor, 0.33H),
5.52 (s, major, 0.66H), 5.81 (s, minor, 0.17H), 5.88 (s, minor,
0.17H), 7.05-7.50 (m, 10H), 9.71 (br s, minor, 0.17H), 9.92
(br s, major, 0.66H), 10.05 (br s, minor, 0.17H), 10.34 (br s,
minor, 0.17H), 10.68 (br s, major, 0.66H), 11.23 (br s, minor,
0.17H); 13C NMR (DMSO-d6), rotamers, δ 27.9, 28.3, 33.0, 42.8,
47.3, 87.4, 124.9, 125.5, 128.1, 128.5, 129.6, 130.5, 137.3, 168.4,
172.0, 172.2. Anal. Calcd for C21H25IN2; C, 58.34; H, 5.83; N,
6.48. Found: C, 58.30; H, 5.53; N, 6.61.
N-(3-An ilin o-5,5-d im eth yl-2-cycloh exen -1-ylid en e)p yr -
r olid in iu m Iod id e (3h ). A solution of aniline (0.279 g, 3.00
mmol) and methoxy salt 2f (0.963 g, 2.81 mmol) in methanol
(1.5 mL) was refluxed for 1 d. Evaporation of the solvent and
crystallization of the residual oil produced yellow crystals of
3h in low yield (0.376 g, 33%): mp 206-208 °C (MeOH/EtOAc);
1H NMR (CDCl3), rotamers A/B, 3/1, δ 1.09 (s, minor, 1.5H),
1.14 (s, major, 4.5H) 2.04 (m, 4H), 2.46 (s, minor, 0.5H) 2.54
(s, 2H), 2.88 (s, major, 1.5H), 3.35 (m, major, 1.5 H), 3.58 (m,
minor, 0.5H), 3.69 (m, 2H), 5.49 (s, major, 0.75H), 6.70 (s,
minor, 0.25H), 7.20-7.50 (m, 5H), 10.30 (s, major, 0.75H),
10.84 (s, minor, 0.25H); 1H NMR (DMSO-d6), rotamers (over-
lapping peaks and shoulders), δ 1.11 (s, 6H), 1.92 (s, 4H), 2.56
(s, 2H), 2.64 (s, 2H), 5.55-5.80 (s, major + br s, minor; 1H),
7.25-7.55 (m, 5 H), 10.43-10.96 (s, major + v br s, minor;
1H); 13C NMR (CDCl3), rotamers, 24.8, 25.3, 28.4, 32.6, 42.2,
43.1, 50.4, 51.0, 89.1, 125.3, 127.7, 129.9, 136.9, 167.6, 168.2;
13C NMR (DMSO-d6), rotamers, 24.9, 25.3, 28.3, 32.6, 41.9,
42.5, 50.5, 51.0, 88.8, 125.0, 127.7, 130.6, 137.8, 166.3, 168.8.
Anal. Calcd for C18H25IN2: C, 54.55; H, 6.36; N, 7.07. Found:
H, 54.57; H, 5.98; N, 7.17.
N-(3-Ben zylam in o-5,5-dim eth yl-2-cycloh exen -1-yliden e)-
p yr r olid in iu m Iod id e (3i). After 2 d at room temperature,
the reaction solution of benzylamine (353 mg, 3.29 mmol) and
methoxy salt 2f (1.02 g. 3.04 mmol) in MeOH (1.5 mL) was
diluted with EtOAc. Concentration (steam bath) and further
enrichment in EtOAc afforded, after cooling, white crystals of
target compound 3i (1.63 g, 93%): mp 151-153 °C; 1H NMR,
rotamers A/B, 9/1, δ 1.00 (s, minor, 0.6H), 1.06 (s, major, 5.4H),
2.01 (m, 4H), 2.26 (s, minor, 0.2H), 2.36 (s, minor, 0.2H), 2.39
(s, major, 1.8H), 2.66 (s, major, 1.8H), 3.28 (m, major, 1.8H),
3.50-3.60 (m, major and minor, 2.2H), 4.54 (d, J ) 6.0, 2H),
4.97 (s, major, 0.9H), 6.37 (s, minor, 0.1H), 7.15-7.40 (m, 5H),
N-(3-Ben zylam in o-5,5-dim eth yl-2-cycloh exen -1-yliden e)-
N-ben zyla m in iu m Iod id e (3m ). As benzylamine (0.472 g,
4.40 mmol) was being added to a solution of ethoxy salt 2e
(1.558 g, 4.03 mmol) in methanol (10 mL), fine white crystals
of product 3m began to form. Magnetic stirring was continued
at room temperature for 1 d. Normal workup provided
compound 3m (1.765 g, 98%): mp 234-236 °C (acetonitrile);
1H NMR (DMSO-d6), rotamers A/B, 6/1, δ 1.00 (s, 6H), 2.48
(s, major + minor, 3.72 H), 2.56 (s, minor, 0.28H), 4.44 (br d,
minor 0.28H), 4.57 (distorted d, major + minor, 3.72H), 5.58
(s, minor, 0.14H), 5.61 (s, major, 0.86H), 7.20-7.40 (m, 10H),
9.24 (br t, minor, 0.14H), 9.54 (br t, major, 1.72H), 9.82 (br t,
minor, 0.14H); 13C NMR (DMSO-d6), tautomers, 27.8, 28.2,
32.7, 32.9, 42.9, 47.1, 85.5, 88.6, 128.4, 129.5, 137.3, 168.3,
170.3, 170.6. Anal. Calcd for C22H27IN2: C, 59.18; H, 6.10; H,
6.30. Found: C, 59.28; H, 5.95; N, 6.36.
N-(3-Ben zylam in o-5,5-dim eth yl-2-cycloh exen -1-yliden e)-
N-ben zyla m in iu m Ch lor id e (3n ). A solution of enaminone
1c (2.29 g, 10.0 mmol) and benzylamine hydrochloride (1.50
g, 10.5 mmol) in acetic acid (2 mL) was refluxed for 22 h in a
sealed (screw plug) heavy-wall pressure tube (15 mL). Heat
was provided by a silicone oil (180 °C) bath. The cooled yellow
solution was diluted with acetonitrile (6 mL) and placed in a
refrigerator freezing chamber. White crystals of the symmeti-
cal vinamidinium salt 3n (1.99 g, 56%) were deposited: mp
1
228-229 °C (EtOH/EtOAc); H NMR (CDCl3), rotamers A/B,
8/1, δ 0.94 (s, 6H), 2.15 (s, minor, 0.22H), 2.47 (s, minor, 0.22H),
2.51 (s, major, 3.56H), 4.28 (d, J ) 6.0, major, 3.56H), 4.41 (d,
J ) 6.0, minor, 0.22H), 4.47 (d, J ) 6.0, minor, 0.22H), 4.91
(s, major, 0.89H), 6.15 (s, minor, 0.11H), 7.10-7.25 (m, 10H),
9.31 (br t, minor, 0.11H), 10.25 (t, major, 1.78H), 10.65 (br t,
minor, 0.11H); 1H NMR (DMSO-d6), rotamers A/B, 6/1, δ 0.96
3104 J . Org. Chem., Vol. 68, No. 8, 2003

Rigid Core Vinamidinium Salts and Their N,N′-Rotamers
(s, 6H), 2.47 (s, 4H), 4.39 (m, minor, 0.28H), 4.54 (m, major,
3.44H), 4.55 (sh, minor, 0.28H), 5.51 (s, major, 0.86H), 5.70
(s, minor, 0.14H), 7.20-7.40 (m, 10H), 9.79 (br t, 0.14H), 10.12
(br t, major, 1.72H), 10.32(br t, 0.14H); 13C NMR (DMSO-d6),
rotamers, δ 27.8, 28.2, 32.7, 32.9, 42.9, 46.8, 85.2, 88.3, 128.3,
128.4, 129.4, 137.6, 168.1, 170.1, 173.4. Anal. Calcd for
nesota, Minneapolis, for solid-state structural data.
Financial support was provided by the Centennial
Scholars Program of Concordia College.
Su p p or tin g In for m a tion Ava ila ble: X-ray crystallo-
graphic date for 3a ; 1H NMR of compounds 2a ,b ,f and
3a ,b,d -e,j; computional results for rotamers 3a A and 3a B.
This material is available free of charge via the Internet at
http://pubs.acs.org.
C
22H27ClN2: C, 74.45; H, 7.67; N, 7.89. Found: C, 74.47; H,
7.52; N, 8.09.
Ack n ow led gm en t. We thank Victor G. Young, J r.,
X-ray Crystallographic Laboratory, University of Min-
J O020654L
J . Org. Chem, Vol. 68, No. 8, 2003 3105