Meta-stable enamines: Synthesis of simple enamines via catalytic isomerization of allylic amine substrates and their polymerization behavior [10]

Full text of DOI:10.1021/ja011609i

J. Am. Chem. Soc. 2001, 123, 11083-11084
11083
Meta-Stable Enamines: Synthesis of Simple
Enamines via Catalytic Isomerization of Allylic
Amine Substrates and Their Polymerization Behavior
Bruce M. Novak*,† and Jeffrey T. Cafmeyer‡
Department of Chemistry, North Carolina State UniVersity
Raleigh, North Carolina 27695
Department of Polymer Science & Engineering
UniVersity of Massachusetts, Amherst, Massachusetts 01003
ReceiVed July 2, 2001
As is the case with enols, primary and secondary enamines
are thermodynamically unstable species that exist in an unfavor-
able equilibrium with their imine tautomer (eq 1).1 Simple ali-
Figure 1. The concentration profiles of reactants and products during
the room temperature isomerization of N-methyl allylamine (1b) with
RhH(CO)(PPh3)3 in benzene-d6 at 22 °C.
phatic enamines in the absence of extraordinary steric or electronic
factors are particularly unstable and have proved to be most
difficult to prepare. Secondary enamines have been generated in
nonequilibrium concentrations by the controlled methanolysis or
hydrolysis of trimethylsilyl, tin, magnesium, or lithium deriva-
tives.2 Primary enamines have been prepared in small quantities
by a retro-Diels-Alder approach from the thermolysis of anthra-
cene adducts for spectroscopic observation.3 Vinylamine, the
prototypical enamine, has been formed in only a few rare situ-
ations, further illustrating the unfavorable thermodynamics of
simple enamines.4 Currently there is a lack of an effective and
efficient synthesis for simple enamines, and therefore their chem-
istry remains largely unexplored. One such area we believe these
enamines to be particularly interesting is in the direct (co)poly-
merization of these “vinylamine” equivalents as a route to poly-
(vinylamine) analogues. In this communication, we describe the
preparation and observed stability of aliphatic enamines using a
mild, catalytic method from allylic substrates, and the further use
of these meta-stable compounds as monomers for polymerization.
Poly(vinylamine) (PVAm) is not prepared from the vinylamine
monomer. Instead, approaches to PVAm have had to rely on
indirect methods such as the chemical modification of preexisting
polymers and the polymerization-deprotection of protected vinyl-
amine monomers.5 Despite the difficulty of their preparation,
polyamines are useful in applications ranging from paper sizing
to pharmaceutical practices.
to be incompatible with simple enamines. Lacking the mild
conditions potentially more amicable to enamine stability, reaction
attempts with primary and secondary allylamines generally
resulted in the exclusive formation of the more stable imine
products.8 Indeed, to the best of our knowledge the only
observation of an isomerized enamine was reported by Hiraki et
al. for the isomerization of N-methyl allylamine (1b) in a modest
10% yield with a ruthenium(II) complex, RuHCl(CO)(PPh3)3.9
Despite this lack of precedent, the very unfavorable thermody-
namics governing enamine/imine behavior can be, in principle,
circumvented by accessing appropriate kinetic pathways.10 In the
context of this study, controlled double-bond migration in primary
and secondary allylamine substrates affords the opportunity to
form the enamine product provided that the isomerization rate
(k1) is greater than that of the tautomerization (k2).
In our own attempts to further optimize through variants of
the above ruthenium(II) catalyst system, we were unable to obtain
complete conversion of the allylic substrate while maximizing
enamine formation the tautomerization rates were far too competi-
tive. Although cationic rhodium(I) complexes were extremely
(5) Jones, G.; Zomlefer, J.; Hawkins, K. J. Org. Chem. 1944, 8, 500. (b)
Dawson, D. J.; Gless, R. D.; Wingard, R. E. J. Am. Chem. Soc. 1976, 98,
5996. (c) Ravve, A. J. Polym. Sci. A-1 1968, 6, 2889. (d) St. Pierre, T.; Vigee,
G.; Hughes, A. R. In Reactions on Polymers; Moore, J. A., Ed.; D. Reidel
Publishing Company: Boston, MS, 1973; p 61. (e) Bicak, N.; Sarac, A. S.;
Tulay, A.; Senkal, F. React. Polym. 1993, 21, 135. (f) Tanaka, H.; Ryoichi,
S. Bull. Chem. Soc. Jpn. 1976, 49, 2821. (g) El Achari, A.; Coqueret, X.;
Lablache-Combier, A.; Loucheux, C. Makromol. Chem. 1993, 194, 1879. (h)
Reynolds, D. D.; Kenyon, W. O. J. Am. Chem. Soc. 1947, 69, 911. (i) Geckeler,
K.; Weingartner, K.; Bayer, E. In Polymeric Amines and Ammonium Salts;
Goethals, E. J., Ed.; Permagon Press: New York, 1979; p 277. (j) Hart, R.
Makromol. Chem. 1959, 32, 51. (k) Emmerling, W. N.; Pfannemuller, B.
Makromol. Chem. 1983, 184, 1441. (l) Treslong, C. J.; Morra, C. F. H. Recl.
TraV. Chim. Pays-Bas 1975, 94, 101. (m) Badesso, R.; Nordquist, A.;
Pinschmidt, R.; Sagl, D. In Hydrophilic Polymers Performance with EnViron-
mental Acceptance; Glass, E., Ed.; American Chemical Society: Washington,
DC, 1995. (n) Pinschmidt, R.; Sagl, D. In Polymeric Materials Encyclopedia;
Salamone, J. C., Ed.; CRC Press: New York, 1995; Vol. 9, p 7095.
(6) Hubert, A. J. J. Chem. Soc. 1968, 2048.
Not being capable of undergoing tautomerization, the catalytic
isomerization of various tertiary allylamines to form stable
enamines has been successfully performed by using strong bases
(t-BuOK, KNH2 on alumina, and KOH on alumina)6 and
heterogeneous basic metal oxides (MgO, CaO, SrO, and BaO)7
as well as homogeneous transition-metal complexes of Mo, Co,
Rh, and Ru.8 Much of this work employs conditions (acidic or
basic, long reaction times, high temperatures) which we believe
† North Carolina State University.
‡ University of Massachusetts.
(1) Hickmott, P. W. Tetrahedron 1984, 40, 2989. Szmuszkovicz, J. In
AdVances in Organic Chemistry: Methods and Results; Rahael, R. A., Taylor,
E. D., Wynberg, H., Eds.; 1963; Vol. 4. (b) Whitesell, J. K. In ComprehensiVe
Organic Synthesis; Trost, B. M., Ed.; Pergamon Press: New York, 1991; Vol.
4, p 703. (c) Enamines: Synthesis, Structure, and Reactions, 2nd ed.; Cook,
A. G., Ed.; Marcel Dekker: New York, 1988; p 717.
(7) Hattori, A.; Hattori, H.; Tanabe, K. J. Catal. 1980, 65, 245.
(8) Tatsumi, T.; Hashimoto, K.; Tominaga, H.; Mizuta, Y.; Hata, K.; Hidia,
M.; Uchida, Y. J. Organomet. Chem. 1983, 252, 105. (b) Kumobayashi, H.;
Akutagawa, S.; Otsuka, S. J. Am. Chem. Soc. 1978, 100, 3949. (c) Inoue, S.;
Takaya, H.; Tani, K.; Otsuka, S.; Sato, T.; Noyori, R. J. Am. Chem. Soc.
1990, 112, 4897. (d) Otsuka, S.; Tani, K. Synthesis 1991, 9, 665. (e) Tani,
K.; Yamamagta, T.; Akutagawa, S.; Kumobayashi, H.; Taketomi, T.; Takaya,
H.; Miyashita, A.; Noyori, R.; Otsuka, S. J. Am. Chem. Soc. 1984, 106, 5208.
(f) Tani, K. Pure Appl. Chem. 1985, 57, 1845. (g) Krompiec, S.; Suwinski, J.
Polish J. Chem. 1990, 64, 505. (h)
(2) Capon, B.; Wu, Z. J. Org. Chem. 1990, 55, 2317. (b) DeJeso, B.;
Pommier, J. J. Chem. Soc., Chem. Commun. 1977, 565. (c) DeJeso, B.;
Pommier, J. J. Organomet. Chem. 1977, 137, 23. (d) Knorr, R.; Weiss, A.;
Low, P.; Rapple, E. Chem. Ber. 1980, 113, 2462.
(3) Ripoll, J. L.; Lebrun, H.; Thuillier, A. Tetrahedron Lett. 1980, 36, 2497.
(4) Albrecht, B.; Allan, M.; Haselbach, E.; Neuhaus, L.; Carrupt, P. HelV.
Chim. Acta 1984, 67, 220. (b) Lovas, F.; Clark, F. J. Chem. Phys. 1975, 62,
1925.
(9) Krompiec, S.; Suwinski, J.; Grobelny, J.; Wagner, P. Polish J. Chem.
1997, 71, 747.
(10) Hiraki, K.; Matsunaga, T. Organometallics 1994, 13, 1878.
10.1021/ja011609i CCC: $20.00 © 2001 American Chemical Society
Published on Web 10/11/2001

11084 J. Am. Chem. Soc., Vol. 123, No. 44, 2001
Communications to the Editor
Figure 2. The kinetic plots of isomerization (a) of allylamine (1a) to the enamine (2a), and subsequent tautomerization (b) as a function of catalyst
concentration, HRh(CO)(PPh3)3 (22 °C, benzene-d6, Teflon tube). The tautomerization is first order in catalyst and the tautomerization is zero order.
efficient for allyl alcohol and tertiary allylamines,11 we found that
they were ineffective at room temperature for primary and
secondary allylamines. During this survey, we discovered the
neutral rhodium(I) complex HRh(PPh3)4 was a very active
isomerization catalyst under mild conditions (22 °C), but unfor-
tunately it also catalyzed a nearly equal tautomerization rate (e.g.,
for allylamine (1a) at 22 °C, k1/k2 ) 4.3 and k2 ) 8.7 × 10-5
s-1). However, and for reasons not well understood, we found
the isoelectronic HRh(CO)(PPh3)3 compound to be a highly
selective catalyst for the double-bond migration of 1a and 1b
under mild conditions (eq 2) to form high concentrations of the
be minimized by using Teflon liners, stainless steel vessels, or
silylated glassware, and half-lives of enamines 2a and 2b of 1.7
and 1.9 days at 22 °C, respectively, have been measured. This
decoupling of the tautomerization step from the catalyst concen-
tration also allows for the use of high catalyst loadings in this
system to increase the rate of isomerization relative to tautomer-
ization. To date, no other complex has shown this behavior.
It was necessary to increase the scale of the isomerization
reactions to generate quantities of enamine suitable for polym-
erization studies. We have been able to successfully isomerize
large-scale batches of 1.0 M allylamine solutions through the use
of stainless steel vessels charged with HRh(CO)(PPh3)3. Once
the isomerization reaction was completed, the volatile enamine
solution was then isolated by vacuum transfer (again underscoring
the kinetic stability of these enamines) and the catalyst reused
for succeeding reactions.
1
corresponding enamines (Figure 1). H NMR kinetic studies of
The availability of enamines allows for the direct incorporation
of amines into polymeric structures without the need for protec-
tion-deprotection strategies. To this end, we have found that 2a
successfully copolymerizes with acrylonitrile (AN) under free
radical conditions to yield the one-to-one alternating copolymer
(eq 3). Enamine 2a was isolated as a 0.8 M solution in benzene
the room temperature isomerization of allylamines 1a and 1b in
benzene (following the loss of the 1 methylene protons) were
performed with HRh(CO)(PPh3)3 as a catalyst.12 The reagents were
handled in the inert atmosphere of a drybox and the reaction vessel
consisted of a sealed NMR tube equipped with a fluorinated poly-
(ethylene-propylene) liner.13 These studies show a first order
dependence on both the concentration of 1 and catalyst (rate R
[cat.]1) for the double-bond migration to form enamine (2) as a
mixture of cis and trans isomers (Figure 2a). At 22 °C, the fast
rate of isomerization (7.1 × 10-5 s-1), relative to the secondary
reaction of tautomerization (4.8 × 10-6 s-1), enabled the formation
of significant concentrations of 2. Subsequently, the tautomer-
ization rates of 2a and 2b were determined through the continued
observation of the original reaction mixture. Furthermore, the
tautomerization rate was found to be independent of catalyst
concentration (rate R [cat.]0) (Figure 2b). It is significant to find
a catalyst that does not catalyze the tautomerization of the
enamine. Enamine is only formed at a background rate that is
highly dependent on the presence of protic sources. This rate can
by vacuum transfer after complete isomerization of allylamine
with HRh(CO)(PPh3)3 in a stainless steel trap-to-trap apparatus.
The reaction vessel was charged with 0.101 g (1.9 mmol) of
acrylonitrile, 2.4 mL of the 2a solution (1.9 mmol) ,and AIBN
(3.8 10-6 mol), sealed ,and irradiated with a 350 nm UV source
for 10 h at 10 °C. The isolated material was characterized as an
alternating copolymer of 2a and AN typical of electron rich/poor
monomer combinations.
In conclusion, this study has shown that the appreciable
formation of primary and secondary enamines is indeed possible.
As a result of this catalytic pathway and increased stability, further
investigations into the chemistry of these otherwise unstable
enamines is now possible. The copolymerization of 2a with
acrylonitrile is the first example of the ability to incorporate an
unprotected vinylamine directly into a polymeric structure.
(11) We have successfully employed this strategy for the generation and
polymerization of enols, see: (a) Cederstav, A. K.; Novak, B. M. J. Am. Chem.
Soc. 1994, 116, 4073. (b) Novak, B. M.; Cederstav, A. K. J. Macromol. Sci.,
Pure Appl. Chem. 1997, A34, 1815.
(12) Bergens, S. H.; Bosnich, B. J. Am. Chem. Soc. 1991, 113, 958.
(13) Typical conditions: [1] ) 0.10 M, [cat.] ) 0.01 M d6-benzene, T )
22 °C.
(14) Our observations suggest that the surface of the glass NMR tubes
contains protic contaminates which catalyze tautomerization and are hence
detrimental to the enamine. To avoid this interaction, PTFE inserts in the
NMR tubes were used.
Acknowledgment. The authors acknowledge the NSF (DMR 96-
34528) for financial support of this work.
JA011609I