2
166
J . Org. Chem. 1999, 64, 2166-2167
Au toca ta lytic Decom p osition of
Sch em e 1
N-Meth ylm or p h olin e N-Oxid e In d u ced by
Ma n n ich In ter m ed ia tes
†
†
,†
Thomas Rosenau, Antje Potthast, Paul Kosma,*
‡
‡
Chen-Loung Chen, and J osef. S. Gratzl
Christian-Doppler-Laboratory, University of Agricultural
SciencessVienna, Muthgasse 18, A-1190 Wien, Austria, and
North Carolina State University, College of Forest Resources,
Biltmore Hall, Raleigh, North Carolina 27695-8005
Received December 1, 1998
N-Methylmorpholine N-oxide (NMMO, 1) is one of the
most important amine oxides in organic synthesis.1 It is
frequently used in transition metal catalyzed oxidations of
2
various organic structures. Apart from these applications
in the laboratory, it is employed on a large industrial scale
3
as a solvent for cellulose in the textile industry. During our
investigations on oxidation reactions, we observed in several
instances that NMMO as the oxidant was consumed far
beyond the stoichiometric ratio, sometimes in fast exother-
mic processes. This excess consumption of 1 appeared to be
rather random and did not obviously correspond to any
changes in the reaction conditions. Furthermore, in these
cases, the formation of large quantities of morpholine (3)
was observed. This agrees with data on the formation of
morpholine in randomly varying amounts during large-scale
industrial applications of NMMO.4
F igu r e 1. Degradation of NMMO into morpholine and HCHO
by Eschenmoser’s salt (2). Decrease in NMMO concentration
followed by capillary ion analysis: (A) NMMO, 1% 2, addition of
acid;11 (B) NMMO‚H2O, 1% 2, no additives; (C) NMMO, 1% 2, no
additives; (D) NMMO, 1% 2, addition of base.12
Despite the differences in these processes, it seemed
reasonable to assume common mechanisms that cause
decomposition of NMMO under specific reaction conditions.
Preliminary experiments showed that this breakdown was
much faster than its reaction with a reductant. This could
only mean that the decomposition of NMMO was caused by
NMMO-derived byproducts present in the system, but not
only by the reductant. Further investigations revealed that
NMMO is completely inert toward its major degradation
products N-methylmorpholine and morpholine and toward
minor byproducts, such as formaldehyde (HCHO, 4) or
formic acid (HCOOH). However, a stoichiometric mixture
of morpholine and HCHO degraded NMMO already when
present in catalytic amounts (approximately 0.1% relative
to 1), a very surprising result. This decomposition proceeded
independent of the solvent used as long as water was present
(Eschenmoser’s salt, 2), a stable carbenium-iminium com-
pound, instead of the morpholine/formaldehyde mixture. As
shown in Scheme 1, N-methylmorpholine N-oxide (1) was
completely degraded by only 1% of this compound (relative
to 1) into morpholine (3) and formaldehyde (4) within 70
min at room temperature, without formation of byproducts.
In these reactions NMMO was either dissolved in chloroform
or present as a solid. Evidently, catalytic amounts of
Mannich intermediates are capable of decomposing NMMO
in a “clean” process,8 a novel reaction that has not been
reported so far.
Investigations into the reaction kinetics9 demonstrated
that in the case of NMMO and NMMO monohydrate the
rates of the degradation of 1 by 1% Eschenmoser’s salt were
fast and similar in magnitude (Figure 1, C and B). However,
5
in trace amounts. In all cases, only 3 and 4 were formed as
6
the reaction products. Consequently, the same compounds
that induce the decomposition of NMMO are in turn gener-
ated in the reaction.
1
0
when NMMO‚2.5H2O, the second stable NMMO hydrate,
To test whether carbenium-iminium ions, i.e., Mannich
type intermediates that can be formed from 3 and 4 in
7
neutral and acidic media, are involved in the reaction as
(8) A typical experimental procedure is described in the following: To a
.1 M solution of NMMO (1) in dry dichloromethane or dry chloroform were
0
active species, we used dimethyl(methylene)iminium iodide
added 1% (relative to 1) of 2 and after 5 min 1% (also relative to 1) of water.
The mixture was stirred at room temperature while flushing with nitrogen
to remove the forming HCHO. In intervals of 10 min, a 0.5 mL aliquot was
taken and analyzed by capillary ion analysis after extraction into 3 mL of
ultrapure water (see ref 9). The reaction was finished when the electro-
pherogram showed only morpholine (3), but no remaining starting material.
The 0.1 M solution of 1 in the above procedure can be replaced with pure
NMMO. Here, the initial reaction temperature has to be set at ap-
proximately 100 °C to obtain a melt and then lowered gradually. Similarly,
it is possible to substitute 2 and water for morpholine (3) (1% relative to 1)
and formaldehyde (4) (1% relative to 1, as 37% aqueous solution).
(9) Kinetic measurements were carried out by quantifying NMMO and
morpholine with capillary ion analysis. A Waters QE4000 instrument with
the following general parameters was used: capillary column 60 cm × 75
µm; indirect UV detection at 214 nm (zinc lamp); hydrostatic sampling,
sample time 10s, run voltage 20 kV. The electrolyte was prepared by
adjusting a solution of 50 mM 4-methylbenzylamine, 50 mM 2-hydroxy-2-
methylpropanoic acid (hydroxy-isobutyric acid), and 20 mM 18-crown-6 in
ultrapure water to a pH of 3.3 ( 0.1 with additional hydroxy-isobutyric
acid. Compounds 1 and 3 can be determined in the concentration range of
0.005 M to 2.5 and 0.001 M to 1.0 M, respectively. The identity of the product
was confirmed by NMR.
†
University of Agricultural Sciences-Vienna.
North Carolina State University.
1) Albini, A. Synthesis 1993, 263.
2) For illustrative examples, see: Godfrey, A. G.; Ganem, B. Tetrahedron
‡
(
(
Lett. 1990, 31, 4825. Suzuki, S.; Onishi, T.; Fujita, Y.; Misawa, H.; Otera,
J . Bull. Chem. Soc. J pn. 1986, 59, 3287.
(
3) Chanzy, H. J . Polym. Sci. Polym. Phys. Ed. 1980, 1137.
4) Buijtenhujs, F. A.; Abbas, M.; Witteveen, A. J . Papier 1986, 40, 615.
(
Brandner, A.; Zengel, G. H. Chem. Abstr. 1982, 977727d.
5) No reaction was observed in carefully dried solvents if HCHO was
(
supplied as a gas. The water provided by addition of HCHO as a 37%
aqueous solution (formalin) was sufficient for the reaction to proceed. On
the other hand, larger quantities of water stopped the reaction, e.g., addition
of water in the double stoichiometric amount of NMMO.
(
6) Both morpholine (3) and formaldehyde (4) were identified by compar-
ison with authentic samples (NMR, MS). Before analysis, HCHO was char-
acterized as 2,4-dinitrophenylhydrazone and dimedone adduct, respectively.
(
see, for instance: Blicke, F. F. Org. React. 1942, 1, 303. Tramontini, M.
Synthesis 1973, 703.
7) Mannich reactions and intermediates have been extensively reviewed,
1
0.1021/jo982350y CCC: $18.00 © 1999 American Chemical Society
Published on Web 03/11/1999