Crystalline anhydrous trimethylamine N -oxide

Tetrahedron Letters,Vo1.27,No.34,pp Printed in Great Britain

CRYSTALLINE

0040-4039/86 $3.00 + .OO Pergamon Journals Ltd.

3961-3962,1986

ANHYDROUS

TRIMETHYLAMINE

E-OXIDE

John A. Soderquist* and Charles L. Anderson 1 Department of Chemistry, University of Puerto Rico Rio Piedras, Puerto Rico 00931 Abstract: A rapid, efficient procedure for the preparation of pure, crystalline anhydrous trimethylamine N-oxide from the com.mercially available dihydrate form removal of the reagent is describ;d. DMF serves to both allow the distillative of water as well as to provide an excellent medium for obtaining large crystals of the pure (.mp 225-7'C (dec)), anhydrous material in excellent (94%) yield. - 2H20 Me3&-O-•2H20

.->

Me3&---ODMF

Trimethylamine involved

in many

N-oxide

fish and marine

animals.'

decarbonylation

of transition

tive routes oxidations

TMANO

procedures wish

to report

anhydrous

ca. -

which

simple

150 higher

is added

DMF

4.90 g torr

large,

fresh,

This

borane

gives

maintains range

DMF

as follows: (130 mL).

which

its 225-7'

(3) selective

of the

commercially

employing

one of

sublimation

several

process.1' the

We

crystalline,

sublimation,

but

of the problem

a pure product

To TMANO'2H20

The solution

Removal

and in vacua

(7

mL)

also, into

which

a

melts

(9.80 g, 88.2 mmol)

is distilled

to reach

a

After

results

melting reported

(3h @ rt,

and workup

is obtained,

for several

is concentrated warmed

as above,

resulting

to

and analytically of the reported8

pure

provides at

30

effect

an additional

in an overall and,

oxidative

yield in

of our

organo-

TMANO.

from dry DMF give material

range. with

0.1 torr) drying

and the mixture

cooling

use anhydrous

of -* ca 35 mL. Slow cooling of the supernatant followed by

The supernatant

is added,

recrystallizations

are routinely

prepara-

and

compounds.

for

gives

(1) oxidative

values.

is spectroscopically

excellent

conversions

Repeated

include:

(2) versatile

aspects

the method

crystals.

(mp 224-6'(dec))

material

in

for preparing

the need

(mp 225-7'(dec)).

of the residue.

1.32 9 of TMANO

hands,

colorless

dry

is

diols,6

reagent

method

oxidant

of 153' and a final volume

(2 x 10 mL dry C5H12)

dissolution

94%.

Moreover,

is described

(74%) of TMANO and

efficient

which

that are contained

the conversion

in a tedious

than previously-reported

temperature

to 00 qives washing

routinely

(bp 153' from CaH2)

distillation

and silicon9

require

and recrystallization

process.

Our procedure"

its uses

compounds,3

and vicinal

not only avoids

the dehydration

single,

systems,

into the anhydrous

culminate

a convenient,

TMANO

combines

applications

natural

of bacteria

carbonyl

pyrrolidines,5

dihydrate

which

metal

aluminum, 7 boron8

of the above

available

processes

In chemical

to aldehydes,4 of organo-

Many

is an important

(TMANO)

of the metabolic

Thus,

while

sublimation 3961

which

lower values

methods,

consistently

in the

our product

208-212' appears

to

3962

be of higher even

purity

than has previously

our crystalline

28' 0 8Q% relative

material humidity.

find that the crystals free-flowing

nature

the sublimed

material.

enhances

this

1. Graduate

student

supported

However,

absorbing

inherent

indefinitely

without

we find that

ca 1% water/min of the reagent,

property

decomposition

the ease of its handling

References

2. Barret,

achieved.'0

is very hygroscopic, Despite

can be stored

greatly

been

when

and

compared

at we its to

and Notes

by ths f!TH-MBRS program

(RR-88102).

E. L.; Kwan,

H. S. -*-* Ann Rev Microbial. 1985, 2, 131. 3. a. Luh, T.-Y. Coord. Chem. Rev. 1984, 60, 255. b. Mondo, J. A.; Berson, J. A. J. Am. Chem. Sot. 1983, 105,340. c. sckson, R. S.; Nesbit, R. J.; PateH.;BaimbridE W.; Patzk, J. M.; White, A. H. Organometallics ras, 1985, 4, 2128. d. Shvo, Y.; Hazum, E. ----~ J. Chem. Sot. Chem. Commun. 1974, 336. e. ibid. 1975, 829. V.; 4. Franzen, Otto, S. Ber. 1961, 2, 1360. b) Franzen, L. D.; Shemyakin, M. M. Vol. v 1967, 47, 96. c) Bergson, nat Ea 1964, 3, 250. _*-.-L.; Chastanet; J.; R.; Benadjila-Iguertsira, 5. Beugelmans, G. Can. J. Chem. 1985, 2, 725. --6. a. Matteson, D. S.; Rahul, R. Tetrahedron Lett. 1988, 3.e. 1980, 1(12, 7590.

V. org. c. Angew. Chem. -Negron, 2,

Coll. Inter-

G.; Roussi,

449. b. -J. Am.

7. Kabalka,

C. W.; Newton, R. J. J. Organomet. -Chem. 1978, 156, 65. 8. a. KBster, R.; Morita, Y. Liebigs -Ann. Chem. 1967, 704, 70. b. KBster, R.; Arora, s . ; Binger, P. Angew. Chem. Int. Ed. 1969, 2, 205. c. Davis, A. G.; Roberts, B. P. J. Chem. Sot. (C)68,47;j;d. Zweifel, G.; Polston, N. L.; Whitney, C. C. 5. Am. Chem 1968, 90, 6243. e. Zweifel, G., personal _. g. communication in Erown, H. C.; Gupta, S. K. J. Am. Chem. Sot. 1972, 94, 4370. f. Pelter, A.; Gould, K. J. J. Chem. Sot. Chem Gmmun 197rl, 1029. g. KabalHedgecock, H. CT ~~~.Chem.iS~i776. h. Kabalka, G. W.; ka, G. w.; Slayden, S. W. J. Organomet. Chem. 1977, 125, 273. 1. Hassner, A.: Soderquist, -J. A. 2. Organomet. Chem. 1977, 131, Cl. TSoderquist, J. A.; Brown, H. C. J. Org. -. 1988, 45, 3571. k. Miller, J. A.; Zweifel, G. Synthesis 1981, 288. 1. ibid. J. Am. Chem. Sot. 1981, 1(13, 6217. m. Fisher, R. P.; On, H. P.; Snow, J. T.; Zweifs, G. Synthesis 1982, 127. n. HofEmann, R. W.; Ditrich, K. Tetrahedron E. 1984, 25, 1781. o. Hoffmann, R. W.; Dresely, S. Angew. -Chem. Int. 1986, 2, 189. p. Soderquist, J. A.; Najafi, M. R. J. 9. m. 1986, 51, Ed. n30. Sakurai, H.; 1986, 27, 75.

9.

Ando,

M.; Kawada,

N.;

Sato,

K.; Hosomi,

A. Tetrahedron

Lett.

The dihydrate (cf. Dunstan, 10. W. R.; Goulding, E. 3. Chem. Sot. 1899, 1004 and Riley, D. P.; zrrea, P. E. 2. Org. Chem. 1985, s, 1563.)was originally dehy rdrated and sublimed (cf. Meisenheimer, J.; Bratring, K. Ann. 1913, 397, 286 W. J.7 "Reactions of Organic Compounds"xngmans Green and and Hickinbottom, co.: New York, 1936, p. 227.) to give mp 208'C. See also ref. 3, 5, 7 and 8. This material melts without noticeable decomposition. anhydrous The pure, reagent decomposes at its higher melting temperature. Distillation of DMF solutions of the dihydrate form4followed by vacuum drying has previously been used to prepare anhydrous TMANO. However, in this case, the crude material was utilized directly without further purification. 11. All experiments were carried out in predried (4 h @ 110'C) glassware under a nitrogen atmosphere employing standard handling techniques for air-sensitive compounds ( cf. Brown, H. C.; Midland, M. M.; Levy, A. B.; Kramer, G. W. "Organic Synzesis via Boranes", Wiley-Interscience: New York, 1975 I. (Received

in USA

27 May

1986)