Base-promoted oxygenation of N-substituted-N-tosylhydrazines - A convenient route to hydroxydeamination of primary amines

Article abstract of DOI:10.1016/S0040-4039(00)60796-7

Treatment of 1-substituted-1-tosylhydrazines with KOH in refluxing ethanol in the presence of atmospheric oxygen affords the corresponding alcohols in high yield. This reaction, proceeding via ethanol reduction of an intermediate hydroperoxide, provides a convenient route to hydroxydeamination of primary amines.

Full text of DOI:10.1016/S0040-4039(00)60796-7

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BASE-PROMOTED OXYGENATION OF N-SUBSTITUTED-N-TOSYLHYDRAZINES --
A CONVENIENT ROUTE TO OF PRIMARY
Frank S. Guziec, Jr.* and Dongchu
Dept. of Chemistry and Biochemistry
New Mexico State University
Las
NM 88003 U.S.A.
Abstract: Treatment of 1-substituted-l-tosylhydrazines with KOH in refluxingethanol in the
presence of atmospheric oxygen affords the corresponding alcohols in high yield. This reaction,
proceeding via ethanol reduction of an intermediate hydroperoxide, provides a convenient route to
hydroxydeamination of primary
In the course of our investigations into the chemistry of
derivatives, we studied the reduction observed upon base treatment of these compounds. The
ready preparation of these 1
hydrazine derivatives from the corresponding
toluenesulfonamides in many cases provides a convenient route to reductive hydrodeamination
(Scheme
While the reaction of the dehydroabietyl derivative (Table,
1) with potassium
RH
THF
reflux
KOH
R-OH
Scheme 1
reflux
in refluxing THF afforded the hydrocarbon in excellent yield, significantly lowered yields
were observed in the case of phenylethyl (Table, entries 4 and 5). Further
examination of the product mixtures indicated that the major by-products were the corresponding
alcohols.
Remarkably, alcohol formation became the major course of the reaction when the basic medium
was changed to sodium ethoxide in refluxing ethanol. When potassium hydroxide in refluxing
ethanol was used, in most cases the corresponding alcohol formed almost exclusively.
No
elimination or ether by-products could be
in the crude isolated product mixtures.
High
isolated yields of nearly pure alcohols could be directly obtained without additional purification
upon aqueous workup of the reaction mixtures (Table).*
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Table.
of
and Hydroxylatlon Products
%
%
2
3
83
91
91
93
50
55
98
95
4
5
C
1. Potassium t-butoxide, THF Reflux
2. Potassium hydroxide, Ethanol Reflux, Atmospheric
The source of the hydroxyl oxygen in the alcohol product was at first difficult to explain. The
ready hydroxylation of the neopentyl center in the dehydroabletylamine derivative as well as a
complete lack of elimination or ether formation in less hindered compounds strongly suggested that
the reaction was not a simple substiiution. This was confirmed when
KOH was used in
the reaction; no significant
labeling was observed in the product alcohol. Alternatively the
reaction could be envisioned as occurring via an anion-promoted
migration from nitrogen
to the sulfonyl oxygen. Subjecting
afforded only unlabeled alcohol.
sulfonylhydrazine to the reaction conditions again
Carrying out the reaction under milder conditions indicated the source of the hydroxyl group was
in fact molecular oxygen. Treatment of with
ethanol at room temperature followed by aqueous workup and chromatography afforded the
corresponding hydroperoxide in 70% yield. The alcohol 7 was also obtained in 30% yield. When
the hydroperoxide was subjected to the typical reaction conditions of KOH in refluxing ethanol, the
corresponding alcohol was isolated in excellent yield, with ethanol presumably acting the

7467
KOH,
Ethanol
Scheme 2
The oxygenation is a remarkably facile reaction.
Substantial amounts of alcohol were obtained
even when the reactions were run under positive nitrogen pressure! Only careful degassing of
solvent with argon reduced oxygenation significantly, promoting reduction to the hydrocarbon.
While the details of the oxygenation are as yet unclear, it is unlikely that
or carbanion
intermediates are involved in the reaction.4 It is possible that a resonance stabilized
radical and superoxide radical are generated by single electron transfer from the tosylhydrazine
anion in the presence of oxygen. Radical recombination followed by base promoted elimination of
and nitrogen extrusion
the intermediate tosylhydrazine derivatives can
the corresponding using
lead to formation of the observed hydroperoxide.
readily prepared by N-amination of
or
this procedure could provide a convenient route for replacement of the nitrogen of a
primary amine by a hydroxyl group -- hydroxydeamination. As previously noted the yields are
excellent and the conditions of this reaction are much milder than those described in the literature
for related reactions where a primary amine is converted to an oxygenated
The scope
and limitations of this hydroxydeamination reaction are currently under investigation.
Acknowledgment: We gratefully acknowledge the helpful suggestions of Dr. David A.
Widdowson and the assistance of Professor Wolfgang Mueller.
References:
1.
2. A general hydroxydeamination procedure is
KOH (200 mg) was added to a solution of 1
(100 mg, 0.313 mmol) in absolute ethanol. The mixture was heated
overnight under positive nitrogen pressure, cooled to room temperature, and poured
Jr., F. S.;
D., J.
Chem.
out as
for the preparation of
hydrazine
to
into water. The mixture was
extracts were washed
wlth 1 N HCI to
and brine. Drying and removal of solvent afforded alcohol
and NMR were identical in all aspects to authentic 7.
and extracted with chloroform. The
7 as a colorless oil, 50 mg, 99% yield.
The products of other hydroxydeamination reactions were also spectroscopically identical to
authentic pure materials.

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3. Hydroperoxide was characterized as follows:
cm-’
NMR
d,
6.86
d),
4.21
t,
Hz), 3.80
s), 3.8
br s), 2.92
t);
NMR
130.2
(s), 129.9 (d), 114.1 (d), 77.8 (t), 55.4 (q), 33.4 (t); Elemental analysis, Calculated: C, 64.27; H,
7.19% Found: C, 64.20; H, 7.01%. It was also identical to hydroparoxide formed by displace-
ment by sodium hydrogen peroxide on the corresponding alcohol mesylate. Williams, H.R.;
H.S., J. Am.
1954,
4. Molecular oxygen is known to promote reductive deamination of
[Kosower, E
193 (and
cf. Hunig, S.; Buttner, G.
Ed.
451.1 Under the basic,
conditions of the reaction, protonation of an
intermediate
should occur much faster than oxygenation.
has been reviewed. [Nelsen,, S. F., in “Organic Free
ACS Symposium American
5. The chemistry of related
Radicals,” W. A.
1978, pp.
6. Tamura,
Ikeda,
Synthesis,
1.
7. Kattftzky, A. R.;
430.
U.; Kenny, D.H.;
8.
A.
9. Barton, D.H.R.;
1114.
10. White, E.H. Am,
11.
12. Katritzky, A.R.; Saba, A.;
13. U.; Katritzky,
N.H.; Uh, H-S. Syn.
Kenny, D.H.;
H.,
in USA 22 July 1992; accepted 17 August 19921