New deoxygenation method for amine n-oxides using dimethylthiocarbamoyl chloride

Article abstract of DOI:10.1080/00397910903370634

A facile and efficient deoxygenation method for various amine N-oxides to their corresponding amines is described. The experimental procedure is quite simple and the products are obtained in excellent yields. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910903370634

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New Deoxygenation Method for Amine
N-Oxides Using Dimethylthiocarbamoyl
Chloride
a
a
Hafize Caliskan & Ömer Zaim
a
Department of Chemistry , Trakya University , Edirne, Turkey
Published online: 13 Sep 2010.
To cite this article: Hafize Caliskan & Ömer Zaim (2010) New Deoxygenation Method for Amine
N-Oxides Using Dimethylthiocarbamoyl Chloride, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 40:20, 3078-3083, DOI:
10.1080/00397910903370634
To link to this article: http://dx.doi.org/10.1080/00397910903370634
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Synthetic Communications , 40: 3078–3083, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903370634
NEW DEOXYGENATION METHOD FOR AMINE
N-OXIDES USING DIMETHYLTHIOCARBAMOYL
CHLORIDE
¨
Hafize Caliskan and Omer Zaim
Department of Chemistry, Trakya University, Edirne, Turkey
A facile and efficient deoxygenation method for various amine N-oxides to their corre-
sponding amines is described. The experimental procedure is quite simple and the products
are obtained in excellent yields.
Keywords: Amine N-oxide; deoxygenation; dimethylthiocarbamoyl chloride; reduction; thiocarbamate
The deoxygenation of amine N-oxides to their corresponding amines is an important
[1]
transformation in organic chemistry. A number of methods have been described
[
for the reduction of amine N-oxides, including agents such as low-valent titanium,
2]
[
3]
[4]
phosphorous and sulfur compounds, tributyltinhydride, Pd=C, tetrathiomolby-
[5]
[6]
[
7]
[8]
[9]
[10]
[11]
date, SmI2, In=NH Cl, TiCl =In, In=pivaloylchloride, Cp TiCl =In, Ga=
[12]
4
4
2
2
[
13]
[14]
[15]
[16]
H O,
2
RuCl Á xH O,
CoCl Á 6H O=In,
MoCl =NaI,
5
Re(NFTPP)O3=
3
[18]
2
2
[19]
2
[
17]
[20]
6
[23]
[21]
PPh3, P I , NiCl Á 6H O=In, Mo(CO) , Zn=HCOONH4, polymethylhy-
2 4
2
2
[
22]
[24]
drosiloxane,
Zn(OTf) and Cu(OTf)2,
HCOONH =Ra-Ni, PhSiH3=
Despite the wealth of
2
[26]
4
[
25]
[27]
[28]
and CS2.
MoO Cl ,
2
CuI-Zn=Al,
(CF CO) O=NaI,
3
2
2
methods described in the literature, each of them bearing its own limitations, it is
desirable to possess alternative procedures to perform an important functional-group
transformation. We herein report a simple and efficient deoxygenation method for
various amine N-oxides with dimethylthiocarbamoyl chloride (DMTCC).
Previously, we reported that, pyridine N-oxides can be deoxygenated by
[
29]
DMTCC,
which is a chemoselective method, and product distribution changes
according to the substituents on pyridine N-oxide. In this study, we have extended
the utility of DMTCC for deoxygenation of various tert-amine N-oxides, which
are likely to follow the same path pyridine N-oxides do to remove their oxygen.
Tertiary amine N-oxides can easily be converted to the chloride salts of
dimethylthiocarbamates with commercially available DMTCC. In a typical example,
when N,N-dimethyldodecylamine N-oxide is treated with DMTCC in methylene
chloride at room temperature, chloride salt of N,N-dimethyldodecylamine N-oxide
dimethylthiocarbamate is formed (Scheme 1).
Received May 4, 2009.
Address correspondence to Hafize Caliskan, Department of Chemistry, Trakya University, Edirne
2030, Turkey. E-mail: hafizecaliskan@yahoo.com
2
3
078

DEOXYGENATION METHOD FOR AMINE N-OXIDES
3079
Scheme 1. The reaction of N-oxide with DMTCC in methylene chloride.
Scheme 2. A possible mechanism for deoxygenation of amine N-oxides.
This and all other salts of amine N-oxides, such as 2, are fairly stable at lower
temperatures but decompose at higher temperatures, giving corresponding amines
such as 3, possibly by the following mechanism (Scheme 2).
Product 4 has never been observed in any reaction. Instead, trace amounts
of dimethylthiourea and bis(dimethylcarbamyl) disulfide were observed besides
the amine. We studied a variety of amine N-oxides, which were synthesized from
[30]
relevant amines by peracetic acid.
Only N,N-dimethyldodecylamine N-oxide
was obtained commercially. All the amine N-oxides were treated with DMTCC
and heated to reflux in acetonitrile. The results are summarized in Table 1.
Although most of the amine N-oxides were deoxygenated as usual,
N,N-dimethylaniline N-oxide decomposed rapidly at room temperature, yielding
many unidentified products besides the desired one. When the compound was
refluxed in (C H ) N, the amounts of side products were reduced. Additionally,
2
5 3
when N,N-dimethylbenzylamine N-oxide was treated with DMTCC, after heating,
we observed that benzaldehyde was the main product with a smaller amount of
N,N-dimethylbenzylamine. When 3 eq. of NaI were used in the reaction, we
obtained the amine as the main product. These results may show that nucleophilic
reagents such as (C H ) N and NaI help to improve the deoxygenation by exceeding
2
5 3
the nucleophilicity over the chloride ion and speeding the process. We also investi-
gated the reduction of amine N-oxides with acetyl chloride and dimethylcarbamoyl
chloride in acetonitrile. Neither of them is effective at causing deoxygenation of
amine N-oxides. For practical use, we tried to perform deoxygenation as a one-pot
reaction by dissolving reactants in acetonitrile without using methylene chloride
and isolating the thiocarbamate, then heating to reflux. The yields of the products
are as good as the ones obtained from the original procedure.
In conclusion, we have demonstrated that the deoxygenation of amine
N-oxides with DMTCC provided various amines in good yields. This is an alterna-
tive and attractive reduction method for many different amine N-oxides.

¨
H. CALISKAN AND O. ZAIM
˙
3080
Table 1. Deoxygenation of amine-N-oxides with DMTCC
a
Entry
1
Substrate
Product
Time (h)
Yield (%)
90
3
2
3
92
3
4
3
3
75
71
b
5
6
7
8
2
3
3
3
49
65
84
80
9
3
3
93
87
1
1
0
1
3
65
1
1
2
3
3
3
75
73
(
Continued )

DEOXYGENATION METHOD FOR AMINE N-OXIDES
3081
Table 1. Continued
a
Entry
Substrate
Product
Time (h)
Yield (%)
1
4
3
72
66
1
1
5
6
3
3
c
85
a
b
c
Isolated yields.
Reflux in (C
eq. NaI used.
2
5 3
H ) N.
3
EXPERIMENTAL
1
13
H NMR and C NMR spectra were recorded in deuteriochloroform solution
with a Varian Mercury Plus 300-MHz spectrometer. Infrared (IR) spectra were
obtained on Shimadzu IR 470 or ATI Unicam Mattson 1000 Fourier transform–
IR spectrophotometers. Thin-layer chromatographic (TLC) analysis was performed
on silica-gel plates (Merck, 60 F-254). All products were purified by column chroma-
tography using aluminium oxide 90, active neutral.
General Procedure for the Reaction
A typical procedure for the deoxygenation of amine N-oxide is as follows: a
solution of DMTCC (148.2 mg 1.2 mmol) in methylene chloride was added to a mag-
netically stirred solution of 4-chloro-N,N-dimethylaniline N-oxide (171 mg,
1
.0 mmol) in methylene chloride. The mixture was stirred 2 h at room temperature,
and then solvent was removed on the rotary evaporator. The remaining solid was
dissolved in acetonitrile and refluxed. The reaction was monitored by TLC. After
completion of the reaction, the resulting mixture was concentrated under reduced
pressure, dissolved in chloroform, and washed with saturated NaHCO . The organic
3
phase was dried over anhydrous MgSO . The crude product was purified by alumina
4
column chromatography (n-hexane) to afford 4-chloro-N,N-dimethylaniline
(130 mg, 84%).
ACKNOWLEDGMENT
We gratefully acknowledge the financial support of the Scientific Research
Project Commission of Trakya University.

¨
˙
H. CALISKAN AND O. ZAIM
3082
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