SHORT PAPER
1747
Novel and Highly Selective Conversion of Alcohols and Thiols to Alkyl Nitrites
with Triphenylphosphine/2,3-Dichloro-5,6-dicyanobenzoquinone/Bu4NNO2
System
S
elective Conver
a
t
ohols
a
o
ndThiols to
o
A
lkyl Nitrite
l
s
Akhlaghinia,* Ali Reza Pourali
Department of Chemistry, Damghan University of Basic Sciences, Damghan, Iran
Fax +98(232)5244787; E-mail: b_akhlaghinia@dubs.ac.ir
Received 16 March 2004; revised 19 April 2004
ethers into their corresponding alkyl halides, cyanides,
Abstract: Alkyl nitrites were prepared in good to excellent yields
by treatment of alcohols and thiols with triphenylphosphine/2,3-
dichloro-5,6-dicyanobenzoquinone/Bu4NNO2 in acetonitrile. This
method is highly selective for the conversion of primary alcohols to
alkyl nitrites in the presence of secondary and tertiary alcohols and
thiols.
and azides.13 Now, we report the transformation of alco-
hols and thiols into alkyl nitrites by using Ph3P/DDQ/
Bu4NNO2 system (Scheme 1).
Ph3P/DDQ/n-Bu4NNO2
RXH
RONO
CH3CN, reflux
Key words: triphenylphosphine, 2,3-dichloro-5,6-dicyanobenzo-
quinone, alkyl nitrite, alcohol, thiol
X = O, S
R = primary, secondary and tertiary alkyl
Scheme 1
Organic nitrites (RONO) belong to a main class of NO do-
nors (O–NO donors).1,2 Nitric oxide (NO) is currently one
of the most studied molecules in the biomedical scienc-
es.3,4 This interest is driven by the multiplicity of roles that
NO plays and by the prospect of developing new drugs to
tackle important disease states. Organic nitrites can gener-
ate NO in vivo.5 It is believed that enzymatic catalysis is
involved in the NO generation.6 Some of them, such as
butyl nitrite (BN), amyl nitrite (AMN), and isoamyl nitrite
(IAMN), have been clinically used as vasodilators for a
long time.7 When used as inhalants they cause vasodila-
tion, increased heart rate, and decreased systolic blood
pressure.8 Also, RONO’s show antianginal effects.1,2,7a
In this method, alkyl nitrites were prepared in good to ex-
cellent yields under neutral and mild reaction conditions.
In order to optimize the reaction conditions, at first the ef-
fect of different ratios of ROH/Ph3P/DDQ/Bu4NNO2, sol-
vent and temperature for conversion of PhCH2OH to
PhCH2ONO were examined. Employing a ratio of 1:2:2:2
in MeCN at reflux gave the best result and produced ben-
zyl nitrite after 30 minutes in 98% isolated yield. These
optimized conditions were applied for conversion of
structurally different alcohols and thiols into their corre-
sponding alkyl nitrites. The results are shown in Table 1.
Apart from wide biological applications of RONO’s, they
have been used for the nitrosation of thiols.9 Transesteri-
fication between tert-butyl nitrite and other alcohols can
also be used to synthesize nitrites.10
As shown in Table 1, Ph3P/DDQ/Bu4NNO2 is the most ef-
ficient system for the preparation of alkyl nitrites from al-
cohols. In comparison with nonbenzylic alcohols,
benzylic ones react faster. Although the capability of
DDQ for oxidation of benzylic alcohols has been demon-
strated,14 in our reactions, no oxidative products were ob-
served. We also applied this method for the conversion of
thiols to their corresponding alkyl nitrites (Table 1, En-
tries 14 and 15).
Organic nitrites can be prepared by reacting alcohols with
nitrous acid or other nitrosating agents such as nitrosyl
chloride (ClNO) in pyridine and nitrosonium salts (NO+
–
–
BF4 , NO+ ClO4 ).11 Recently, it was reported that alkyl
nitrites could be synthesized from the reaction of alcohols
with gaseous NO in the presence of air, where nitrous an-
hydride, generated in situ, likely serves as the nitrosating
agent.12
The characteristic 1H NMR, 13C NMR signals and IR ab-
sorptions bands for CH2–ONO appeared at about 5.6 ppm,
159.7 ppm and 1645 cm–1, respectively.15
In this paper, the use of a novel and cheap reagent for ef-
ficient conversion of alcohols and thiols to alkyl nitrites is
reported.
To estimate the selectivity of this new method, we studied
the reaction of some binary mixtures of substrates. Excel-
lent selectivity was observed in the conversion of primary
alcohols to the corresponding nitrite in the presence of
secondary and tertiary alcohols (Scheme 2, Table 2, en-
tries 1–3). Diphenylmethanol, a benzylic secondary alco-
hol was selectively converted to the corresponding nitrite
in the presence of 1-adamantanol (Table 2, entry 4).
Recently, we among others have studied the application of
Ph3P/DDQ/R4NX (X = Cl, Br, I, CN, N3) for the conver-
sion of alcohols, thiols, selenols and tetrahydropyranyl
SYNTHESIS 2004, No. 11, pp 1747–1749
x
x.
x
x
.
2
0
0
4
It was observed that in a binary mixture of benzyl alcohol
and benzyl thiol, the thiol was intact and the alcohol was
Advanced online publication: 01.07.2004
DOI: 10.1055/s-2004-829122; Art ID: Z05604SS
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