O-acylation of 3-methylpyrazol-5-ones with acylisothiocyanates

Article abstract of DOI:10.1081/SCC-120030702

3-Methylpyrazol-5-ones 1 react by the O-acylation pattern with acylisothiocyanates 2 in the solvent mixture ethanol-dioxane in the presence of the equimolar amount of potassium hydroxide to produce 5-acyloxy-3-methyl-1H-pyrazoles 3.

Full text of DOI:10.1081/SCC-120030702

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O‐Acylation of 3‐Methylpyrazol‐5‐ones with
Acylisothiocyanates
Mykhaylo V. Vovk a , Andrij V. Bol'but a & Pavlo S. Lebed' a
a Institute of Organic Chemistry , National Academy of Sciences of Ukraine , Murmans'ka
str. 5, Kyiv, 02094, Ukraine
Published online: 21 Aug 2006.
To cite this article: Mykhaylo V. Vovk , Andrij V. Bol'but & Pavlo S. Lebed' (2004) O‐Acylation of 3‐Methylpyrazol‐5‐ones
with Acylisothiocyanates, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 34:8, 1507-1513, DOI: 10.1081/SCC-120030702
To link to this article: http://dx.doi.org/10.1081/SCC-120030702
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 8, pp. 1507–1513, 2004
O-Acylation of 3-Methylpyrazol-5-ones
with Acylisothiocyanates
*
Mykhaylo V. Vovk, Andrij V. Bol’but, and Pavlo S. Lebed’
Institute of Organic Chemistry, National Academy of Sciences of
Ukraine, Kyiv, Ukraine
ABSTRACT
3-Methylpyrazol-5-ones 1 react by the O-acylation pattern with acyl-
isothiocyanates 2 in the solvent mixture ethanol–dioxane in the presence
of the equimolar amount of potassium hydroxide to produce 5-acyloxy-
3-methyl-1H-pyrazoles 3.
Key Words: O-Acylation; 3-Methylpyrazol-5-ones; Acylisothiocyanates;
5-Acyloxy-3-methyl-1H-pyrazoles.
*
Correspondence: Mykhaylo V. Vovk, Institute of Organic Chemistry, National
Academy of Sciences of Ukraine, Murmans’ka str. 5, Kyiv 02094, Ukraine;
E-mail: mvovk@i.com.ua.
1507
DOI: 10.1081/SCC-120030702
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

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Vovk, Bol’but, and Lebed’
INTRODUCTION
The problem of selective O-acylation of pyrazol-5-ones has been
attracting an active synthetic interest since the first report of Himmelbauer
in 1896.[1] The most common route to prepare 5-acyloxypyrazoles is acyl-
ation of 1,3-disubstituted pyrazol-5-ones with acyl chlorides in varied
conditions: without[2] or with solvents such as benzene,[1] benzene in the
presence of sodium carbonate,[3] dioxane in the presence of calcium
hydroxide,[4] pyridine,[5,6] and also under solvent-free microwave acti-
vation.[7] For 5-acetoxypyrazoles to be obtained, acylation of pyrazol-5-
ones with acetic anhydride is normally invoked.[6,8–10] The esters of
carboxylic acids have been reported to serve as acylating agents as
well.[11,12] As found, it is the conditions of the reaction between 1,3-disub-
stituted pyrazol-5-ones and acyl chlorides that dictate, as a rule, the consti-
tution of the final products. For instance, 3-methyl-1-phenylpyrazol-5-ones
reacts with benzoyl chloride in the absence of a solvent to give the
O-acylated product, whereas the same reaction conducted in ethanol in
the presence of calcium hydroxide leads to the C-acylated product.[2] Like-
wise, the mentioned substrate, reacted with dicarboxylic acid dichlorides,
provides the O- or C-acylated product according to whether the reaction
is run in benzene in the presence of sodium carbonate or in pyridine in
the presence of calcium oxide.[3]
Acylisothiocyanates are known to be highly reactive electrophiles and
hence promising thiocarbamoylating reagents with respect to most of O–H,
N–H, and C–H nucleophiles.[13] In particular, 3-methyl-1-phenylpyrazol-
5-one has recently been demonstrated to react by the C-thiocarbamoylation
pattern with 7-chloro-1,3-dioxa-5-thia-s-indacen-6-carbonylisothiocyanate
on heating in benzene.[14] At the same time, a number of examples are avail-
able in the literature in which the NCS group of acylisothiocyanates manifests
its pseudohalogen nature and thus enables acylation of alcohols[15–18] or
amines.[19]
In the present paper, we suggest a facile method for O-acylation of
pyrazol-5-ones based on the efficient acylating action of acylisothiocyanates.
It has been revealed that 3-methylpyrazol-5-ones 1 react with acylisothio-
cyanates 2 at room temperature in the solvent mixture ethanol–dioxane in
the presence of the equimolar amount of potassium hydroxide to furnish
5-acyloxy-3-methyl-1H-pyrazoles 3 in reasonable and high yields.
As shown, acylisothiocyanates 2 can be entered into this reaction without
purification as soon as they are obtained from the corresponding acyl
chlorides and potassium isothiocyanate in dioxane at 708C. It is noteworthy
that the method is of prime importance in selective O-acylation of
1-unsubstituted 3-methylpyrazol-5-one. This compound reportedly[20] reacts

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O-Acylation of 3-Methylpyrazol-5-ones
1509
with benzoylchloride to produce the N,O-diacylated product, 1-benzoyl-
5-benzoyloxy-3-methyl-1H-pyrazole.
The structures of 5-acyloxypyrazoles 3 are supported by the CO absorp-
tion bands (1730–1755 cm21) in the IR spectra as well as by the characteristic
singlet peaks of the C4–H pyrazole protons (5.86–6.28 ppm) in the 1H NMR
spectra. The yields and melting points for the compounds synthesized are
listed in Table 1.
Thus, the novel method for O-acylating 3-methylpyrazol-5-ones has been
elaborated.
EXPERIMENTAL
Melting points were measured with a Tomas Hoover apparatus and are
reported uncorrected. IR spectra were recorded on a UR-20 spectrophotometer
1
in KBr tablets. H NMR spectra were registered in D6-DMSO on a Varian
VXR-300 instrument at 300 MHz with TMS as internal standard.
5-Acyloxy-3-methyl-1H-pyrazoles 3a–k: General Procedure
A solution of acylisothiocyanate 2 [obtained by heating the corresponding
acyl chloride (0.005 mol) with KSCN (0.535 g, 0.0055 mol) in dioxane (5 mL)
at 708C over 3 hr] was added to a stirred solution of pyrazol-5-one 1
(0.005 mol) and KOH (0.28 g, 0.005 mol) in ethanol (5 mL). The reaction
mixture was stirred for 2 hr, allowed to stand for 12 hr, and then poured into
water (100 mL). The precipitate formed was filtered off, dried, and recrystal-
lized from 50% aqueous ethanol.
3a. IR: 1730 (C55O). 6MP 1H, d 2.29 (s, 3H, CH3), 5.86 (s, 1H, C4–H),
7.54 (t, 1H, J ¼ 7.4 Hz), 7.69 (t, 2HAr, J ¼ 7.4 Hz), 8.13 (d, 2HAr, J ¼ 8.0 Hz),
12.15 (s, 1H, NH).
3b. IR: 1750 (C55O). 6MP 1H, d 2.29 (s, 3H, CH3), 6.27 (s, 1H, C4–H),
7.33 (t, 1HAr, J ¼ 7.4 Hz), 7.46 (t, 2HAr, J ¼ 7.7 Hz), 7.51 (d, 1HAr,
J ¼ 7.9 Hz), 7.69–7.76 (m, 4HAr), 7.98 (dd, 1HAr, 1J ¼ 7.9 Hz, 2J ¼ 1.5 Hz).

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Vovk, Bol’but, and Lebed’

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O-Acylation of 3-Methylpyrazol-5-ones
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3c. IR: 1745 (C55O). 6MP 1H, d 2.29 (s, 3H, CH3), 6.24 (s, 1H, C4–H),
7.32 (t, 1HAr, J ¼ 7.4 Hz), 7.45 (t, 2HAr, J ¼ 7.8 Hz), 7.54–7.60 (m, 4HAr),
8.05 (d, 2HAr, J ¼ 8.7 Hz).
3d. IR: 1755 (C55O). 6MP 1H, d 2.30 (s, 3H, CH3), 6.28 (s, 1H, C4–H),
7.35 (t, 1HAr, J ¼ 7.4 Hz), 7.48 (t, 2HAr, J ¼ 7.8 Hz), 7.52–7.57 (m, 3HAr),
1
2
7.81 (dd, 1HAr, J ¼ 8.7 Hz, J ¼ 2.2 Hz), 8.08 (d, 1HAr, J ¼ 2.2 Hz).
3e. IR: 1745 (C55O). 6MP 1H, d 2.27 (s, 3H, CH3), 6.24 (s, 1HAr, C4–H),
7.28 (t, 1HThienyl, J ¼ 4.3 Hz), 7.32 (t, 1HAr, J ¼ 7.4 Hz), 7.47 (t, 2HAr,
J ¼ 7.8 Hz), 7.59 (d, 2HAr, J ¼ 8.0 Hz), 7.98 (d, 1HThienyl, J ¼ 3.6 Hz), 8.09
(d, 1HThienyl, J ¼ 4.8 Hz).
3f. IR: 1755 (C55O). 6MP 1H, d 2.31 (s, 3H, CH3), 6.28 (s, 1H. C4–H),
1
2
7.33 (dd, 1HAr, J ¼ 7.8 Hz, J ¼ 1.8 Hz), 7.47 (t, 1HAr, J ¼ 7.8 Hz), 7.56–
7.63 (m, 3HAr), 7.70 (t, 1HAr, J ¼ 1.8 Hz), 7.75 (t, 1HAr, J ¼ 7.5 Hz), 8.09
(d, 2HAr, J ¼ 8.4 Hz).
3g. IR: 1750 (C55O). 6MP 1H, d 2.30 (s, 3H, CH3), 6.25 (s, 1H, C4–H),
7.47 (d, 1HAr, J ¼ 8.8 Hz), 7.58 (t, 2HAr, J ¼ 7.8 Hz), 7.63 (d, 1HAr, J ¼
8.8 Hz), 7.74 (t, 1HAr, J ¼ 7.4 Hz), 8.08 (d, 2HAr, J ¼ 8.2 Hz)
3h. IR: 1755 (C55O). 6MP 1H, d 2.32 (s, 3H, CH3), 6.31 (s, 1H, C4–H),
7.56 (d, 2HAr, J ¼ 8.4 Hz), 7.60 (d, 1HAr, J ¼ 7.9 Hz), 7.68 (t, 1HAr,
J ¼ 7.9 Hz), 7.92 (d, 1HAr, J ¼ 7.9 Hz), 7.97 (s, 1HAr), 8.06 (d, 2HAr,
J ¼ 8.4 Hz).
3i. IR: 2260 (CN), 1755 (C55O). 6MP 1H, d 2.20 (s, 3H, CH3), 2.96
(t, 2H, CH2, J ¼ 6.3 Hz), 4.27 (t, 2H, NCH2, J ¼ 6.3 Hz), 6.05 (s, 1H, C4–H),
7.61 (t, 2HAr, J ¼ 7.7 Hz), 7.76 (t, 1HAr, J ¼ 7.5 Hz), 8.17 (d, 2HAr, J ¼ 8.0 Hz).
3j. IR: 2260 (CN), 1755 (C55O). 6MP 1H, d 2.20 (s, 3H, CH3), 2.96
(t, 2H, CH2, J ¼ 6.3 Hz), 4.25 (t, 2H, NCH2, J ¼ 6.3 Hz), 6.08 (s, 1H,
C4–H), 7.54 (t, 1HAr, J ¼ 7.4 Hz), 7.63–7.68 (m, 2HAr), 8.17 (d, 1HAr,
J ¼ 7.6 Hz).
3k. IR: 1750 (C55O). 6MP 1H, d 2.20 (s, 3H, CH3), 5.25 (s, 2H, CH2),
6.03 (s, 1H, C4–H), 7.06 (d, 1HAr, J ¼ 8.5 Hz), 7.26 (dd, 1HThienyl
,
2
1
2
1J ¼ 5.0 Hz, J ¼ 3.8 Hz), 7.30 (dd, 1HAr, J ¼ 8.5 Hz, J ¼ 1.9 Hz), 7.46
1
2
(dd, 1HAr, J ¼ 1.9 Hz), 7.95 (dd, 1HThienyl, J ¼ 3.8 Hz, J ¼ 1.2 Hz), 8.02
1
2
(dd, 1HThienyl, J ¼ 5.0 Hz), J ¼ 1.2 Hz).
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Received in the UK June 26, 2003

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