A Mild and Convenient Synthetic Method for Arylhydrazones of Methyl Benzoate

Article abstract of DOI:10.1081/SCC-120027715

A series of ester arylhydrazones were prepared by treating methyl benzimidate hydrochloride with arylhydrazine hydrochlorides. Treatment of benzimidate hydrochloride with a mixture of arylhydrazine hydrochlorides and sodium methoxide in absolute methanol at room temperature produced the arylhydrazones of methyl benzoate with moderate yield.

Full text of DOI:10.1081/SCC-120027715

This article was downloaded by: [Washington University in St Louis]
On: 03 January 2015, At: 15:09
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer
House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
A Mild and Convenient Synthetic Method for
Arylhydrazones of Methyl Benzoate
G. S. Zhang a & Z. Suo a
a Department of Biochemistry , The Ohio State University , 484 West 12th Ave.,
Columbus, Ohio, 43210, USA
Published online: 16 Aug 2006.
To cite this article: G. S. Zhang & Z. Suo (2004) A Mild and Convenient Synthetic Method for Arylhydrazones of Methyl
Benzoate, Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
34:4, 673-678, DOI: 10.1081/SCC-120027715
To link to this article: http://dx.doi.org/10.1081/SCC-120027715
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained
in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of
the Content. Any opinions and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied
upon and should be independently verified with primary sources of information. Taylor and Francis shall
not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other
liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or
arising out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any
form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://
www.tandfonline.com/page/terms-and-conditions

SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 4, pp. 673–678, 2004
A Mild and Convenient Synthetic Method
for Arylhydrazones of Methyl Benzoate
*
G. S. Zhang and Z. Suo
Department of Biochemistry, The Ohio State University,
Columbus, Ohio, USA
ABSTRACT
A series of ester arylhydrazones were prepared by treating methyl
benzimidate hydrochloride with arylhydrazine hydrochlorides. Treatment
of benzimidate hydrochloride with a mixture of arylhydrazine hydro-
chlorides and sodium methoxide in absolute methanol at room tempera-
ture produced the arylhydrazones of methyl benzoate with moderate
yield.
Key Words: Arylhydrazine hydrochloride; Methyl benzimidate hydro-
chloride; Arylhydrazones of methyl benzoate.
Ester arylhydrazones can be used as intermediates in the syntheses of
heterocyclic compounds. Two methods to synthesize ester arylhydrazones
*
Correspondence: Z. Suo, Department of Biochemistry, The Ohio State University,
484 West 12th Ave., Columbus, OH 43210, USA; E-mail: suo.3@osu.edu.
673
DOI: 10.1081/SCC-120027715
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

ORDER
REPRINTS
674
Zhang and Suo
Scheme 1.
have been explored in the literature: substitution reactions of orthoesters and
arylhydrazines, and the reactions of imidates with arylhydrazines. The former
method has been extensively investigated.[1] The hydrochlorides of 2-nitro-,
4-nitro-, and 2,4-dinitrophenylhydrazine react with orthoesters to produce
arylhydrazones of the ethyl esters of the corresponding carboxylic acids in
yield of 31–86%.[1] The latter method, however, has not been extensively
investigated. Imidates are susceptible to nucleophilic attack by amino
compounds. The usual pathway involves the loss of alcohol from an imidate
and the formation of an amidine (Sch. 1). For example, it was reported
previously that acyl hydrazines reacted with imidates to yield N1-
acylamidrazones.[2,3] Alternatively, the loss of ammonia and its replacement
by a nucleophile may also occur (Sch. 2). Ester formylhydrazones were
obtained from the reaction of alkyl imidate hydrochlorides with formylhy-
drazines.[4] As to ester arylhydrazones, only one compound of this type has
been prepared by the reaction of phenylhydrazine and an imino ester.[5]
Generally, arylhydrazines react with imino esters to yield N-arylamidrazones
due to the decreased activity of the aryl nitrogen of the hydrazine.[6,7] In this
paper, we systematically investigated the reactivity of several arylhydrazine
hydrochlorides in their reaction with methyl benzimidate hydrochloride.
3-Nitro-, 4-nitro-, 2-chloro-, 3-chloro-, 4-chloro-, 3-bromo-, 4-bromo-, and
4-methoxyphenylhydrazine hydrochloride reacted with methyl benzimidate
hydrochloride to produce arylhydrazones of methyl benzoate in moderate
yield (Table 1). The reaction was performed by adding one equivalent of
methyl benzimidate hydrochloride to the mixture of one equivalent of an
arylhydrazine hydrochloride and one equivalent of sodium methoxide in
absolute methanol with stirring at room temperature (Sch. 3). In addition,
benzimidates can be obtained easily from their corresponding nitriles.[8]
In conclusion, a convenient and easy method for the preparation of
arylhydrazones of benzoates under mild conditions has been established.
Scheme 2.

ORDER
REPRINTS
Synthetic Method for Arylhydrazones
675

ORDER
REPRINTS
676
Zhang and Suo
Scheme 3.
Table 2. IR and NMR data for the products listed in Table 1.
IR (cm21 H1-NMR
)
Product
NH
C55N
Ar-H
CH3
3310
1600
7.13–8.19
(m,9H)
3.90
(s,3H)
3344
3300
3320
1621
1610
1590
7.39–8.08
(m,9H)
3.87
(s,3H)
7.05–7.70
(m,9H)
3.92
(s,3H)
6.90–7.80
(m,9H)
3.80
(s,3H)
3368
1595
6.80–7.70
(m,9H)
3.90
(s,3H)
3270
3290
3200
1605
1605
1620
6.95–7.58
(m,9H)
3.80
(s,3H)
7.00–7.58
(m,9H)
3.82
(s,3H)
6.83–8.07
(m,9H)
3.94,3.83
(2s,6H)

ORDER
REPRINTS
Synthetic Method for Arylhydrazones
677
REACTION PROCEDURE
Equimolar amounts of arylhydrazine hydrochloride and sodium
methoxide in absolute methanol were first mixed in a round bottom flask.
Then, an equimolar amount of methyl benzimidate was added. The resulting
mixture was stirred at room temperature. The reaction was monitored by TLC.
After the reaction reached completion, the solvent was removed under
diminished pressure. The residue was dissolved in dichloromethane, washed
with water several times, and dried over anhydrous Na2SO4. Dichloromethane
was then evaporated under reduced pressure. The crude products were further
purified by column chromatography on silica gel (2239 þ 400 mesh, S.A.
500–600 m2/g) with varying proportions of petroleum ether and dichloro-
methane (15 : 1 to 5 : 1). The purified products were analyzed by CHN
elemental analysis (Table 1), NMR (Table 2), and IR (Table 2). The Rf values
and melting points of these products were determined (Table 1). In addition,
the purified products derived from Entry 6 and Entry 8 were analyzed by MS
analysis, giving the m/z: 305 (Mþ þ H) and 257 (Mþ þ H), respectively.
ACKNOWLEDGMENTS
We thank Dr. Edward J. Behrman to allow us using his laboratory facility.
We also thank him for his critical reading of this manuscript.
REFERENCES
1. Runti, C.; Nisi, C. Reactions between orthoesters and organic nitrogen
compounds. J. Med. Chem. 1964, 7, 814.
2. Glover, E.E.; Rowbottom, K.T.; Bishop, D.C. Synthesis and oxidation of
quaternary salts of 1-aminoimidazoles. J. Chem. Soc. Perkin I 1972, 34, 2927.
3. Watson, K.M.; Neilson, D.G. The chemistry of amidrazones. In The
Chemistry of Amidines and Imidates; Patai, S., Ed.; John Wiley & Sons:
London–New York–Sydney–Toronto, 1975; 503 pp.
4. Ikizler, A.A.; Yildirim, N.J. A study on ester formylhydrazones.
Heterocyclic Chem. 1998, 35, 377.
¨
5. Schmidt, E. Uber Alkylierte Iso-[acryl-glykokkollester] und Phenylhy-
drazidoester. Ber. 1914, 47, 2545.
6. Neilson, D.G. Imidates including cyclic imidates. In The Chemistry of
Amidines and Imidates; Patai, S., Ed.; John Wiley & Sons: London–
New York–Sydney–Toronto, 1975; 457 pp.

ORDER
REPRINTS
678
Zhang and Suo
7. Nineham, A.W. The chemistry of formazans and tetrazolium salts. Chem.
Rev. 1955, 55, 355.
8. Neilson, D.G. Imidates including cyclic imidates. In The Chemistry of
Amidines and Imidates; Patai, S., Ed.; John Wiley & Sons: London–
New York–Sydney–Toronto, 1975; 389–399.
Received in the USA August 14, 2003

Request Permission or Order Reprints Instantly!
Interested in copying and sharing this article? In most cases, U.S. Copyright
Law requires that you get permission from the article’s rightsholder before
using copyrighted content.
All information and materials found in this article, including but not limited
to text, trademarks, patents, logos, graphics and images (the "Materials"), are
the copyrighted works and other forms of intellectual property of Marcel
Dekker, Inc., or its licensors. All rights not expressly granted are reserved.
Get permission to lawfully reproduce and distribute the Materials or order
reprints quickly and painlessly. Simply click on the "Request Permission/
Order Reprints" link below and follow the instructions. Visit the
U.S. Copyright Office for information on Fair Use limitations of U.S.
copyright law. Please refer to The Association of American Publishers’
Fair Use in the Classroom.
(AAP) website for guidelines on
The Materials are for your personal use only and cannot be reformatted,
reposted, resold or distributed by electronic means or otherwise without
permission from Marcel Dekker, Inc. Marcel Dekker, Inc. grants you the
limited right to display the Materials only on your personal computer or
personal wireless device, and to copy and download single copies of such
Materials provided that any copyright, trademark or other notice appearing
on such Materials is also retained by, displayed, copied or downloaded as
part of the Materials and is not removed or obscured, and provided you do
not edit, modify, alter or enhance the Materials. Please refer to our
Website
User Agreement for more details.
Request Permission/Order Reprints
Reprints of this article can also be ordered at
http://www.dekker.com/servlet/product/DOI/101081SCC120027715