Utilization of Ethyl 3-Aryl-2-bromopropanoates in the Synthesis of
5-R-benzyl-2-iminoselenazolidin-4-ones
Mykola D. Obushak*, Vasyl S. Matiychuk,
Volodymyr M. Tsyalkovsky, Roman M. Voloshchuk
Department of Organic Chemistry,
Kyryla & Mefodiya 6,
E-mail: obushak@in.lviv.ua
Received: July 2002 / Uploaded August 2002
Abstract: Ethyl 3-aryl-2-bromopropanoates were prepared by reaction of ethyl
acrylate with arenediazonium bromides in the presence of CuBr (Meerwein
arylation). These compounds react with selenourea to form
5-R-benzyl-2-iminoselenazolidin-4-ones.
Key
words: selenazole, 2-selenazolidin-4-one, selenourea,
cyclization, Meerwein arylation.
Much interest to the method of synthesis of
selenazole derivatives has been stipulated by their biological activities1-5.
A convenient method to obtain the substituted selenazoles is the interaction
between a-halogenoketones with compounds containing selenoamide fragment – H2NC(Se)R1,2. The interaction of these
compounds with a-halogenocarboxylic acids and their derivatives to receive 2-selenazolin-4-ones have been studied considerably
less6,7.
We suggest the approach to synthesis of
2-selenazolin-4-one derivatives through the products of Meerwein arylation of
acrylates. Arenediazonium bromides 1a-n
react with ethyl acrylate in acetone in the presence
of CuBr yielding ethyl 3-aryl-2-bromopropanoates 2a-n. We have reported about the synthesis of similar compounds
earlier8. They are obtained with 40–60% yield.
Scheme 1
It has been established that esters 2a-n react with selenourea forming
selenazole ring. Selenourea alkylated by a-bromoesters
while boiling in ethanol in the presence of pyridine to afford selenouronium
salts 3a-n. Under the
conditions of reaction they have cyclized up to
5-R-benzyl-2-iminoselenazolidin-4-ones 4a-n
with high yields.
Scheme 2
Table 1.
5-R-benzyl-2-iminoselenazolidin-4-ones
|
Entry |
R
|
Yield (%) |
|
4a |
H |
81 |
|
4b |
2-Me |
66 |
|
4c |
4-Me |
72 |
|
4d |
4-Et |
75 |
|
4e |
4-Bu |
80 |
|
4f |
4-F |
78 |
|
4g |
2-Cl |
83 |
|
4h |
4-Cl |
74 |
|
4i |
4-Br |
78 |
|
4j |
3-NO2 |
84 |
|
4k |
4-CO2Et |
65 |
|
4l |
2,3-Cl2 |
67 |
|
4m |
2,5-Cl2 |
72 |
|
4n |
3-Cl-4-Me |
70 |
It is necessary to stress, that the compounds 2a-n in the presence of basis
can eliminate HBr forming cinnamic esters. However, under the given conditions
we can escape such reaction.
In this reaction selenourea is more efficient
than thiourea8: time of reactions – 20–30 min and 2–3 h
respectively.
Compounds of such type are characterized by
imino-amino tautomerism6. According to 1H NMR spectra in
DMSO-d6 compounds 4a-n exist in imino form (two signals
of NH groups app. ~8.5 and ~9.0 ppm).
The described method of designing of
selenazoline cycle is the first which gives the opportunity to obtain
selenazole derivatives, containing benzyl substituents. Besides, the
availability of amidine fragment makes it possible to utilize these compounds as a reagents in reactions of various types.
Thus, the performed research demonstrated the possibility to obtain 5-R-benzyl substituted
selenazoles through the products of bromoarylation of acrylates. Selenazoles 4a-n can be easily transformed into the
corresponding selenazolidin-1,4-diones 5a,b.
Scheme 3
It is worth mentioning that among 5-R-benzylthiazolidin-4-ones a range of antidiabetic agents is known9,10.
References:
1.
Litvinov, V.P.; Diachenko,
V.D. Selenium-containing heterocycles. Russ. Chem. Rev. 1997, 66
(11), 923.
2.
Larsen, R. 1,3-Selenazoles, Vol. 3, Chapt. 8, Shinkai, I. Ed. in Comprehensive
Heterocyclic Chemistry II, Katritzky, A.; Rees, C.W.; Scriven, E.F.V.;
Eds.; Elsevier Science, Oxford, 1996.
3.
In Organic Selenium
Compounds: Their Chemistry and Biology. Wiley,
4.
Kumar, Y.; Green, R.; Wise,
D.S.; Wotring, L.L.; Townsend, L.B. J. Med. Chem. 1993, 36,
3843-3848.
5.
Kumar, Y.; Green, R.; Wise,
D.S.; Wotring, L.L.; Townsend, L.B. J. Med. Chem. 1993, 36,
3849-3852.
6.
Comrie, A.M.; Dingwall, D.;
Stenlake, J.B. J. Chem. Soc. 1963, 5713.
7.
Koketsu, M.; Takenaka, Y.;
Ishihara, H. Synthesis 2001, 731.
8.
9.
Lohray, B.B.; Bhushan, V.;
Reddy, A.S.; Rao, P.B.; Reddy, N.J.; Harikishore, P.; Haritha, N.;
Vikramadityan, R.K.; Chakrabarti, R.; Rajagopalan, R.; Katneni, K. J. Med.
Chem. 1999, 42 (14), 2569 and cited therein.
10. Parulkar, A.A.; Pendergrass, M.L.; Granda-Ayala, R.; Lee, T.R.; Fonseca,
V.A. Ann Intern Med. 2001, 134, 61-71.