Synthesis of Nitriles and Esters of 2-(3

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Synthesis of Nitriles and Esters of 2-(3-Acylureido)benzoic and

2-(3-Acylureido)thiophene-3-carboxylic Acids via Deselanation and Desulfanation Reaction

Jiří Šibor and Pavel Pazdera

Department of Organic Chemistry, Faculty of Science, Masaryk University, Kotlářská 2,

Brno, CZ-611 37, Czech Republic, e-mail: [email protected]

, [email protected]

Synthesis of 3-acylureas derived from nitriles and esters of 2-aminobenzoic and

2-aminothiophene-3-carboxylic acids

via

deselanation and desulfanation reaction have not been described so far. The desulfanation reaction of nitriles and esters of 2-(3-acylthioureido)benzoic and 2-(3-acylthioureido)thiophene-3-carboxylic acids with mercuric oxide in the presence of primary and secondary amines is known

1,2

. This reaction gave the corresponding substituted guanidines and products of their cyclization,

i.e.

fused pyrimidine derivatives.

The usual method of acylureas synthesis is an addition reaction of the amino compounds to acylisocyanates

3

. This method is not suitable for acylureas synthesis because acylisocyanates are compounds with a very low stability. The method using S-allylester of Nbenzoylthio-carbamic acid

4

for reaction with the corresponding esters 2-aminoarenecarboxylic acids was also unsuccessful. The nucleofility of amino group (the group which attacked the carbon atom of thiocarbamic group) is lower – electronwithdrawing group in

position 1. This group is also very bulky. Electronic and steric effects are so the reason of low product yields.

The desulfanation (deselanation) reaction of acylthioureas (acylselenoureas) could be suitable for synthesis of the title acylurea derivatives. We successfully applied both methods.

The desulfanation reaction was performed by application of mercury oxide (threefold molar excess) in the presence of triethylamine as a base. The acetone/water system was used as a solvent mixture.

X

NH C

NH C

S O

R

HgO

Et

3

N acetone/water

X

NH C

NH C

O O

R

X ... CN, COOEt

R ... Ph,

tert

-Bu

X

...

X

X

H

3

C

X

S H

3

C S

Scheme 1: Desulfanation reaction

If the desulfanation reaction was carried out in a heterogeneous mixture by mechanical stirring the reaction was completed in about one week. The reaction time may be reduced by using a higher excess of mercury oxide and by intensification of stirring. It is known that ultrasound

5

may be applied for acceleration of heterogeneous reaction. Our experiments were performed in ultrasonic apparatus for this reason. In this case the reaction time was lowered to two hours. In addition, the molar excess of mercury oxide could be diminished to half. The reaction yield of crude product was about 95 %.

The deselanation reaction was carried out in a similar way. Air oxygen was used as an oxidizing reagent. Acylselenourea in 80 % ethanol was bubbled with air oxygen. The reaction time of deselanation was about two hours for using of 50 mmol acylselenourea. The reaction time was decreased by the application of ultrasound. The yield of crude acylurea derivatives were almost quantitative.

X

O

2

EtOH

NH C

NH C

Se O

R

Scheme 2: Deselanation reaction (legend see scheme 1)

X

NH C

NH C

O O

R

References:

1.

Pazdera P., Preissová I.: Chem. Papers

1992

,

46

, 396.

2.

Pazdera P., Potůček V.: Chem. Papers

1991

,

45

, 677.

3.

Petersen S.: IN Methoden den Organischen Chemie (Houben-Weyl) (E. Müller, Ed.), p.

128, George Thieme Verlag, Stuttgart 1952.

4.

Kutschy P., Dzurilla M., Ficeri V., Koščík D.: Collect. Czech. Chem. Commun.

1993

,

58

,

575.

5.

Kalinská V., Toma Š.: Chemické listy

1988

,

82

, 729.

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