CHEMICAL SYNTHESES AND TECHNOLOGIES
FOR THE SUSTAINABLE DEVELOPMENT II.

Synthesis of 1-Alkylated Benzouracils
via
Alkylation Reactions of 4-Methoxyquinazolin-2(1H)-one Started
by sonochemical s-l PTC¹

Pavel PAZDERA

Research Group for Chemical Syntheses and Technologies of the Sustainable Development, Department of Organic Chemistry, Masaryk University, CZ-611 37 Brno, Czech Republic; pazdera@chemi.muni.cz

Abstract

Procedure for the synthesis of 1-alkylated benzouracils via an alkylation reactions of 4-methoxyquinazolin-2(1H)-one supported by environmental friendly ultrasonochemical solid – liquid phase transpher catalysis (US s-l PTC) was found.

1. Introduction
2. Results and discussion
3. References

1. Introduction

   It is very well known that alkylation reactions proceed on benzouracil in the presence of a base, only. Alkylating reagent binds in the first step at nitrogen in position 3 and subsequently to N1 under formation of 1,3-dialkylsubstituted products² (Scheme 1).

Scheme 1. Sequent alkylation of benzouracil

     Therefore, 4-methoxyquinazolin-2(1H)-one (1) might be suitable precursor for an alkylation of quinazoline skeleton in the position 1because a transformation of methoxy group to oxo- moiety proceeds under mild conditions with an excellent yield. Title quinazoline 1 may be synthesized by cyclization reaction of methyl 2-cyanophenylcarbamate in boiling methanol under action of sodium methanolate³ (Scheme 2).
On the other hand, the strong bases (LDA, NaH) and a very low temperature are necessary² for a deprotonation of 1.

Scheme 2. Synthesis of benzouracil via protected quinazoline 1

     This problem may be solved at the instance of chemistry methods for the sustainable development by an application of the ultrasonic s-l PTC deprotonation at conventional conditions.

2.      Results and discussion

 Now it has been found that 4-methoxyquinazolin-2(1H)-one 1 reacts with model alkylating reagents (methyl iodide, benzyl bromide, allyl bromide, 2,3,4,6-tetra-O-acetyl-D-gluco-pyranosyl bromide, acrylonitrile, methyl acrylate) in the presence of equimolar mixture of calcium carbonate and calcium oxide as a base in dioxane solution at the temperature 50°C under action of the phase transfer catalyst (Cetrimide) and ultrasound in the course of 30-60 min. 1-Alkylsubstituted 4-methoxyquinazolin-2(1H)-ones were isolated in very good yields (85-95%) and purity (Scheme 3).

   The final 1-alkylated benzouracils were obtained by acid hydrolysis² of the above-mentioned alkylated products (Scheme 3).

   IR, ¹H, ¹³C NMR and mass spectra confirmed identity of all synthesized products.

RX … methyl iodide, benzyl bromide, allyl bromide, 2,3,4,6-tetra-O-acetyl-D-glucopyranosyl bromide

CH₂=CH-Y ... acrylonitrile, methyl acrylate

R´... R, CH₂CH₂-Y

Scheme 3. Alkylation of quinazoline 1 via ultrasonic s-l PTC deprotonisation

References:

1. Supported by the grant of Ministry of Education of the Czech Republic
   (Grant No. MSM 143100011).
2. Brown D. J. in Quinazolines (Supplement I), The Chemistry of Heterocyclic Compounds (Taylor E. C., Editor; Weissberger A., Founding Editor), J. Wiley, New York 1998, p. 236 and references herein.
3. Armarego W. L. F. in Fused Pyrimidines, Part I: Quinazolines, The Chemistry of Heterocyclic Compounds (Brown D. J. Editor; Weissberger A., Founding Editor), J. Wiley, New York 1974, p. 99 and references herein.