Synthesis and Biological Activity of New Fused Sulfur and Nitrogen Heterocyclic Systems
Asma Omar Abo El-Kasem Errayes;
Abstract
This work illustrates the versatile role of tetrahydropyrimidine moiety in the synthesis of different heterocyclic systems from readily obtainable materials.
The work has been divided into three main parts:-
i- First part deals with tetrahydropyrimidine derivative.
ii- Second part deals with β-enaminonitrile.
iii- Third part deals with chemical behaviour of hydrazinopyrimidine moiety towards different electrophiles.
First part: Synthesis and reactions of tetrahydro-pyrimidine derivative.
Tetrahydropyrimidine derivative 1 was prepared via condensation of thiourea with arylidene ethyl cyanoacetate in refluxing ethanol. Some fused heterocyclic systems namely, thiazolo[3,2-a]pyrimidine derivatives 2 and 3 have been isolated via treatment of tetrahydropyrimidine 1 with bromomalononitrile and/or chloroacetamide respectively.
Condensation of compound 3 with substituted aromatic aldehydes namely, 4-chlorobenzaldehyde and / or 4-methoxybenzaldehyde afforded the corresponding benzylidene derivatives 4a,b.
Chlorination of tetrahydropyrimidine 1 with a mixture of phosphorus pentachloride and phosphorus oxychloride as a chlorinating reagent gave the chloropyrimidine derivative 5 which has been allowed to react with glycine, sodium azide and / or anthranilic acid to afford dihydropyrimidine 6, tetrazolopyrimidine 7 and pyrimidoquinazolinone 8 respectively.
Alkylation of tetrahydropyrimidine 1 with ethyl iodide in the presence of sodium ethoxide furnished S-alkylated product 9 which has been chlorinated to afford the chlorinated product 10. Pyrimidine derivative 10 underwent thiation under the effect of thiourea to give thioxodihydropyrimidine 11. Alkaline hydrolysis of tetrahydropyrimidine 1 using 10% alcoholic sodium hydroxide solution gave dioxotetrahydropyrimidine derivative 12 [cf. scheme I].
Second part: Reactions of β-enaminonitrile.
Enaminonitrile 2 is the key starting material for design and synthesis of fused novel heterocyclic systems. Thus, when enaminonitrile 2 was allowed to react with formamide, formic acid and / or sodium nitrite, it afforded pyrimidothiazolopyrimidine derivatives 13 & 14 and pyrimidothiazolotriazine 15 respectively.
On the other hand, treatment of enaminonitrile 2 with ethyl chloroacetate, carbon disulfide, neat triethyl orthoformate and /or diethyl malonate furnished thiazolopyrimidine 16, 17, pyrrolothiazolopyrimidine 19 and/ or thiazolo-pyrimidine derivative 20 respectively [cf. scheme II].
The work has been divided into three main parts:-
i- First part deals with tetrahydropyrimidine derivative.
ii- Second part deals with β-enaminonitrile.
iii- Third part deals with chemical behaviour of hydrazinopyrimidine moiety towards different electrophiles.
First part: Synthesis and reactions of tetrahydro-pyrimidine derivative.
Tetrahydropyrimidine derivative 1 was prepared via condensation of thiourea with arylidene ethyl cyanoacetate in refluxing ethanol. Some fused heterocyclic systems namely, thiazolo[3,2-a]pyrimidine derivatives 2 and 3 have been isolated via treatment of tetrahydropyrimidine 1 with bromomalononitrile and/or chloroacetamide respectively.
Condensation of compound 3 with substituted aromatic aldehydes namely, 4-chlorobenzaldehyde and / or 4-methoxybenzaldehyde afforded the corresponding benzylidene derivatives 4a,b.
Chlorination of tetrahydropyrimidine 1 with a mixture of phosphorus pentachloride and phosphorus oxychloride as a chlorinating reagent gave the chloropyrimidine derivative 5 which has been allowed to react with glycine, sodium azide and / or anthranilic acid to afford dihydropyrimidine 6, tetrazolopyrimidine 7 and pyrimidoquinazolinone 8 respectively.
Alkylation of tetrahydropyrimidine 1 with ethyl iodide in the presence of sodium ethoxide furnished S-alkylated product 9 which has been chlorinated to afford the chlorinated product 10. Pyrimidine derivative 10 underwent thiation under the effect of thiourea to give thioxodihydropyrimidine 11. Alkaline hydrolysis of tetrahydropyrimidine 1 using 10% alcoholic sodium hydroxide solution gave dioxotetrahydropyrimidine derivative 12 [cf. scheme I].
Second part: Reactions of β-enaminonitrile.
Enaminonitrile 2 is the key starting material for design and synthesis of fused novel heterocyclic systems. Thus, when enaminonitrile 2 was allowed to react with formamide, formic acid and / or sodium nitrite, it afforded pyrimidothiazolopyrimidine derivatives 13 & 14 and pyrimidothiazolotriazine 15 respectively.
On the other hand, treatment of enaminonitrile 2 with ethyl chloroacetate, carbon disulfide, neat triethyl orthoformate and /or diethyl malonate furnished thiazolopyrimidine 16, 17, pyrrolothiazolopyrimidine 19 and/ or thiazolo-pyrimidine derivative 20 respectively [cf. scheme II].
Other data
| Title | Synthesis and Biological Activity of New Fused Sulfur and Nitrogen Heterocyclic Systems | Other Titles | " تشييد والنشاط البيولوجي لبعض الأنظمة غير متجانسة الحلقة الملتحمة الجديدة المحتوية علي الكبريت والنيتروجين " | Authors | Asma Omar Abo El-Kasem Errayes | Issue Date | 2015 |
Recommend this item
Similar Items from Core Recommender Database
Items in Ain Shams Scholar are protected by copyright, with all rights reserved, unless otherwise indicated.