الفهرس 
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Abstract
The aim of this workis the synthesis of new heterocyclic compounds through multicomponent reaction and this work is divided into two parts
Part1:
In this part we direct forthe synthesis of di-pyrimidines under solvent free conditions.
Scheme 76 notes the synthesis of 4,4`-(1,4-phenylene)-dipyrimidine derivatives 200a-c under different conditions. Initially, the dipyrimidine200a were synthesized by allowing the interaction of the three-components terephthalaldehyde (29), 2-acetylthiophene (197a) and S-benzylthiouronium chloride (14d) in aqueous PEG-400 in the presence of potassium hydroxide at room temperature in 85% yield (Scheme 76).
Further we examined the scope of this reaction by replacing aqueous PEG-400 with other polar solvent such as EtOH in the presence of potassium tertiary butoxide and/or EtONa and/or NaOH and/or K2CO3to give80%, 78%, 76% and/or 73% yields of 200a, respectively(Table 1).However, when the reaction was attempted in the absence of any solvent using NaOH as a base at 70C, the reaction time reduced dramatically to 30 minutes and yielded 91% of the desired product 200a after a simple workup. The yields were affected by the solvent and catalyst, as shown in Table 1. This comparative study on different bases, showed that the best result was obtained under solvent-free conditions (Table 1).
The conclusion was that when the reaction was carried out to form compound 200a, whether using polyethylene glycol in the presence of KOH or using ethanol in the presence of different bases or without solvent in the presence of NaOH, we foundthat the effective condition for the synthesis of compound 200a is without solvent, so we direct for the synthesis of 200b, 200c and all the compounds in the research by using this condition.
A probable mechanism for the formation of dipyrimidines 200a-c is shown in Scheme 76. Initially, heterocyclic ketones 197a-cundergo base catalyzed condensation with terephthalaldehyde(29) to give bis-chalcones 198a-c. The bis-chalcones 198a-c then react with S-benzylthiouronium chloride (14d) to produce the intermediates 199a-c. Presumably, the dihydropyrimidines199a-c are air oxidized during the reaction 129 as this intermediate was never observed, and dipyrimidines200a-c were the only isolated product.
We also proved and confirmed the pathway of the reaction through a two-component condensation of bis-chalcone198a-c (which were formed by the
reaction of terephthalaldehyde (29) with heterocyclic ketones 197a-c according to published literature)143, 149, 150 with S-benzylthiouronium chloride (14d)using sodium hydroxide as a base, under solvent-free conditions at 70C, and the reaction performed smoothly in short time and the corresponding compounds 200a-c could be obtained with 85%, 88%, 84% yields, respectively. It is proved that one pot three component reaction is the preferred method for the synthesis of these compounds(Scheme 76).
The protocol was extended for the synthesis of dipyrimidine203a,b (Scheme 77). Thus, the synthetic strategy can be carried out as follows: the mixture of terephthalaldehyde(29),nitriles 11a,b,S-benzylthiouronium chloride (14d) and sodium hydroxide was place into flask, then the mixture was heated at 70C, and the reaction performedsmoothly in short time and the corresponding di-pyrimidine 203a,b could be afforded with high yields (Scheme 77).
As an extension of our synthetic methodology, we used different amidines 14a-d to react with ethyl cyanoacetate (16) and terephthalaldehyde (29) and a series of bis-pyrimidinones 205a-d could be gained with 90 %, 91 %, 89%, 90 % yields, respectively.The reaction was carried without solvent in the presence of NaOH at 70 °C (Scheme 78). Structures of 205a-d was assigned to this product on the basis of spectral data and elemental analysis.
Part2:
In this part we direct for the synthesis of novel dihydropyridine-3,5-dicarbonitrilein presence of DAHP as a catalyst
Herein we report a simple synthesis of dihydropyridine-3,5-dicarbonitrile by refluxing of aldehydes, malononitrile and cyanoacetamides in aqueous medium. The reaction was catalyzed by DAHP. (Scheme 79). In order to optimize the reaction conditions the catalytic amount of DAHP was varied finding that 5mmol of DAHP afforded the best yields.
Scheme 79. Synthesis of dihydropyridine-3,5-dicarbonitril210a-g.
There are two pathways for the formation of compounds 210a-g and we confirmed them byrefluxing of arylidenes179208b,c,q,s with cyanoacetamide derivatives in water in presence of DAHP to give the final products 210a-g (Scheme 79).
We suggest that DAHP is an effective catalyst for the formation of iminium ion 211in a reversible reaction with the aldehydes 7. The higher reactivity of the iminium group is utilized to facilitate Knoevenagel condensation between aryl aldehydes 7and malononitrile 11, which proceeds via intermediate 212and, after dehydration, olefin 208 is produced. DAHP also catalyzes the generation of a proposed enamine intermediate 213, which is formed from cyano acetamides derivatives 98and DAHP. Enamine intermediate 213adds to olefin 208 to generate 214, after proton transfer, tautomerization and hydrolysis of intermediate 214the final products 210 are formed (Scheme 80).