Facile Synthesis of Aryl-Substituted 1,2,5,6-Tetrahydropyrimidines and Their Stereochemical Investigation

Abstract

The present work is devoted to the investigation of 2,4,6-triaryl-1,2,5,6-tetrahydropyrimidine derivatives. A new facile approach to their synthesis based on the reaction of α,β-unsaturated ketones, carbonyl compounds and ammonia was developed. Some stereochemical features of the compounds obtained were fixed on the base of NMR data (including COSY and NOESY experiments).

Ultrasonic-Promoted Three-Component Synthesis of Some Biologically Active 1,2,5,6-Tetrahydropyrimidines

“…Hence, the spectral data of the synthesized compounds correspond to structures 23 and 24 . The proton spin−spin decoupling experiments and COSY tetrahydropyrimidines 23a − d and f − j demonstrated the presence of a long-range interaction between the H atoms in positions 2 and 5, as described in our previous publication 3a…”

“…A very similar situation was found when we compared sonication and magnetic stirring. A plot of the reaction rates based on HPLC data for compound 23b is shown in Figure As indicated in our previous investigation, in many cases, the three-component reaction carried out without ultrasonic activation had a heterogeneous character, low yields, and led to the formation of 1-aryl- N , N ‘-bis(aryliden)methanediamines 25 (Chart ) as competitive products.

1 Reaction rates: ultrasonic vs shaking.

1 Competitive Reaction Products

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“…Ultrasonic irradiation also significantly expanded the possibilities of this three-component reaction. The use of some heterocyclic aldehydes in case of mechanical shaking led to formation of 1,3-diaryl-3-[(hetaryl-2-ylmethylene)amino]propan-1-ones 26 (Chart ) 3b. However, the use of ultrasonic irradiation in the reactions of heterocyclic aldehydes 13 − 16 with the appropriate chalcones and ammonia yielded the target 1,2,5,6-tetrahydropyrimidines 23f − j in good yields (75−90%).…”

“…Among them, few studies have been performed on 1,2,5,6-tetrahydropyrimidines because of a paucity of efficient synthetic routes. To date, only two practically acceptable synthetic approaches for these compounds have been described. , …”

“…The second method is the treatment of α,β-unsaturated ketones, carbonyl compounds, and ammonia at room temperature. This method was first developed for the synthesis of alkyl-substituted 1,2,5,6-tetrahydropyrimidenes 2b in aqueous media and then, in our previous work, was extended for the aryl derivatives . This method enabled the independent variation of four substituents on the pyrimidine ring and synthesis of large libraries of target heterocycles.…”