Efficient Synthesis of Tetrahydropyrimidines and Pyrrolidines by a Multicomponent Reaction of Dialkyl Acetylenedicarboxylates (=Dialkyl But‐2‐ynedioates), Amines, and Formaldehyde in the Presence of Iodine as a Catalyst

Abstract

Iodine was explored as an efficient catalyst for the synthesis of tetrahydropyrimidines 4 and pyrrolidines 5 by a multicomponent reaction of dialkyl acetylenedicarboxylates (¼ dialkyl but-2-ynedioates) 1, amines 2, and HCHO 3 at room temperature (Scheme). When the molar ratios of these substrates were 1 : 2 : 4 and 1 : 1 : 4, tetrahydropyrimidines and pyrrolidines were formed, respectively. The products were obtained in high yields (73 -85%) within a short period of time (25 -35 min , and antifungal agents [6]. However, the compounds were prepared earlier only by a few methods involving the reactions of amines or nitro compounds, dialkyl acetylenedicarboxylates (¼ dialkyl but-2-ynedioates) and HCHO at high temperature or in the presence of acid catalysts [7 -12]. Moreover, the pyrrolidines initially prepared by Jiang and co-workers [10] were originally characterized as oxazine derivatives whose structures have recently been revised [11]. Actually, there are only these two reports of a similar procedure for the preparation of pyrrolidines starting from amines following the stated method. Thus, the chemistry of tetrahydropyrimidines and pyrrolidines are interesting. Here, we report an alternative efficient mild method for the preparation of these heterocycles.

Molecular iodine-catalyzed multicomponent reactions: an efficient catalyst for organic synthesis

“…84,85 2.14 Synthesis of tetrahydropyrimidines, pyrrolidines, tetrasubstituted pyrroles and dihydro-2-oxypyrroles from dialkylacetylene dicarboxylate A short and simple synthesis of tetrahydropyrimidine 93 and pyrrolidine 94 derivatives were accomplished in good to excellent yields at room temperature by the reaction of dialkylacetylene dicarboxylate (DAAD) A, amines B, and formaldehyde C in the presence of molecular iodine at room temperature (Scheme 36). 86,87 Interestingly, when the molar ratios of A, B and C were 1 : 2 : 4 and 1 : 1 : 4, tetrahydropyrimidine 93 and pyrrolidines 94 respectively, were formed.…”

Catalyst-free multicomponent synthesis of novel adamantyl-containing tetrahydropyrimidine carboxylates

“…Also, Das et al described [21] a three-component reaction of nitroarenes, formaldehyde, and dialkylacetylenedicarboxylates for the synthesis of 1,3,4,5-tetrasubstituted 1,2,3,6-tetrahydropyrimidines using indium as catalyst in dilute aqueous HCl at room temperature. The authors further extended their work and reported a multicomponent synthesis of tetrahydropyrimidines employing iodine as catalyst [22]. However, the reported methods use only dimethyl acetylenedicarboxylate, produce 1,3-identically substituted derivatives, need acid catalysis or/are performed in ionic liquids.…”

“…Our literature survey at this stage revealed that there are some reports [18][19][20][21][22] on the synthesis of tetrahydropyrimidine derivatives containing an ester group in position 5. Khan and coworkers reported [18] the synthesis of substituted tetrahydropyrimidine and bis-tetrahydropyrimidine derivatives in good-to-excellent yields involving the reaction of dimethyl acetylenedicarboxylate, amines/diamines, and formaldehyde in the presence of (HClO 4 -SiO 2 ) as catalyst.…”

An Efficient Phosphotungstic Acid Catalysed Synthesis of 4,5‐Dioxopyrrolidines and Study of the Mechanistic Effect of the Solvent on the Reaction

“…In one of those examples, Das and his group synthesised dioxopyrrolidines using HCl as catalyst . In addition, in another report, they synthesized the same products using I 2 . Again, in few reports, the exchange of the functional groups of the alkynoates with the solvents was observed whereas, in some cases, the solvent did not attach to the product.…”