Recyclization Reactions of N-Arylmaleimides with Polynucleophilic Compounds*

Abstract

The interaction of N-arylmaleimides with N-substituted biguanides and amidinothiourea gave new substituted imidazolinones and thiazolinones.Substituted imidazolinones and thiazolinones are known to possess a wide range of biological activity [1][2][3]. At the same time, the presence of several reactive functional groups in the structure offers opportunities for using these compounds as substrates in the synthesis of new heterocyclic compounds. On the other hand, N-arylmaleimides are frequently used for molecular design of various heterocyclic linearly linked and condensed matrices [4][5][6][7][8][9][10]. Previously it has been demonstrated that N-arylmaleimides react as C(3)-electrophiles with various 1,4-bisnucleophiles, resulting in the formation of six-membered heterocyclic systems: piperidinones [6], hydrogenated thiazinones [11][12], and oxazinones [13]. At the same time, arylmaleimides react with 1,3-bisnucleophiles less predictably and may serve as С(3)-electrophiles, forming five-membered heterocyclic systems: pyrrolidines [4,8], imidazolinones [7], thiazolinones [14-16], or serve as С(4)-electrophiles, leading to six-membered heterocycles, respectively [7-9, 17]. Mixtures of five-membered and sixmembered heterocyclic systems are often formed [7,9].The goal of this work was to study recyclization reactions of N-arylmaleimides in the presence of N,N-and N,S-polynucleophiles, such as N-substituted biguanides and amidinothiourea.Despite the fact that N-substituted biguanides 1а-c represent polynucleophilic compounds, cyclization with N-arylmaleimides involved the guanidine fragment. The reactions were performed by refluxing the starting materials in methanol for 5-7 h. Apparently, the first step involved addition of the amino group in terminal guanidine fragment of bisguanide to arylmaleimide double bond [18], while in the second step the succinimide fragment was attacked by the nucleophilic nitrogen atom of imino group, resulting in recyclization with the formation of imidazolinone ring. This reaction was used for the synthesis of a range of substituted N-aryl-(4-oxo-4,5-dihydro-1Н-imidazol-5-yl)acetamides 2а-e. The use of dioxane or DMF as solvent decreased the yields of target products due to the occurrence of many side reactions.

New Aspects of the Reaction of Thioacetamide and N-Substituted Maleimides

“…In the reactions of N-arylmaleimides with thiourea and its derivatives, five-and sixmembered heterocycles are usually formed: thiazoles B [1,7,[13][14][15][16][17][18] and thiazines C [20]. Reactions of N-arylmaleimides with polynucleophilic reagents, such as amidinothiourea and thiosemicarbazones proceed at 1,3-S,N-binucleophilic centers with the formation of the corresponding thiazolines [2,3,21,22]. The reaction of N-arylmaleimides with heterocyclic 1,3-N,S-binucleophiles (for example, 2-thioquinazolines [7] and 2-mercapto-1,2,4-triazoles [5]) leads to the formation of condensed systems, such as thiazolo [2,3-b]quinazolines and thiazolo [3,2-b] [1,2,4]triazoles, respectively.…”

“…The addition of S-nucleophiles by the Michael reaction to the double bond of N-substituted maleimides is widely used in organic synthesis [24][25][26][27]. Similar intermediates are also formed in reactions with other binucleophilic substrates [6,19,21].…”

“…N-substituted maleimides are promising organic substrates that are used to build a wide range of fused and linearly linked heterocyclic scaffolds with biologically active properties [1][2][3][4][5][6][7][8][9]. The reactive feature of maleic acid imides is their ability to enter into 1,3-dipolar addition reactions [8][9][10][11][12] and into recyclization reactions under the action of binucleophilic reagents-in particular, 1,3-S,N-binucleophiles [1][2][3][4][5][6][7][13][14][15][16][17][18][19][20][21][22][23]. In such reactions, the addition of a more nucleophilic sulfur atom to the activated double bond of N-substituted maleimide usually occurs at the first stage, and the recyclization of the succinimide ring under the action of the nucleophilic nitrogen atom occurs at the second stage [19,21] (Scheme 1, adduct A).…”

Synthesis and some reactions of 5-carbmethoxymethylidene-4-oxo-1,3-thiazol-2-ylguanidine

“…mp. 250-252 °C34 ); IR (cm -1 ): 3481, 3294, 3084 (NH), 1689 (C=O, ester), 1656 (C=O, oxothiazol), 1641 (C=С), 1244, 1170 (C-O, ester); 1 H NMR (500 MHz, (CD3)2SO): δH 3.37 (3H, s, CH3), 6.60 (1H, s, CH), 7.6 (2H, s, NH2), 8.39 (s, 2H, 2NH); 13 General procedure for the preparation of compounds (17). A mixture of methyl (2Z)-[2[(diaminomethylene)amino]-4-oxothiazol-5(4H)-ylidene)acetate 9 (228 mg, 1.00 mmol), primary aliphatic amine (1 mmol), and formaldehyde (37%) (1.46 mL, 2.00 mmol) was heated in isopropyl alcohl (20 mL) for 3-5 h. The precipitate formed upon cooling to room temperature was filtered and dried.…”

“…Another urgent task in organic chemistry is to study the reactions of polynucleophilic compounds with polyelectrophiles which, depending on the reaction conditions utilized, can lead to the formation of various heterocyclic systems. [13][14][15][16] In this regard, amidinothiourea is a polynucleophilic substrate that, depending on the structure of the electrophile, behaves like a 1,3-N,S-, [17][18][19] 1,3-N,N- [19][20] or 1,5-N,N- 21 binucleophile. In addition, imethylacetylene dicarboxylate is widely used in organic synthesis for the construction of five-, six-, and seven-membered heterocyclic systems.…”