Spiroheterocyclization of Methyl 1-Aryl-3-cinnamoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates by the Action of 3-(Arylamino)-1H-inden-1-ones

Methyl 1-aryl-3-cinnamoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates interact with 3-(arylamino)-1H-inden-1-ones to give the corresponding 1,1'-diaryl-3'-cinnamoyl-4'-hydroxy-1H-spiro[indeno[1,2-b]pyrrole-3,2'-pyrrole]-2,4,5'(1'H)-triones in good yields.


Introduction
Spiro compounds represent an important class of naturally occurring substances characterised by their highly pronounced biological properties [1][2][3]. On the other hand, over the past three decades spiro compounds have received considerable attention owing to their diverse chemotherapeutic potential, including antineoplastic activities [4]. Some spiro compounds have been implemented as antimicrobial, antitumour and antibiotic agents [5,6]. In the arena of photochromism, spiro compounds, due to their steric constraints, equilibrate with the corresponding non-spiro analogue and exhibit various photochemical phenomena. Some related applications based on this equilibrium are self-development photography, actinometry, displays, filters and lenses of variable optical density, etc. [7][8][9].

Results and Discussion
During the course of our studies on nucleophilic transformations of monocyclic 1H-pyrrole-2,3diones under the action of bifunctional nucleophiles, we have examined an interaction between methyl 1-aryl-3-cinnamoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates 1 and 3-(arylamino)-1H-inden-1-ones 2. As a result we have found that refluxing of 1 and 2 taken in a 1:1 molar ratio in dry toluene for 5-6 h under TLC monitoring provides the corresponding 1,1'-diaryl-3'-cinnamoyl-4'-hydroxy-1Hspiro[indeno [1,2-b]pyrrole-3,2'-pyrrole]-2,4,5'(1'H)-triones 3 in good yields (Scheme 1, Table 1).  Compounds 3 are red crystal substances readily soluble in DMSO and DMF, poorly soluble in other common organic solvents, and insoluble in saturated hydrocarbons and water. The products give a positive test (cherry-red coloration) with iron(III) chloride for the presence of enol hydroxyl groups. The IR spectra of 3 have absorption bands inherent to stretching vibrations of the enolic hydroxy group (3161-3188 cm −1 , broadened band), two lactam carbonyl groups C 5' =O (1763-1781 cm −1 ) and C 2 =O (1715-1732 cm −1 ), and two ketone carbonyl moieties C 4 =O (1667-1680 cm −1 ) and C 3' -C=O (1640-1647 cm −1 ). 1 H-NMR spectra of 3 display signals of protons in the aromatic rings and substituents attached thereto, two doublets from the protons of the ethylene fragment of the cinnamoyl substituent (δ 7.64-7.66 and 7.72-7.75 ppm) with coupling constant ( 3 J) values of about 16 Hz, and a broadened singlet from the enolic hydroxy proton (δ 13.31-13.45 ppm). In the 13 C-NMR spectra of 3d we have observed carbon atom signals of the aromatic and aliphatic fragments, the carbonyl carbon atom of the cinnamoyl moiety (δ 182.46 ppm), ketone carbonyl carbon atom C 4 (δ 183.74 ppm), lactam carbonyl carbon atoms C 2 (δ 171.89 ppm) and C 5' (δ 165.38 ppm), and spiro carbon atom (δ 68.34 ppm). The structure of 3c was unambiguously confirmed by single-crystal X-ray crystallography (Figures 1 and 2).  According to the XRD study two independent molecules of compound 3c are crystallized in the centrosymmetric space group P2 1 /n of monoclinic crystal system in the solvated form. Due to thermal disordering solvate atoms are not positioned with good precision and the SQUEEZE procedure in the PLATON program [18] was applied for its treatment. A general view of one independent molecule is presented on Figure 1; the second molecule has similar geometry and numeration of its atoms has an additional index "A".
Bond lengths and bond angles in compound 3c are close to standard values. The measured angle between the planes of the heterocycles at the spiro-node amounts to 89. The formation of compounds 3 occurs due to the addition of the β-CH group of the enamino fragment of indenones 2 to the atom C 5 of pyrrolediones 1, followed by the closure of the pyrrole ring through the intramolecular attack of the amino group of indenones 2 on the ester carbonyl group in the position 5 of the pyrroledione with simultaneous elimination of methanol (Scheme 2). Our attempts to isolate intermediates 4 of this transformation failed. Presumably, the rate of intramolecular cyclization compounds 4 higher than the rate of their formation.

General
Melting points were recorded on a Gallenkamp apparatus. IR spectra (mineral oil) were recorded on an FMS-1201 spectrophotometer. The 1 H-and 13 C-NMR spectra were recorded on a Bruker AM 400 spectrometer (at 400 MHz for 1 H-NMR and 100 MHz for 13 C-NMR) with DMSO-d 6 as solvent and TMS as internal reference, chemical shifts are expressed as δ ppm. All reactions were followed by TLC (silica gel, aluminum sheets, Silufol, 5:1, benzene-ethyl acetate). X-Ray analyses were performed using an "Xcalibur 3" diffractometer.

Conclusions
The described reaction presents a rare example of a regioselective synthesis of a hardly accessible spiroheterocyclic system-spiro[indeno [1,2-b]pyrrole-3,2'-pyrrole] including various functional substituents in both heterocyclic fragments. Overall, we have succeeded in developing a method for synthesis of new functionalized spiro[indeno [1,2-b]pyrrole-3,2'-pyrroles derivatives of potential synthetic and pharmacological interest from the reaction of 1H-pyrrole-2,3-diones with 3-(arylamino)-1H-inden-1-ones. Our work presents a very simple reaction performed under neutral conditions and in the absence of any catalyst. From a structural viewpoint, the products are polycarbonyl compounds suitable for further elaboration. High yields and simple reaction and purification procedures are the key advantages of this approach.