An unusual rearrangement of 1-( 2-isothiocyanoaryl )-2-( 2-furyl ) ethane under Friedel-Crafts conditions

Treatment of 1-(2-isothiocyanoaryl)-2-(2-furyl)ethane with anhydrous aluminum chloride under Friedel-Crafts conditions yielded a pyrrolo[1,2-a]quinoline derivative via electrophilic attack of the activated isothiocyano group onto the furan ring. The analogous diarylethane under these conditions underwent intramolecular cyclization leading to an eight-membered thioamide.


Introduction
Interaction of arylisothiocyanates with aromatic hydrocarbons was studied for the first time by Gatterman as early as in 1892. 1 Now it is well known that under acid catalysis isothiocyanates react with aromatic and heteroaromatic compounds as C-electrophiles leading to thioamide derivatives. 2If isothiocyanates are linked with the aromatic or heteroaromatic rings by some tether, intramolecular cyclizations proceed under treatment with Lewis acids or PPA. 3 However, direct thiocarbamoylation of furans with isothiocyanates under the Friedel-Crafts conditions has not been reported, a fact that can be attributed to the known sensitivity of furan compounds to acids.The known furan thioamides are usually synthesized by use of lithiated furan derivatives. 4he first example of intramolecular interaction of furan with an isothiocyano group in the presence of acid catalyst was reported by us in 1997.It was demonstrated that treatment of 2-[bis(2-furyl)methyl]aryl isothiocyanates 1 with perchloric acid in 1,4-dioxane led to formation of 2,4-difuryl-4H-3,1-benzothiazines 2 (Scheme 1). 5 Later we found that this transformation can be efficiently realized under catalysis with anhydrous AlCl 3 and showed that this process is also applicable for thiophene analogs 6 and triarylmethanes.

Scheme 1
Obviously, one of the most important factors favoring furan ring migration is the intermediacy of the stable cation A; otherwise the reaction is impossible.It was of interest to study the intramolecular interaction of furan and isothiocyano group in substrates wherein the furan ring migration is impossible due to structural peculiarities of the molecule.In recent work, we showed that treatment of 2-alkyl-5-(2-isothiocyanoaryl)furans 3 with AlCl 3 is accompanied with furan ring opening followed by formation of thieno [2,3-

Results and Discussion
The synthesis of the starting isothiocyanate 11 is depicted in Scheme 3. Acylation of 2-tertbutylfuran 6 with homoveratric acid 5 in chloroform solution of trimethylsilyl ester of polyphosphoric acid 9

Scheme 3
Transformation of isothiocyanate 11 was performed at room temperature in 1,2dichloroethane in the presence of an equimolar amount of anhydrous AlCl 3 .It would be logical to suppose the formation of compound 12 is via intermolecular cyclization.However, similarly to the case of arylfurans, furan presented one more surprise to us.Pyrroloquinoline 13 (Scheme 4) was isolated as a single product.Its structure was confirmed unambiguously by spectroscopic methods and X-ray crystallography (Figure 1).The mechanism of this reaction is still unclear and calls for further study, which is under way.

Scheme 5
Under the treatment of the isothiocyanate 18 with a threefold excess of anhydrous AlCl 3 azocanethione 19 was isolated as the main product in 30% yield.In this case the reaction proceeded as expected via a common intramolecular cyclization leading to cyclic thioamide (Scheme 6).

Experimental Section
General Procedures.The microanalyses were carried out in the Laboratory of Physico-Chemical Methods of Research, Department of Chemistry, M.V. Lomonosov Moscow State University.Melting points are uncorrected. 1H NMR and 13 C NMR spectra were recorded in CDCl 3 on a Bruker AM 300 spectrometer.Chemical shifts are reported in ppm relative to tetramethylsilane as an internal standard and coupling constants (J) are given in absolute values in Hz to the nearest 0.1 Hz.Mass spectra were recorded on a Kratos MS-30 instrument with 70 eV electron impact ionization at 200 °C.IR spectra were measured as KBr plates on InfraLUM FT-801 instruments.Column chromatography was performed using silica gel KSK (50-160 µm) manufactured by LTD Sorbpolymer.
Crystallographic data for the structure 13 in this article have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 686650.Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax; +44(0)-1223-336033 or E-mail: deposit@ccdc.cam.ac.uc].Each request should be accompanied by the complete citation of this paper.(7).Homoveratric acid 5 (4 g, 20 mmol) and tert-butylfuran 6 (2.73 g, 22 mmol) were added to a solution of silyl ester of polyphosphoric acid in CHCl 3 (50 mL).The mixture was stirred under refluxing for 40 min (TLC monitoring), then poured into 300 mL of water, stirred and extracted with CH 2 Cl 2 (3 × 40 mL).The combined extracts were dried over anhydrous Na 2 SO 4 , and the solvent evaporated under reduced pressure.The obtained oil was dissolved in hexane, solution was filtered through a pad of silica gel and left until crystallization of product.Yield   (9).To a cooled (0-5 °C) solution of ketone 8 (5.9 g, 17 mmol) in tetrahydrofuran (120 mL), anhydrous AlCl 3 (4.6 g, 34 mmol) and NaBH 4 (1.3 g, 34 mmol) were added portionwise under stirring.The resulting suspension was stirred at 0-5 °C for 20 min and then brought to reflux.After 2 h when the starting compound 8 vanished (TLC monitoring), the reaction mixture was cooled and poured into 500 mL of ice water.The product was extracted with EtOAc (3 × 50 mL).The combined extracts were dried over anhydrous Na 2 SO 4 , and the solvent evaporated under reduced pressure.The obtained yellow oil 9 (3.85 g, 68%) was used in the next step without further purification.

1-(5-tert-Butyl-2-furyl)-2-(2-amino-3,4-dimethoxyphenyl)ethane (10).
To an ethanolic solution (20 mL) of compound 9 (1.87 g, 5.6 mmol) Raney nickel (1.5 g) and hydrazine hydrate (2 mL) were added and the reaction mixture was refluxed for 1-1.5 h.After completion of the reaction (TLC monitoring), the catalyst was filtered off and the filtrate was evaporated under reduced pressure.The obtained yellow oil 10 (1.51 g, 89%) was used in the next step without further purification.(11).A solution of thiophosgene (0.5 mL, 6.5 mmol) in CH 2 Cl 2 (10 mL) and NaHCO 3 (1.3 g, 15.5 mmol) in water (50 mL) were simultaneously added at room temperature to a stirred solution of compound 10 (1.5 g, 5 mmol) in CH 2 Cl 2 (15 mL).When the reaction had finished (TLC monitoring), the mixture was poured into water (150 mL) and stirred for 6 h.The organic layer was separated and water layer was extracted with CH 2 Cl 2 (2 × 40 mL).The combined organic layers were dried over anhydrous Na 2 SO 4 , the dried extract was reduced to the half of its volume, and petroleum ether was added until the solution became cloudy.The solution was filtered through a pad of silica gel, evaporated to one third of its volume, and left to allow crystallization of the compound 11.Yield

7
gave rise to ketone 7. Its nitration with fuming HNO 3 in acetic acid furnished nitroketone 8. Reduction of the compound 8 with NaBH 4 in the presence of equimolar amount of anhydrous AlCl 3 led to diarylethane 9. Nitro group of 9 was then reduced with NH 2 NH 2 in the presence of Raney Ni to yielding amine 10.Isothiocyanate 11 was obtained by the treatment of the compound 10 with CSCl 2 and an aqueous solution of NaHCO 3 .