Synthesis and reactions of di(thiophen-2-yl)alkane diones: Cyclocondensation

Known 1,6-di(thiophen-2-yl)hexane-1,6-dione (2) and novel 1,7-di(thiophen-2-yl)heptane-1,7-dione (4) were obtained from the reactions of thiophene with the corresponding diacyl chlorides. Furthermore, compounds with furan and pyrrole units in place of thiophene units in compound 2 were obtained in the same way. Bromination of 2 and 4 gave bromides regioselectively. The reaction of each of the compounds 2 and 4 in HOAc medium yielded cyclocondensation products. In total, four known and eleven novel compounds were synthesized.

The residue was crystallized to give dibromide 13 (320 mg, 82%, pale yellow crystals) from EtOAc. Mp Br 81 BrO 4 S 2 ; for: 436.87032; found: 436.87468. 2.8. Reaction of 2 in the mixture of HCl/HOAc: Standard procedure for cyclocondensation After addition of HCl (37%, 6 mL) at RT to a stirred solution of 2 (1.2 g, 4.3 mol) in HOAc (20 mL), the formed mixture was continued to be stirred for an additional 1 h at RT. Check with TLC showed that the reaction was complemented. After quenching by NaHCO 3 solution (saturated, 40 mL) and its extraction with CH 2 Cl 2 (2 × 50 mL), combined the organic phases were dried over Na 2 SO 4 , filtered, and its solvent was evaporated. The residue was submitted on silica gel column chromatography (60 g) with EtOAc:hexane (1:19). Respectively, the products 14 (720 mg, 64%, yellow crystal) and 15 (viscous, 225 g, 20%) were obtained from this purification. Thiophen

Synthesis of (E)-N'-(thiophen-2-yl(2-(thiophen-2-yl)cyclopent-1-en-1-yl)methylene)acetohydrazide (16)
After hydrazine hydrate (250 mg, 7.81 mmol) was added to a stirred solution of 14 (300 mg, 1.15 mmol) in HOAc (20 mL) and the mixture was refluxed for 3 days, it was poured into mixture of ice-water (200 g). While neutralization of the mixture realized by a solution (concerted) of NH 3 , it was controlled with pH paper. One day later, it was observed that no precipitate formed in the mixture. After extraction with CH 2 Cl 2 (3 × 70 mL) of the mixture and drying over Na 2 SO 4 of combined the organic phases, it was filtered and CH 2 Cl 2 was removed. Crystallization of crude with EtOAc gave product 16 (125 mg, 34%, white crystals

Synthesis of thiophen-2-yl(2-(thiophen-2-yl)cyclopentyl)methanone (17)
Pd/C catalyst (10 mg), the compound 14 (370 mg, 1.42 mmol) and MeOH (25 mL) were placed in the flask (100 mL, two necked, round-bottomed) provided with a spinbar at RT. The gas that was first air in the flask was replaced 3 times with hydrogen gas, which is in the balloon attached to the flask and about 1 atm, and then the 14 was reacted with hydrogen gas for 6 days. Filtering the reaction mixture through a filter paper to remove the catalyst followed by evaporation of MeOH gave the compound 17 (345 mg, 93%, yellow liquid) as the sole product.

Result and discussion
Based on a method in the literature [6], each of compounds 2 and 4 was obtained as a result of the reactions of thiophene with the corresponding diacyl chlorides (adipoyl chloride or pimeloyl chloride) (Scheme 1).
Compounds with pyrrole and furan units in place of thiophene units in compound 2 are known. However, to the best of our knowledge, these compounds 10 and 11 were not synthesized in the presence of AlCl 3 [7][8][9]16]. Each of these compounds was also synthesized in the presence of AlCl 3 (Scheme 2).
Some compounds are condensed (or rearranged) to give products under different conditions, and these products may be mechanistically significant. In fact, they may be a targeted compound or starter product for some compounds. 1,6-Diketones cyclocondensed (rearranged) to give compounds including a five-membered ring in acidic media [10,11,[21][22][23]. To detect cyclocondensation (arrangement) in compound 2, it was mixed with HOAc/HCl and monitored by thinlayer chromatography (TLC) at RT. After completion of this reaction and purification of the crude product by silica gel column chromatography, two products were obtained (Scheme 3). According to the NMR spectra of these products, all the carbons and hydrogens in the molecules were different and there was one carbonyl group in both molecules. In addition, one of the products has olefinic hydrogen (at 4.70-4.63 ppm as m and 1H). Thus, the products with and without olefinic hydrogen were identified as 15 and 14, respectively. These products must be cyclocondensation or rearrangement products like known compounds in the literature [10,11,21,24].
Derivatives of compound 14 may be important because it is an α, β-unsaturated compound. Compound 14 was reacted with hydrazine hydrate in HOAc. The presence of a large number of products was observed in the reaction mixture according to monitoring with TLC and its 1

Conclusion
Compound 2, which is known, and compound 4, which is novel, each containing two CO and thiophene groups, were obtained from the reaction of thiophene with the corresponding adipoyl and pimeloyl chlorides in the presence of AlCl 3 , respectively. Synthesis in different ways of each of the known diketones 10 and 11, containing pyrrole and furan rings in place of the thiophene rings in diketone 2, was reported [7][8][9]16]. They were also synthesized similarly to how 2 was synthesized. This is an additional synthesis method for them.
Reactions such as bromination, condensation, and reductions of compounds 2 and 4 were carried out. Among these reactions, the cyclocondensation reactions are more important than others because the products 14, 15, 21, and 22 were formed from reactions of compounds 2 or 4 in HOAc/HCl. The formations of the cyclocondensation products 14, 15, 21, and 22 may also be described as rearrangement. Cyclocondensation products containing five or six-membered rings contain two thiophene units. To the best of our knowledge, cyclocondensation products containing five or six-membered rings, including two heteroaromatic rings such as thiophene, are unknown.
Molecular bromine with the α hydrogen of the carbonyl group in 2 and 4 gave the substitution reactions. Products with bromine in the thiophene rings were not obtained by bromination of 2 and 4. As can be seen in Schemes 3 and 4, bromides 13, 18, and 19 were regioselectively obtained. While the thiophene ring reacts rapidly with bromine even at low temperatures (≤0 °C) [1], the reason why the thiophene rings in compounds 2 and 4 do not react with bromine is thought to be the carbonyl groups attached to the thiophene rings. Carbonyl groups reduce the electron density of thiophene rings because they are electron-withdrawing groups. While cyclopropane rings react with reagents such as Br 2 and H 2 (with Pd/C), cyclopropane rings attached to the ester group do not react with these reagents [25,26].
In the present work, four known compounds (2 and 10-12) and eleven novel compounds (4, 13-22) were synthesized. The purification and structure determination of all the compounds synthesized were achieved by various methods.