Microwave assisted synthesis of annelated benzosuberone as new penta-heterocyclic ring systems

Derivatives of novel penta-heterocyclic ring systems, namely, 5,6,7,11-tetrahydro-15 H - benzo[6',7']cyclohepta[1',2':4,5]pyrido[2,3-d ][1,2,4]triazolo[4,3-a ]pyrimidin-15-ones ( 9a-g ) and 6,7-dihydrobenzo[6',7']cyclohepta[1',2':4,5]pyrido[2,3-d ][1,3]thiazolo[3,2-a ]pyrimidin-15(5 H )- ones ( 11a-d ) were easily prepared via reactions of 3-thioxo-2,3,4,7,8,9-hexahydro-1 H - benzo[6',7']cyclohepta[1',2':4,5]pyrido[2,3-d ]pyrimidin-1-one ( 3 ) with hydrazonoyl halides and active methylene compounds, respectively. The foregoing reactions were carried out with conventional heating as well as pressurized microwave irradiation and a comparative study was employed.


Introduction
][6][7] Thiazolo[3,2-a]pyrimidine derivatives have been ascertained as a new type of acetyl cholinesterase inhibitor for the treatment of Alzheimer disease. 8In this context, we have prepared novel pentacyclic ring systems incorporated benzo-cycloheptapyridines and both of 1,2,4-triazolopyrimidines and thiazolopyrimidines.Despite recent interest in microwave as energy source which enhances the reaction rates and improves the regioselectivity, [9][10][11][12] the use of microwave in reactions of hydrazonoyl halides has received limited study. 13

Scheme 2
As depicted in Scheme 2, the reaction proceeded through S-alkylation 23 to give S-alkylated products 7 followed by Smiles rearrangement, 24 affording intermediates 8 which eliminated hydrogen sulfide gas to give the desired products 9a-g.The assignment for the structure of the products and reaction mechanism can be manifested by alternate synthesis.Thus, treatment of 6-[(dimethylamino)methylene]-6,7,8,9-tetrahydro-5H-benzo [7]annulen-5-one (1) with 7-amino-1,3-diphenyl [1,2,4]triazolo [4,3-a]pyrimidin-5(1H)-one (10)  25 in acetic acid led to formation of product that proved to be identical in all respects (mp, mixed mp and IR) with compound 9a (Scheme 2).A comparative study of the yields of the products under pressurized microwave irradiation (method A) and conventional heating (method B) (Table 1) showed that the use of microwave irradiation substantially reduced the reaction times from hours scale to minutes scale and appreciably increased the yields.
Tabel 1. Formation of 9a-g using pressurized microwave and conventional heating procedures  2).The structure of the isolated products was established on the basis of IR, 1 H NMR, mass spectra and elemental analyses (see Exprimental Section).

Conclusions
We described in this context a synthetic route for new penta-heterocyclic ring systems from hydrazonoyl halides and tetra-heterocyclic thione in one-pot reactions.The microwave-assisted process, in contrast to conventional heating, gave the desired products in higher yields with shorter reaction times.In pressurized microwave, the solvent can be heated up to temperatures from 2 to 4 times their respective boiling points which enhanced the reaction rates.

Experimental Section
General Procedures.All melting points were determined on an electrothermal Gallenkamp apparatus and are uncorrected.Solvents were generally distilled and dried by standard literature procedures prior to use.The IR spectra were measured on a Pye-Unicam SP300 instrument in potassium bromide discs.The 1 H and 13 C-NMR spectra were recorded on a Varian Mercury VXR-300 spectrometer (300 MHz for 1 H-NMR and 75 MHz for 13 C NMR) and the chemical shifts were related to that of the solvent DMSO-d 6 .The mass spectra were recorded on a GCMS-Q1000-EX Shimadzu and GCMS 5988-A HP spectrometers, the ionizing voltage was 70 eV.Elemental analyses were carried out by the Microanalytical Center of Cairo University, Giza, Egypt.Microwave experiments were carried out using CEM Discover Labmate microwave apparatus (300 W with Chem.Driver Software).[28][29][30][31] General procedures for the synthesis of

,3-d]pyrimidin-1-one (3). Pressurized microwave method (method A)
To a solution of 3 and the appropriate hydrazonoyl halides 6a-g (1 mmol of each) in dioxane (20 mL) was added triethylamine (0.14 mL, 1 mmol) at room temperature.The reaction mixture was irradiated in a pressurized microwave (17.2 Bar, 140 o C) for 6-10 min.at a power of 300 W. After cooling to room temperature, the solution was extracted with chloroform (3X10 ml).The organic extracts were dried over anhydrous magnesium sulfate, and then evaporated under reduced pressure.The solid residue was recrystallized from the appropriate solvent to give products 9a-g.Thermal method (method B).To a solution of 3 and the appropriate hydrazonoyl halides 6a-g (1 mmol of each) in dioxane (20 mL) was added triethylamine (0.14 mL, 1 mmol).The reaction mixture was refluxed till all of the starting materials had disappeared (20-24 h, monitored by TLC).The solvent was evaporated and the residue was triturated with methanol.The solid formed was collected and recrystallized from the appropriate solvent to give products identical to those produced by microwave method.10) 25 (0.303 g, 1 mmol) and enaminone (1) (0.215 g, 1 mmol) in acetic acid was refluxed for 6 hours.After cooling, the mixture was poured into ice and the solid product was filtered off and recrystallized from (ethyl acetate/ petroleum ether) mixture to give compound 9a.