SYNTHESIS OF SOME DIAZINE AND TRIAAZOLE DERIVATIVES FROM FURFURAL

The synthesis of heterocyclic compounds especially when their structure containing nitrogen ,oxygen and sulfur atoms are growing up due to their wide spread in nature ,many mechanistic pathways to reach the target with nearly negligible loss of their dose and there are numerous me thods to derivatives their structures There for the development in hetero cyclic synthesis will provide new metabolic pathways when these compounds have succeeded to be used as drug ,Moreover it was known for long time that about 95 % of cancer drugs are heterocyclic compounds .There are also many methods found in the literature for the synthesis of both triazoles and trdiazines from different routes In this investigation furfural was used as precursor for the synthesis of some new diazine and triazole derivatives (3-11).The synthesized compounds were characterized by IR ,and 1HNMR and are discussed.


Introduction
Heterocyclic compound are important class of organic chemistry due to their wide spread in nature and there is versatile ways to synthesize them and also many site are available of functionalization for a given structure. Different metabolic pathways of heterocyclic compounds associated with living organism encouraged researchers to introduce different ways for synthesizing these types of compounds ,These researchers spent much efforts to design these types of compounds as drugs [1][2][3][4].Since drugs needs to reach the target at certain time to penetrate through body tissue without interference with other cells and maintain it's does through this pathway. Accordingly, heterocyclic compounds were found to be used for many biological, clinical and pharmaceutical applications [5][6][7]. Furfural for example 2-(2-furyl) [1,3] dioxane,5-nito(1,3-imidazolyl-2,5-dion)-3-yl furfurlidine was found to be used for treatment of urinary tract [8][9][10] also furfural derivatives were used for different biological applications [11,12] It was also known that many triazoles and diazines compounds were synthesized from different routes [13][14][15][16] . Some heterocyclic compound derived from furfural were prepared previously [17] and here we are going to complete  this work by using furfural as precursor for other new heterocyclic compounds which might find  an applications as drugs ,since Triazoles such as fluconazole, Isavuconazole, Hexaconazole,  epoxiconazole, difenoconazole, tebuconazole etc.,) were commercially used as a fungicidal drugs [18]. In this investigation we use furfural molecule as a core compound for heterocyclic synthesis including diazoles ,triazoles so that to increase their activity through introducing furfural moiety toward their synthesis in a way that will make them suitable for this type of studies which will be investigated in our next work .The synthesized compounds were studied by IR and one of them by 1 HNMR and used for elucidating their structures..

Experimental
Melting point were measured using electrothermal melting point apparatus type IR spectra were measured using Infra-red spectrophoto meter model Tensor 27 Bruker 1HNMR spectra were performed using Bruke 400 MHz. All chemical compound were supplied by Aldrich, Fluka,BDH chemical companies . Compound 1 was prepared using the published procedure [19], compounds 2 was prepared following the else were published procedure [20 ], Their mp. and IR , 1 HNMR spectra were the same of the published one.

Synthesis of 5-Azido-6-phenyl-2-benzoyl pyridazin-3(2H)-one (8)
A mixture of (0.005 mol.,1.8g.) of compound (7) and 0.01 mol. 0.65g. of sodium azide in 10ml of acetonitrite, the mixture was left at r.t for 24 hour.,25 ml of water was then added after this period .the final mixture was extracted with ether, the ether layer was then washed with 5% solution of sodium thio sulfate then with water . the solvent was evaporated under reduced pressure resulting in the formation of with solid which was recrystallized from methanol to give white powder mp 137-139°C, yield 62%, IR: 2154 cm -1 , 1655 cm -1 and 1456-161 cm -1 .

5-Bromo-6-phenyl pyradazine-3-(2H)-one (7)
This compound was prepared from the reaction of compound (3) with benzoyl chloride as shown in scheme (1). It is characterized by the following IR absorption bands : 1697 cm -1 for C=O of pyradazine ring ,1658 cm -1 for C=O benzoyl amide group and 1496-1621 cm -1 for aromatic and C=N which appeared within the same region and finally C-Br absorption at 870 cm -1 .
IR characterization of this compound showed the following absorbation bands cm -1 ,2154,1697,1655,1456-1601, for N3, C=O of pyradazine ring, C=O of benzamide group while C=N, C=C for aromatic appeared within the same region.

2-Benzoyl-6-phenyl-5-N (substituted triazoyl) pyradazine-3(2H)-one-(9-11)
The above compounds were prepared from the treatment of compound (8) with Dimethyl cyclohexene, acetylene dicarboxylate (DMAD) and dichloro ethylene as it was stated in the experimental part the reaction involve 1,3-diplor addition between (DMAD) and the azido group resulted into the formation of the corresponding triazoles. compound (9) as shown in scheme (1) Compound (9) was afforded by treatment of cap (8) with DMAD while compounds 10 and 11 were obtained by treatment of compound (8) with cyclohexene and dichloro ethylene respectively. All compounds were characterized by the following IR main absorption bands : cm -1 : 1640-1661 for C=N and C=O of amide group while the aromatic C=C absorbed within the same of C=N region the ester stretching bands appeared at 1739 and finally the C-Cl stretching band absorbed at 721 Cm -1 .

Conclusion and Recommendations
We conclude from the above study that triazole ,compound(5)when allowed to react with furfural derivative compound (4) resulted into the formation of new type of triazoles (6a and 6b) while compound (7) which is derived from furfural when allowed to react with sodium azide it forms azidido derivative which intern allowed to react with alkenes or alkyne they cyclized into new triazole derivatives(10a,b and 11) These compounds are new nitrogen based heterocyclic compounds. We knew as stated before that nearly 65% of anti -cancer drugs granted market approved by FDA between 210-1015 are heterocyclic compounds and about 95% of heterocyclic compounds are drugs so this type of compounds drew attention of researchers to synthesize this valueable compounds. In our work we have synthesized the above heterocyclic compounds having new nitrogen-based heterocycles which need further studies.