Synthesis and Spectral Study of some New α, β-Unsaturated Carbonyl Compounds and Pyrazole Derivatives

This work includes the synthesis of some new pyrazole derivatives from the reaction of new  - unsaturated carbonyl derivatives with hydrazine hydrate.  - Unsaturated carbonyl derivatives which are prepared in several ways by reaction of hydrazide-hydrazone A 2 with substituted aromatic aldehydes in the presence of triethylamine as a base, and also prepared by reaction of hydrazide-hydrazone A 2 with phenylisothiocyanate and (ethyl chloro acetate or dimethyl sulfate) or A 2 with carbon disulfide and (ethyl chloro acetate or dimethyl sulfate) in the presence of potassium hydroxide in dry dimethyl formamide. The structures of these new synthesized compounds were confirmed by physical and spectroscopic methods (FT-IR, 1 H-NMR, 13 C-NMR)


INTRODUCTION
The hydrazide-hydrazone compounds are organic compounds used in the synthesis of heterocyclic compounds due to their interaction with the electrophile and nucleophile (Belskaya et al., 2010), and it is an important class responsible for many pharmaceutical applications because of its structure that contains the azomethine group (NH-N=CH) attached to carbonyl group responsible for these applications (Rollas and Güniz, 2007), An important characteristic of hydrazones its automeric form, that is, appear as keto-enol form (Ray et al., 2008) and it also has an important biological activity, as anti-cancer (Kumar et al., 2012), anti-HIV (Jin et al., 2010) ,anti-microbial (Özkay et al., 2010), anti-tuberculosis (Mahajan et al., 2011), antioxidant (Belkheiri et al., 2010), anti-parasitic (Caputto et al., 2011) and anti-inflammatory (Almasirad et al., 2005, as well as insecticides (Monfared et al., 2007).
As well as one of the most important materials used in organic synthesis is the α,β-unsaturated carbonyl compounds, which are the unite building of organic chemistry and therefore have the attention of many researchers during the last decades (Zhang et al., 2020). As well as being used in many industries, as starting materials for compounds such as, plastics, resins (Banner and Hong, 1993), dyes (Asiri, 2003) as well as perfumes (Bianco et al., 2004). In addition to having many biological activities, as an antibacterial (Liu et al., 2013), antiviral (Nowakowska, 2007), antifungal (Sortino et al., 2007), antitumor (Katsori andHadjipavlou-Litina, 2009), antioxidant (Raghavendra et al., 2007), anti-inflammatory (Dabbagh et al., 2012) (Cheng et al., 2008 and antimalarial. Also, α, βunsaturated compounds were well-known by their use as intermediates for the synthesis of heterocyclic compounds (Al-Sabawi, 2015).
Encouraged by these observations it is worthwhile to synthesize hydrazide-hydrazone and some new α, β-unsaturated compounds in different methods and studying their reactivity toward nucleophiles to synthesize pyrazole compounds shown in the scheme (1).

B-Synthesis of various compounds for α, β-Unsaturated Carbonyl Compounds
Preparation of α, β-Unsaturated Carbonyl Compound A 11 (Salman, 2013) Adding the KOH (0.56 g, 0.01mol) suspended in dry DMF (10 ml) to hydrazine hydrazone A 2 (2.31g, 0.01mol) with stirring continues for (30 min), then phenylisothiocyanate (1.35 g, 0.01mol) was added gradually to the reaction mixture with continuous stirring for (12 hours) at room temperature to form an intermediate compound followed by the addition of ethyl chloro acetate (1.22 g, 0.01mol) with continuous stirring for (6 hours). The reaction mixture is poured over crushed ice with stirring, and the precipitate formed is separated by filtration, then leave to dry and recrystallized with ethanol/DMF, the result is dark yellow, m.p (175-173 °C), yield (63%).

Preparation of α, β-Unsaturated Carbonyl Compound A 13 (Salman, 2013)
Adding of KOH (1.12 g, 0.02) suspended in (10 ml) of dry dimethyl formamide (DMF) with (2.31 g, 0.01mol) of hydrazide-hydrazone A 2 . The mixture was cooled in an ice bath at 10 o C, then (0.76 g, 0.01mol) of CS 2 was added to it gradually, with stirring for (6 hours) to form the intermediate compound, then (1.225 g, 0.01mol) of ethylchloro acetate was added with continuous stirring for (3 hours), then it is gradually poured over crushed ice containing (10 drops) of conc. HCl with stirring, filtered off and dried to obtain an orange precipitate, m.p (150-148°C), yield (95%).

Preparation of α, β-Unsaturated Carbonyl Compound A 15 (Salman, 2013)
Adding of KOH (0.56 g, 0.01mol) suspended in (10 ml) of dry DMF with (2.31 g, 0.01 mol) of the starting material hydrazide-hydrazone A 2 is dissolved in (0.76 g, 0.01 mol) of CS 2 in an ice-bath at 0 o C and the mixture was stirred for (12 hours) to form the intermediate compound, then followed by adding (2 M. 20 ml) of conc. HCl drop by drop to the reaction mixture with continuous stirring for one hour, the reaction mixture then poured over crushed ice with stirring to complete the precipitation process, then filtered off and recrystallized from ethanol to give a yellow precipitate m.p (174°C), yield (87%).

2-The Second pathway Synthesis of Pyrazole Derivatives A 16-A 23 (Shams et al., 2010)
A mixture of (0.001 mol) of the compounds A 3-A 10 produced in the first pathway with hydrazine hydrate 88 % (0.002 mol) in (15 ml) of absolute ethanol, then refluxed for (4-5 hours), the mixture was concentrated to half the quantity, then leave until a precipitate is formed, then filtration and dried. The physical properties are shown in the ( Table 2).

Synthesis of Pyrazole Derivatives A 25-26 (Zelenin et al., 2001)
A mixture of compound A 14 (0.91 g, 0.003 mol) obtained from the first path with hydrazine hydrate 88% (0.25 g, 0.005 mol) or phenylhydrazine in (15 ml) absolute ethanol was refluxed (3 hours), the formed precipitate was cooled, filtration and recrystallized with ethanol, then dried, the physical properties are shown in the (Table 3).

Synthesis of Pyrazole Derivative A 27 (Salman, 2013)
A mixture of compound A 12 (0.12 g, 0.0004 mol) obtained from the first path with hydrazine hydrate (0.25 g, 0.005 mol) in (15 ml) absolute ethanol was refluxed (3 hours), the formed precipitate was cooled and filtered off and recrystallized from ethanol, then dried to obtain a yellow precipitate m.p (190 -189 °C), yield (40%)

RESULT AND DISCUSSION
In the content of this research, we discuss how to synthesize new pyrazole derivatives through two pathways starting with the use of hydrazide-hydrazone A 2 , the first pathway involves obtain a new α, β -unsaturated carbonyl compounds. While the second pathway included obtain a new pyrazole derivative. Which is expected to be of biological importance as similar pyrazole derivatives that were prepared before.
The hydrazone-hydrazide A 2 was synthesized by reaction of cyanoacetohydrazide with piperonal using ethanol as a solvent, as shown in equation (1), The structure of the A 2 was confirmed by physical and spectroscopic properties (FT-IR, 1 H-NMR), in the FT-IR spectrum an absorption band appears at (3307 cm -1 ) for the NH group and two absorption bands at (1687 cm -1 ), (1597 cm -1 ) for C=O and C=C groups respectively, as well as an absorption band at (2258 cm -1 ) for the CN group , In addition to the symmetric and asymmetric (C-O-C) ring ether bands, respectively, which appeared at (1037 cm −1 ) and (1257 cm −1 ), also the characteristic band that gave clear evidence of the formation of the compound is the C=N band, which appeared at (1670 cm -1 ), while the 1 H-NMR spectrum of compound A 2 showed the following chemical shifts (δ,

Equation 1: Preparation of hydrazide-hydrazone compound A 2
The new derivatives of -unsaturated carbonyl compounds were prepared by two methods, one part of which was prepared by reaction of hydrazide-hydrazine A 2 with substituted aromatic aldehyde in a basic medium of triethylamine (TEA) and using absolute ethanol as a solvent, while the second part was prepared by adding other components mentioned in the method of experimental on the hydrazone hydrazone A 2 using KOH suspended in dry DMF solvent, as in scheme (1), the structure of the new product A 11 was confirmed by physical and spectroscopic properties (FT-IR, 1 H-NMR, 13 C-NMR), in the FT-IR spectrum, a characteristic absorption band of the functional group (C=C) appeared at 1587 cm -1 , which gave clear evidence of the formation of the compound A 11 . As well as, absorption bands at 1661 and 1741 cm -1 for the carbonyl groups (C=O) amide and lactum respectively, in addition to the absorption bands at 2200 cm -1 for the (CN) group, at 1635 cm -1 for the (C=N) group and at 3269 cm -1 for the (NH) 1H,, As well as the 13 C-NMR spectrum, which showed additional carbon signals, which proved that the required new compound was obtained. The results were identical to the proposed compound A 11 , as shown in the ( Table 9).
The new pyrazole derivatives A 16-A 27 were prepared by reacting the products of the first pathway A 3-A 10, A 12 , A 14 with hydrazine hydrate in absolute ethanol except for the pyrazole derivative A 24 it was prepared directly from the reaction of hydrazone-hydrazide A 2 with hydrazine hydrate using an ethanol as a solvent, as in scheme (1). The (FT-IR) spectrum of all compound produced shows a characteristic absorption band for the (NH 2 ) group with the disappearance of the band (CN) at the same time, which gave a good indication of the reaction that takes place and the formation of the required product. For example, the FT-IR spectrum of the compound A 23 gave a characteristic absorption band for the (NH 2 ) group at 3300 cm -1 with the disappearance of the band (CN). As well as the bands that appear at 1665 cm -1 for the carbonyl group (C=O), at 1602 cm -1 and 1627 cm -1 for groups (C=C) and (C=N) respectively, also, the absorption band for (NH) group which appeared at 3157 cm -1 . In addition to the substituent group band (C-Br) which appeared at 607 cm -1 , also this compound was confirmed using the 1 H-NMR, which showed following chemical shifts (δ,