Chemical Sciences

The papear include synthesis of four of pyrazole derivatives from the reaction of chalcones with substituted hydrazine. FT-IR, Mass, and H 1 -NMR spectra identified the compounds. The new pyrazoles (Py1-Py4) studies as anti-bacterial against negative and positive gram stain. The prepared compounds gave the high and different abilities to inhibit these bacteria according to the type of the substituted group. The inhibition ratio of pyrazole substituted by the COOH group (Py1) was 28 mm, while pyrazole substituted by OH in the meta position was less able to inhibit.


ydrazine.FT-I
, Mass, and H 1 -NMR spectra identified the compounds.The new pyrazoles (Py1-Py4) studies as anti-bacterial against negative and positive gram stain.The prepared compounds gave the high and different abilities to inhibit these bacteria according to the type of the substituted group.The inhibition ratio of pyrazole substituted by the COOH group (Py1) was 28 mm, while pyrazole substituted by OH in the meta position was less able to inhibit.

Introduction

Heterocyclic compounds are included in the composition of many compounds.They have a wide range f biological activities as antioxidants, agricultural chemicals, and veterinary products.They also have clinical applications described as anti-fungal, anti-viral, anti-inflammatory, and anti-tumor drugs.That is what made researchers focus on preparing these compounds (1) .The most important heterocyclic compounds have five-and six rings.Pyrazole compounds have biological activity and are

cluded in the synthesis of many pharmaceutical compounds.

P
razole is considered a heterocyclic organic compound with a five-membered ring consisting of three carbon atoms and two adjacent nitrogen atoms and has two double bonds (2) .pyrazoline is a pyrazole added to two hydrogen atoms and contains only a double bond (3) .In comparison, pyrazolidine is a pyrazole involved four hydroge atoms and thus does not have a double bond (4) .Figure (1).


Figure (1) structure of pyrazole, pyrazolin and pyrazolidin

Pyrazole derivatives have biological and pharmacological activity.For example, they are used as antidepressants (5) , for epilepsy, convulsions, infections, microbes, fungi, bacteria, cancer, and antioxidants (6) .It is also used as apain relief (7) , antipyretics (8) , and blood pressure and cholesterol suppressants (9) .

In the last of nineteenth century, Fischer and Knoevenagell described the reaction of acrolein with phenylhydrazine to prepare a compound of the type (2pyrazoline).The scientist (Auwers) (10) and his colleagues confirmed that the product of this reaction is (1-phenyl-2-pyrazoline).After these pioneering studies in the last century, many (2-pyrazoline) were prepared by reacting (β,α-enone) with hydrazines.This convenient and straightforwa

preparation method is one of the most common methods of prepa
ing (2-pyrazoline) (11) .

Due to the multiplicity of use of pyrazole compounds and its derivatives,the researchers were interested in their preparing them.The researchers

Shehab) prepared pyra
ole derivatives through the interaction of Chalcone compounds with hydrazine and phenylhydrazine compounds, and they were effective as corrosion inhibitors (12) .schemes (1).


schemes (1) prepared cycles by researcher (Khudhair & Shehab)

Also, the researchers (Khalil & Refaat) (13) prepared a series of pyrazoline derivatives and studied their effectiveness as an anti-inflammatory on mice.the equation (1).


…. (1)


Materials and Methods:

The incorrect mel

ng point was measured with the
Electrothermal melting point apparatus.I.R. spectra were recorded using KBr disk on Shimadzu FT-IR-8300 spectrophotometer in Basrah University, Science college, Chemistry department.H 1 -NMR spectra were taken at Tehran University (Iran) on Avance DRX 500 MHz (from Bruker), using dimethylsulphoxide (DMSO) as the internal standard.The antibacterial experience was done on Biotech Technology in Basrah(Iraq) .

Preparation of Chalcones (14) An equivalent mixtur (0.01m

le) of 2,4-dichlorobenzaldehyde (1
72g) and acetophenones was dissolved in 45 ml of Ethanol (96%).25 ml of aqueous NaOH 20 % was added gradually to the mixture.The reaction mixture was stirred at 0•C overnight.100 ml of cold water was added to the mixture and acidified with acetic acid.The precipitate was filtrated and recrystallized in absolute Ethanol.ethyl acetate: n-hexane (3:1) was used as eluent solvents.Equation 2….(2)


Preparation of Pyrazole Compounds

Equivalent moles (0.01 mol) of chalcone H with hydrazine derivatives, Table (1) according to the weights shown in Table (2) were dissolved in around bottom flask with (35) ml of absolute Ethanol with continuous mechanical stirring.A few d

ps of glacial acetic aci
were added to the mixture with stirring.Reflux was carried out for 3-6 hours, where the reaction was followed up by TLC (thin layer chromatography) technique with ethyl acetate: n-hexane (3:1), and the R f value was calculated.The mixture was left to cool, then filtered,

ried, and recrystallized
using absolute Ethanol, and the resultant yield was calculated, and its melting point was measured.


Anti-bacterial Activity

ehT

ffective
ess of the prepared compounds on the most common types

bacteria that develop from diseases, namely, Escherichia coli and
taphylococcus aureus, with two concentrations (500-1000 µg/ml).DMSO is used as a solvent and control for the hole sensitivity test.


Results and Discussion:

Pyrazole derivatives were prepared using cyclization of chalcone H with hydrazine derivatives to give the

..(3)

According to the propose
mechanism in the diagram (1)


Diagram (1) the proposed mechanisms of prepared pyrazole compounds

The physical properties of prepared compounds are included in Table (3).Table (4)  shows the structure of the prepared pyrazole compounds.The products were characterized by infra-red (Table5), 1 (Table 6 and Figures 1-4), and Mass spectra (Table7).


Table (5): FT-IR Spectra data of prepared compounds


IR data(cm


Anti-Bacterial Activity


Staphylococcus aureus bacteria

The activity of pyrazole compounds was tested on Gram-positive Staphylococcus aureus, where all compounds showed high inhibition activity as shown in Table (8), and Figure We found compounds that have withdrawing groups (COOH and NO 2 ), the Py1compound is more effective than the Py2 compound.It was also noted that the compounds containing the donor group (OH) in the para-site are more effective than the compounds containing the withdrawing groups (COOH and NO2), which indicates that the activity depends on the charge of the compound, meaning that the attachment is electrostatic between the compound and the target (the receptor inside the bacteria ) so that the higher the charge, the more effective the inhibition, because the NO2 group was mor

eness decreased, while the
COOH group was less cloudy, the charge increased and the efficiency increased.Table (9) (15) Table (9) values of the electronic effect of the donor and withdrawing groups


Table (8) Inhibition Zoon of the prepared pyrazoles against S-aureus bacteria

In the case of the donor groups (compounds containing the OH group), the activity of the substituted compound in the para-site Py3 was more effective than the substituted compound in the meta-site Py4 (Figure 6), which indicates that the steric shape of the compound affected the way it binds to the target (16) .


Figure (6) Geometry of the Py3 and Py4 compounds


Escherichia coli bacteria

The activity of the prepared pyrazole compounds was tested on Gram-negative Escherichia coli bacteria, where all compounds showed high inhibition activity as shown in Table (9), and Figure (7).When comparing the compounds (Py1) containing the COOH group (the least drawn) was more effective than the compound (Py2) containing the NO2 group