Introduction

Heterocyclic compounds constitute a key component in a lot of natural products, to name a few; vitamins, hormones, alkaloids, a wide range of antibiotics, pharmaceutical products, herbicides, anti-aging medicines, and plenty other industrial products of high importance (different types of dyes, corrosion inhibitors, stabilizing agents, sensitizers, etc.) [1]. Aryl diazonium salts are easily prepared, common, and highly applicable intermediates in synthetic organic chemistry because of their high reactivity and varied reactions. They are synthesized starting from primary aromatic amines by diazotization and coupling with aromatics like phenols (or primary aromatic amines). Azo dyes are industrially very important for technical purposes. Azo compounds have many applications such as their use as antioxidants, polymeric biodegradable pro-drugs, and many of them are used in the food, cosmetics, and drug industry as synthetic colorants [2]. Pyrazoles heterocyclic compound has a five-membered ring containing two nitrogen atoms prepared by many methods, one of these methods is the condensation of hydrazine or substituted hydrazine with α, β- unsaturated carbonyl compounds [3]. Azo compounds are well known for their medicinal importance and are recognized for their applications as antifungal, antidiabetics, antineoplastics, anti-inflammatory, antiseptic [4]–[6], and other useful chemotherapeutic agents. They are involved in many biological reactions such as inhibition of DNA, RNA, carcinogenesis, protein synthesis, and nitrogen fixation [7]. Azo compounds are valuable in the medicinal and pharmaceutical fields [8].                                   

Material and methods      

In this research, all starting material and solvents that used obtained from (Sigma-Aldrich, and Fluke Company, Germany). FT-IR spectra (KBr disc) were recorded with Affinity-1 Shimadzu as an FT-IR spectrometer using KBr pellets. ¹HNMR spectra scanned on Bruker Spectro spin ultrashield magnets 400 MHz instruments. 

Synthesis of 1-methyl-2-(2-amino-thiazole-4-yl) amino-4-oxo-4,5-dihydro imidazoline[9](1).

A mixture of thiourea (0.01 mol, 0.76 g) and (0.005 mol, 0.94 g) of 2-N-chloro acetamido Creatinine dissolved in 100 mL of CH₃OH in the flask and refluxed for 3–4 hr. The initial product cooled then poured into cold H₂O. The solid separation was collected by filtration. The residue obtained was dried and purified by using C₂H₅OH. 

Synthesis of 1-methyl-2-(2-diazenyl-2,4-dioxo-3-pentane--thiazol-3-yl)amino-4-oxo-4,5-dihydro imidazoline[10](2).

Compound [1] (0.21 g, 0.001 mmol) was dissolved in 2 mL conc. HCl. Cooled at 0 °C, then NaNO₂ (0.07 g, 0.001 mol) in (5 mL) of H₂O was added dropwise with stirring for 30 min. in an ice bath at 0-5 °C, then acetylacetone (0.1 g,0.001 mol), CH₃COONa(0.16 g, 0.002 mmol) in CH₃CH₂OH (5 mL) was added drop by drop. The mixture was then stirred for (30 min.). The product was purified by methanol. 

Synthesis of 1-methyl-2-[(2-(3,5-dimethyl-pyrazol-4-yl)diazinyl] amino-4-oxo-4,5-dihydro imidazoline derivatives[11](4-6).

NH₂-NH₂ derivatives (0.006 mol) were added to compound [3] (0.19 g, 0.006 mol) in (10 mL) EtOH. The mixture was stirred and refluxed for (10-12 hour), then the solvent was evaporated and the product was washed with H₂O then (C₂H₅)₂O.

Synthesis of 1-methyl-2-(2-amino-thiazole-4-yl)amino-4-oxo4,5-dihydro imidazoline[12](7).

A (0.01 mole) of pyrrole was dissolved in ethanol (10 mL) and CH₃COONa (0.3 g) was added and the mixture cooled and stirred. Cold solution of ArN₂Cl salt of compound (1) was then added dropwise for 1 hr at (0-5 °C) and the mixture kept in a cold place for 3 hr and then poured into ice H₂O.   

Synthesis of 1-methyl-2-[(2-(4-subs.)benzylidene] amino-1-methyl-4-oxo-4,5-dihydro imidazoline [13](8-9).

A (0.01 mol) solution of compound 1 was dissolved in 2 mL eq. HCl. It was cooled and 0.7 g of sodium nitrate was slowly added, 2-N-arylidene amino creatinine (0.01 mol) was dissolved in 10mL C₅H₅N and 0.3 g of sodium acetate was added to the mixture and then the mixture was stirred and cooled in the cold place. cold solution of ArN₂Cl salt of compound (1) was added dropwise for 1hr at (0-5 °C). The reaction mixture was kept in ice-bath for 3hr. The resulting dark-color mass was filtered, washed with H₂O until C₅H₅N removed. The product was purified from absolute CH₃CH₂OH.

Biological activity [14].

By using the agar plate diffusion method, the prepared compounds screened in vitro for two types of bacteria staphylococcus (gram-positive) and E-coli (gram-negative). Inhibition zone of bacterial growth show in Table 3.            

Results and discussion

In this research, synthesis of azo-compounds from 2-N-chloro acetamido creatinine was done, as shown in the Scheme 1. The azo-derivatives of creatinine measured by IR and some derivatives by ¹HNMR. 

SCHEME 1 Syntheses new azo-derivatives from creatinine

Synthesized compounds (1-9) were detected by spectral (FTIR & ¹H-NMR). In the compound (1) 1697 cm^-1 due to amide group [15]. The ¹HNMR of compound (1) δppm in DMSO-d₆ solvent showed singlet signal at δ(1.15) ppm due to (-CH₃) protons, singlet signal at δ(2.48) ppm due to (C=O-CH₂-N-CH₃) proton, singlet signal at δ(3.05) ppm due to (CH-S-thiazole ring)  singlet signal at δ(7.13) ppm due to (creatinine ring-NH- thiazole ring), and a single signal at δ(4.13) ppm due to NH₂ protons of thiazole ring. The presence of the band in compound (3) at 1546 cm^-1 indicates the formation N=N and 1740 cm^-1 that refer to C=O of diketone. In pyrazole compounds (3-5) the absorption band in compound (5), and ¹HNMR for compounds 5,6, and 7 are show in Table 2.

Orcid:

Raad M. Muhiebes:

https://www.orcid.org/0000-0003-0181-5837