Synthesis & Characterization of Heterocyclic Amide Derivative via Ugi Reaction

Synthesis of heterocyclic amid derivative (cyclohexanecarbox-amide) by the reacting four-compound [Formaldehyde], [N-(phenethyl)formamide], [Cyclohexanecarboxylic acid], and [Creatinine] as amine source. This reaction is practical extension of (Ugi reaction). The derivatives have been performed with other catalytic agents under temp (-10°C) and the organic synthesis was monitories by TLC [thin layer chromatography] and the formation of final compound proofed by Nuclear Magnetic Resonance Spectra [1HNMR] [13CNMR] BRUKER (500MHz, CDL3), (125MHz, CDL3 and Infra-Red spectra [FTIR] (shimadzu).


INTRODUCTION
Ugi reaction one of most important reactions in organic synthesis based on the four -chemical compound which is react together so this reaction [1,2] [multi component reaction, MCRs], the use of multi component reaction is expand in contemporary chemical biology and medicinal chemistry and developed to synthesized diverse type of drugs.This reaction very strong and include condensation of four compound (Amine, Aldehyde, Carboxylic acid, isocyanides) [3,4] at the end of MCRs we will collect substituted peptide as seen in Figure 1.
The [isocyanides] is unlike the other three compounds is commercially restricted so its formed by pulling out [H2O] [7,8] using dehydrating agent of Formamide derived from Amine as seen in Figure 2.
The reaction depends on the nature of Carboxylic acid.For example, the Carboxylic acid formed (α-Amino acyl amide) this reaction become so wide and more interested by isolation of functionalize structure generating of isonitrile compound which used as intermediate to the schistosomiasis drug [5,6].After that transferred to (separation funnel) after dissolved in [DCM] then washed by water saturated with (sodium perchlorate) [2*20ml] then dried [sodium Sulfate Na2SO4] (10g) as drying agent then solvent removed under reduced pressure [14,15].

RESULT AND DISCUSSION
Reagent and solvents which used in this preparation are commercially supplied from (SigmaAldrich USA) and used without further purification.The reaction was monitored by [TLC EMD gel] visualized with iodine fume.
The final product was proofed by (infra-red) spectra [FT-IR SHIMADZU] the table below shows the FT-IR data (Table 2).Multi component reaction are very useful synthetic tools for combinatorial of (Ugi) four coupling reaction have great for accessing synthetic heterocyclic chemistry compound potential bioactive scaffolds building blocks for complex natural products and its analogues to test for their ability in treating various diseases such that (Praziquantel) was developed by [Bayer AG] medication used to treat a number of types of parasitic worm infections [12].
Collecting the result solution by [1000ml] round-bottom-flask and concentrated by rotary evaporation [35 0 C 7.1 mmHg].The final -step the crude product (red/brown) oil purified by silica gel chromatography by [Hexane and Ethyl estate as solvent.Collected fractions concentrated by vacuum filtration for 6hrs (45°C 0.02 mm Hg) yield reddish brown solid crystals with purity [46%] as heterocyclic amid derivative seen Figure 3 reaction equation.

Table 1 .
Physical properties of formed compound