INTRODUCTION:

Amoxicillin is one of the most important heterocyclic compounds. It has two nitrogen atoms (N) and a lot of different rings. It has a lot of different properties in pharmaceutical chemistry because it has the primary amine group (NH₂), which can be used in many reactions, like Schiff reactions¹.

The resulting compounds where they are liquid crystals of this type of organic compound that pass through an intermediate state between the regular solid and the random liquid that is known in nature according to the nature of the formation. The thermotropic liquid depended on the temperature, and scientists found many compounds that go through this intermediate state by increasing the temperature². It is classified into three phases based on molecular organization: the nematic phase, which is the simplest of the phases in the form of strips³, the cholesteric phase, also known as the twisted nematic phase⁴, and the semticite phase, which is similar to soap because of its viscosity, and this phase is found in several types, SC, SA, SB,.... HtoSK, in alphabetical order^5,6. The formation of a thermotropic liquid crystal (non-amphiphilic) depends on temperature. The change in temperature leads to the emergence of intermediate phases, which are known as compounds that exhibit at least one phase between the melting point and an isotropic liquid^7,8.

Isotropic liquid → liquid crystal intermediate phase → solid phase and these compounds that show these phases in the states of heating and cooling are called bi-state. Intermediate Enantiotropy⁹. As for the compounds that show the intermediate state by cooling only, they are called monomers of the intermediate state. The geometric shapes of the thermotropic molecules are either rod-like or flat like plates (like lath)¹⁰. Some compounds give the intermediate phases of two classes together: thermotropic and lyotropic. Ionomeric Liquid Crystal¹¹. Liquid crystals possess some properties of liquid phases and solid forms, such as the property of flow of the liquid and the property of double refraction of the solid crystal (fringe bier). This is important in applications of photoelectricity as well as the important electromagnetic property (electricity ferroelectric). concerning the crystalline and chemical composition of the substance. Also, the amplitude of spontaneous polarization and the electrical changes with temperature (thermoelectric effect) are used in a photoelectricity display^12,13.

Experiment:-

1-Acids react to prepare alkyl bromide:

Prepared of Alkyl bromide by taking acid HBr, and adding H₂SO₄, then adding (number of mol) from each of the: (butanol, pentanol, hexanol, and heptanol), and adding volume of H₂SO₄, and heating it for many hours. After separated the mixture, dried by calcium chloride anhydrous¹⁴.

2-Reaction of alkyl bromide with para-hydroxybenzaldehyde to form alkoxides (4, 5, 6, 7 and 8).

A hydroxybenzaldehyde (number of mol) its dissolve in ethanol. After that adding potassium hydroxide, and adding the appropriate alkyl bromide. The mixture was placed for an hour on the electric heater and magnetic stirred, and the product was extracted by petroleum ether, so the color of the product was yellow¹⁵.

3-Preparation (2S,5R,6R)-6-{[(2R)-2-actamide-2-(hydroxyl phenyl)acetyl]amino}-3-,3-dimethyl-7-oxo-4-thia-1azabicyclo[3.2.0] heptane-2-carboxylic acid.

In a beaker containing 500ml of water, 18.3ml of concentrated HCL, and (gm, 0.22mol 23.98) (2S, 5R, 6R) - 6-{[(2R)-2-amine- 2-(4-hydroxyphenyl) acetyl] amino} - 3,3-dimethyl- 7-oxo-4-thia-1-azabicyclo [3.2.0] heptane-2-carboxylic acid pure Stir until dissolved, then add 25.6ml of acetic anhydride (drops of H₂SO₄ acid were added). As soon as the solution was made (33gm of sodium acetate in 100ml of water), it was poured on to it. Then, it was stirred vigorously, put on ice, and cooled down on the Buechner apparatus, washed with cold water, dried, and used for the next experiment¹⁶.

4-Preparation (2S,5R,6R)-6-{ [(2R)-2-actamide-2-(4-alkokxyphenyl)acetyl]amino}-3-,3-dimethyl-7-oxo-4-thia-1azabicyclo[3.2.0] heptane-2-carboxylic acid.

The first experiment compound (3.75gm, 0.025mol) was dissolved in 15 ml of ethyl alcohol in a round base level flask with a capacity of 100ml and slowly stirred with a magnetic stirrer until a potassium hydroxide solution (1.85gm, 0.033mol) was dissolved in a minimum volume of 1.5ml water, then gradually added the appropriate alkane bromide solution (0.025mol). Warm up the mixture using a suitable refining condenser and stir for more than 1 hour. Additionally, give the mixture a sufficient volume of distilled water and cool it well in an ice bath. The formed pink precipitate was filtered out ¹⁷.

5-Preparation (2S,5R,6R)-6-{[(2R)-2-amino-2(4-alkokxyphenyl)-acetyl] amino}- 3,3-dimethyl- 7-oxo- 4-thia- 1- azabicyclo [3.2.0] heptane- 2-carboxylic acid.

In a round-bottom flask (100ml), heat a mixture consisting of the previous compound (12.5ml) and (0.025 mol) of ethyl alcohol by stepwise heating using a suitable refining condenser while stirring with a magnetic stirrer. A solution of potassium hydroxide (20 M) was added to the hot mixture slowly, and the mixture was kept hot and stirred for three hours. Then, the white precipitate was filtered out^18,19.

6-Synthesis of Schiff basis compounds from alkoxyAmoxicillin.

Compound of alkoxides Amoxicillin dissolved in ethanol, and acetic acidglacial, and then adding equal moles to alkoxides Amoxicillin from (4-alkoxy benzaldehyde, 4-hydroxy benzaldehyde, and 4-chlorobenzaldehyde) dissolvedin ethanol. The mixture was placed on the electric heater, and magnetic stirred (8 h) at 120 C. The product has been recrystallized^19,20.

Figure 1. showing the reaction mechanism

FT.IR-dataof compounds:

In the spectrum of the original compound ^21,22.23, it can be seen the presence of two double bands with the primary amine group (NH₂) at the site (3456-3525), as well as the presence of an alcoholic (OH) group, as well as the usual (OH) group of the acid group, which appeared at the sites (2824-3043) and the CH-aromatic group (CH-3043). The carbonyl group (CO) of acid at (1776) and (C=C) at (1583), the (NH) group at (317), the carbonyl group (CO) of ketones at (1687), and the carbonyl group (CO) of amide at (1510) can all be found at the site (2970).

When preparing acetamide (NHCOCH₃) from the amoxicillin compound, we notice the disappearance of the top of the (NH₂) group and the survival of two groups (NH-), which appeared at (3452), acidic (CO) at (1776), and carbonyl group (CO) of ketone at (1685). As for the spectrum of the compound prepared from 4-alkoxy Amine, you notice the presence of the primary amine group at the site (3471-3481). As well as the presence of the secondary amine group (NH-) at the site (3328) and the peak at (3550). We return to the aromatic (CH) and note the presence of the peak at (1075), then we return to the etheric CO, in addition to the presence of a group (C-O-C) displacement due to the groups withdrawing to their content, which appeared at (1411-1448). As for the spectrum of the compounds resulting from the reaction of (4-alkoxy amine) with (4-alkoxy benzaldehyde, the peak (3435) returns to the hydroxyl group and the acid in the original compound, and we note the disappearance of the amino-functional group as a result of its interaction with the aldehyde functional group and the appearance of the new azomethine group peak at the position (1600) that is sharp and clear. In addition, the acid carbonyl remains at (1693), the ketone carbonyl at (1635), and the amide carbonyl at (1577).

Figure 2. FTIR analysis ofAmoxicillin

Figure 3. FTIR analysis of Acetamide

Figure 4. FTIR analysis of alkoxy Amoxicillin

Figure 5. FTIR analysis of Alkoxy benzaldehyde

Figure 6. FTIR analysis of Schiff base

Table 1. shows the structural formula and some physical properties of the prepared compounds with polarized optical microscope

No. of comp.	MP.	Color	Yield	Chemical structure
1	296	Yellow	65%
2	293	Yellow	68%
3	290	Yellow	70%
4	286	Yellow	65%
5	283	Yellow	80%
6	279	Yellow	75%
7	293	Yellow	73
8	291	Yellow	85%
9	290	Yellow	67%
The images of a polarized optical microscope^{24, 25}

The images of a polarized optical microscope^{24, 25}. A-nematic phase at 275°C by cooling, B-nematic phase at 260°C by cooling, C-Liquid crystal form (unidentified smectic) at 250°C by cooling, D-nematic phase at 240°C by cooling, E-nematic phase at 245°C by cooling, F-Smectic phase at 247°C by cooling, G-nematic phase at 255°C by cooling, and H-nematic phase at 230°C by cooling.

The H1NMR-Spectrum showed a signal at (7.811) that returns (CH=N) a proton from the Imine group in the compounds, as well as a signal at (12,238) that returns (COOH) the proton of the carboxylic acid group of amoxicillin acid, as shown in the table ²⁶.

Table 2. H1NMR-data (δ ppm, DMSO) of some compounds.

Comp. No	HNMR (only important groups1)
1	(OH) of carboxylic acid, (8.579)proton of (C=O-NH2), proton at (0.776-0.719) to (CH2), (CH3),(CH=N) proton in(7.811) to imine group, proton in (6.778-7.766) to phenyl ring.
2	(OH) of carboxylic acid,proton in (8.50) to(C=O-NH2), proton in (0.776-0.719) to (CH2),(CH=N) proton in (7.814) to imine group,proton in (7.814), tophenyl ring,proton in (6.59) to phenol group.

Applications Industrial:

Industrial Applications Liquid crystals are used in display devices because of their important advantages, including small size, high adaptability to rapid display changes, low energy consumption, and variation in physical characteristics. The nematic phase is used, which is more sensitive to the electric field, and this feature is used to benefit advanced display systems because the nematic phase is one-dimensional, so it can respond directly to the electrical stimulus. Research has proven that fish chiral liquid crystals have a high photoelectric response, so it is one of the most popular and has a future in display media applications. One of the important industrial applications of liquid crystals is their use in smart windows, as they work in smart windows to control the amount of light passing through them by changing the response of liquid crystals to electrical charges ²⁷.

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Received on 22.05.2022 Modified on 30.07.2022

Research J. Pharm. and Tech 2023; 16(4):1761-1766.

DOI: 10.52711/0974-360X.2023.00290