Chemistry 251 Laboratory -- Spring 2005
Liquid Crystal Project Home Page

Index

• Students working on this project
• Table of Reagents and Amounts Available
• Notes on Step 1
• Notes on Step 2
• Notes on Step 3

Synthesis and Characterization of Liquid Crystalline Benzoic Acid Derivatives

Faculty Mentor: Eric Scharrer

Reference: Neubert, M. E.; DeVries, A. Mol. Cryst. Liq. Cryst. 1987, 145, 1.

The liquid crystalline phase represents a unique state of matter; molecules in this state possess less order than molecules in the solid state, but more order than molecules in the liquid state. Liquid crystals are useful in displays for watches, calculators, lap top computers, etc. This project involves the synthesis of some 4-alkoxybenzoic acid derivatives. Once prepared, these compounds will be analyzed for liquid crystallinity using polarizing microscopy and differential scanning calorimetry (DSC) These techniques are commonly used by researchers in the field of materials science. The target compounds will be accessed using the three step synthesis shown below (Scheme 1). The first step involves a Fischer esterification of 4-hydroxybenzoic acid with ethanol. Alklyation of the hydroxy group is then carried out using S_N2 conditions. Finally, the ester is hydrolyzed under basic conditions. After acidification, the target compound is obtained. In order to examine how small structural changes affect liquid crystallinity, each group will be expected to prepare several different derivatives by varying the length of the alkyl chain.

Students Working on This Project

Table of Reagents and Amounts Available for this Project

The table below lists the chemicals that we will have available for this project. If you need something that is not on this list, consult with the mentor for your project. Also note the "Amount/group" column. This is the total amount of material available for each group to use on the project.

Reagent	Source	Amount/group	Location	Comments
4-hydroxybenzoic acid	Aldrich Cat. # H2,005-9	10 g	TA room	Irritant
iodohexane	Aldrich Cat. #23,828-7	6 g	TA room	Irritant, Light sensitive
iodoheptane	Aldrich Cat. #17,785-7	6 g	TA room	Irritant, Light sensitive
iodooctane	Aldrich Cat. #23,829-5	6 g	TA room	Irritant, Light sensitive
iodononane	Aldrich Cat. #25,186-0	6 g	TA room	Irritant, Light sensitive
iododecane	Aldrich Cat. #23, 825-2	6 g	TA room	Irritant, Light sensitive
iodoundecane	Aldrich Cat. #28,004-6	6 g	TA room	Irritant, Light sensitive
iodododecane	Aldrich Cat. #23,826-0	6 g	TA room	Irritant, Light sensitive
Sulfuric Acid (Conc.)			Under the hood	Toxic, oxidizer, wear gloves when handling .
Hydrochloric Acid (37%) (i.e. Concentrated HCl)			Under the hood	Corrosive, wear gloves when handling.
DMSO (Dimethyl sulfoxide)Ethanol			TA roomTA room	Wear gloves when handling DMSO. It is readily absorbed through the skin! This is especially important since you don't want to absorb any of the alkyl halide with the DMSO.

Step 1: Formation of Ethyl 4-hydroxybenzoate

1.  
   • 4-hydroxybenzoic acid (5 g, 36.2 mmol) was dissolved in 100 ml of Ethanol in a 250 ml round bottom flask equipped with a water condenser. Concentrated sulfuric acid (about 1 ml) was added and the solution was refluxed overnight (It's best to add this before you attach the condenser). After cooling to room temperature, water was added and the mixture was extracted 3X with ether. The aqueous washings were back extracted once with ether and the ether extracts were combined and dried over MgSO₄. This solution was then filtered and the solvent was removed to give a white crystalline material (3.34 g, 56% yield).
   • ¹H-NMR (acetone-d₆) 7.92 ppm (2H, d), 6.94 (2H, d), 4.32 (2H, q, J = 7.1 Hz), 1.36 (3H, t, J = 7.1 Hz).
   •  
   • Notes:
   • 1) This will be a common starting material for all of your derivatives. Since this reaction works well, I advise doing the first run with 4 g.
   • 2) Please note that the NMR spectrum of ethyl 4-hydroxybenzoate is obtained in deuterated acetone (it is not very soluble in chloroform).
   • 3) You will also need to obtain an IR spectrum and melting point on this product (and all of your products).

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     Step 2: Alkylation of Ethyl 4-hydroxybenzoate

      

     Ethyl 4-hexyloxybezoate

     
     
     

     • Ethyl 4-hydroxybenzoate (0.50 g, 0.0030 mol) was dissolved in 40 ml DMSO in a 250 ml round bottom flask equipped with a stir bar. Pulverized KOH (0.34 g, 0.0061 mol) was added and this solution was stirred for approximately 30 minutes and 1-iodohexane (0.79 g, 0.0038 mol) was added. The reaction mixture was stirred for 22 hours and then quenched with water (50 ml). Ether was added and the organic layer was washed 3X with water. Then, the combined aqueous fractions were back extracted with fresh ether. The combined organic layers were dried with MgSO₄, filtered, and solvent was removed by rotary evaporation to give a clear oil. The crude product was purified by flash chromatography (1:1 hexane: dichloromethane, R_f= 0.37) to give 0.43 g (57 % yield) of product as an oil.
       
       ¹H NMR (300 MHz, CDCl₃) 8.0 (d, 2H, J= 7.1 Hz), 6.9 (d, 2H, J=7.1 Hz), 4.3 (q, 2H, J= 7.1 Hz), 4.0 (t, 2H, J=6.6 Hz), 1.8-1.9 (mult, 2H), 1.2-1.6 (mult., 9H), 0.9 ppm (t, 3H, J= 6.9 Hz).
     •  
     • Notes:
     • 1) DMSO readily absorbs through the skin. Please were gloves when using this solvent. This is particularly important since you will be using DMSO in conjunction with alkyl halides (which are irritants)
       
     • 2) DMSO is miscible with water. We will have a special waste container for your DMSO/water waste.
     • 3) I would like you to look up alternative alkylation procedures using Beilstein.
       
       4) Some dialkylated product (hexyl 4-hexyloxybenzoate) may form. This is due to a small amount of ester hydrolysis under the basic conditions. In the crude NMR spectrum, look for a shoulder on the peak at 4.3 ppm. Fortunately, this byproduct can be separated using flash chromatography.
       
       

       Step 3: Ester hydrolysis

       4-nonyloxybenzoic acid

       • In a 100 ml round bottom flask, KOH (0.207 g, 3.48 mmol) was dissolved in 20 ml of ethanol. Ethyl 4-nonyloxybenzoate (0.51 g, 1.71 mmol) was added, the flask was equipped with a reflux condenser, and the reaction mixture was refluxed for 1.5 hours. The reaction was cooled and ethanol was removed by rotary evaporation to give a white solid. This material was redissolved in 30 ml of water and 3 ml of 6 M HCl was added. The carboxylic acid precipitated out and the flask was cooled in an ice bath. The product was collected by Buchner filtration and then recrystallized from ethanol to give 0.249 g (54% yield) of material.
         
         ¹H NMR (CDCl³) 8.06 ppm (2H, d), 6.93 (2H, d), 4.02 (t, 2H, J=6.7 Hz), 1.79 (2H, mult), 1.55-1.16 (12H, mult), 0.88 (3H, t).
     • Notes:
     • 1) Use the minimum amount of ethanol for your recrystallization. If you use too much, you won't recover much product.