1,3-Bis(p-carboxyphenoxy) propane/hexane (CPP or CPH) Preparation

Synthesis.

NOTE: The diacid molecules are very stable, so a large scale reaction is described. Adjust reagent amounts accordingly if you want to work on a smaller scale. Although the synthesis described is for CPP, the steps are identical for CPH. Simply use 1,6-dibromohexane instead of 1,3-dibromopropane in step 7.

Overall reactions:

1) Place 152 g (1.1 mole) of 4-hydroxybenzoic acid (HBA) into a 1000 ml 3-neck round bottom flask.

2) Dissolve 110 g (2.75 moles) of NaOH in 400 ml of DI-H₂O to prepare a 6.9 M solution. This large excess is needed to ensure deprotonation of both sites on the HBA. (CAUTION: this will get HOT – dissolve the NaOH in stages and/or chill the solution. Do not use more than the stated 400 ml of water. Once you add this to the flask and begin stirring, it will essentially be at maximum capacity).

3) Place the 3-neck flask in a heating mantle. Fit one of the necks with a condenser (making sure to grease the joint) and the center neck with an overhead stirrer (see Figure)

4) Turn on the water to the condenser. Pour the NaOH solution into the flask slowly and begin stirring to dissolve the HBA.

5) Fit the remaining neck with an addition funnel with at least a 60 ml capacity, again greasing the joint to ensure a good seal (see Figure).

6) Begin heating the solution until a gentle reflux is reached.

7) Put 50.8 ml (0.5 moles) of 1,3-dibromopropane (DBP) into the addition funnel. Cover the opening with a rubber septa. NOTE: If you want CPH use 77.2 ml (0.5 moles) of 1,6-dibromohexane instead of DBP.

8) Maintaining the reflux, add the DBP slowly – about 8-10 drops/minute.

9) Once all the DBP has been added, reflux the solution overnight. After the reflux, turn off the heat and cool the solution to room temperature.

At some point in the reaction, the solution should become heterogeneous and white precipitate will be obvious. This may occur once all the DBP has been added or not until the solution is cool and it crashes out.

Work-up.

1) Filter the solution and collect the precipitate.

2) Put the collected solid in a 2000 ml beaker and wash with ~ 1000 ml of methanol. This will remove the NaBr salts that formed during the reaction.

3) Filter the solution and collect the precipitate. Keep a small amount to analyze by NMR.

4) Put the collected solid in a 3000 or 4000 ml vessel. Set up the overhead stirrer. Add about 1500 ml of DI-H₂O and stir to dissolve the solid.

5) Continue the stirring and begin adding sulfuric acid. Precipitate should form almost immediately. Continue adding sulfuric acid until the consistency of the mixture becomes like cottage cheese. If stirring becomes very difficult, add more water.

6) Once no more solid crashes out, filter the solution and collect the precipitate. Lyophilize to dry. Common yield is about 50%.

7) NMR analysis can be performed on the salt form (kept from step 3) using D₂O as the solvent. Comparison of the integrals for the aromatic protons to those for the central propyl group will provide the overall % substitution achieved.