¹See Tarcha, et al., J. Polym. Sci, Part A, Polym. Chem. 2001, 39, 4189.

Synthesis.

NOTE: Although the synthesis described is for (1,3-bis(p-carboxyphenoxy))propyl dimethacrylate (CPPDM), the steps are identical for CPHDM. Simply use 1,3-bis(p-carboxyphenoxy)hexane instead of 1,3-bis(p-carboxyphenoxy) propane in step 2.

Overall reaction:

1) Determine the amounts of reagents. Use 2.2 equivalents of methacryloyl chloride (MACl) and triethylamine (TEA) relative to the moles of 1,3-bis(p-carboxyphenoxy) propane (CPP) you will be using.

2) Add CPP to a 3-neck round bottom flask (of the appropriate size) fitted with an addition funnel on the center neck and containing a stir bar. Cover the addition funnel with a rubber septa. NOTE: If you want CPHDM, use 1,3-bis(p-carboxyphenoxy) hexane for this step.

3) Place the set-up on top of a stir plate in a dish that will accommodate an ice bath.

3) Dilute the CPP with approximately 10 times the amount of methylene chloride (MeCl) as CPP (e.g. 15 g CPP in 150 ml MeCl). The CPP will not dissolve. The solution will look like a suspension.

4) Fill the dish with ice to chill the reaction.

5) Add the TEA and cover the remaining necks with rubber septa. Bubble with inert gas for 1 hour (argon or nitrogen) while stirring at 0°C. The majority of the CPP should dissolve at this point, leaving a slightly heterogeneous, possibly light brown solution.

6) Remove the bubbling gas line. Add the MACl to the addition funnel via a syringe.

7) Add the MACl to the CPP solution dropwise over about 1 hour, depending on the scale.

7) Once addition is complete, stir for 4 hours while maintaining the ice bath.

Purification.

1) Remove any visible triethylamine-hydrochloride salts via vacuum filtration.

2) Remove any remaining salts by extracting the organic layer with 2 washes of saturated sodium bicarbonate followed by 2 washes with deionized water. The volume of the aqueous layer should be about equal to that of the organic layer (e.g. 250 ml of MeCl = 250 ml of water).

3) Collect the organic layer and dry over sodium sulfate.

4) Remove the drying agent via gravity filtration.

5) PRIOR TO ANY FURTHER STEPS - add some type of inhibitor. This will prevent significant oligomerization of the anhydride monomer. Good inhibitors include 2+3-t-butyl-4-methoxy-phenol or if cellular compatibility is desirable, Vitamin D can also be used.

6) After addition of the inhibitor, use a rotovap to remove the MeCl, preferably at 0°C using a strong vacuum to minimize the chances of oligomerization.

7) The CPPDM can be characterized via NMR using chloroform-d as the solvent. The methacrylation efficiency can be calculated based on the ratio of the integrals for the vinyl resonances to those for the aromatic protons. Common % methacrylation = 90-95%.