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Synthesis of Heterobifunctional Carboxylic Acid PEG Polymer Silane
Jonathan Duhon
Introduction:
Heterobifunctional molecules possess a structure that allows for binding at two different
sites. Applications for these compounds include the linkage of macromolecules to surfaces and
site-specific targeting of drugs and the functionalization of nanoparticles for drug delivery. These
compounds are used extensively due to their lack of toxicity. When bound to other molecules,
PEG increases their solubility in aqueous environments to improve circulation times in vivo.
Experimental:
Obtain a 250 mL round bottom flask and set it atop a hot plate at 90 Β°C, spinning at 360
rpm with a stir bar. Weigh out 3 grams of PEG and place inside the round bottom flask. Clamp
the round bottom flask with a vacuum tube on the top, and a stopper on its side. Turn vacuum on
and let the PEG dehydrate for 24 hours. After 24 hours have past, let oil bath cool to 55 Β°C. Turn
off vacuum and hook up a bottle of THF to the nitrogen tank to ensure that no water gets inside
the round bottom flask. Syringe out 100 mL of the THF into the round bottom flask. Next,
weight out 181.6 mg of NaH and place inside round bottom flask. Let mixture react for 30
minutes, then gather .55 mL of tert-butyl-bromoacetate to put inside mixture. Let mixture react
for 24 hours at room temperature, spinning constantly.
After mixture has reacted at room temperature for 24 hours, transfer contents to another
round bottom flask that is 250 mL. Obtain a trap flask and clamp it to the Rotoevaporator, with
the new round bottom flask attached at the bottom. Turn on Rotoevaportor, vacuum, and turn the
faucet on low. Put the RPM to max, and the temperature of the Rotoevapor on 50 Β°C. To speed
up process, turn the temperature up. Once precipitation is done, take off the round bottom flask
(not the trap flask) and fill it with ether until mixture is observed. Retrieve a large filter sheet and
fold in half twice, then shape filter sheet into a cone. Place cone filter that was previously made
into a funnel, and filter into a 600 mL beaker. Set aside this filtered cone with solid precipitate.
Once precipitate is set aside, obtain clean column, DCM and MeOH. Get a 1000 mL
graduated cylinder and pour 900 mL of the DCM and 100 mL of the MeOH into the graduated
cylinder. Obtain two beakers and weigh out 245 grams of silica. Place half of the silica in one
beaker, with the other half of the silica in the other beaker. Pour mixture of DCM and MeOH
into the two beakers with silica, then pour this mixture into the column. Keep pouring DCM and
MeOH mixture into column until there is a uniform band that forms in the column. Take
precipitated product in cone filter, and scape into a round bottom flask. Dissolve this precipitate
with the DCM and MeOH solution. Once precipitate is dissolved, obtain pipette and rubber
stopper to slowly drip mixture alongside of the column until a ring forms in column. Fill the rest
of the column up with the DCM and MeOH mixture. Make fractions of this solution in the
column into around 75-100 test tubes. Use TLC plates to locate the product in the reaction by
using four spots on each TLC plate. Use DCM and MeOH compound in TLC plates. Once
chromatography is done, place plates in (amber bottle) and use blowtorch.
From the use of TLC plates, the product in the fractions can easily be located. Place the
test tubes with the product inside of a 250 mL round bottom flask and place in Rotoevaporator
machine again at the same RPM and temperature. Once complete, take round bottom flask and
mix chloroform inside of it. Take mixture and place inside NMR tube to see if the correct
product was synthesized.
Observations:
250 mL round bottom flask atop hot plate with PEG, THF, NaH, and tertbutylbromoacetate
Discussion:
3 πππππ ππΈπΊ (1 πππ ππΈπΊ
2000 πππππ ππΈπΊ) (
1 πππ πππππ’ππ‘
1 πππ ππΈπΊ) (
2113 πππππ πππππ’ππ‘
1 πππ πππππ’ππ‘)
= 3.1695 πππππ πππππ’ππ‘
. 629 πππππ
3.1695 πππππ β 100 = 19.85 %
. 539 πππππ
3.1695 πππππ β 100 = 17.01 %
. 492 πππππ
3.1695 πππππ β 100 = 15.52 %
β’ The calculation for the percent yield for this reaction is shown above. Dimensional
analysis was used to find the theoretical yield of the synthesis. Once that was calculated,
a ratio was used to find the actual percent by dividing the actual yield by the previously
calculated theoretical yield then multiplying the decimal by 100. The three best percent
yields are shown above. Problems with this synthesis include:
β’ Incorrect vacuum setting
β’ Incorrect cooling temperature
β’ Incorrect round bottom flask placement
β’ Incorrect product filtration solvent
β’ Incorrect uniform ring formation of product in column
β’ All of the above could have the potential in receiving a low percent yield for the synthesis
due to possible error
Infrared spectroscopy was used to determine the different functional groups inside the
molecule. An alcohol, ester, and carbon-hydrogen stretching are present due to the broad peak at
3000, broad peak at 1700, and small peaks at 3000 respectively. To retrieve more information on
the structure of the molecule synthesized, proton NMR was used to differentiate the hydrogens
that are inside the molecule. The proton NMR showed important peaks at 1.4, 3.6, and 4.0. The
peak at 1.4 was determined to be the tert-butyl group at the end of the molecule. The methine
peaks at 3.6 and 3.7 are the hydrogens next to the alcohol at the end molecule. The last hydrogen
at 4 is the methine group next to the carbonyl. Carbon NMR was used to differentiate the carbons
that are contained inside the molecule. The significant peaks on the carbon NMR appeared at 28,
65, 66, and 70. The peak at 28 was determined to be the carbons on the tert-butyl group on the
molecule. The peaks at 65 and 66 were the carbons apart of the ester inside the molecule. The
last carbon had a peak at 70 which is the carbon next to the alcohol group in the molecule.