Title: Intramolecular and Intermolecular Cyclopropanation Studies using Ethyl 2diazo3oxonon8enoate and Cyc
1 Intramolecular and Intermolecular
Cyclopropanation Studies using Ethyl
2-diazo-3-oxonon-8-enoate and Cyclohexene
- Presented by Matthew Shelnutt
2Research Objectives
- Nature of the competition occurring inter- and
intra-molecularly during a cyclopropanation. - Reaction utilizing rhodium (II) acetate as a
catalyst and cyclohexene as an intermolecular
competitor. - The length of the carbon chain varied per
research student.
3Uses of Cyclopropanation
- Cyclopropanation reactions are used in a variety
of fields - They provide key intermediates in the synthesis
of pyrethroid insecticides such as permethrin.
Permethrin is commercially available for use in
pet sprays and crop dusting. - Pharmaceutically, they provide the cyclopropanes
found in antifungal drugs such as ambruticin.
Permethrin Structure
4Intended Products
We hoped to end up with these products according
to the following mechanisms, including the
synthesis of all of the starting materials
5Overall Chemical Equation to form the Dienolate
Reaction Mechanism
6Overall Chemical Equation to form the Keto Ester
Reaction Mechanism
ethyl 3-oxonon-8-enoate
7Overall Chemical Equation to form
para-Toluenesulfonyl azide
Reaction Mechanism
8Overall Chemical Equation to form Ethyl
2-diazo-3-oxonon-8-enoate
Reaction Mechanism
9Cyclopropanation using Ethyl 2-diazo-3-oxonon-8-en
oate, Cyclohexene, and a Rhodium (II) Catalyst
10Laboratory Synthesis
- Initial synthesis proceeded as follows
- LDA in a 200 mL round bottom flask
- 0 C, Nitrogenous atmosphere
- Ethyl Acetoacetate added dropwise with stirring
- 5-bromopent-1-ene added dropwise to the resulting
solution to form dienolate
Synthesis Apparatus
11Laboratory Synthesis
- Wash with 10 sulfuric acid
- Solution extracted 3 times with ether
- Ether collected and dried over BaSO4
- Now anhydrous solution placed on rotary
evaporator to remove solvent.
Liquid-Liquid Extraction
The Product
12Purification
- To isolate our compound from impurities, we
implemented the technique of gravity column
chromatography. - The solvent used was a mixture of 2 Ligroine 1
Petroleum Ether 1 Ethyl Acetate
Column Chromatography Purification Apparatus
13Further Purification
- The initial column showed little separation. A
new column was set up, but this time with a new
solvent. Possible choices were - 3 MTBE 1 Isopropyl alcohol
- 3 Methylene Chloride 1 Methanol
- 3 Hexanes 1 Ethanol
- Toluene, with a methanol flush
- Toluene with methanol flush chosen to run the
column.
Running TLC Plate
14Vacuum Distillation
- Solution added to round bottom flask, and fitted
with condenser tube. - Hot oil bath made with electrical current.
- Heated so that impurities with lower boiling
points will evaporate and condense out.
Distillation Apparatus
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17GC/MS Analysis of Products
- Product retention time is 6.310.
- Extremely small peak cant be seen
- Mass Spec. data shows molecular weights of all
ions detected. - Includes 198, the peak for the product.
- Larger ions peaks appear to be rearrangements of
the product. - The product wasnt there in enough quantity to be
used, and so the procedure was deemed
unsuccessful.
18Laboratory Synthesis II
- Creating our own starting products might have
been a little too ambitious. - Using the standard Grignard reaction procedure,
we decided to create an enoate compound using
bromobutane and Magnesium to create Grignard
reagent, and then reacting that with diethyl
amine and 4-bromo-pent-1-ene to produce the
desired dienoate as shown
19Grignard Mechanism
20Grignard Mechanism CONT.
Ethyl 3-oxooct-7-enoate
21Grignard Procedure
- Typical Grignard Magnesium chips, ether, and
bromobutane are added to 500 mL round bottom
flask. - Reflux started by mild heating.
- Diethyl amine added in dropwise to a the
resulting Grignard reagent at 0 C. - Ethyl acetoacetate added dropwise at 0 C, and
stirred for 30 minutes. - Allyl bromide is added at 0 C and allowed to stir
overnight to ensure reaction completion. - Rinsed with acid to dissolve remaining solid,
extracted using ether, and run through the GC.
Synthesis Apparatus
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24In the future..
- In the process of attempting to synthesize a
suitable dienoate for our competition reactions,
we discovered how difficult it was to use
chemicals such as LDA to get a meaningful yield. - To correct for this, and one of the last
syntheses done, we utilized a Grignard mechanism
to produce the dienoate. - We are going to continue research on the
production of enoates using Grignard-like
reactions to make a more undergraduate friendly
way to produce them. - 4 or 5 other alkyl halides will be used in a
similar process to ensure the same great yield
and to ensure reproducibility.
25Recognitions
- Dr. Hornbuckle, my wonderful advisor
- Clayton State University
- The Natural Sciences Faculty and Staff
- The Department of Natural Sciences for funding
our research - Dr. Furlong, Department Head
- Joe Holak, partner
- Hieu Dinh, partner