linolenic+acid



Since we need to begin the reaction with no greater than 8 C, we could start with 1 Bromo-2-octyne and add 8 Chloro-1-octyne which gives 1-chlorohexadecadiyne 7, 11. Could we start it in same way Linoleic acid is developed since it is so similar? --April Weliever

Source: Synthesis of Unsaturated Fatty Acids: Linoleic Acid by Walter Gensler and George Thomas

Using the same article, 1-chlorohexadeca-7,11-diyne is reated with 1. potassium iodide and 2. malonic ester to produce octadeca-9,12-dienoic acid. That is hydrolyzed with a metal catalyst to produce lenoleic acid C18H32O2. -Meaghan Bartlett

Source: Gensler, Walter J. and Thomas, George R. Synthesis of Unsaturated Fatty Acids:Linoleic Acid. Oct. 1951

April, I was thinking on the way home about the possibility of turning the linoleic acid into linolenic acid? Since there's only a 2 H difference and one double bond, I wonder if there's a way to remove 2 Hydrogens leaving a carbon carbon double bond? The hard part may be targeting it to that one spot. -Meaghan

April, and Meaghan: THis strategy of using alkynes is exactely what I have envisioned. I am glad that you found a reference that treats it this way. I think that the lindlar catalyst could be used all in one step once all of the alkynes are attached together. Since they are not conjugated, they should act as isolated alkynes and each react individually. The nice thing is that lindlar catalyst should be very specific to alkynes and not react with anything else on the molecule. Nice research. If you need help putting this into a visual synthetic scheme, please tell me. The type of dialogue that you are having on this synthesis is what I had hoped would happen with the wiki format. Bruce Bondurant

In looking at the previously referenced article and the sigma aldrich site, it looks like this could be a way to synthesize linolenic acid:

1. Combine 3-bromo-1-propyne with 8-chloro-1-octyne to form 11-chloro-,1,4 diundecyne. 2. Add 1 bromo-2-pentyne and this should form 1-chloro- (7,10,13) trihexadecyne. 3. To form linolenic acid, complete the process with a malonic ester synthesis.

From my research, this seemed to be a way to derive it....April Weliever

I drew the synthesis in ChemShetch but when I transferred it over to the wiki, it came out distorted. Please let me know if you can't read it so I can try to fix it. All the steps here are described above by April. -Meaghan Bartlett April, It's been great working with you on this! Good Luck on the final! -Meaghan



Meaghan and April: This is a really neat synthesis that you have come up with. The step-wize addition of 3-bromo propyne is a good idea, and the SN2 with the malonic ester is excelent. This is condensation chemistry that you will study in Chapter 22 at the end of next semester It is realy powerful, because it provides a carbon nucleophile with a pKa of about 10 to 12. the extra carboxyl group of the malonic acid decarboxylates spontaneously when you hydrolize in dilute acid. The only things I would suggest are that you edit the second to the last figure so that the triple bonds are in the right places, and that you put int he reaction conditions and reagents. Bruce Bondurant

Dr. Bondurant, Something went wrong when I uploaded my picture. Your linolenic acid structure is replaced with mine. I don't know if it is just my computer or not. Ryan: I think it was that your file had the same name. I re-uploaded it with a different name and it seems to work fine. I think this synthesis is on the right track. My only suggestion is that you may want to wait until you do all of the acetylide chemistry before you oxidize to the acid. The carboxyl group is reactive toward the acetylide, but if you make a tert butyl ether or a tetra-hydro-pyranyl (THP) derivative of the alcohol, This would be stable to the acetylide, and could be deprotected in mild acid conditions, then oxidized to the acid with a less acidic oxidizing agent such as pyridinium dichromate (PDC). With these changes, I think you have a winner. There is also a neat way into the 8-bromo-1-octanol. You just take 1,8-octanediol, and reflux it in toluene with 1 equivalent of concentrated hydrobromic acid. The diol will partition into the acid, but the mono-brominated compound will partitioninto the organic phase, where it is less likely to react. Do you have an e-copy (pdf) of the JACS paper that you cite? If you do, could you please upload it? I think it would be interesting for people to see. Bruce Bondurant

Dr. Bondurant, Is this what you are asking? The article I used was about synthesizing unsaturated fatty acids, mainly linoleic acid. I didn't save it, so I can't upload it.

Yes that's exactly what I'm thinking of Dr. Bondurant, I can't get the full text, but here is the site I was talking about. http://pubs.acs.org/doi/abs/10.1021/ja01154a029 Thanks, This is good.

It seems to get fuzzier every time I re-do it! -Meaghan Fuzzi or not, This is a good synthesis Bruce Bondurant Thanks for posting it up Meaghan... good to work together with you as well.. April Weliever