Klute
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Synthesis of gamma-nonalactone (Coconut aroma)
This is a very easy preparation of gamma-nonalactone, or 4-pentyl-gamma-butyrolactone, a naturally occuring aroma.
The downside is that it starts from heptaldehyde, which isn't available to nayone... I gues it could be made by oxidizing heptanol by TEMPO-mediated
reactions, but you still need to find the alcohol...
The reaction is composed of two steps:
-malonic synthesis of a b,gamma-unsaturated acid
-intramolecular cylization to the lactone.
Sorry, no photos this time, my camera is broken for the moment...
Preparation of the unsaturated acid
4.16g (40 mmol) of malonic acid where charged in a 250mL 3-neck RBF equipped with a condenser, an addition funnel, a thermometer and magnetic
stirring.
5,6 mL (40 mmol) of heptaldehyde were added, followed by 8mL triethylamine (60 mmol). the addition of the amine caused some milkyness to appear as the
malonic acid dissolved, and quickly gave place to a clear, colorless solution. The mixture was heated to 100-110°C for 1H.
The now slight yellow limpid solution was transfered to an seperating funnel, and the flask rinced with 2x20mL Et2O. An aqueous layer dropped out.
40mL of 4N HCl were then added, and the layers shaken. The slightly opaque yellow ethereal layer was then washed with 2x10mL dH2O.
40mL 1.25N NaOH were then added, the aqueous layer turning light redish, and the organic staying light yellow. The aq. was seperated, and the organic
washed with 2x10mL dH2O.
The solution was washed with 2x10mL Et2O, and acidified with 40mL 4N HCl, a red/purple oily compound crashing out. The acid was extracted with 3x20mL
Et2O, washed with 20mL brine, and dried over Na2SO4.
The solvent was then removed, leaving 4.7g (30,13 mmol, 75,33%) of light amber oil, single spot by TLC (Pet ether:AcOEt 6:4, Rf= 0.52).
Cyclisation to the lactone
The crude product obtained in the first step was dissolved in 30mL heptane, giving a very slightly amber limpid solution. An equal weight of Amberlyst
15 cationic resin was added, and the mixture heated to reflux for 1H with strong stirring.
The flask was then cooled, and the colorless limpid supernatant decanted into a 100mL flask. The resin was washed with 3x10mL Et2O, which were added
to the heptane solution.
The solvents were removed, leaving 4.6g (29.45 mmol, 97.74%) of a pale yellow oil, with a strong coconut smell, very "natural" smell.
The lactone was thus obtained in a 73.63% yield from the aldehyde.
The Amberlyst-catlyzed reaction was very clean and effective, I am surprised at the selectivity of this catalyst, considering the extremly simple
workup an dthe fact that it can be recyled numerous times.. Agreed, it is a bit expensive, but worth the effort IMHO... I think I will try it with
other acid-catalyzed condensations and see how it goes!
I think this reaction is generaly applicable for substitued lactones, using various aldehydes.
\"You can battle with a demon, you can embrace a demon; what the hell can you do with a fucking spiritual computer?\"
-Alice Parr
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panziandi
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Hexan-1-ol and Octano-1-ol are more widely available than the heptan-1-ol in my experience atleast.
Perhaps chain extension of the acids from butanoic acid or similar would be feasible for people who want to make it for the fun of it and then reduce
to the heptanol and oxidise to heptanal?
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Klute
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Well, 1-halogenohexane could bve made from the alcohol, the grignard reagent prepared and reacted with formaldehyde to the heptanol, which could then
be oxidized...
In anycase, the preparation of the aldheyde is even harder than the reaction tiself, which is a pity... Maybe other (shorter) aldheydes give a
simialr smell? There is another dicyclic butyrolactone wich is said to have a coconut smell:
"Coconut decanone"
This is basicly a cyclized 4-pentylbutyrolactone with a methyl attache don the 3 position of the side chain, so maybe a straight octan chain will
behave similarily? Only experimenting can tell! 
\"You can battle with a demon, you can embrace a demon; what the hell can you do with a fucking spiritual computer?\"
-Alice Parr
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panziandi
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Tempting! I have some hexanal kicking about I think but not sure about the malonic acid. Maybe if I have some time I may try it with that.
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Klute
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I think you can substitute malonic aicd for diethyl malonate, although I'm not a 100% certain this might no cause the elimination to happen between
the alpha et beta carbon..
\"You can battle with a demon, you can embrace a demon; what the hell can you do with a fucking spiritual computer?\"
-Alice Parr
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Ebao-lu
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Very interesting reaction, because usualy knoevenagel is known to give a,b-unsaturated products.
Also, the gamma-lactones can be prepared from AcOH, Mn(OAc)3 and alkenes - but i've seen it only in a book, without procedure.
As for heptanal, probably it can be made from olein acid(sunflower oil major fat acid) - via epoxidation and oxidation of diol (hypervalent
iodine/DMP)
[Edited on 17-10-2008 by Ebao-lu]
[Edited on 17-10-2008 by Ebao-lu]
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Klute
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Indeed, I was pretty surprised at first, I suppose the dehydratation to the unsaturated acid occurs before the decarboxylation, and that the acidic
methylene H-R (alpha from the carboxylic acids) is too delocalized by the malonic acid synthon to be favored in the formation of the double bond from
the carbocation compared to the gamma H-R. I would have thought that the conjugated a,b-unsaturated acid would be more energetically farvored, but
apparently not so. I also quite surprised there isn't any isomeration during the reflux with the amberlyst resin. I guess it would happen if there was
presence of water (so maybe usual acids like H2SO4 or H3PO4 would not work here?)
Has anybody got a definate explanation for the unusual regioselectivity?
\"You can battle with a demon, you can embrace a demon; what the hell can you do with a fucking spiritual computer?\"
-Alice Parr
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Ebao-lu
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I think, firstly conjugated unsaturated acid is formed indeed(like in usual knoevenagel), but then it is isomerised to the beta-gamma unsaturated,
that is probably more stable for such long-chain carbonic acids because of some reasons.. Thats because the beta-gamma unsaturated product can not
result from eliminaton of H2O, because the gamma-hydrogen is not acidic.
As for regioselectivity of amberlyst, thats probably because it is a "mild" catalyst that does not form a reactive carbocation(that can be further
isomerised), it just activates the double bond a bit. And the gamma lactones are the most stable and easily formed because of steriochemical reasons
also
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Klute
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Thank you for your interpretation, it makes sense. making the aldehdye from oleic acid is indeed a very good idea. I will ahve a look on the diol
oxidation, to see if anything else can be used.
\"You can battle with a demon, you can embrace a demon; what the hell can you do with a fucking spiritual computer?\"
-Alice Parr
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Ebao-lu
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Heptanal seems to be avaliable product. Just read that it is produced in industry from castor oil and recinoleic acid methyl ester via decomposion at
500C and reduced pressure. While distillation of castor oil at normal pressure heptanal also forms, but as for yield i dont know. Anyway, technical
heptanal should be avaliable, not more expensive then hexanal etc.
As for diol breakup, i think it is possible to use hypervalent iodine compounds, like phenyl iodosoacetate PhI(OAc)2, which is highly selective to
diol oxidaion. It is prepared from phenyliodide, 30%H2O2 and AcOH(or maybe Ac2O, i forgot). The most interesting thing is to combine epoxidation
step(by AcOH/H2O2) and oxidation of diol in one reaction, or at least one pot reactions, and make phenyliodide a catalyst at small quantities. I
should inquire, weather Ac2O or AcOH is used for PhI(OAc)2 preparation.
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Ebao-lu
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forgot to say, phenyl iodosoacetate reacts with diol to give PhI back
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Klute
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I think it's Ac2O. I have no problem accesing heptanal, but that's because I cna purchase chemicals from suppliers, which isn't the case of lot of
people here. Working on a pretty clean reaction from vegetal oil and recycleable reactant seems like a good idea
\"You can battle with a demon, you can embrace a demon; what the hell can you do with a fucking spiritual computer?\"
-Alice Parr
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Ebao-lu
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I've checked, in that procedure indeed Ac2O was used. But fortunately, i found another one, that uses AcOOH/AcOH
http://www.orgsyn.org/orgsyn/prep.asp?prep=cv5p0660
Peracetic acid is easily formed from AcOH and H2O2 in the presence of catalytical H2SO4 (even in procedure they seemed to use an equilibrium mix).
Due to comperatively high yields of PhI(OAc)2 (83-91%) and fast reaction, the formation of PhI(OAc)2 from catalytical PhI should not be an issue also.
Now i'll look for any procedure of glycol oxidation by PhI(OAc)2, if it is carried out in same mild conditions or not..
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