Hello, I am new to the forum, and I was hoping that someone could help out a bit, I am trying to synthesize a "tris-malonate" macrocycle
using TEG, malonyl chloride, KF all in methylene chloride. The benzyltriethylammonium chloride is the phase-transfer catalyst. I've found this
reaction in a paper using KF as nucleophile.
I'm trying to figure out why use fluoride, wouldn't the acyl chloride do a fine job on its own?
I'm doing the following reaction right now at RT~4h stirring,
it's stirring in the hood.
Any help would be great, the reaction I drew above lists only the first product of the reaction, the second would be a bis-malonate and then finally a
tris malonate adduct.
Thank you,
Andre
[Edited on 12-15-2009 by andre178]Nicodem - 14-12-2009 at 14:32
I've found this reaction in a paper using KF as nucleophile.
...and just what is the reference? Members here are not mind readers and I am certainly not going to search for that paper myself when it is about
your convenience.
Quote:
I'm trying to figure out why use fluoride, wouldn't the acyl chloride do a fine job on its own?
You don't see any F atoms in the product, do you? So KF is not used as a nucleophile as you thought. It is only the base used to make the alcohol
react with the acid chloride and scavenge any HCl. Many alcohols react slowly with some acid chlorides. The most commonly employed base for
esterifications is simply pyridine. Unless you give the pertaining reference we can only guess on why specifically KF was used. In the synthesis of
macrocyclic ethers, often bases with large cations are used so that their chelation guides the cyclisation. In this case, at the beginning of the
reaction, you mostly have only the benzyltriethylammonium cation in the solution. This however, to my knowledge, can only be very poorly chelated (at
least when compared to metal cations, so maybe K(+) takes this function).andre178 - 14-12-2009 at 14:41
good points! my bad, the paper is:
Selective Syntheses of Novel Polyether Fullerene Multiple Adducts, by Zhiguo Zhou, David I. Schuster, and Stephen R. Wilson*J. Org. Chem., 2003, 68
(20), pp 7612–7617
DOI: 10.1021/jo034542l
just updates on the reactions: the organic turned out a mellow yellow-orange
and I began to run a flash column with ethyl-acetate:hexanes (4 to 1)
12AX7 - 14-12-2009 at 20:14
FYI, you drew four ethylenes in your mono product.
I suppose there would also be polymers of various length, unless cyclicization is specifically selected (which could be where the potassium comes in).
Tim
[Edited on 12-15-2009 by 12AX7]Nicodem - 15-12-2009 at 00:40
Andre178, the authors already answer to your question in the discussion part of the paper: "Macrocycles 5 and 6 with two and three identical
linkers, respectively, were prepared from the condensation of malonyl dichloride with triethylene glycol under solid-liquid phase-transfer-catalysis
(PTC) conditions using KF as base and template, triethyl(benzyl)ammonium chloride (TEBA) as catalyst, and dichloromethane as solvent (Scheme 2).[ref
20] Macrocycles with different ring size were separated by flash chromatography. Macrocycles with more than three malonate units were also obtained.
The yields of 5 and 6 were improved, compared with those in the absence of PTC conditions."
For the synthesis of 5 and 6, they do not use dilution to induce cyclisation, so a template guided cyclisation is a reasonable assumption (on the
other hand, in the synthesis of the macrocycle 1 they use pyridine and thus the high dilution technique). The only thing they do not give any
hypothesis for is the beneficial role of 4 mol% TEBA. The observation that the yields of higher macrocycles 5 and 6 are improved by the use of PTC
conditions is in opposition to their claim that KF is used for a template, unless it is about an optimum compromise between base catalysis (PTC
preventing HCl build up which would perhaps inhibit chelation) and potassium cation template guided cyclisation. You might want to find that reference
20 they give for more details.
