[GinaTageldin]

Does the different methods of thionyl chloride addtion affect ester formation as carboxylic acid suspended in alchol then addtion of SOCL2 dropwise or mix both SOCL2 with alchol then addtion of carboxylic acid . Does they had the same mechanism or not and what is the need of pyridine or DMF addtion? Thanks in advance

[orgopete]

This appears to be a question about different mechanisms. If an alcohol is present, than thionyl chloride is being used as a source of HCl and absorb water. This is a Fischer esterification. If thionyl chloride is added to an alcohol, it can form an alkyl chloride. It would not react under Fischer reaction conditions, so the order can be important.

The other is to first form an acid chloride. DMF is a catalyst in acid chloride formation. Pyridine is a catalyst/acid acceptor in a reaction of an acid chloride.

[Altered State]

This appears to be a question about different mechanisms. If an alcohol is present, than thionyl chloride is being used as a source of HCl and absorb water. This is a Fischer esterification. If thionyl chloride is added to an alcohol, it can form an alkyl chloride. It would not react under Fischer reaction conditions, so the order can be important.

The other is to first form an acid chloride. DMF is a catalyst in acid chloride formation. Pyridine is a catalyst/acid acceptor in a reaction of an acid chloride.

Wouldn't to have a stirring mixture of carboxylic acid and alcohol and then add SOCl2 work well?

Mixing SOCl2 with only alcohol will definitely yield the alkyl halide, and mixing it with just carboxylic acid, will yield acid chloride, but... Can't the esterification be performed in a more handy way like I described on my first line?

[GinaTageldin]

1st thanks alot for the reply the problem is the tradtional method using H2SO4 was imperfect since alot of impurities on TLC and small yeild so switched to socl2 method since i suspended the acid in alcohol and dropping the socl2 wisely at 0 degree then reflux after 8 hrs all components melted then TLC contains 2 spots 1 for ester and the 2nd for the acid then cooling it and the 2nd day add extra SOCL2 , reflux and then acid spot became fainter or disappeared my question is this method i followed like tradtional and not through acid chloride formation am i right and i need the mechanism 2nd one how many moles of socl2 added excess or corresponding to acid  does excess alcohol affect ester formation as it will consume socl2 and form alkyl halide , please i need the help finally i ppt the cpd using ice water with sodium bi carbonate and use solid directly with no extraction with CH2CL2 and evaporation on rotavap

[Mellitic]

Orgopete already gave a good answer for this.  I've never seen an example of adding SOCl₂ to a mixture of the acid and alcohol before.  From you post, it seems like your acid is not fully dissolved in your alcohol, correct?  Without base, your alcohol is going to be a better nucleophile than the acid, so it is likely you are forming the alkyl halide first and HCl which is then catalyzing the fischer esterification.  This reaction also forms water, which will also be trapped by the SOCl₂ to give SO₂ and more HCl, so a slow addition of SOCl₂ will likely give you a better reaction.  As for the number of equivalents of SO₂, start with one equiv. and continue to add 0.1 until you have complete conversion; I do not think there is a definitive answer we can give you.

Also, why not just make the acid chloride first and then make the ester?  Are you really saving time or material pursuing this new method?

[salteen]

I have run this type of esterification before and can attest to its effectiveness (at least in my case, which was the esterification of benzoic acid derivatives).  Orgopete's suggest is the standard approach; pre-mix the alcohol and carboxylic acid, then dropwise addition of SOCl₂.  This should generate the acyl chloride in situ which will quickly be converted to the ester.

You theoretically only need 1 equivalent of SOCl₂ but if you're still seeing starting material present after a while, try 1.5 or 2 equivalents.  I typically keep the mixture cold upon addition (-20 - 0°C) and try to preserve anhydrous conditions since water will destroy the thionyl chloride.  Pre-distilling the SOCl₂ is a good idea as well if you're having problems.

[GinaTageldin]

1s t thanks for your particepation in solving my problem sir mellitic that method i foumd it in many papers but the time suggested to finalize the reaction 8 hrs but due to the 2nd addtion on next day it takes about 16 hrs i tried to form acid chloride but the amount needed from thionyl chloride was to high also for the solvent and the reaction was very impure while montoring by tlc and also the acid chloride is quite unstable ,yup my acid makes a suspention with the alchol on cold but ifheated after socl2 addtion became melted  the question is does the excess alchol will affect ester formation or not as it react with it and form alkyl halide  and not give achance for acide chloride formation ,please sir salteen fom your expermental experience  how wil be the ratio between acid ,thionyl  chloride ,and alchol also i couldn,t redisilled socl2 but it works as it is new one

[orgopete]

You must remember that a Fischer esterification (which this is) is an equilibrium reaction. An ester and water, with an acid catalyst will yield yield the carboxylic acid and alcohol. This is the reverse. Normally just HCl (g) or conc sulfuric acid can be used. It is advantageous these acids also sequester water.

I would anticipate that thionyl chloride will both yield HCl and react with water to give SO2. I don't think it will require a full equivalent to absorb water, but you could just try it. I doubt you will find an ideal stoichiometry. As the carboxylic acid concentration decreases, the reaction rate will also decline. It is an equilibrium reaction and side reactions can also occur. I suggest you find a set of conditions from an economy of time and material.

If you have the choice of reacting either directly or via an acid chloride, just use which works best. You could also use different HCl sources, phosgene, diphosgene, oxalyl  chloride, or acetyl chloride. You could also use the acid chloride to generate HCl, but it would probably react too slowly.

[GinaTageldin]

iam sorry but am confused is my reaction followed fiescher or acid chloride intermediate ( alchol and acid suspension ) then dropwise addtion socl2  i think it followed both mechanisms  and does excess alchol affect estrification or not?  thanks alot

[orgopete]

iam sorry but am confused is my reaction followed fiescher or acid chloride intermediate ( alchol and acid suspension ) then dropwise addtion socl2  i think it followed both mechanisms  and does excess alchol affect estrification or not?  thanks alot

It is a Fischer esterification. Even though we do not have complete details, I think we have enough information. As stated, the acid chloride is aromatic and it reacts slowly. (Benzoyl chloride can be reacted with amine in water under Schotten-Baumen conditions attesting to a lower rate of reaction.) If the reaction went via the acid chloride, TLC would have shown a fast moving acid chloride present rather than a slow moving acid.

Re: excess alcohol
The reaction is an equilibrium reaction, Le Chatliere's principle, an excess of alcohol will increase the rate and shift the equilibrium toward ester. Because I don't know what is being reacted, I can only guess at what might occur. However, thionyl chloride could react with the acid to make some acid chloride, but it could also react with the alcohol to make some alkyl chloride. The net effect of this reaction would be to reduce the alcohol concentration, but it would also generate HCl.

I'm sure you can find procedures in which some of the other HCl sources were used. If you were making an ethyl ester, you could use acetyl chloride and an excess of ethanol. Direct reaction would give volatile ethyl acetate while an indirect reaction acetic acid. These reagents are used as alternates to gaseous HCl. By the way, how well does the reaction work if you do a classical Fischer esterification with gaseous HCl?