[mangolite2]

What are the reasons behind the choice of base and the solvent for conducting reactions?

1) alcohol + TBSCl ----> TBS protected alcohol
experimental condition : Imidazole  (base) + DMF (aprotic solvent)

2) primary amine + Benzylchlroformate ---> ester protected amine
experimental condition : Triethylamine (base) + THF (aprotic solvent)

realised tat both triethyl amine and imidazole are bases and THF and DMF have the same solvent properties, so why do we use different conditions for the different reactions?

[movies]

Imidazole can actually catalyze the reaction with TBS-Cl.  It's definitely the best base for that reaction.

[mangolite2]

Hi movies!

Thanks! I googled and i found an article saying imidazole may act as a catalyst for group transfer in Nucleophilic attack. The alcohol + TBSCl is an SN2 reaction am I right? But it states that imidazole is a catalyst for acylation rxn.  How does it work as a catalyst here?


I still have other questions and I hope you don't mind answering, cuz my puny brains can't seem to get an answer to it and i've tried googling like a gazzilion times but to no avail!!

Can we use imidazole instead of triethylamine for reaction 2 since both are tertiary amine bases? I read that  we have to take into account the pKa values of the two bases. But how do make sure that the pKaof the base compliments the reaction?

Also, what are the factors that affect the choice of solvents for a reaction? Example, THF, DMF and DMSO are all aprotic solvents rite? i do not understnad why can't we use them interchangably? The experimental procedures specifically demands us to use a certain solvent for certain reaction.

I have been using benzene for one of the procedures, but i read that its CARCINOGENIC!! gosh!! We can use toluene instead of benzene as solvent right? but when i used toulene, i got my whole reaction burnt!!
=( why??

[movies]

In this case the imidazole works by attacking the TBS-Cl first to displace the Cl and make TBS-imidazole which is then more reactive than TBS-Cl alone.

As for your pK_a question, yes matching that correctly is important, but imidazole would probably work in the second reaction as well.  I think TEA is usually more convenient to use in practice though.  However, another great catalyst for acylation reactions is 4-(dimethylamino)pyridine (DMAP), which works very similarly to imidazole in the TBS reaction.  In general for pK₂ matching, you just need to make sure that the conjugate acid you are making is sufficiently less acidic than whatever acid you are generating.  In this case, the acid is HCl, so most any base will work.  TEA is quite a bit more basic than imidazole though.  One reaction where pK_a matching is particularly important is the Mitsonobu reaction.

For the solvents, I think the key is the difference in the rate determining step of the reaction.  For example, in the TBS case, since the silicon is somewhat hindered, you need dipolar aprotic solvent to accelerate the nucleophilic attack of the imidazole (or alcohol) at the Si.  In the second case with an acid chloride, the nucleophilic attack is much faster and you really just need to drive the equilibrium of the reaction, so solvent is so necessary to accelerate that step of the reaction.  This might be another reason to use a stronger base in the benzoyl chloride reaction: to drive the equilibrium toward products.  If you were to use TEA and DMF then the resultant ammonium salt would be a lot more soluble, but in THF that particular salt is pretty insoluble, which also drives the equilibrium.  As for the particular nature of the solvents, THF is polar, but it's not really in the same league as the dipolar aprotic solvents like DMF and DMSO.  Check out their relative dielectric constants.  A high dielectric constant generally means that the are better at stabilizing a polarized transition state (like the intermediate in an S_N2 inversion).

Benzene isn't really as bad as it's made out to be, but you are right that toluene is a lot safer (practically non-toxic).  I'm surprised that your reaction would work in benzene, but not toluene.  It really should.  I would stick with the solvents you listed above, DMF and THF, respectively.  Those reactions are highly optimized and those conditions are really reliable.  You can also use CH₂Cl₂ for the benzoyl chloride reaction as well, however.  Again, THF is better because the triethylammonium salt is so insoluble.

I hope all that is helpful to you.