[kriggy]

Hi guys, Im looking for a base with similar pka as sodium acetate to perform an alkylation reaction. I know that pyridine has similar pka  but im not sure if it wont react with benzyl bromide Im using. Is there any list of the bases (and possibly with acids) that would allow me to do quick search to find out the base/acid with properties I want?

[Enthalpy]

One table with just pKa values would be there:
www.chem.wisc.edu/courses/116/otherdoc/pkas_of_organic_acids_and_bases.pdf
Hill order, not ordered by pKa, but there are only 600 to go through...

[TheUnassuming]

I've always liked the Evans pKa table for a good starting point.

[Babcock_Hall]

IIUC the nucleophilicity of pyridine occasionally makes it a good solvent catalyst.  I don't know whether or not this would be true in your application.

[Dan]

Pages for your bookmarks:

http://www.chem.wisc.edu/areas/reich/pkatable/
http://research.chem.psu.edu/brpgroup/pKa_compilation.pdf
http://evans.rc.fas.harvard.edu/pdf/evans_pKa_table.pdf

[orgopete]

I don't get the premise. I don't see why a weak base should be used in the alkylation? If two acids are present, the result will be the salt of the strongest acid provided the base is sufficiently strong. It won't matter how strong the base was as the result will still be the salt of the strongest acid. You could use BuLi, NaH, NaOAc, NaOMe, NaOH, etc., and get the same result. What don't I understand?

[kriggy]

That is what I thought too. The molecule has N-substitued benzimidazol-2-one and indazole moyety. Using base like NaOH or Na₂CO₃ i got mixture of products. If I used weak base like sodium acetate, I get only one product and my starting material unless I use excess of benzyl bromide (40eq of benzyl bromide give aprox. 75% conversion). The reaction didnt proceed without base at all. Heating didnt realy help the reaction but I suppose I could try it once more.

Its realy weird, I understand that i get mixture using strong base because it deprotonates both nitrogens. Maybe its because the acidobasic intermolecular reaction doesnt proceed in alcohols fast enough?

[TheUnassuming]

Are you trying to N-alkylate the indazole at the 1 position or the non-substituted nitrogen of the imidazol-2-one?  You also mention an alcohol around?  I don't think NaOAc is basic enough to deprotonate any of those positions, so it should just be acting to mop up any acid formed.   

Another problem might be that sodium acetate is probably nucleophilic enough to react with your benzyl bromide to make the ester, which would explain the large excess needed. Could try the massive excess BnBr without NaOAc to test that theory.   

[kriggy]

Im trying to alkylate the benzimidazole nitrogen. I did run the reaction with different amounts of BnBr and/or acetate and the amount of acetate doesnt realy have any effect on the reaction. I did run the reaction in MeOH, MeOH+water, DMSO, DMF.. and the best is MeOH. I also see the TLC stain that match the benzyl bromide

[orgopete]

Okay, some progress. No base, no reaction. So, even though NaOAc may not generate much anion, but presumably it was the sodium salt that reacted, no? I recognize that one cannot just add a base, except maybe NaH. There will also be additional agents, e.g., acetic acid.

Since methanol gave the best result, what happens if base is added slowly to the reaction mixture with BzlBr present?

From the description, you aren't finding the result of reaction of the alkylated product are you? If so, that would explain why a stronger base would leave to lower yields, not because the reaction failed, but because the product is more labile in the reaction conditions.

[TheUnassuming]

Hrmm... that nitrogen should have a pka in the range of 11-13 which would make a difference of pKa with NaOAc on the order of 6-8.  With the equilibrium essentially 1 million:1 in favor of nitrogen being protonated, I don't think that is the likely cause of the reaction progression to ~75%.

Definitely agree with orgopete that you might be getting alkylation of your product with stronger bases. 

Random thought, can you catalyze alkylation with acid or would acid cause your compound to rearrange to make a more nucleophillic species that could attack the BnBr?

[TheUnassuming]

Could also try throwing in some catalytic NaI to see if that helps.

[kriggy]

I am getting alkylation with stronger bases, I might have not explained it well:
acetate or HCO₃^- -> single product but low conversion unless big amount of BnBr is used (10eq = 50% 40eq =
75%) The conversion is area of peak in HPLC since im just trying it in little amounts (0,2mmol)
KOH, K₂CO₃ -> mixture of mono and dialkylated products (at least 4 compounds + some unreacted starting material)

I tried 1eq NaI and got mixture of products. Might try catalytic amount maybe it makes a difference