[sMgz]

I was recently posed with an exam problem asking me to sythesize butanoic acid from a starting material of propanoic acid using any one carbon compound and any inorganic reagents.

I was awarded 3 points out of 12 for my synthesis, but no explanation was given for why my synthesis was wrong, I was wondering if anyone could help me identify the problem.

Any help is appreciated.

-Chris

[DeadFish]

The first step, I think you need to turn it into an acid halide before treating it with LiAl4 and H+, and between step 3 to 4, you can't treat it with PCC, DCM anymore because the alcohol is no longer primary.

[nj_bartel]

You certainly can reduce carboxylic acids with LiAlH₄, and PCC will oxidize secondary alcohols to ketones.  From my knowledge of organic, there's nothing wrong with that reaction scheme.  Judging from where he began the cross out, the only thing I can think of is that he's counting PCC as an organic with more than one carbon, but that would be incredibly obnoxious, as it's not used to lengthen the carbon framework.

[macman104]

Longer than necessary?

Reduce to alcohol, convert to bromide, grignard attack on formaldehyde, oxidize alcohol.

[DeadFish]

You certainly can reduce carboxylic acids with LiAlH₄, and PCC will oxidize secondary alcohols to ketones.  From my knowledge of organic, there's nothing wrong with that reaction scheme.  Judging from where he began the cross out, the only thing I can think of is that he's counting PCC as an organic with more than one carbon, but that would be incredibly obnoxious, as it's not used to lengthen the carbon framework.

I thought it was potassium permanganate or sodium dichromate in acid and water that oxidizes secondary alcohols.

[nj_bartel]

Both of those do it as well.


And macman - that's a better explanation than what I came up with, but taking 9/12 points off for doing a viable 6 stepper than seeing the 4 stepper?  That's unbelievably harsh.

[macman104]

I agree, taking that many points off is pretty harsh.

[Squirmy]

I'd think macman's answer is what they were looking for. It might be as simple as: the grader had a key with those 4 steps that divided them into 3pts/each and they just gave you credit for the reduction.

There's a problem with grading synthesis questions, which rarely have one "right" answer. Do you have an answer key that allows little variation, but makes grading very objective and fast? Or do you allow the grader to evaluate the overall synthesis (much more time-consuming) and come up with a very subjective grade?

Personally, I pick the latter, but having graded for classes with >400 students I can understand the former.

[cundi]

Have you considered Arndt-Eistert Synthesis?

[sjb]

There are also possible issues with the oxidation of the cyanohydrin - I don't think I've seen precedent for that and as far as I know most conditions will revert it back to the aldehyde; and subsequent Wolff-Kishner style reduction of the acyl cyanide - again I don't know of precedent.

Just some early thoughts

S

[sMgz]

Have you considered Arndt-Eistert Synthesis?

I hadn't heard of this before. I'm in my second semester of organic chem, and that wasn't even mentioned in the chapter on carboxylic acids. Organic Chemistry: Structure and Function, Vollhardt + Schore, 5th E

There are also possible issues with the oxidation of the cyanohydrin - I don't think I've seen precedent for that and as far as I know most conditions will revert it back to the aldehyde; and subsequent Wolff-Kishner style reduction of the acyl cyanide - again I don't know of precedent.

Just some early thoughts

S

How would it become an aldehyde? My reasoning behind it is that if anything the electron withdrawing cyanide group would make it more reactive towards oxidation, and with PCC in DCM where is the H- going to come from? My only doubt in the synthetic chain was the Wolff-Kishner reduction, because I had never seen it used with anything other than an alkyl group attached to the carbonyl carbon.


I go to a very large school, so it doesn't surprise me that my synthesis was marked wrong solely for being different from the answer key (the answer key went the reduction, halogenation, grignard, oxidation route). They have hundreds of papers to grade. I just wanted to make sure that my synthesis wasn't completely off base. Thanks for the help everyone.

[nj_bartel]

Ask the professor to look at it.  May get some points back.

[Rishi]

Cundi is right.....Arndt-Eistert synthesis would be the best to step up the carboxylic acid with one more carbon.
The mechanism goes something like this....

R-COOH + SOCl2  R-COCl
R-COCl + CH2N2    RCO-C=N=N
R-CO-C=N=N + Ag2O/H2O  R-CH2-COOH