[Meter]

How can we compare the reactivity of aldehydes/ketones with the reactivity of acyl chloride/esters? The former undergoes nucleophilic addition upon reacting with a Grignard reagent, whereas the latter undergoes nucleophilic substitution. But let us say I have a mixture of an aldehyde and some ester in equivalent amounts. How would we predict the major product? Repeat the same type of thinking for other pairs of of carbonyls.

[rolnor]

No, acyl chlorides and esters also undergo addition, forming tertiary alcohols. Acyl chlorides gives substitution if the Grignard first is conveted to a dialkyllithiocuprate.

[Meter]

What do you mean? I'm pretty sure this is what would happen. And similarly with esters, but with some alkoxide leaving group.

[rolnor]

Sorry, I did not specify each step the way you have but gave the total outcome of the reactions, you are right.
I dont see a simple experiment to try this. But the acid chloride will probably react faster than ketone but maybe at the same speed as an aldehyde and the ester will react slower than the rest. Aldehydes does not  react with cuprates but acid chlorides does but thats not the same as Grignards. For esters and Grignards is not the first step addition?

[OrganicH2O]

How can we compare the reactivity of aldehydes/ketones with the reactivity of acyl chloride/esters? The former undergoes nucleophilic addition upon reacting with a Grignard reagent, whereas the latter undergoes nucleophilic substitution. But let us say I have a mixture of an aldehyde and some ester in equivalent amounts. How would we predict the major product? Repeat the same type of thinking for other pairs of of carbonyls.

Stuff like this can be tricky to give full answer, but a rough relative order for electrophilicity is:

acid chloride > anhydride > aldehyde > ketone > ester ~carboxylic acid > amide > carboxylate

Reactivity in some cases might depend on the type of nucleophile, and other factors. For example Carboxylic acids have an issue where they tend to get deprotonated under basic conditions, greatly reducing their electrophilicity. And there are myriad other exceptions depending on the precise conditions.

This trend is rationalized based on how electron donating or withdrawing the groups are that are bonded to the carbonyl carbon. E.g. chlorine is very electron withdrawing, alkyl is moderately electron donating, and a nitrogen lone pair or negative oxygen are both very strongly electron donating. A second issue is steric hindrance: more sterically hindered groups make the carbonyl less electrophilic also.

For aldehyde vs ester specifically, I think an aldehyde would always be more reactive than an ester during the addition of any kind of nucleophile. The only tricky thing there is that some addition products with aldehydes might form very reversibly, e.g. hydrate or hemi-acetal formation would be very easily reversible.

[Meter]

Thanks for the answers guys.

[OrganicH2O]

Sorry, I did not specify each step the way you have but gave the total outcome of the reactions, you are right.
I don't see a simple experiment to try this. But the acid chloride will probably react faster than ketone but maybe at the same speed as an aldehyde and the ester will react slower than the rest. Aldehydes does not  react with cuprates but acid chlorides does but thats not the same as Grignards. For esters and Grignards is not the first step addition?

I did feel the most unsure about where to place an aldehyde on the list I made. I believe I've seen examples where an aldehyde seems to be reacting faster than an anhydride. I am partially just aggregating what a few different professors have told their students during introductory classes. A full list is difficult to find in textbooks, probably because the order can change depending on the conditions.

Among other things, certainly the choice of nucleophile can change which electrophilic site is more reactive. For example soft vs hard nucleophiles, alternative mechanisms when transition metals are involved, and whether the reagent is very nucleophilic (e.g. LiAlH4) vs somewhat electrophilic (e.g. BH3 or DIBAL)

[rolnor]

OrganicH2O, the question here was wether its addition or substitution, whats your thoughts, does ester give substitution or addition with Grignards as the first step? When I think about it its not 100% clear if acyl chlorides gives substitution as the first step, it could be a mixture of substitution or addition or either really. Again, not easy to prove this experimentaly with such extremely reactive species.

[OrganicH2O]

OrganicH2O, the question here was wether its addition or substitution, whats your thoughts, does ester give substitution or addition with Grignards as the first step? When I think about it its not 100% clear if acyl chlorides gives substitution as the first step, it could be a mixture of substitution or addition or either really. Again, not easy to prove this experimentaly with such extremely reactive species.

The original question was difficult for me to decipher perfectly, but I think Meter was asking about an aldehyde reacting vs an ester reacting. In that case, I think the aldehyde is more reactive in almost every context with a nucleophile.

With ester + grignard alone, I would call that a substitution followed by addition process. Initial substitution (via addition/elimination) makes a ketone, and then subsequent addition would make an alcohol. I think in most cases you can't stop at the ketone because the ketone intermediate is more reactive than the original ester. To stop at the ketone would would need something special, like a Weinreb amide. One exception to this might be a strained lactone, like a beta lactone, that is much more reactive than your average ester.

With acid chloride + grignard, I believe I read in the Clayden textbook that it's sometimes possible to stop it at the substitution process, because an acid chloride is theoretically a stronger electrophile than a ketone. But in practice that may be difficult to achieve, because grignards simply react very quickly with ketones, also. Therefore its better to create the ketone with a cuprate nucleophile + the same acid chloride. A professor in an introductory class might demand that the student use a cuprate for this process.

[rolnor]

You say that the first step with Grignard is addition/elimination, is this possible with acid chlorides as well? I agree that the main question from the beginning was comparison between aldehyde/ester reactivity and thats not difficult but I think there are other questions also. I already covered the use of cuprates+acyl chlorides (see above).

[OrganicH2O]

Acid chloride + grignard would have the same mechanism as ester + grignard, I always assumed. I don't know the specific evidence for it. It's just how I've always seen it written. The only difference would be in the practical outcome, and how it should be easier (but not always possible) to stop at substitution product. If the original poster is still reading, that is definitely how it would be expected in an introductory class. Any further discussion is WAY beyond the scope of anything the original poster needs to know.

What alternative mechanism were you proposing? Sn2? Sn2 seems very wrong, but I can only think of theoretical reasons and not experimental evidence. Single electron transfer? I'm not very well versed in SET mechanisms, but I just googled and reminded myself that aromatic ketones undergo additions with grignards via this mechanism: https://pubs.acs.org/doi/abs/10.1021/ja00406a070 . I don't know if acid derivatives also commonly do SET mechanisms.

Edit: also, they agree with me here: https://www.organic-chemistry.org/namedreactions/grignard-reaction.shtm . It shows an abbreviated mechanism for acid chloride + grignard.

[rolnor]

I agree with you completely. It is Meter who discuss a difference in the reaction between aldehydes and ketones with Grignards vs acid chlorides and esters with Grignards. In all cases it is initially addition so there is no difference. Aldehydes and ketones  can not give substitution so thats the difference.

[Meter]

You could react a half equivalent of the Grignard reagent, you would then get a mixture of addition and substitution products. And my intuition tells me the addition product would be formed in excess (if the reagent is slowly added into a dilute reaction solution).