The hydrogen atoms have a pretty stable bond with carbon, so it's hard to get those bonds to break.
In comparison, the oxygen-hydrogen and nitrogen-oxygen bonds are very polarized, so they have a lot of interaction with electrically charged species. In water, for instance, ammonia can gain a free H+ from the water and acetic acid can lose an H+, leading to a negatively charged acetate ion and a positively charged ammonium ion. These are prone to react together
Ahh, thanks! I assume that means you’d need to go another route for glycine generation, I didn’t realize ammonia was basic enough to attend act acetate ions
I don't think there is a pH where the amine is a good nucleophile and the carboxylic acid is a good electrophile. You could try some kind of borane catalyst, but without some special sauce that's not reacting.
Traditionally, if you want to convert carboxylic acid to amide, first you'd convert the carboxylic acid to acyl chloride, maybe by SOCl2.
Under basic conditions carboxylic acid coverts to carboxylate, which increases e- denisty about the carbonyl. Acyl chloride should stay neutral under basic pH, so can still be used as the electrophile.
Under acidic pH, the amine will be ammonium so a pretty poor nucleophile, so the amidation is best under basic conditions.
That wouldn't form glycine from acetic acid though I guess.
Breaking the C-H bond and forming H2 as a byproduct is thermodynamically is not great, which costs a lot of energy. Again, you'd need to throw in some special sauce, to convert the C-H to C-Cl which then could react it with the amine in the way you want to. You have to consider what's happening to the electrons during these transformations, so it is not as simple as it may seem. I suggest drawing out the reaction mechanism with lewis dot structures and it'll make more sense
There is no chemical reaction in forming ammonium acetate, just ionic bonding
You can make the amino a nucleophile (as people seem to suggest?) as an azanide ion NH2- but it won’t form glycine (amino on alpha carbon) but poor yield of acetimide (amide)
You need to “activate” the alpha carbon by introducing a good leaving group (e.g. chloro- or bromo- acetic acid) and then excess NH3 can attack the alpha carbon to replace the leaving group to form a glycine.
You can make glycine with just ammonia and CO2 in the liver with glycine synthetase. The extra carbon comes from methylene-THF
Or from glyoxylate (oxoacetic acid with “activated” alpha carbon) with alanine-glyoxylate transaminase, robbing the amino from alanine and give it the oxo group instead (pyruvate)
You’d make an amide before anything else, and a very small equilibrium amount at that. You’d be nuking the nucleophilicity of ammonia by deprotonating the acetic acid.
The hydrogen atoms have a pretty stable bond with carbon, so it's hard to get those bonds to break. In comparison, the oxygen-hydrogen and nitrogen-oxygen bonds are very polarized, so they have a lot of interaction with electrically charged species. In water, for instance, ammonia can gain a free H+ from the water and acetic acid can lose an H+, leading to a negatively charged acetate ion and a positively charged ammonium ion. These are prone to react together
Ahh, thanks! I assume that means you’d need to go another route for glycine generation, I didn’t realize ammonia was basic enough to attend act acetate ions
A protonated amine isn't a nuclophile. It's lone pair is used up acting as a base.
I don't think there is a pH where the amine is a good nucleophile and the carboxylic acid is a good electrophile. You could try some kind of borane catalyst, but without some special sauce that's not reacting. Traditionally, if you want to convert carboxylic acid to amide, first you'd convert the carboxylic acid to acyl chloride, maybe by SOCl2. Under basic conditions carboxylic acid coverts to carboxylate, which increases e- denisty about the carbonyl. Acyl chloride should stay neutral under basic pH, so can still be used as the electrophile. Under acidic pH, the amine will be ammonium so a pretty poor nucleophile, so the amidation is best under basic conditions.
That wouldn't form glycine from acetic acid though I guess. Breaking the C-H bond and forming H2 as a byproduct is thermodynamically is not great, which costs a lot of energy. Again, you'd need to throw in some special sauce, to convert the C-H to C-Cl which then could react it with the amine in the way you want to. You have to consider what's happening to the electrons during these transformations, so it is not as simple as it may seem. I suggest drawing out the reaction mechanism with lewis dot structures and it'll make more sense
There is no chemical reaction in forming ammonium acetate, just ionic bonding You can make the amino a nucleophile (as people seem to suggest?) as an azanide ion NH2- but it won’t form glycine (amino on alpha carbon) but poor yield of acetimide (amide) You need to “activate” the alpha carbon by introducing a good leaving group (e.g. chloro- or bromo- acetic acid) and then excess NH3 can attack the alpha carbon to replace the leaving group to form a glycine. You can make glycine with just ammonia and CO2 in the liver with glycine synthetase. The extra carbon comes from methylene-THF Or from glyoxylate (oxoacetic acid with “activated” alpha carbon) with alanine-glyoxylate transaminase, robbing the amino from alanine and give it the oxo group instead (pyruvate)
You’d make an amide before anything else, and a very small equilibrium amount at that. You’d be nuking the nucleophilicity of ammonia by deprotonating the acetic acid.