[steph90]

I am looking for confirmation of how I understand the selective synthesis of mono-BOC-cystamine.
I have already successfully synthesized the product, however, am lacking a few of the details to completely understand the reaction.

A referral of the mechanism: https://www.jkchemical.com/post/556

1. 1 mol. eq. of cystamine dihydrochloride in MeOH was brought to 0.5 celsius (what is the purpose of this solution being so cold?)
2. Taken off the ice, 3 mol. eq. of triethylamine (TEA) was stirred in the cold solution for 30 min. allowing it to come to room temperature (are 2 mol. eq. of the TEA used up here to deprotonate the primary amine salt?)
3. Boc₂O was added dropwise over 3 hours. To describe the mechanism, is this a nucleophilic attack of the amine nitrogen to the carbonyl carbon?
4. Following the amine attack of Boc₂O, an electron transfer occurred from the nitrogen to carbonyl oxygen. Can you say that this formed a carbamate intermediate or a tetrahedral intermediate? The extra electron pair then transfers to the sp3 hybridized C-O bond and further to the next internal C-O bond, cleaving tert-butyl carbonate.
5. The result of the cleavage leaves a protonates mono-BOC-amine, where the last molar equivalent of TEA deprotonates this.
6. If the above use of TEA as a base is correct, then I don't understand why the protocol I followed uses 1 M of NaOH for the extraction with DCM. Originally, I thought that the NaOH was basifying (or free-basing) any salt form of amine left (or maybe this is still true)?

[rolnor]

Cystamine is unstable as free base, so cooling is for avoiding heat I think. 1Mole is a large amount so it could evolve heat when TEA is added.. The TEA only partially makes the free base, its a equilibrium. I dont see if you make the di-BOC compound or mono-Boc? The NaOH is for washing salts away.
Here you see the mechanism. Its nuc attack on the carbonyl, carbondioxide+t-BuOH is formed as byproduct.

https://en.wikipedia.org/wiki/Nucleophilic_acyl_substitution

[steph90]

Thanks for your response rolnor.

The purpose was to make mono-BOC-cystamine. After purchasing the pure product to make an HPLC-MS standard curve, I calculated my purity to be only 17.6%.

Maybe it would have made more sense if I also had mentioned that Boc2O was added in 1 molar equivalent. So 1 part cystamine to 1 part Boc2O. Then there were 3 parts TEA.

Also, thanks for clarifying the mechanism.