Sciencemadness Discussion Board

amine reactivity

rannyfash - 23-4-2012 at 07:32

what factors change how easily substituted an amine will be, basically will the size or number of substituted groups affect the reactivity towards other nucleophiles?

GreenD - 23-4-2012 at 09:02

Yes, carbon is slightly electron donating, which makes substituted amines more nucleophilic (generally speaking) than lesser unsubstituted amines.

However, if the substitutents are very bulky (Iso-propyl) the amine will have a hard time attacking an electrophilic group.

An example is DIPEA (Di-isopropylethylamine or Hunig's base). This is a very nucleophilic nitrogen, but the substituents are so bulky it cannot attack an electrophile. It is very good at ripping off small hydrogens though. So it is used as a base, where an electrophile is present. An example would be in the case of 1,3-diketones- you may want the middle (2) carbon to become a nucleophile, without causing a nucleophilic attack on the carbonyl group, so a strong "non-nucleophilic base" like hunig's base would be used.

So generally, say methylating a primary amine with methyl Iodide will give you a quaternary ammonium cation.

As the first alkl addition happens, the amine becomes more nucleophilic due to the addition of the slightly electron-donating methyl group, and so does it again, and again to the quaternary compound.



[Edited on 23-4-2012 by GreenD]

Nicodem - 23-4-2012 at 09:06

The reactivity of nucleophiles is called nucleophilicity. The problem of this concept of nucleophilicity is in that it is an empirical value that does not account the many effects on the reactivity that might be outside of the frame of the empirical measurement, such as the specific properties of other electrophiles, the use of other solvents and other counterions (most notably, it ignores the HSAB principles, solvation, coordination and reversibility).

Amines and related N-nucleophiles are nucleophilic because of the high electron density at the lone electron pair (terminology from the frontier orbital theory would be more exact, but less educational). From this you can easily deduce that any substituent that reduces the electron density at the nitrogen will decrease the nucleophilicity. For example, anilines are less nucleophilic than ammonia and this is less nucleophilic than methylamine. The influence of adding alkyl groups was already discussed on the forum so UTFSE for more info. For the same reason amino acids are generally less nucleophilic than their des-carboxy counterparts. Both inductive and resonance effects can have influence. For example, amides (resonance) and 2,2,2-trifluoroethylamine (purely inductive effect) both have reduced nucleophilicity as well as basicity when compared to ammonia (the nucleophilicity can be dramatically increased by deprotonation which hugely increases the electron density at the nitrogen).
On the other hand, there are exceptions, hydrazine and hydroxylamine are better nucleophiles than ammonia even though the substituent (NH2 and OH respectively) is electron withdrawing. This is due to a so called alpha effect.

Besides the electronic effects, the steric effects are the major ones. Essentially, the more crowded the access to the lone pair, the lower the nucleophilicity.

rannyfash - 23-4-2012 at 11:44

i came across chloroformate esters which are impossible as i would have to synthesise them myself and phosgene is too dangerous to even contemplate, i wanted to synthesize rhodamine b and i have around 11g of 3-aminophenol, will i get better yields of 3-diethylaminophenol if i mix molar amounts in dilute solutions, or are there any better less toxic reagents that can form protecting groups that can be reduced to an ethyl group,

Nicodem - 23-4-2012 at 12:01

Quote: Originally posted by rannyfash  
i came across chloroformate esters which are impossible as i would have to synthesise them myself and phosgene is too dangerous to even contemplate, i wanted to synthesize rhodamine b and i have around 11g of 3-aminophenol, will i get better yields of 3-diethylaminophenol if i mix molar amounts in dilute solutions, or are there any better less toxic reagents that can form protecting groups that can be reduced to an ethyl group,

You totally lost me here! What exactly are you talking about? What procedure you are asking about and where is the reference? What does it have to do with this thread?

rannyfash - 24-4-2012 at 08:14

http://www.sciencemadness.org/talk/viewthread.php?tid=19864#...