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How does one determine the relative basicity of a nitrogen in a molecule?
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+ Biochemistry
Posted by
Mel Siegel
How does one determine the relative basicity of a nitrogen in a molecule?
Use a combination of
the exclusion principle: sort out the unlikely centres with low electron density and
paper work to figure out those nitrogen atoms for which the additional positive charge can be distributed over a larger part of the molecule without moving the proton.
In the case of caffeine (1) the amide and the imide are rather unlikely centres for protonation! You have probably already ruled out the amide nitrogen in the benzamide case (your second molecule) in favour of the aniline site.
From an initial number of four possible centres in 1, only two remain.
Now, let's see whether the positive charge resulting from protonation can be stabilized.
This looks fair, but creates a quarternary ammonium ion for which no obvious charge distribution seems to be available.
Let's examine the last possibility:
Would you agree that this looks much more promising?
the exclusion principle: sort out the unlikely centres with low electron density and
paper work to figure out those nitrogen atoms for which the additional positive charge can be distributed over a larger part of the molecule without moving the proton.
In the case of caffeine (1) the amide and the imide are rather unlikely centres for protonation! You have probably already ruled out the amide nitrogen in the benzamide case (your second molecule) in favour of the aniline site.
From an initial number of four possible centres in 1, only two remain.
Now, let's see whether the positive charge resulting from protonation can be stabilized.
This looks fair, but creates a quarternary ammonium ion for which no obvious charge distribution seems to be available.
Let's examine the last possibility:
Would you agree that this looks much more promising?
For the first molecule for example, the double bonded nitrogen is less basic due to increasing s character (closer to nucleus, less likely to bind to H).
I think most of your examples can be reasonably thought out with these two key points.
For the first molecule for example, the double bonded nitrogen is less basic due to increasing s character (closer to nucleus, less likely to bind to H).
I think most of your examples can be reasonably thought out with these two key points.
Use a combination of
the exclusion principle: sort out the unlikely centres with low electron density and
paper work to figure out those nitrogen atoms for which the additional positive charge can be distributed over a larger part of the molecule without moving the proton.
In the case of caffeine (1) the amide and the imide are rather unlikely centres for protonation! You have probably already ruled out the amide nitrogen in the benzamide case (your second molecule) in favour of the aniline site.
From an initial number of four possible centres in 1, only two remain.
Now, let's see whether the positive charge resulting from protonation can be stabilized.
This looks fair, but creates a quarternary ammonium ion for which no obvious charge distribution seems to be available.
Let's examine the last possibility:
Would you agree that this looks much more promising?
Use a combination of
the exclusion principle: sort out the unlikely centres with low electron density and
paper work to figure out those nitrogen atoms for which the additional positive charge can be distributed over a larger part of the molecule without moving the proton.
In the case of caffeine (1) the amide and the imide are rather unlikely centres for protonation! You have probably already ruled out the amide nitrogen in the benzamide case (your second molecule) in favour of the aniline site.
From an initial number of four possible centres in 1, only two remain.
Now, let's see whether the positive charge resulting from protonation can be stabilized.
This looks fair, but creates a quarternary ammonium ion for which no obvious charge distribution seems to be available.
Let's examine the last possibility:
Would you agree that this looks much more promising?
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For amine basicity:
Basicity decreases with increasing s character
Basicity decreases with increasing stability, due to resonance/ delocalization
https://www2.chemistry.msu.edu/faculty/reusch/virttxtjml/amine1.htm (taken from this webpage)
For the first molecule for example, the double bonded nitrogen is less basic due to increasing s character (closer to nucleus, less likely to bind to H).
I think most of your examples can be reasonably thought out with these two key points.
For amine basicity:
Basicity decreases with increasing s character
Basicity decreases with increasing stability, due to resonance/ delocalization
https://www2.chemistry.msu.edu/faculty/reusch/virttxtjml/amine1.htm (taken from this webpage)
For the first molecule for example, the double bonded nitrogen is less basic due to increasing s character (closer to nucleus, less likely to bind to H).
I think most of your examples can be reasonably thought out with these two key points.
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