[tush]

Why Purines give two isomers (N9 and N7) during alkylation ?

[Babcock_Hall]

What are your thoughts?  It is a forum rule that you must give your attempt to answer a question or your thoughts, before we can help you.

[tush]

Hi,
At basic pH the deprotonated purine (or purine derivatives) N9 and N7 resonance forms are more stable than others. From my practical experience of alkylation of 6-chloropurine we get major N9 product and minor N7 product. I can not understand that why N7 isomer is unavoidable. (There are literature stating that exclusive N9 product formation, but I doubt as the yields are not quantitative and N7 products are overlooked because of minor amounts (but they still exists !!))

[phth]

Thermodynamics dictates any product distribution ratio.  The way to favor one outcome over the other is by raising or cooling the temperature.  If you're following a written procedure and getting a different result, then the simple explanation is that you did not follow their procedure correctly.  If you are able to repeat the same result, then you can change things.  I think that it probably has to do with a concentration effect. They may say dropwise, but they may be doing it for longer than you did....there is always selectivity if rates are unequal.

[AWK]

Phth

Thermodynamics dictates any product distribution ratio

what about kinetic effect?

Tush

Why Purines give two isomers (N9 and N7) during alkylation ?

There are methods of high selectivity at N9.

[Babcock_Hall]

tush,

Which journal articles have you consulted so far?

[kamiyu]

Thermodynamics dictates any product distribution ratio.  The way to favor one outcome over the other is by raising or cooling the temperature.  If you're following a written procedure and getting a different result, then the simple explanation is that you did not follow their procedure correctly.  If you are able to repeat the same result, then you can change things.  I think that it probably has to do with a concentration effect. They may say dropwise, but they may be doing it for longer than you did....there is always selectivity if rates are unequal.

1. I agree that this is mainly a matter of thermodynamic factor

2. Apart from temperature, solvent effect is also very important here (I am wondering if the -ve charge on N9, together with the N3, can form sort-of a cyclic structure with some cation, resulting in additional stability. this can be solvent-dependent)

3. I have to say that many procedures in the literature are not reproducible. I personally witnessed synthesis in the Nature paper is just plain wrong (I did the synthesis myself and got the crystal structure and found the data in the Nature paper just plain wrong)

[kamiyu]

Because the -ve charge on N9 and N7 are resonance-based (i.e. they are not relationship of precursor or successor of each other), kinetic factor is not likely.

[phth]

Thermodynamics dictates any product distribution ratio.  The way to favor one outcome over the other is by raising or cooling the temperature.  If you're following a written procedure and getting a different result, then the simple explanation is that you did not follow their procedure correctly.  If you are able to repeat the same result, then you can change things.  I think that it probably has to do with a concentration effect. They may say dropwise, but they may be doing it for longer than you did....there is always selectivity if rates are unequal.

1. I agree that this is mainly a matter of thermodynamic factor

2. Apart from temperature, solvent effect is also very important here (I am wondering if the -ve charge on N9, together with the N3, can form sort-of a cyclic structure with some cation, resulting in additional stability. this can be solvent-dependent)

3. I have to say that many procedures in the literature are not reproducible. I personally witnessed synthesis in the Nature paper is just plain wrong (I did the synthesis myself and got the crystal structure and found the data in the Nature paper just plain wrong)

I agree with you.  In addition, it's easy to prove experimentally solvent effects by switching between polar and non polar solvents.