[minimal]

Hi all, I have a fairly general question, but feel free to make it as specific as you like.

I am currently reading The Art of Writing Reasonable Organic Reaction Mechanisms.  I was wondering how it would be possible to determine reaction conditions for reactions that you are unfamiliar with.  Would you look at bond energies to assume a standard enthalpy change of reaction in order to determine the free energy change.  Could you do the same thing with a model of the supposed transition state in order to determine the activation energy?  Would you be able to relate this to a particular temperature reliably? 
Also, so often a reagent must be added very slowly to a reaction.  How is it possible to know this beforehand? Or is it?  Is there a way to reliably predict at which conditions competing reactions will dominate, or is it mostly done experimentally until optimal conditions are found?

Thanks.

[azmanam]

By far my favorite chemistry book.  You'll be in great shape when you get through that book. Good for you:)

Typically reaction conditions are not known before hand.  Reaction conditions are usually developed before a complete mechanism is elucidated, though.  That's the field of new reaction methodology.  I think you'll be better able to determine reaction conditions through practice and extensive literature reading.  Minimal to extensive optimization is almost guaranteed. 

After a few years of reading the literature and doing wet chemistry yourself, you'll probably be ok at predicting standard conditions for standard transformations (protections, Swern, etc).  For complex compounds, uncommon reactions, or hindered functional groups, optimization may be necessary.

To a first approximation, though, you can probably guess stoichiometry and maybe solvent ok. 

[minimal]

Great, thanks, you're always a big help. I had a feeling that was what the answer was. What sites for trawling through the literature would you recommend in order to get better acquainted with reaction conditions?

[azmanam]

In order of how often I used them: scifinder, beilstein, encyclopedia of reagents for organic synthesis, isi web of science, Green's protective group book, Kurti's Strategic Application of Named Reactions in Organic Synthesis, March's Advanced Organic Chem

then get yourself an rss feed reader (i use thunderbird) and start browsing the literature daily/weekly.  JOC, Org Lett, JACS, Angewandte, Nature Chem, Acc Chem Res, and Chem Rev are the ones I browse daily.

[orgopete]

… I was wondering how it would be possible to determine reaction conditions for reactions that you are unfamiliar with. …
Also, so often a reagent must be added very slowly to a reaction.  How is it possible to know this beforehand? Or is it?  Is there a way to reliably predict at which conditions competing reactions will dominate, or is it mostly done experimentally until optimal conditions are found?

Thanks.

Since you are looking at reaction mechanisms, there are two generalities about reactions for which conditions can be predicted. If you have an irreversible reaction, then the conditions are generally related to solvent compatibility. Grignard reactions are carried out in aprotic solvents. While ether is commonly used, the reaction can tolerate a much wider variety.

If a reaction is reversible, then conditions must be chosen that can effect reagent concentrations. For example, enamines are formed reversibly. If water is removed from a reaction, the equilibrium favors enamine. If an enamine is added to water with an acid present, the reaction will hydrolyze the enamine.

The other option for conditions probably relates suppression of by-products. If a Grignard reaction is carried out by adding the Grignard to an enolizable carbonyl compound, then as the reaction proceeds, alkoxide intermediate concentration will grow. If that catalyzes a side reaction with the carbonyl compound, then it may be better to add the carbonyl compound to the Grignard. For issues like this, no hard rules will be found. It is often a case of determining the by-products and adjusting the reaction to suppress them as a secondary process to initially just attempting a reaction.