[Babcock_Hall]

Suppose I have reagents A and B, which I hope to make into P and perhaps Q.  Method 0 is to combine them all at once.  Method 1 is to add A drop-wise to a solution of B, and Method 2 is to add B drop-wise to a solution of A.  Let's assume that there is little or no literature precedent.  In general how does one make a choice among these three methods?  An old thread of mine here, plus some recent work in my lab have prompted me to think about this question.  I can supply this specific example at some point.

[kriggy]

Well its difficult to tell you without specifics IMO. I guess you have to try but I guess good start is
to add reagent in excess into the other one (to avoid reaction going too fast). Probably adding the reagents slowly is good too for starters so the stuff dont explode into your eyes.
I could find some examples where it matters but not sure how useful it might be for you

[Babcock_Hall]

http://www.chemicalforums.com/index.php?topic=68832.0

We can start with the example that motivated my question.  This link is an old thread of mine, and we recently attempted to repeat one such reaction (between cysteine and bromoacetylpyridinium bromide) and attempted a similar reaction at the same time (http://www.chemicalforums.com/index.php?topic=86735.0).  Briefly, this reaction sometimes works in our hands but sometimes gives side products or other unexpected results.  One possible side reaction is that the thiolate is capable of reducing the product sulfidoketone to a ketone, an undesired reaction.

Let's let A be the thiol and B be the halomethylketone.  I can see why the order of addition might matter.  If you add the B drop-wise to A (Method 2), then P (the sulfidoketone) will be present in large amounts at the same time that A (the thiol or thiolate) is present.  If you add A drop-wise to B (method 1), then P is present at the same time as B (the halomethyketone).  Perhaps there would be less opportunity for a side reaction with method 1.  I actually used Method 0 when I did this work a few weeks ago.

[phth]

I agree with method 1.  Keeping the probability of the thiolate interacting with the haloketone can be controlled by keeping the concentration low to preclude side reactions.  The order of addition does matter for example acid to base or base to acid?  Base to acid causes the solution to diffuse inwards, and opposite for acid to base. Base to acid causes more heat.

[zarhym]

Method 0: this method does not have any stoichiometry control of the reaction. If the reaction is not stoichiometry sensitive, it is OK to use this method.

Method 1: The B is the excess reagent/reactant during the reaction, especially at the beginning of your reaction. If B can react with 2eq of A, it's very likly to happen.

Method 2: It's the opposite of method 1.

Another thing is to consider the nature of the reagent.
When A and B are mixed together, does the mixture give out a lot of heat/gas/peciptations?
If so, you have to choose the methods carefully to have good controls of the heat/gas/peciptations generated.