CHE 230

University of Kentucky

Are the reaction conditions acidic or basic?

1. Look for a good acid. The acid may be:
   • indeterminate, such as H⁺ or H₃O⁺;
   • a strong mineral acid such as HCl, HBr, or H₂SO₄;
   • a carboxylic acid such as AcOH, perhaps written as RCOOH or RCO₂H;
   • a sulfonic acid such as TsOH, MsOH, or TfOH;
   • an ammonium salt of any of the above, such as pyrH^{+ –}OTs or Et₃NH^{+ –}OAc.

   Note that neither water nor an alcohol ROH counts as an acid for the purposes of determining what the reaction conditions are!

2. Failing (1), look for any of the following indicators of basic conditions:
   • Anions such as MeO^–, EtS^–, F^–, etc.;
   • Salts of alkali metals such as Li, Na, or K, or nonhalide salts of Mg such as CH₃MgBr;
   • Amines such as NH₃, NEt₃, i-Pr₂NEt, or pyridine;
   • Typical nonnucleophilic bases that may fall into any of these three categories, such as DBU (an amine), LDA (contains an N-Li bond), or t-BuOK.

   (Note: Alkali metal salts of the heavier halogens such as NaCl, LiI, and KBr can exist under acidic as well as basic conditions. However, if no strong acid is present, then you can act as if the conditions are basic.)

3. Failing (1) and (2), if either a substitution or elimination reaction of the electrophile will generate a strong acid such as HBr or TsOH as a coproduct, the conditions are "stealth acidic". (To see if a mineral acid is produced, draw a substitution or elimination product, and then balance the equation.) The electrophiles that react under stealth acidic conditions have a halide or sulfonate leaving group (not OH) and usually form a low-energy carbocation (heavily substituted or stabilized by resonance) when the leaving group leaves.

4. Failing (1), (2), and (3), if you see a molecule that contains a neutral, heavy congener of N or O with a lone pair, such as Ph₃P or Me₂S, the conditions can be considered basic.

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