synthesis - Why are solid phase organics often conjugated to HCl?

Many uncharged organic compounds are sold in solid phase with HCl conjugate - e.g. the antihistamine diphenhydramine.HCl or the derivitizing agent pentafluorobenzyl hydroxylamine.HCl, among many others. Assuming the compound will be dissolved at relatively low concentrations in a buffered medium (for instance when a drug enters the bloodstream) the HCl shouldn't have much chemical effect. Why is it there - does it aid crystallization, or perhaps it's leftover from synthesis and is difficult to separate?

Answer

Does it aid crystallization?

Yes.

All of the drugs that you see as "hydrochlorides" are alkaloids - a class of basic natural products containing one or more amine functional groups. The dimethylamino group in the upper right of the structure of diphenhydramine (below) is a prime example.

Many of these compounds are not crystalline (at best amphorous, at worst waxy or liquid). These compounds are expensive to purify, since the inexpensive method of recrystallization is not an option. Chromatography is an expensive and wasteful process on the industrial scale.

Reacting alkaloids with HCl (or other acids - for example dextromethorphan HBr) usually produces a crystalline compound. These crystalline compounds are easier to purify.

There is a second more important benefit associated with the hydrochloride salts - they have higher bioavailability than the freebases. The freebase is nonpolar and poorly soluble in water. The hydrochloride salt has an ionic group, which increases water solubility.