Q22-65E - Organic Chemistry (Mcmurry)

Question

Sodium pentothal is a short-acting barbiturate derivative used as a general anesthetic and known as a truth serum in popular culture. It is synthesized like other barbiturates (see the Something Extra at the end of this chapter), using thiourea, (H₂N)₂C=S, in place of urea. How would you synthesize sodium pentothal?

                                                            

Step-by-Step Solution

Answer

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Step 1: What are Barbiturates and the initial step for their formation:

Barbiturates, a large class of drugs with a wide variety of uses, constitute one of the earliest successes of medicinal chemistry.

The synthesis and medical use of barbiturates goes back to 1904 when Bayer, a German chemical company first marketed a compound called barbital, trade named Veronal, as a treatment for insomnia 

Diethyl malonate commonly has two α hydrogens flanked by two carbonyl groups.

Therefore, it is readily converted into its enolate ion, which can be alkylated by reaction with an alkyl halide. A second alkylation can also be carried out if desired since acetoacetic ester has two acidic hydrogens:

 

Step 2: Reaction with thiourea, (H 2 N) 2 C=S , then gives the product barbiturates by a twofold nucleophilic acyl substitution reaction of the ester groups with the NH 2 groups of thiourea