Benzaldehyde Chloramphenicol

The synthetic route to chloramphenicol is described in U.S. Patent 2,4B3,BB4 as follows 1.1 g of sodium is dissolved in 20 cc of methanol and the resulting solution added to a Solution of 5 g of benzaldehyde and 4.5 g of /3-nitroethanol in 20 cc of methanol. After standing at room temperature for a short time the gel which forms on the mixing of the reactants changes to a white insoluble powder. The precipitate is collected, washed with methanol and ether and then dried. The product thus produced is the sodium salt of... 

Warfarin sodium Benzal acetophenone Alkofanone Benzaldehyde Butalamlne HCI Chloramphenicol Fenipentol Isocarboxazid Oxacillin sodium Penicillin G benzathine Phenylpropanolamine HCI Tripelennamine Benzaldehyde cyanohydrin Ethotoin... 

The production of benzal chloride is relatively insignificant in comparison with that of benzyl chloride. Benzal chloride is mainly used to make benzaldehyde, obtained by alkaline hydrolysis (Na2C03) or in an acidic medium (ZnCl2) at 120 to 130 °C, Benzaldehyde however can also be recovered as a byproduct of the oxidation of toluene to benzoic acid, occurring in quantities of between 5 and 8% this route leads to benzaldehyde which is distinguished by the lack of chlorine impurities. The main uses for benzaldehyde are the production of benzyl alcohol (see Chapter 6.3.1.1), chloramphenicol, 2-phenylglydne and cinnamaldehyde. 

The antibiotic chloramphenicol, which is mainly used in veterinary medicine, is produced by the Boehringer Mannheim process from dnnamic alcohol, which in turn is obtained from benzaldehyde through aldol condensation with acetaldehyde and reduction of the intermediate cinnamaldehyde. 

As an example, the photodegradation products of chloramphenicol (nitroso-compounds and paranitro-benzaldehyde) are considered carcinogenic. These products will be formed in vitro and in vivo and can reach the bone marrow in rats [37]. Chronic use of chloramphenicol has been coimected with bone marrow depression, not caused by chloramphenicol itself. Apart from the question if this risk is estimated well [38], it can be avoided completely if the patient covers his skin if a dermal preparation has been applied and only use chloramphenicol as eye ointment 1 % at night. See also Sect. 10.5. 

Example 9.3 Structure and stereochemistry of the antibiotic (—)-chloramphenicol is presented in (lf ,2/ )-TM 9.2. Propose the retrosynthesis of racemic TM 9.2 neglecting absolute configurations at stereogenic centers and then suggest the synthesis from benzaldehyde and 2-nitroethanol and propose the simple synthesis of 2-nitroethanol. Indicate a reaction step that can be completed diastereo- and enantioselecti vely ... 

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