Organic Synthesis

Organic Synthesis

1. HSW:Artificial Sweeteners

   • Sweetness with few calories
   • The first - Saccharin (benzoic sulfinide)
     • Unstable when heated
     • Does not react chemically with other food ingredients
     • Stores well
     • Unlike sucrose, it has no energy value
       • Calorie free
     • Fahlberg and Remsen
     • High doses → bad health?
   • Cyclamate
     • Discovered accidentally by Sveda
     • Not as sweet as saccharin but does not leave aftertaste
     • Sodium or calcium salt of cyclamic acid
       • Prepared by sulfonation of cyclohexylamine
         • Cyclohexylamine it believed to be toxic in animals
   • Aspartame
     • Dipeptide of phenylalanine and aspartic acid
     • 1965 Schlatter
     • 200 times sweeter than sucrose and dissolves readily in water
     • Tends to interact with other chemicals in food
     • Decomposes hen heated strongly
     • Bacterial Fermentation, Synthesis, Purification

2. Identifying organic molecules for synthesis

   • Sensitive chemical analysis
     • Step by Step
     • Consider toxic, hazardous compounds
     • Consider optical isomers: stereo-selectivity
   • Quantitative methods
     • % of elements
     • Combustion analysis: % C,H
     • Empirical formula
       • Mass spectrometer → RMM → Molecular formula
   • Characteristic reactions of functional groups
   • Modern techniques
     • IR spectroscopy
       • Functional groups
     • Mass spectrometry
       • RMM
       • Ion fragments → possible groups
     • Nuclear Magnetic Resonance (NMR)
       • Groups of H atoms

3. Difficult, more steps → more difficult

4. Predicting properties of organic compounds

   • Physical
     • Isomers
     • Functional group → H bond → ↑ mp/bp
   • Chemical
     • Functional group
       • Electrophiles, neutrophiles
       • Addition, Sustitution
       • Oxidation, reduction
     • Acid, base
     • Solubility

5. Planning synthetic routes

   • Now may use computers
   • +/- C from organic molecule
     • +: RX reflux with KCN dissolved in ethanol → nitrile, hydrolysis → RCOOH
     • +: Friedel-Crafts alkylation
     • -: Hofmann's degradation (amide + Br2 + KOH + heat → amine)
     • -: Hunsdiecker reaction
   • Reaction pathways
   • Choosing synthesis route
     • Starting material, mass production e.t.c.

6. Synthesis of stereo specific drugs

   • Enantiomeric drugs
     • SN1 → racemic mixture
       • Usually only one enantiomer is useful, the other may be harmful
         • Thalidomide
       • Separate and test enantiomers
   • Making single enantiomers
     • Reduced amounts can be given → less side effects
     • Separate enantiomers
       • Thin-layer chromatography
       • £££
     • Asymmetric synthesis
       • Make only one enantiomer
       • £££
       • Extreme condtions
     • Chiral auxillaries
       • Direct functional groups
       • Keep costs down
     • Enzymes
   • HSW: thalidomide
     • Still used in treatment of leprosy, cancer

7. Control measures for hazards

   • Fume cupboard, reduce scale, safer route or reactants
   • Hazard: the potential to cause harm
     • Hazcard
   • Risk: the likelihood of harm
   • Risk assessment
     • Control measures to reduce risk

8. Combinatorial chemistry

   • Enables automated processes to carry out routine reactions very quickly and accurately
   • Used to make structurally similar compounds
     • Data libraries → drug development
   • Similar drugs, possible uses
   • Save time, more compounds synthesised