Part 6: SYNTHESIS

Answers to the synthesis problems are given below.  These answers have been selected as they are short and efficient, but there are probably other reasonable solutions.  Note some targets have specific stereochemistry that needs to be considered.

When planning syntheses, one should try to work backwards by functional group analysis. The top part of the diagrams show the "retrosynthesis" - the design or plan (the "backgound work") and then below that, the "solution", a reaction scheme step-by-step with all the reagents (as required in the question). Red arrows try to show carbon-carbon bond forming reactions, blue arrows are functional group manipulations. The blue text rationalise the retrosynthetic analysis and information about important reactions are given in green.


1A

synthesis of meta-chlorobenzaldhyde

Common errors : (1) attempting to use Friedel-Crafts reactions to make the aldehyde directly which does not work (HC(=O)Cl decomposes) (2) inefficient introduction of Cl


1B

synthesis of alkyl aromatic amine

Common errors : counting C atoms !


2A

via intramolecular aldol

Common errors : (1) extra steps... (a) no need to dehydrate the initial aldol product (b) use intramolecular aldol rather than Dieckmann


2B

Grignard and epoxide ring opening

Common errors : efficiently managing the regiochemistry of the -OH group


General comments.... Some students started from hydrocarbons with 4 C or less and then made errors in making the materials they could have just used as starting materials.

Common errors included:

(1) incorrect counting of C atoms
(2) trying Friedel-Crafts reactions on deactivated systems
(3) trying to use Friedel-Crafts to directly make aldehydes, acids, amides or esters (it can only be used to give aromatic ketones)
(4) trying to use Grignard reagents to alkylate hydrocarbons rather than adding them to carbonyls or epoxides
(5) poor management / control / incorrect regio and/or stereochemistry
(6) pKa issues....i.e. using strong nucleophiles (i.e. strong bases) in the presence of acidic groups
(7) incorrect reagents, missing reagents, missing work-ups
(8) syntheses of structures that did not match the questions asked !!!!