F324 Synthesis Synthetic Chemistry

Synthetic routes for an organic molecule containing several functional groups: (i) identify individual functional groups (only those encountered in the specification) (ii) predict properties and reactions; devise multi-stage synthetic routes for preparing organic compounds

In industry, a multi-step synthesis of a complex organic molecule starts from commercially available raw material. Crude oil, or a substance derived from it, is the starting points for many manufactured organic compounds. Naturally-occurring molecules which can be extracted from/produced by organisms provide a more sustainable supply of raw materials for synthetic routes. Organic synthesis is often presented as a puzzle. You simply have to KNOW the reactions and conditions you have met at AS and A2. (see map at the end of these notes) Don't let unfamiliar or complicated molecules put you off. Remember that organic chemistry is about functional groups - consider each functional group in your molecule and the reactions which modify it. Keys: - check what effect your reagents may have on other functional groups which are present - work backwards from the target molecule and forwards from the starting molecule - check your equations are balanced ! - make sure you can account for every atom Simple synthesis examples: 1) propene propanone Logic: Working backwards, we can make propanone from propan-2-ol (oxidation of a secondary alcohol reflux with acidified sodium dichromate). That is the only reaction we know at A-level which could make propanone. So the problem becomes how to make popan-2-ol from propene. This is done using phosphoric acid as a catalyst, and steam. Step1: Step 2: H2C=CHCH3 + H2O(g) CH3CH(OH)CH3 CH3CH(OH)CH3 + [O] CH3COCH3 + H2O

2) 3-chloropropan-1-ol 3-hydroxypropene Logic: The only reaction we know at A-level for making alkenes is dehydration of an alcohol using hot, conc. sulphuric acid as a catalyst. We would therefore need to dehydrate propane-1,3-diol or propane-1,2-diol. The first of these can be made by nucleophilic substitution, refluxing 3-chloropropan-1-ol with aqueous sodium hydroxide to hydrolyse it.

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F324 Synthesis

Step 1: Step 2:

ClCH2CH2CH2OH + OH- HOCH2CH2CH2OH + ClHOCH2CH2CH2OH H2C=CHCH2OH + H2O

3) phenylethanone poly(phenylethene) Logic: The polymerisation requires phenylethene as the monomer. Phenylethene can only be made from phenylethanol, using A-level reactions (dehydration of the alcohol using hot, conc. sulphuric acid). Phenylethanol can be made by reduction of phenylethanone using aqueous sodium borohydride. Step 1: Step 2: Step 3: C6H5COCH3 + 2[H] C6H5CH(OH)CH3 C6H5CH(OH)CH3 C6H5CH=CH2 n C6H5CH=CH2 -[C6H5CHCH2]-n

NOTE: You might potentially be presented with a new unfamiliar reaction, which is explained in the question, and expected to use this within a synthesis route. Possible examples of reactions not on the syllabus which might be used in this way: a) replacement of Cl2 with an alkyl chloride e.g CH3Cl or C2H5Cl in an electrophilic substitution using a halogen carrier e.g. AlCl3. Here the electrophile is CH3+ or C2H5+ and it attacks the ring in the same way as Cl+ or NO2+. This is a good way of adding an alkyl group to a benzene ring. e.g. suggest a synthetic route for creating 4-methylphenylamine starting with benzene. - nitration of the ring using conc HNO3 and conc H2SO4 at 55C - reduction of the NO2 group using Sn/conc. HCl under reflux - followed by addition of the methyl group using CH3Cl/AlCl3 b) nucleophilic addition of CN- ion to a C=O group The conditions are HCN in the presence of NaCN/KCN e.g. RCHO + HCN
CN R C H OH

or nucleophilic substitution of halogen group by CN- ion Conditions: reflux in ethanol solvent with KCN reagent RX + CN- RCN + XThese are useful reactions because they add to the carbon chain

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F324 Synthesis The CN group can subsequently be: hydrolysed to -COOH (reflux with HCl(aq)) reduced to CH2NH2 (by LiAlH4 in dry ether) For example, you might be asked to turn CH3CH2Br into CH3CH2COOH: Step 1: nucleophilic substitution of Br by CN Step 2: hydrolysis of CN to COOH %Yield Revisited In industry the %Yield is very important, and in a synthetic route each step has the potential for yield to be lost. %Yield = actual mass of product made theoretical mass of product x 100

Typically we know how much product we need to make for commercial use, and from experience we may know the %yield to expect from our process. The challenge is to work out how much raw material we'd need to buy and feed in - the mass of reactant actually required is GREATER than the mass that should be required theoretically if %yield was a perfect 100%. mass of reactant actually required = 100 % Yield x theoretical mass of reactant required

Method calculate moles of product needed use mole ratio to calculate moles of reactant that should be used (if yield is 100%) calculate theoretical mass of reactant that should be required (if yield is 100%) calculate the mass of reactant that is actually required for yield less than 100%: e.g. The synthesis of caprolactam (C6H11NO) from cyclohexanone is very efficient and can be achieved with a 99% yield of product. Calculate the mass of cyclohexanone (Mr = 98) needed to produce one tonne of caprolactam. Give your answer to two significant figures. (The equation for the reaction has a 1:1 mole ratio) Mr of caprolactam (C6H11NO) = 113 Moles of caprolactam in 1 tonne = 1,000,000/113 = 8849.6 Moles of cyclohexanone theoretically needed = 8849.6 (1:1 mole ratio) Mass of cyclohexanone theoretically needed = 8849.6 x 98 = 867,257g Mass of cyclohexanone actually needed = (100/99) x 867,257 = 876,017g

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F324 Synthesis

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