OCR 2016 A Level Chemistry A Topic Exploration

© OCR 2016

A Level Chemistry A Topic Exploration Pack – Organic Synthesis Two-step synthesis © OCR 2016

To begin… • The easiest way to begin thinking about synthesis is to start with one-step reactions. • Identify the functional groups in the reactants and products. • Find them on the synthesis map. • Find the easiest route between them. © OCR 2016

• • In the reactant the functional group is a haloalkane. In the product the functional group is a nitrile group. Find them both on the synthesis map. The only route is to react the haloalkane with CN– in ethanol. CN–/ethanol Haloalkane © OCR 2016 Nitrile

• • In the reactant the functional group is an acyl chloride. In the product the functional group is a 2 o amide. Find them both on the synthesis map. The only route is to react the acyl chloride with a primary amine, but now determine which! Acyl chloride primary amine © OCR 2016 2 o Amide

• The chain highlighted in green is in both the reactant and product. • The functional group in red is the amide. • The chain highlighted in blue is new and must be part of the primary amine. • It contains two carbons. • It must be ethlyamine: © OCR 2016

Try these © OCR 2016

Haloalkane Alkene Na. OH(aq) H 2 O (steam)/H 3 PO 4 or H 2 SO 4, heat sodium halide / H 2 SO 4 Alcohol 1° 2° K 2 Cr 2 O 7/H 2 SO 4, reflux Na. BH 4 Ketone The first reaction changes a secondary alcohol into a ketone. K 2 Cr 2 O 7 with H 2 SO 4 under reflux is the only option. © OCR 2016

Alcohol The second reaction changes an ester into a carboxylic acid. Refluxing with dilute acid is the only option. The alcohol propanol will also be formed. carboxylic acid/ conc. H 2 SO 4 OR acid anhydride Ester OH– heat Carboxylate © OCR 2016 alcohol/conc. H 2 SO 4 dilute acid, heat Carboxylic acid alcohol Acyl chloride

Haloalkane Alkene Na. OH(aq) H 2 O (steam)/H 3 PO 4 or H 2 SO 4, heat sodium halide / H 2 SO 4 Alcohol 1° 2° K 2 Cr 2 O 7/H 2 SO 4, reflux Na. BH 4 Ketone The last reaction changes an alcohol to an alkene. While there is a benzene ring, it is unchanged from reactant to product. Refluxing with an acid catalyst will cause this dehydration. © OCR 2016

Two-step synthesis This gets a lot more complicated as the number of possible functional groups available increase. E. g. starting with a haloalkane: © OCR 2016

Two-step synthesis • In one step a haloalkane can change to three other functional groups. • In two steps this increases to eight. © OCR 2016

Two-step synthesis To help reduce the number of options you can remove certain possibilities quickly with the following questions. • Are there any benzene rings or phenol groups which change? - See the aromatic / phenol reaction pathways map. • Is there the same number of carbon atoms in reactant and product? - This suggests addition of a nitrile or formation of an ester/amide. • Are there other elements in the main chain which change? - Look for esters/amides. © OCR 2016

Two-step synthesis Try this one © OCR 2016

• The reactant has an alkene • The product has a carboxylic acid. © OCR 2016

The easiest route is through primary alcohol to carboxylic acid. © OCR 2016

1. Add H 2 O across the double bond. • This requires steam and acid catalyst, e. g. H 3 PO 4. • This step produces two products: hexan-1 -ol and hexan-2 -ol. • Hexan-2 -ol is the major product (Markownikoff’s rule). 2. Use the minor product (1° alcohol) to form the carboxylic acid. • This step requires K 2 Cr 2 O 7/H 2 SO 4 under reflux. © OCR 2016

Is this a useful way to synthesise hexanoic acid? Think about yield / atom economy. © OCR 2016

Two-step synthesis Try this one. © OCR 2016

• The reactant has a benzene ring and a ketone group. • The product has a benzene ring with a chlorine attached an alcohol group. • This is two separate functional groups requiring two different syntheses! © OCR 2016

• The two reactions are straightforward: – Na. BH 4 to reduce the ketone – Cl 2 and a halogen carrier to add chlorine to the benzene ring. • In a question like this it is important to think about which reaction to do first. © OCR 2016

Which to do first? • Does the reduction in step 2 affect the chlorine in the intermediate? In this case no. or You can do this reaction in either order. (See directing group rules. ) © OCR 2016 • Does the alcohol affect the position of the chlorine? The ketone and alcohol both direct the Cl toward position 3. So no.

Next Steps • The best way improve is to practise. • The process becomes more difficult when you do not have the synthesis map in front of you. Like in the exam. • As you improve try to do more without using the map, or use the blank map which does not show the reagents needed. • Have a go at the two-step synthesis sheet. • Then, start thinking about multi-step syntheses. © OCR 2016

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