Multi-step conversions and unknown compounds

Working backwards

A conversion asks you to go from compound A to compound B. Do not start at A. Look at B first.

1. Count the carbons. If B has more carbons than A, which reaction adds them? The usual ones are cyanide (plus 1), a Grignard reagent with CO$_2$ (plus 1), an aldol (joins two), Friedel-Crafts acylation (plus 2 for an acetyl group) and the Perkin reaction (plus 2). If B has fewer carbons, use soda lime or the haloform reaction (minus 1).
2. Name the groups. What functional group does B have? Which compounds can give that group?
3. Go back one step at a time. Ask what could make B, then what could make that, until you reach A.
4. Check the reagents. Does a reagent also attack another group in your compound? If so, protect it or choose another reagent.

Worked conversions

Ethanal to butan-1-ol (2 steps). The carbons double, so use an aldol. Dilute NaOH and heat give but-2-enal. Hydrogen over nickel reduces both the C=C and the C=O: $\text{CH}_{3}\text{CH}{=}\text{CHCHO} + _{2}\text{H}_{2} \xrightarrow{\text{Ni}} \text{CH}_{3}\text{CH}_{2}\text{CH}_{2}\text{CH}_{2}\text{OH}$.

Ethanoic acid to propanoic acid (4 steps). A carbon must be added, so use a Grignard reagent and CO$_2$. Reduce the acid with LiAlH$_4$ to ethanol. Make bromoethane with PBr$_3$. Form the Grignard reagent with magnesium in dry ether. Pour it over CO$_2$, and add dilute acid.

Bromobenzene to acetophenone (2 steps). Make the Grignard reagent, then add ethanenitrile and hydrolyse. The carbon of the nitrile becomes the carbonyl carbon.

Toluene to benzaldehyde (3 steps). Oxidise to benzoic acid with alkaline permanganate. Use SOCl$_2$ to make benzoyl chloride. Reduce it by the Rosenmund method. Etard does the same in one step, but a three-step route is a good exercise in yields.

The yield of a route

The yields of the steps multiply. A route of three steps at $85\ \%$, $90\ \%$ and $80\ \%$ gives only $61\ \%$. A route with many steps loses much of its material, so shorter is better.

Set the three yields to $90\ \%$ each, and the overall yield is $73\ \%$. Make one of the steps $50\ \%$, and the whole route falls. The poorest step matters most.

Practise with new numbers

Naming an unknown compound

Suppose a compound has the formula $\text{C}_8\text{H}_8\text{O}$. Work in four moves.

1. Degree of unsaturation. $\dfrac{2C + 2 - H}{2} = \dfrac{2 \times 8 + 2 - 8}{2} = 5$. Four of the five units are a benzene ring. The fifth is a C=O or a C=C.
2. Functional group. Test with 2,4-dinitrophenylhydrazine: an orange solid shows a carbonyl group.
3. Aldehyde or ketone. Tollens' reagent. A silver mirror shows an aldehyde. If there is none, the compound is a ketone.
4. Detail. Iodine in base. A yellow precipitate shows a CH$_3$CO group. Hot permanganate on the side chain, or ozonolysis, can finish the job.

A compound of formula $\text{C}_8\text{H}_8\text{O}$ that gives the 2,4-DNP solid, no silver mirror and the iodoform test is acetophenone.

Other tests help. A compound that gives CO$_2$ with NaHCO$_3$ is a carboxylic acid. Brominated water decolorises with C=C bonds or with phenols. The sodium salt of the oxidation product, heated with soda lime, shows the carbon skeleton.

A route finder in Python

You can treat reactions as a map. Each compound class is a place, and each reaction is a road. The program finds the shortest route between two places with a search that looks at all the one-step neighbours first, then the two-step ones, and so on. This is breadth-first search.

Common mistakes

• Starting at the starting material. Start at the target.
• Adding yields. They multiply.
• Using a reagent that attacks a second group. Check every group in the molecule.
• Forgetting the carbon count. If the carbons change, a carbon-carbon bond must be made or broken.
• Treating one test as proof. A positive iodoform test is also given by ethanal and by secondary alcohols with CH$_3$CH(OH)-.

Remember these

• Work backwards from the target. Count the carbons first.
• Cyanide and Grignard with CO$_2$ add 1. Aldol joins two. Soda lime and haloform remove 1.
• Overall yield is the product of the step yields.
• Use the degree of unsaturation and the tests, in order, to name an unknown.

Check yourself

Try each one on your own first. If you are stuck, open a hint. Then check with Show the answer.

1. How do you convert bromoethane into propanoic acid in two steps?

2. What is the degree of unsaturation of $\text{C}_9\text{H}_{10}\text{O}$?

3. A compound gives an orange solid with 2,4-DNP and a silver mirror with Tollens' reagent, but no red solid with Fehling's solution. What does this show?

4. Three steps have yields of 70 %, 80 % and 50 %. What is the overall yield?

References

• Clayden, Greeves and Warren, Organic Chemistry, the chapters on retrosynthesis and on the carbonyl group.
• Morrison and Boyd, Organic Chemistry, the chapters on aldehydes and ketones and on carboxylic acids.
• NCERT, Chemistry Part II for Class XII, Chapter 8.