1 Before you start
A quick baseline. Your answers aren't graded now. You'll see the same questions at the end to measure what you've learned.
2 Why chemists draw this way
A skeletal formula is not a picture of a molecule. It is a convention, and like any convention it has to be learnt before it can be read. This module teaches you to read one fluently, because everything else in this course and everything you will do in computer-aided drug design starts here.
Here is caffeine written out in full: every carbon labelled, every hydrogen drawn. Now here it is as a chemist would draw it. The second version has the same information and about a fifth of the ink, and once you can read it, it is very much faster to take in.
The trick is that two things are left implicit. Every vertex and every line end is a carbon atom unless a letter says otherwise. Every carbon then has as many hydrogens attached as it needs to reach four bonds. Nothing has been hidden: it has been agreed in advance, so it does not need saying.
Caffeine
Heteroatoms — anything that is not carbon or hydrogen — are always labelled. So are hydrogens attached to them, because an N-H or an O-H is a hydrogen bond donor and that matters enormously. A hydrogen on carbon is almost never a donor, which is exactly why it can be left out.
3 Reading the hydrogens back
Carbon makes four bonds. Count the lines meeting at a vertex, subtract from four, and that is the number of hydrogens. A vertex with two lines has two hydrogens; a line end has one line, so three hydrogens, a methyl group. A double bond counts as two.
In a skeletal formula, how many hydrogens are on a carbon at the end of a plain line?
Reading ibuprofen off the page
How many hydrogens sit on each carbon of ibuprofen's isobutyl group?
Step 1: study the solution
- Find the branch point: it has three lines, so one hydrogen
- The two carbons hanging off it each have one line, so three hydrogens each — two methyls
- The carbon joining the branch to the ring has two lines, so two hydrogens
Step 2: fill the blanks
Now do the same for the carbon bearing the acid.
Step 3: now you try
Count its lines, then subtract from four.
4 Wedges, dashes and the third dimension
A page is flat and a molecule is not. The convention for putting the missing dimension back is simple: a plain line lies in the plane of the page, a solid wedge comes towards you, and a hashed wedge goes away from you. The wide end of a wedge is the end nearer you.
You will meet this properly in module 7, when stereochemistry gets a module of its own. For now, notice only that a wedge or a dash is never decoration. If a drawing has them, the person who drew it is telling you something specific about arrangement in space, and leaving them off changes what molecule you have described.
Ibuprofen
The 3D model · drag to rotate
What you would draw · this exact viewpoint
5 The shorthand you will meet unexplained
Papers and patents abbreviate relentlessly, and nobody stops to define the abbreviations. These are the ones that account for almost all of it:
- Me methyl, CH₃ — one carbon.
- Et ethyl, CH₂CH₃. Pr propyl, iPr isopropyl (branched), Bu butyl, tBu tert-butyl (three methyls on one carbon).
- Ph phenyl — a benzene ring attached by one of its carbons. Bn benzyl — a phenyl plus a CH₂ between it and the rest.
- Ac acetyl, CH₃C(=O)–. Boc and Ts are protecting groups you will see in synthesis schemes rather than in drugs.
- R is a placeholder: 'something goes here, and it does not matter what for the point I am making'. A drawing full of R groups is describing a family, not a compound.
Ph and Bn are not the same, and confusing them is the commonest of these errors. Benzyl has an extra CH₂. That one carbon changes the geometry, the flexibility and, often, the metabolism.
A paper describes a compound as having a benzyl group where the previous analogue had a phenyl. What changed?
6 Four pictures of the same thing
A condensed formula, a skeletal formula, a ball-and-stick model and a space-filling model are four representations of one object, and each answers a different question. The condensed formula tells you the atom count. The skeletal formula tells you the connectivity, which is what you need in order to reason about chemistry. Ball-and-stick shows you geometry: bond angles and which groups are near which. Space-filling shows you the shape a protein actually meets — a surface, not a wire frame.
Aspirin
Which representation would you use to decide whether a substituent will fit into a narrow pocket?
7 Describing a structure out loud
Chemists describe a molecule in a fixed order, and copying that order will make you sound like you know what you are doing long before you feel like it. Core scaffold first, then substituents, then stereochemistry.
So ibuprofen is not 'a carboxylic acid and a benzene ring and some methyls'. It is: a benzene ring, para-substituted, carrying an isobutyl group on one side and a propanoic acid on the other, with a single stereocentre at the carbon bearing the acid. That sentence is the molecule.
Describe paracetamol in that order — scaffold, then substituents, then stereochemistry — in one sentence.
8 Now draw ten
Reading is not the same as writing, and the only way to find out whether you can really read a structure is to be made to produce one. Draw each of the following from its description. The sketchpad checks what you draw against the real structure.
Draw ethanol.
Draw benzene.
Draw acetic acid (ethanoic acid).
Draw phenol.
Draw acetaminophen (paracetamol): a benzene ring with an OH and, para to it, an NH joined to an acetyl group.
Draw aspirin: a benzene ring bearing a carboxylic acid and, next to it, an oxygen carrying an acetyl group.
Draw diethyl ether.
Draw pyridine — benzene with one CH replaced by N.
Draw ibuprofen.
Draw caffeine.
9 What you should be able to do now
Given an unfamiliar structure, you should be able to say how many carbons it has, where its hydrogens are, which atoms are heteroatoms, and what the abbreviations mean. You should be able to draw a molecule from a spoken description and check it yourself.
You cannot yet say what any of it does. That starts in the next module, with valence and charge, and then in module 3, where the groups you have been drawing acquire consequences.