Arenes benzene Chemistry Organic chemistry

Aromatics I part 2

OK welcome back, I hope by now that you have worked out the mechanism of the nitration of benzene by the mixture of nitric and sulfuric acids.

Please spell sulfur and all related words using the f verion, when I was a PhD student the UK’s national chemistry organisation (Royal Society of Chemistry) instructed all chemists to stop using the ph version of sulfur and thus instead of writing sulphur we should write sulfur. As PhD students we found it fun to rebel by writing sulphur but please do not do this.

The first step in the reaction is to create the true electrophile for the reacton, in most cases benzene rings will not react with nitric acid. What is needed is sulfuric acid to protonate the nitric acid.

We can explain this reaction using curved arrows, keep in mind that just because there is no carbon atoms does not mean we can not use the curved arrow. Keep in mind that there are more than two ways to protonate nitric acid, just because we can draw a reasonable looking mechanism does not mean it is true. The other way to protonate nitric acid is to put the proton onto the oxygen atom which already bears the hydrogen.

Some Italian work from the 1980s suggests that in the gas phase that this second protonation is thermodynamically favored. It also indicates that in the gas phase the break up of the protonated nitric acid into a water molecule and a NO2 (Nitronium) cation is very easy. This will occur according to the following reaction. The concentrated sulfuric acid will help the reaction, water reacts with concentrated sulfuric acid thus the sulfuric acid acts as a dehydration reagent.

The tetrafluoroborate of this cation has been characterized by X-ray crystallography. If you want to see details of the work see I. Krossing, I Raabe and E Birtalan, Acta Crystallographica, Section E: Structure Reports Online, 2007, 63(2), i43-i44 or just look below.

What happens next is that the NO2 (Nitronium) cation will attack the benzene ring as an electrophile. The aromatic ring will stop being aromatic for a moment. The positive charge will be spread out over three carbon atoms, after forming the cationic intermediate a proton is lost and the ring returns to being aromatic. Thus we have formed nitrobenzene.

We can add lots of different things to benzene rings using different reagents which electrophiles. Using our imagination we can come up with lots of different useful transformations. Now in the same way as I gave out a lovely set of mathematical functions in my Magnum Opus on the MONIAC I am going to share with you a cheat sheet which may help get you out of some sticky problems.

SynthonTypical reagentProductComments
Cl+Cl2 / FeCl3PhClWorks for bromine but not well for fluorine or iodine
+SO3H H2SO4 or H2S2O7PhSO3Used to make anionic surfactants
+P(S)S2P(S)+P4S10Ph2P2S4 Works best on electron rich aromatics, used to make Lawesson’s reagent 
R+RCl / AlCl3 PhR The R group can change into an isomer
RCO+RCOCl / AlCl3PhCORNo rearrangement of R but the product poisons the Lewis acid catalyst
Ar-N=N+ArNH2 + HNO2PhN=NArOnly works well on electron rich arenes, this is used to make diazo dyes
RH++ RR’CO / H+ Ph2CRR’Used to make DDT and bisphenol A

Now before we go any further I will tell you a story, I hope that you are sitting comfortable and now I will begin. Oh, no lets give you a chance to nip off for a bowel of popcorn, a fizzy drink and an ice cream. OK now I start

A long time ago in the green and rainsoaked land of Loughborough there were those who worked in the lab of Derek Woollins. One of the these was a 21 year old man by the name of Mark Foreman, one afternoon he seized a round bottomed flask and put within it ferrocene (5.2 grams. 28 mmol), xylene (50 ml) and P4S10 (3 grams. 7 mmol). He boiled this mixture under reflux (30 minutes) before allowing it to cool. He collected the solid on a filter and washed it with toluene before drying it in vacuum. He was rewarded with 5.9 (78 %) of a orange solid. He showed it to Derek and he saw that it was good. Derek commanded Mark to crystallize it, Mark dissolved some of it in hot toluene and slowly cooled it thus making crystals. Mark gave the crystals to Alex Slawin. Alex performed a crystallography experiment upon it and saw that it was 2,4-diferrocenyl-l ,3,2,4-thiadiphosphetane 2,4-disulfide. The three looked upon it and it was good.

Here is a picture of the molecule, this was obtained using X-ray diffraction.

Now that was a nice and pleasant story, now before we go any further it is important to note that ferrocene is an electron rich aromatic compound while xylene is a less electron rich compound. The density of xylene is 860 grams per litre, so as the formula mass of xylene is 106 grams per mole then one litre of xylene is 8.11 moles per litre. Thus in 50 ml of xylene we have 406 mmol of xylene. This is almost 15 times as many xylene molecules as the number of molecules of ferrocene.

The fact that the dilute solution of ferrocene reacted faster than the xylene indicates to us that the nature of the aromatic molecule has a great effect on the rate of reaction with the electrophile. If the xylene and the ferrocene had similar abilities to react with the electrophile then Mark would have had a very small yield of his Fc2P2S4, he would have then needed another method of making the starting material for much of his PhD project.

Q3: Predict the major products from the following combinations of reagents. You use conditions where the aromatic is in excess to limit the reaction to monosubstitution. Please give the mechanisms for the reactions.

a. P4S10 and 2-tert-butyl-1-methoxybenzene

b. Bromine (with a Ferric bromide catalyst) with toluene (methyl benzene) in the dark

c. Methyl benzoate with a mixture of nitric and sulfuric acids

d. Phenol (hydroxybenzene) with nitric acid (this one does not need the sulfuric acid)

e. Chlorobenzene with chloral (Cl3CHO) and sulfuric acid

f. 2-Nitrotoluene and a mixture of nitric and sulfuric acids

Q4: The aromatics in Q3 state which ones would react faster than benzene and which would react more slowly than benzene under the same conditions.

When you have considered these problems then please click here to move to the next page.

Arenes benzene Chemistry Organic chemistry

Aromatics II

OK welcome back it is time to talk about aromatic mechanisms again. The first example in question three was one from Mark Foreman’s PhD days. Back in the days when he was in his early 20s working in Derek Woollins’s lab in a tranquil semi-rural location in a lab with a great view.

Much of the early part of Mark’s PhD project was reacting P4S10 and aromatic compounds. The thing to keep in mind is that sulfur is more electronegative than phosphorus so the phosphorus atoms in P4S10 have a partial positive charge on them. P4S10 has the following structure.

But when P4S10 is heated to 175 oC it is known to decompose into sulfur, P4S9, P2S5, P2S4, PS2 and PS. These things on cooling reform P4S10. While the boiling point of anisole is a bit lower (154 oC) than this temperature it is reasonable to imagine that some conversion of P4S10 into P2S5 occurs. The phosphorus sulfur side of the reaction looks like a “mechanistic mess” but the organic side of the mechanism is clear it is an electrophilic aromatic substitution reaction. We can summarize the organic mechanism with the following diagram.

We should note that the reaction occurs para to the methoxy group, this is due to the fact that the methoxy group has a far stronger activating ability than the tert-butyl group. The positive charge which is on the carbons in the ring which exists in the intermediate can be accommodated on the oxygen atom. The lone pair of the oxygen can be donated into the ring, this spreads the positive charge over more atoms. By lowering the charge density of the intermediate cation we lower its energy.

There are two bits of following chemistry which finish off the synthesis. Firstly the fragments from the phosphorus sulfide will lose hydrogen sulfide. One pair of equations which rationalize it are shown below.

While the organic side of the chemistry is finished off by the formation of a dimer of the product.

The dimer on cooling comes out of the reaction mixture as a crystalline solid. This has been characterized by crystallography along with almost every spectroscopic method I can think of.

When you are ready to move to the discussion of the answer to the second example (bromine as the electrophile with toluene) click here.


Aromatics I

Benzene is a very important molecule, it is also a very challenging molecule which has helped greatly the development of organic chemistry both “in thought and deed“. The reason I mention thoughts and deeds is that aromatic chemistry is very important in the lab and in industry (deeds) and also benzene (and other aromatic chemistry) has enabled (or maybe provoked) organic chemists to think about molecules in a different way.

Aromatic molecules include neurotransmitters, hormones, pesticides, building blocks for polymers, drugs and more things. Here is a selection of four randomly chosen aromatic molecules.

Now I am sure that many of you will have heard of prozac, I recall the era of wild excitement about prozac and reading the late Elizabeth Wurtzel’s memior on the long train ride to a job interview in Aberdeen (I got the job).

The late Elizabeth Wurtzel (1967-2020), photo by Lynne Winters.

Elizabeth Wurtzel (1967-2020) at the end of her book painted a glorious picture of fluoxetine. My view as a chemist of fluoxetine is that it is an important drug which changed society and science’s view of depression but it is not a panacea.

Q1: a key part of fluoxetine can be regarded as a benzene ring which has two groups attached. the structure of benzene was a great challenge to chemists. Consider how many dimethyl benzene isomers could be formed if benzene had one of these alternative structures. For the purpose of the teaching event the benzene isomer on the top left should be regarded as having fixed single and double bonds. The one on the bottom right with the circle means that the single and double bonds are not fixed, instead the bond order between the carbons is 1.5.

Some alternative (and wrong) structures for benzene along with the correct one.

Now before we go any further I know that there is a thing which makes some organic chemists rage, emit steam or blow a gasket. That is the representation of a benzene ring with a circle in the middle rather than alternating single and double bonds. We will get back to this later.

With benzene rings it is important to understand that the bond order of the bonds between the carbon bonds is 1.5. Benzene rings have a special stability. It is important for you to understand that the double bonds are not fixed in a benzene ring. In the following diagram the interconversion of the two benzene resonance forms is occurring.

It is important to accept that all the resonance forms exist at the same time, they all make a contribution to the overall reality but these contributions are not always equal. The higher the energy an individual resonance form would have if it was a isolatable species the lower its contribution is to the overall reality. We can draw out more resonance forms for benzene.

There are some rules,

  1. The locations of atoms cannot change from one resonance form to another.
  2. The hybridization of atoms cannot change from one resonance form to another.
  3. Only pi bonds and lone pairs are involved in the resonance, the sigma bonds normally stay out of the resonance.
  4. The more charges we have in a resonance form normally the higher the energy will be.

Here are some resonance forms of benzene, I have included the two low energy resonance forms which are commonly seen along with five higher energy forms which are not commonly drawn.

There is a convention in organic chemistry, when you draw resonance you use a two ended straight arrow. When it is resonance to a form which makes a minor contribution (due to a high energy) it is common to use a smaller arrow. For example.

Please also do not “wrap around” curved arrows from one side of the paper to the other. Some years ago myself and Björn were grading exam papers and we saw that a student had drawn something like this.

Please do not do this, also do not use a curved arrow to move an atom. Next time we might not be quite so sympathetic. Please look at this simple reaction mechanism below. It is the deprotonation of a phenol by a methoxide anion. I have shown the correct and the wrong use of the curved arrows.

OK curved arrow lesson over we can now move onto some reactions of benzene and other aromatics. Lets go for a gentle one first. Please draw out the mechanism of the reaction of benzene with a mixture of nitric and sulfuric acids to form nitrobenzene.

When you have drawn out the mechanism please click here to move to the next page.

Alkenes Arenes benzene Olefins orbitials Organic chemistry quantum mechanics

Resonance and pi systems

We are going to start with something within chemistry which has been deeply controversial. In the early Soviet Union there was a collision between political ideology (Dialectical materialism) and chemical thought.

Pauling’s “idealized resonance structures with no real independent existence” were deemed to be “antimaterialistic and hence anti-Soviet“. Now some might laugh at this but sadly this sort of nonsense continues to this day. It is important to note that this sort of nonsense continues to appear. It is important to note that there is no such thing as a socialist atom, nor are there capitalist molecules. Atoms and molecules lack morals and emotions. There was a case of some years ago which I got involved with, I was glad to drive a steak through the heart of the nonsense and thus help rid the world of it.

But on with the chemistry, now it is important to understand that the resonance forms do not exist independently of each other. If we have benzene we have two main resonance forms.

A bottle of benzene does not contain a mixture of the two, instead both resonance forms coexist in the same molecule at the same time. It is vital to understand that the benzene ring is special, it is not three isolated alkenes. There is a vast amount of evidence that the benzene ring is special. For example if we make a solution of bromine in benzene then this solution will be stable at room temperature with or without light. If we were to make a solution of bromine in an alkene it would react quickly in the dark to form a 1,2-dibromo compound.

Also the UV spectrum of benzene is very different to an alkene, the wavelength that benzene adsorbs at it much longer than that which a simple isolated alkene will adsorb at. This indicates that we have in benzene a much larger pi system than that found in an alkene such as ethylene.

Now I want to give you a short pep talk. To help us understand resonance we should consider this cation.

This cation exists as at least three different resonance forms. Here are the main ones.

Now this might just seem to some people like Mark Foreman and his mates in the organic chemistry world have come up with something to vex and trouble students which has nothing to do with real life. But this would be far from the truth.

Consider for a moment the following reaction, it is known as an allylic rearrangement. There is a reaction in a patent taken out by Bayer the German chemical compound (Bayer Aktiengesellschaft, US4515801, 1985, A). I have to confess this is the first one which I found in a search of the chemical literature.

In this reaction it looks like the “wrong” carbon in the bromo compound has attached to the oxygen attached to the benzene ring. We might ask how it has happened.

There is an older paper from the days of Teddy Boys and jive, C.A. Vernon, Journal of the Chemical Society, 1954, 423-428 in which the reaction rates for a series of chloro compounds with formic acid with a tiny trace of water was measured. Here is part of the data which was obtained at 100 oC.

Now here are the rate constants obtained by titrations with silver nitrate at different times in a bar chart, note that the y axis is a log scale.

What you should be able to see is that the alkene group on the left hand side of the molecule greatly increases the rate of the reaction. The allyl cation is able to spread the positive charge over two different carbons by means of resonance.

We can draw two resonance forms for the allyl cation.

What we can also see is that by adding chlorine atoms to the allyl cation we make a marginal increase in the stability (lower energy) of the cation.

There were further experiments in 1:1 water / ethanol. Using this new set of molecules we have more data.

Keep in mind that the y axis in the next chart is linear. It shows the effect of the location of the methyl group on the reaction rate.

Now these graphs tell us a lot. What they tell us is that there is a special stability of the following cation, also the location of the methyl groups matter. The methyl group in the cation from 2 is in the middle and it is not attached to a carbon where the positive charge is in one of the resonance forms.

Now I will give you a clue, the more alkyl groups attached to a carbon bearing a positive charge (a carbocation) the more stable the carbocation will be. If you imagine the two resonance forms as isolatable carbocations then the methyl group will not have a strong effect on making the carbo cation more stable.

Now if we move the methyl group to a different position then we can change the stability of the different resonant forms.

The form on the left hand side will have a greater stability than the one on the right. As the energy of the cation is affected by the energies of all the forms the energy of the cation is lowered further.

If we consider for a moment an alternative hypothesis that the rate limiting step is the attack of a second molecule on the carbon bearing the chlorine atom, then the methyl group in 3 should get in the way of the incoming second molecule and slow the reaction down. Also compound 4 should react at the same rate as compound 1 as the methyl group in 4 is remote from the reacting centre.

It is interesting if we look at the titration data for 3-methylallyl chloride being reacted in 99.5 : 0.5 and 90 : 10 mixtures of formic acid and water that when the water content is increased the rate constant for the reaction increases. We can see how the reaction went faster with the relative dielectric constant of the medium was higher. This is a change which will favor carbocations.

What is likely to have happened in the chemistry from the patent is that the allylic bromide formed a 1,1-dimethylallyl cation by the loss of a bromide anion. Then the charge was distributed by resonance between two carbons, the nucleophile mainly reacted at the less hindered end of the cation.

OK I have done enough for a while, time for you to do something. I want you to draw at least six of the resonance forms for two organic molecules with the formula C10H8. These are naphthalene (on the left )and azulene (on the right). By the way I will give you a clue about the second one, azulene has a permanent electric dipole moment while naphthalene does not.

When you are done click here to move onto the answers.

Arenes Chemistry orbitials Organic chemistry Uncategorized

Resonance forms

OK welcome back, I hope by now that you have drawn plenty of resonance forms of naphthalene and azulene. The usual resonance forms of naphthalene which are drawn and thought about are.

It is important to note that unlike benzene there is one resonance form which has the lowest energy of all of them, as a result the bond order in naphthalene between some carbons is higher than it is between some others. Here is a diagram of octafluoronaphthalene taken from the literature onto which I have added the carbon carbon bond lengths.

The shortest carbon carbon bonds (1.357 Å) and the longer carbon carbon bonds on the perimeter of the aromatic system indicate that the central bond (1.432 Å) is closer to being a double bond. The longer bonds on the perimeter (1.416 and 1.396 Å) are best thought of as carbon carbon bonds which are close to single bonds.

There are lots and lots of resonance forms of naphthalene, I think that we would be here until next Christmas if we were to draw them all out. Well maybe that is an exaggeration but it would take a long time to draw out all of them if we were to include the high energy ones with lots of charges. Here are some of them along with the three normal ones.

When you are finished thinking about the naphthalene we can move onto the blue coloured azulene. There are four resonance forms which should be obvious and have low energies. It is important to accept that aromatic rings do not always have six atoms in them. There are aromatic rings with other numbers of atoms. Also there are aromatic rings with different numbers of pi electrons to six. In fact an aromatic ring can have 4n+2 pi electrons. The number n can vary from zero to a very high integer.