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 All my advanced level aromatic chemistry notes

7.8.2 The electrophilic substitution mechanism for the Friedel-Crafts acylation of arenes

A Friedel-Crafts synthesis of aromatic ketones using an acid/acyl chloride.

Note that the catalyst aluminium chloride (AlCl₃) has a vacant orbital and can act as a Lewis acid, accept a pair of electrons, and, in this context, facilitate the formation of a more powerful electrophile [RC=O]⁺ in step (1) of this acylation of benzene electrophilic substitution mechanism. Its the same situation for the catalysts AlBr₃, FeCl₃ and FeBr₃.

mechanism 25 - electrophilic substitution by an acyl group in the benzene ring

for R = H, benzene: C₆H₆  +  R'COCl  ===> C₆H₅COR'  +  HCl   [see mechanism 25 below]

[mechanism 25 above] If ethanoyl chloride, CH₃COCl, was used (R=CH₃-), benzene forms phenylethanone, C₆H₅-CO-CH₃.

Step (1) Although the acid chloride molecule is polar, it is still not a strong enough electrophile to disrupt the pi electron system of the benzene ring.

The aluminium chloride reacts with an acid chloride molecule to form an acylium ion, RCO⁺ (another type of carbocation), which is a much stronger electron pair accepting positive electrophile than the original acid chloride (either RCO⁺ or an AlCl₃-RCOCl complex - details not needed for A level).

Step (2) An electron pair from the delocalised pi electrons of the benzene ring forms a C-C bond with the electron pair accepting carbocation forming a second highly unstable carbocation.

It is very unstable because the stable electron arrangement of the benzene ring pi electrons is partially broken to give a 'saturated' C (top right of ring.

Step 2 has the highest activation energy and is the rate determining step (see mechanism diagram 81E below).

Step (3) is a proton transfer, as the tetrachloroaluminate(III) ion [formed in step (1)], abstracts a proton from the second highly unstable intermediate carbocation to give the ketone product, 'waste' hydrogen chloride gas and reforming the aluminium chloride catalyst.

In forming the aromatic ketone product, you retain the stabilising effect of the complete pi electron system of the benzene ring.

for R = CH₃, methylbenzene: C₆H₅CH₃  +  R'COCl  ===>  R'COC₆H₄CH₃  +  HCl

and again there is the potential to form three position isomers by substituting in the 2, 3 or 4 position on the ring.

The overall acylation reaction is the substitution of -H by RC=O

Mechanism diagram 81A: The acylation of benzene using ethanoyl chloride

In the first step the aluminium chloride abstracts a chlorine atom from the ethanoyl chloride to give the acylium ion CH₃CO⁺ (a type of carbocation).

The acylium carbocation is a much more powerful electrophile (electron pair acceptor) than the original acyl chloride.

A pair of pi electrons are donated to the attacking CH₃CO⁺ electrophile forming a ring carbon - carbon bond in the benzene molecule.

The intermediate is unstable because the stabilising ring of pi electrons is broken - one of the benzene ring carbons is temporarily saturated.

A tetrachloroaluminate ion abstracts a proton from the intermediate to yield the final product of 1-phenylethanone.

With the formation of the aromatic ketone product, the stable and complete pi electron ring system is reformed in the benzene ring - overall electrophilic substitution instead of electrophilic addition.

 

Mechanism diagram 81E shows the reaction progress profile for the acylation of benzene with an acid chloride. Note the two transition state 'humps'.

The first step here, forming the unstable intermediate acylium ion (a type of carbocation), has the highest activation energy and is the slower rate determining step.

The final step yielding the final product, with the reformed stable benzene ring of the aromatic ketone, has the lower activation energy and is much faster.

 

Mechanism diagram 81B: The acylation of methylbenzene using ethanoyl chloride

In the first step the aluminium chloride abstracts a chlorine atom from the ethanoyl chloride to give the acylium ion CH₃CO⁺ (a type of carbocation).

The acylium carbocation is a much more powerful electrophile (electron pair acceptor) than the original acyl chloride.

A pair of pi electrons are donated to the attacking CH₃CO⁺ electrophile forming a 2nd ring carbon - carbon bond in the methylbenzene molecule.

The intermediate is unstable because the stabilising ring of pi electrons is broken - one of the benzene ring carbons is temporarily saturated.

A tetrachloroaluminate ion abstracts a proton from the intermediate to yield the final aromatic ketone product of 1-(2/3/4-methylphenyl)ethanone.

With the formation of the aromatic ketone product, the stable and complete pi electron ring system is reformed in the benzene ring - overall electrophilic substitution instead of electrophilic addition.

I drawn the mechanism for substitution at the 2 and 4 ring positions of the benzene ring, since these are the two principal products.

TOP OF PAGE and sub-index

7.8.3 The physical properties of aromatic aldehydes and aromatic ketones

Abbreviations used:

mpt = melting point ^oC;   bpt = boiling point ^oC;   sub. = sublimes

dec. = thermally decomposes;   liq. = liquid at room temperature ~20^oC

Name of aromatic aldehyde	Structure	Mpt/oC	Bpt/oC	Comments
benzaldehyde		-26	179	Insoluble in water.
2-hydroxybenzaldehyde		-7	196	Very slightly soluble in water. Salicylaldehyde - fragrant oil in meadowsweet and other plants
3-hydroxybenzaldehyde		108
4-hydroxybenzaldehyde		116
2-methylbenzaldehyde		liq.	>208
3-methylbenzaldehyde		liq.	199
4-methylbenzaldehyde		liq.	204
2-chlorobenzaldehyde		liq.	>208
3-chlorobenzaldehyde
4-chlorobenzaldehyde		49	>213
2-nitrobenzaldehyde		44
3-nitrobenzaldehyde		58
4-nitrobenzaldehyde		106
2-aminobenzaldehyde		40
3-aminobenzaldehyde
4-aminobenzaldehyde		71
2-methoxybenzaldehyde		3	244
3-methoxybenzaldehyde		35
4-methoxybenzaldehyde (Anisaldehyde)		0	248	'Anisaldehyde' has a sweet, floral and strong aniseed odour
Name of aromatic ketone	Structure	Mpt/oC	Bpt/oC	Comments
1-phenylethanone (acetophenone)		20	202	IUPAC preferred name is 1-phenylethan-1-one. Insoluble in water.
1-(2-methylphenyl)ethanone 2-methylacetophenone				Pale yellow liquid with a nutty coconut aroma, insoluble in water.
1-(3-methylphenyl)ethanone 3-methylacetophenone		-9	219
1-(4-methylphenyl)ethanone 4-methylacetophenone		23	226	Used in flavours and scents
diphenylmethanone (diphenylketone)		48	306	Insoluble in water.
1-(2-hydroxyphenyl)ethanone Preferred IUPAC name		19	213	Very slightly soluble in water.

Further comments on the data table

(a) Most of those listed above are colourless or pale yellow liquids at room temperature.

(b) Those with a hydroxy group in the ring can hydrogen bond and that usually raises the melting point above room temperature.

Others, with another highly polar group e.g. nitro NO₂, are also usually solids at room temperature with the increased contribution to the intermolecular attractive forces of the permanent dipole - permanent dipole interactions.

TOP OF PAGE and sub-index

7.8.4 Selected chemical reactions of aromatic aldehydes and aromatic ketones

(a) The reaction with 2,4-dinitrophenylhydrazone  (24DNPH for short)

The above diagram gives the equations for benzaldehyde and 1-phenylethanone reacting with 2,4-dintrophenylhydrazine to give orange-yellow precipitates of the 2,4-dinitrophenylhydrazones.

This is a test for a carbonyl compound, but does not distinguish between aldehydes and ketones because they both undergo the same condensation reaction.

 

(b) The reaction with hydrogen cyanide

1-phenylethanone undergoes nucleophilic addition of hydrogen cyanide to form a hydroxynitrile.

The hydroxynitrile, 2-hydroxy-2-phenylpropanenitrile, can hydrolysed by refluxing with strong acid or alkali solution to give a hydroxy carboxylic acid, 2-hydroxy-2-phenylpropanoic acid.

The ammonia would not be free, the reaction is far to slow with water, and the ammonium salt of the acid would form i.e. RCOO^-NH₄⁺. You need a strong acid or base to effect the hydrolysis.

Refluxing the nitrile with sodium hydroxide produces free ammonia, which is boiled off, leaving the sodium salt of the carboxylic acid in solution, RCOO^-Na⁺.

The organic acid is freed by adding stronger mineral acid.

RCOO^-  +  H⁺  ==> RCOOH

Refluxing the nitrile with dilute hydrochloric/sulfuric acid yields the free acid and the corresponding ammonium salt.

 

(c) Reduction of aromatic aldehydes and ketones using lithium tetrahydridoaluminate(III), LiAlH₄

The reaction is carried out in dry ethoxyethane ('ether') and the product hydrolysed with dilute mineral acid.

Benzaldehyde is reduced to phenylmethanol (primary alcohol).

1-phenylethanone is reduced to 1-phenylethanol (secondary alcohol(.

 

(d) The iodoform reaction

Only aromatic methyl-ketones can give the iodoform reaction.

If 1-phenylethanone is gently warmed with iodine and sodium hydroxide solution, a yellow precipitate of triiodomethane forms. Sodium benzoate is left in solution.

 would all give the iodoform reaction.

 

(e) Other tests for aldehydes and ketones

Tests for aromatic aldehydes and aromatic ketones (apart from 24DNPH reaction)

Benzaldehyde gives a silver mirror with ammoniacal silver nitrate (Tollen's reagent), which would distinguish it from other aromatic ketones.

BUT, Fehling's solution is a weaker oxidising agent and no red-brown precipitate is given by benzaldehyde and most other aromatic aldehydes.

The pi electrons of the benzene ring overlap with the pi electrons of the carbonyl bond, stabilising benzaldehyde and lowering the reducing power of benzaldehyde - enough to give a negative test with Fehling's solution.

would give similar results.

The diagram shows the overlap of the electron clouds of the benzene ring (C₆H₅) and the carbonyl group (C=O) of the aldehyde function group in benzaldehyde.

The nitration of 1-phenylethanone and reduction of the product to an aromatic amine

1-phenylethanone can be nitrated using a nitrating mixture of conc. nitric acid and conc. sulphuric acid. It also works with 'fuming' nitric acid (nasty!). The major product is 3-nitroacetophenone.

This is a typical electrophilic substitution reaction of an aromatic compound with a benzene ring.

add orientation rule to various pages

The major products can separated and reduced to 3-aminoacetophenone H₂NC₆H₄COCH₃.

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7.8.5 The uses of aromatic aldehydes and aromatic ketones

The aromatic nature of these compounds gives them characteristic odours and many are used in scents and fragrances.

Some are found in nature and are used as flavourings in the food industry.

Many of such useful compounds are synthetically manufactured and the 'collection' added to by synthetic analogues to those found in nature.