Today's mail service is on the Friedel-Crafts alkylation and acylation reactions. Carbon-Carbon bond forming  reaction time! Whoo hoo!

summary of friedel crafts alkylation and acylation what bonds form and break limitations and substrates

Table of Contents

  1. Quick Recap on Electrophilic Aromatic Commutation: Onward To Carbon-Carbon Bail Forming Reactions!
  2. Friedel-Crafts Alkylation Of Aromatic Rings
  3. The Function of The Lewis Acid In Friedel-Crafts Alkylation Is To Activate The Alkyl Halide
  4. The Key C-C Bail Forming Stride  Is Assault Of The Aromatic Ring Upon  The Carbocation (or carbocation-like) Electrophile
  5. Picket Out! Carbocation Rearrangements Can Occur In The Friedel-Crafts Alkylation Reaction
  6. If A Hydride Shift Or Alkyl Shift Will Result In A More Stable Carbocation, Assume It Will Happen
  7. Limitations of the Friedel-Crafts Alkylation
  8. Friedel-Crafts Acylation
  9. The Mechanism Of The Friedel-Crafts Acylation Reaction
  10. No Rearrangements Occur In The Friedel-Crafts Acylation
  11. Limitations of The Friedel-Crafts Acylation
  12. Summary: Friedel-Crafts Alkylation and Acylation
  13. Notes
  14. Quiz Yourself!
  15. (Advanced) References and Further Reading

i. Quick Recap On Electrophilic Aromatic Exchange: Onward To  Carbon-Carbon Bond Forming Reactions!

This is the third in a series of three posts on the key electrophilic aromatic substitution (EAS) reactions in introductory organic chemistry.

  • In Part 1 we covered halogenation (chlorination, bromination, and iodination) of aromatic rings via EAS.
  • In Part 2 we covered nitration and sulfonylation of aromatic rings via EAS.

Taken together, so far we have learned reactions to grade carbon-element of group vii, carbon-nitrogen, and carbon-sulfur bonds.

What important class of bail is missing so far?

Carbon-carbon bail forming reactions! [notation]

In this mail service, we'll cover two important C–C bond-forming electrophilic aromatic exchange reactions which bear the names of their discoverers, Charles Friedel and James Crafts: Friedel-Crafts alkylation and Friedel-Crafts acylation.

We'll also see that these reactions follow the familiar three-step blueprint seen in previous electrophilic aromatic substitution reactions, namely:

  • activation of electrophile with a Lewis acrid
  • assault of the "activated" electrophile past the aromatic ring
  • deprotonation to restore aromaticity

2. Friedel-Crafts Alkylation Of Aromatic Rings

When an alkyl halide is treated with a Lewis acid in the presence of an aromatic ring,  the alkyl group tin can exist added to the band (forming C-C) with the loss of a C-H bond. This electrophilic aromatic substitution reaction is known as the Friedel-Crafts alkylation reaction.

Mostly, no reaction occurs in the absenteeism of Lewis acid. A common pick for the Lewis acid is aluminum chloride, AlCl3, but many others may be used, such as FeCl3 amidst others.

Alkyl halides (typically chlorides, bromides, and iodides) must be used, as the reaction fails completely for alkenyl and alkynyl halides.

generic example of friedel crafts alkylation of benzene with alkyl halide giving new alkyl group with lewis acid no alkenyl or alkynyl

Here'southward a specific case using ethyl chloride:

friedel crafts alkylation reaction specific example with ethyl chloride and alcl3 giving ethylbenzene

3. The Role of The Lewis Acid In Friedel-Crafts Alkylation Is To Activate The Alkyl Halide

If no reaction occurs in the absenteeism of a Lewis acrid, then what is the role of the Lewis acrid hither?

Similar nosotros saw in the ii previous posts on electrophilic aromatic substitution reactions, Lewis acids "activate" the electrophile past coordinating to the leaving grouping, making it a weaker base, and a better leaving group(AlClfour – is a weaker base than Cl– ). The terminate result is that coordination of the Lewis acrid to the electrophile makes the species ameliorate electrophile.

For example, with isopropyl chloride (below), the start footstep is coordination of  coordination of AlCliii to the chlorine cantlet. This weakens the C-Cl bond, with the event that the Cl can depart (as AlCliv – ) to give a secondary carbocation (a improve electrophile than isopropyl chloride itself).

  • With secondary and 3rd halides, full dissociation to a carbocation can occur.
  • In the case of primary (and methyl) alkyl halides, the electrophile is probable not a "free" carbocation, merely a "carbocation-like" species where the C–Cl bond is considerably weakened/lengthened.
  • As we mentioned briefly, no reaction occurs with alkenyl or alkynyl halides, largely because the carbocations of these species are so unstable and difficult to generate.

step 1 of friedel crafts alkylation mechanism activation of electrophile with lewis acid

Note: that although here we are showing the carbocation electrophile in the Friedel-Crafts equally existence generated from an alkyl halide and a Lewis acid, there are other means to generate a carbocation [such as through protonation of an alkene, come across beneath]. We generally define the Friedel-Crafts alkylation equally being the reaction of an effluvious band with a carbocation (or carbocation-like) intermediate. See this footnote for case.

4. The Key C-C Bond Forming Footstep  Is Attack Of The Aromatic Ring Upon  The Carbocation (or carbocation-like) Electrophile

Once the electrophile has been activated, the next step of the Friedel-Crafts is assault of the activated electrophile by the aromatic ring. This is besides the rate-determining step, as it disrupts the aromaticity of the band (and its ~36 kcal/mol of resonance energy).

In this step a C–C (pi) bond from the aromatic ring breaks, and a new C–C sigma bail is formed, leading to a carbocation intermediate:

step 2 of friedel crafts alkylation mechanism attack of electrophile by aromatic ring

The last step is deprotonation of  C–H past a weak base (e.grand. Cl – ) to restore aromaticity at the ring:

step 3 of friedel crafts alkylation mechanism deprotonation of aromatic ring giving benzene

[another way to depict the curved arrows in this reaction is to dissociate Cl– from AlCl4 –and and so employ it as the base. Either way information technology works out to the same thing].

Note that AlCliii is regenerated here, allowing it to be used again in footstep 1 with another equivalent of the alkyl halide. Hence, AlCl3 can human activity as a goad in this reaction, since it increases the rate of reaction just is not consumed by information technology.

5. Look Out! Carbocation Rearrangements Can Occur In The Friedel-Crafts Alkylation Reaction

Many university scientific discipline courses are taught in units, where what yous learn in one module has pretty much zero overlap with what you learn in some other.

Needless to say,organic chemistry is not like this.Y'all've probably already experienced a situation where concepts you lot learned in Org 1 reflect back to Org 2 chapters in unexpected ways. Well, get prepare for another fun case.

We showed in a higher place how ethyl chloride reacts with benzene and AlCl3 in the Friedel-Crafts alkylation to provide ethylbenzene.

Extension of this reaction from ethyl chloride to propyl chloride should correspondingly give propylbenzene.

Correct?

example of rearrangement of alkyl halide in the friedel crafts alkylation reaction

What the…. isopropylbenzene?

How did this happen?

Quick trip downwardly retentivity lane.  Call up this beloved reaction from Org 1?

mechanism for 1 2 hydride shift in the friedel crafts alkylation reaction

Ah, the hydride shift. Carbocations can rearrange via hydride and alkyl shifts such that a less stable carbocation is transformed into a more than stable carbocation.

In the Friedel-Crafts, we've seen that coordination of a Lewis acid to an alkyl halide resulted in a carbocation (or in the case of principal alkyl halides, at least a "carbocation-like" species) that is then attacked by the effluvious ring in the rate-determining step.

6. If A Hydride Shift Or Alkyl Shift Volition Effect In A More Stable Carbocation, It Will Happen

So what is happening here is actually no different:if a carbocation can rearrange to a more stable carbocation through a hydride or alkyl shift, it will do so.

Organic chemistry two: the course where start-semester concepts come back to bite yous in the ass.™

Here's what happens in the case of propyl chloride.

friedel crafts alkylation reaction carbocation rearrangement

A shift of hydride from Cii to C1 results in a secondary carbocation, which is and then attacked by the aromatic ring.

Bottom line for the Friedel-Crafts alkylation reaction:

  • presume the alkyl halide goes through a carbocation
  • presume that if the carbocation tin can rearrange to form a more stable carbocation through a hydride (or alkyl) shift,  it will.

Another example of a rearrangement in the FC alkylation included in the footnotes but for fun. [Annotation]

seven. Limitations of the Freidel-Crafts Alkylation

Final note on the Friedel-Crafts alkylation: a few drawbacks.

  • First, as we've seen, carbocation rearrangements can occur. [In that location are ways of circumventing this result indirectly, which we'll hint at below [skip to bottom].
  • Second, the Friedel-Crafts alkylation tends not to work well with electron-poor effluvious rings, particularly strongly deactivating substituents such as CFthree, NO2, ThenthreeH, and so forth. Halogens are OK.
  • Third – and this is more of a practical event than annihilation else, and then is ofttimes ignored – the product of the FC alkylation is oft a better nucleophile than the starting material. (Recall that alkyl groups are activating.)  The result can be a fleck like the Cookie Monster in a Chips Ahoy! mill – it can't stop at simply ane, resulting in multiple alkylations.

viii. Friedel-Crafts Acylation

A procedure related to the Friedel-Crafts alkylation, chosen Friedel-Crafts acylation, was discovered by Friedel and Crafts around the same time (1877). If a Lewis acrid is added to an acyl halide in the presence of an aromatic ring, an electrophilic aromatic substitution reaction can occur whereby the acyl group adds to the aromatic ring (with loss of HX).

As with the F.C. alkylation, the specific Lewis acid in the Friedel-Crafts acylation can vary. Aluminum chloride (AlCliii) is often used, but FeCl3 and other Lewis acids will also do the job.

Here's a full general example of the Friedel-Crafts acylation:

friedel crafts acylation reaction example generic lewis acid acyl halide bonds formed and broken

A specific case is the reaction between acetyl chloride and benzene catalyzed past aluminum chloride:

specific example of friedel crafts acylation reaction benzene acetyl chloride alcl3

9. The Mechanism Of The Friedel-Crafts Acylation Reaction

So how does the Friedel-Crafts acylation reaction work?

As with FC alkylation, the beginning step is activation of the electrophile. Lewis acrid coordinates to the halogen, and divergence of the halogen (equally AlClfour –) results in a fairly stable, resonance-stabilized carbocation know as the "acylium ion".

mechanism of friedel crafts acylation step 1 activation of electrophile with lewis acid

The acylium ion is the active electrophile in the Friedel-Crafts acylation reaction. One time formed, the acylium ion is attacked by the aromatic band:

mechanism of friedel crafts acylation step 2 attack of activated electrophile by benzene

As with the Friedel-Crafts alkylation, the final step is deprotonation at carbon to regenerate the effluvious ring.

friedel crafts acylation mechanism step 3 deprotonation restoring aromaticity

10. No Rearrangements Occur In The Friedel-Crafts Acylation

Unlike the Friedel-Crafts alkylation, no rearrangement occurs with the Friedel-Crafts acylation.

This opens upwards a "workaround" to use the Friedel-Crafts acylation to obtain products that are otherwise hard to obtain through the Friedel-Crafts alkylation due to carbocation rearrangements. (We'll talk about this in detail in a time to come article, but hither we'll merely give a sense of taste).

For instance, allow'southward look at how we could utilize this to produce propylbenzene, which nosotros saw could not be made from the Friedel-Crafts alkylation reaction of benzene with AlCliii and 1-propylchloride.

The starting time step hither is to perform a Friedel-Crafts acylation reaction between benzene and propionylchloride, perhaps catalyzed past AlCl3. This gives the states ethyl phenyl ketone.

The next stride is to perform a reduction of the ketone to an alkane, which (as we'll soon encounter) tin can be performed in diverse ways. This gives us i-propylbenzene.

rearrangement workaround in the friedel crafts acylation giving an alkylation equivalent wtih no rearrangement

[Commenter Victor, from the Chemistry Help Center, helpfully notes that there is a fourth way of doing it – converting the ketone to a thioketal, and so reducing it down to the alkane with Raney nickel. ]

Nosotros will talk more well-nigh synthetic pathways for effluvious molecules in a time to come post.

xi. Limitations of The Friedel-Crafts Acylation

  • Similarly to alkylation, Friedel-Crafts acylation tends to neglect on aromatic rings with strongly deactivating groups such as nitro, CF3, sulfonyl and then on. Halogenated aromatics even so work, withal.
  • Put this in the "probably don't need to know category", merely catalyst turnover in the Friedel-Crafts acylation isn't corking. In "real life", a stoichiometric amount of AlCl3 is generally required since the AlClthree coordinates strongly to the ketone product.

12. Summary: Friedel-Crafts Alkylation and Acylation

Since they grade carbon-carbon bonds, the Friedel-Crafts alkylation and acylation reactions are peculiarly important electrophilic aromatic substitution reactions.  Together with bromination, chlorination, nitration, and sulfonylation they circular out the six core electrophilic effluvious substitution reactions.

Earlier nosotros finish our treatment of electrophilic aromatic substitution, information technology's worth going into item on i more than facet of the Friedel-Crafts that ofttimes gives students headaches; theintramolecularversions.

Next Post: Intramolecular Friedel-Crafts Reactions

Notes

Notation. Bonus points if y'all said "carbon-oxygen"  as a type of bond we oasis't seen formed in EAS.  Direct electrophilic oxygenation of benzene rings is catchy to do in the lab. For our purposes, forming C-O on an aromatic ring is ordinarily done indirectly, by means other than a straight EAS. Two ways nosotros'll explore in due course are the Baeyer-Villiger oxidation and sure reactions of diazonium salts.

 Another manner of performing a Friedel-Crafts alkylation is to generate the carbocation through protonation of an alkene. This works best when a adequately stable carbocation is generated, such as the t-butyl carbocation generated through protonation of 2-methylpropene.

addition of acid to alkenes gives carbocation tert butyl group

Notation. Bonus instance with alkyl shift.

rearrangement in friedel crafts alkylation with 1 2 shift of alkyl group

Footnote. Last postal service we learned that sulfonyl groups can be removed with strong acrid, and I alluded to another group that tin be removed that would be covered in the adjacent postal service (i.e. this post).  That group ist-butyl, which can be removed under forcing atmospheric condition, with stiff acrid. This works because thet-butyl carbocation is relatively stable and the reverse of the Friedel-Crafts alkylation is therefore feasible.

strong acid in friedel crafts can remove tert butyl group

Quiz Yourself!

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(Avant-garde) References and Further Reading

Friedel-Crafts alkylation:

  1. Jie Jack Li describes in his book Name Reactions:
    "The discovery of the Friedel–Crafts reaction was the fruit of serendipity and corking observation. In 1877, both Friedel and Crafts were working in Charles A. Wurtz's laboratory. In order to fix amyl iodide, they treated amyl chloride with aluminum and iodide using benzene as the solvent. Instead of amyl iodide, they ended upward with amylbenzene! Unlike others before them who may have simply discarded the reaction, they thoroughly investigated the Lewis acid-catalyzed alkylations and acylations and published more than 50 papers and patents on the Friedel–Crafts reaction, which has go one of the most useful organic reactions."
    DOI: 10.1007/978-3-642-01053-8_101
  2. Sur une nouvelle methode generale de synthese d'hydrocarbures, d'acetones, etc.
     Friedel and J. M. Crafts
    Compt. Rend. 1877 84, 1392-1395
    The archetype, original paper in French by Friedel and Crafts on the alkylation of aromatics (benzene in this case) with alkyl chlorides with AlCl­three.
  3. REARRANGEMENTS IN THE FRIEDEL-CRAFTS ALKYLATION OF BENZENE
    HENRY GILMAN and R. North. MEALS
    The Journal of Organic Chemistry 1943, 08 (ii), 126-146
    DOI: 10.1021/jo01190a003
    This paper by the legendary American Chemist Prof. Henry Gilman (Iowa State) carefully studies the alkylation of benzene by long-concatenation alkyl halides (C10 and in a higher place). This is a monumental effort, peculiarly considering this was prior to mod chromatographic or spectroscopic techniques (e.g. GC or NMR) that would brand assay of mixtures and characterization of these compounds so much easier.George A. Olah, who received the Nobel Prize in Chemical science in 1994, was well-known for his work in superacid and Friedel-Crafts chemistry. Hither are a selection of his papers relevant to Friedel-Crafts alkylation:
  4. Effluvious Substitution. Half-dozen. Intermediate Complexes and the Reaction Mechanism of Friedel-Crafts Alkylations and Acylations
    G. A. Olah and S. J. Kuhn
    Journal of the American Chemical Gild 1958, 80 (24), 6541-6545
    DOI:     10.1021/ja01557a022
  5. Effluvious Substitution. Xvi.1 Friedel-Crafts Isopropylation of Benzene and Methylbenzenes with Isopropyl Bromide and Propylene
    George A. Olah, Sylvia H. Alluvion, Stephen J. Kuhn, Maryanne E. Moffatt, and Nina A. Overchuck
    Journal of the American Chemic Society 1964, 86 (vi), 1046-1054
    DOI:     1021/ja01060a016
  6. Effluvious Substitution. Eighteen.1 Friedel-Crafts t-Butylation of Benzene and Methylbenzenes with t-Butyl Bromide and Isobutylene
    George A. Olah, Sylvia H. Flood, and Maryanne Eastward. Moffatt
    Journal of the American Chemical Order 1964, 86 (6), 1060-1064
    DOI:     1021/ja01060a018
  7. Aromatic Substitution. XIX.1 Friedel-Crafts Isopropylation and t-Butylation of Halobenzenes
    George A. Olah, Sylvia H. Inundation, and Maryanne Due east. Moffatt
    Journal of the American Chemical Society 1964, 86 (6), 1065-1066
    DOI:     1021/ja01060a019
  8. Aromatic Substitution. XXV.1 Selectivity in the Friedel-Crafts Benzylation, Isopropylation, and t-Butylation of Benzene and Toluene
    George A. Olah and Nina A. Overchuk
    Periodical of the American Chemical Society 1965, 87 (24), 5786-5788
    DOI:     1021/ja00952a047
    The outset sentence in this paper is of note: "Friedel-Crafts alkylations are notorious for their unreliable kinetic beliefs". This is considering they are largely heterogeneous, or occur in ii phases. Too, the footnote indicates that inquiries should exist addressed to the Department of Chemistry at the Western Reserve University, Cleveland, OH – before it merged and became Instance Western Reserve Academy.
  9. Aromatic exchange. XXVIII. Mechanism of electrophilic aromatic substitutions
    George A. Olah
    Acc. Chem. Res., 1971, four (7), 240-248
    DOI:     10.1021/ar50043a002
    An account by Prof. Olah on the work he had carried out studying the mechanism of diverse types of electrophilic effluvious substitution reactions – nitration, halogenation, as well as Friedel-Crafts acylation and alkylation.
  10. Effluvious substitution. XXXVII. Stannic and aluminum chloride catalyzed Friedel-Crafts alkylation of naphthalene with alkyl halides. Differentiation of kinetically and thermodynamically controlled product compositions, and the isomerization of alkylnaphthalenes
    George A. Olah and Judith A. Olah
    Journal of the American Chemical Society 1976, 98 (7), 1839-1842
    DOI:     1021/ja00423a032
    This is a like paper by Prof. Olah and his wife, Judith Olah, on the mechanism of Friedel-Crafts alkylation, except using naphthalene instead of benzene. Naphthalene is different in that there are two sites for monosubstitution – the a and b positions.
  11. Friedel-Crafts alkylation of anisole and its comparing with toluene. Predominant ortho-para substitution under kinetic conditions and the upshot of thermodynamic isomerizations
    George A. Olah, Judith A. Olah, and Toshiyuki Ohyama
    Journal of the American Chemic Order 1984, 106 (18), 5284-5290
    DOI:     1021/ja00330a042
    A surprising judgement in this paper: "No systematic study of the alkylation of anisole was, all the same, yet reported. Consequently we undertook such a study and report our results". Sometimes science has these low-hanging fruit, and thoroughly reading the literature tin can lead you to them.The following papers are related to dealkylation, isomerization, or transfer alkylation under Friedel-Crafts weather:Friedel-Crafts acylation:
  12. DESOXYBENZOIN
     F. H. Allen and W. E. Barker
    Org. Synth. 1932, 12 , 16
    DOI:     10.15227/orgsyn.012.0016
    A fairly representative experimental procedure for a Friedel-Crafts acylation in Organic Syntheses, a well-known source for reliable, independently tested constructed organic experimental laboratory procedures. The product desoxybenzoin would be better known today as dihydrochalcone.
  13. Aromatic Exchange. XXII. Acetylation of Benzene, Alkylbenzenes, and Halobenzenes with Methyloxocarbonium (Acetylium) Hexafluoro- and Hexachloroantimonate
    George A. Olah, Stephen J. Kuhn, Sylvia H. Flood, and Barbara A. Hardie
    Journal of the American Chemical Society 1964, 86 (xi), 2203-2209
    DOI:     1021/ja01065a020
    This paper deals with the acetylation of aromatics with preformed CHthreeCO+ salts, which Prof. Olah figured how to isolate using SbFv. Also, notation where these papers were submitted from – Prof. Olah fled from Hungary in the 1950's to Canada and joined the Dow Chemical Visitor at that place.
  14. Aromatic substitution. XXIX. Friedel-Crafts acylation of benzene and toluene with substituted acyl halides. Result of substituents and positional selectivity
    George A. Olah and Shiro Kobayashi
    Journal of the American Chemic Social club 1971, 93 (25), 6964-6967
    DOI: 1021/ja00754a045
    This is a mechanistic written report of Friedel-Crafts acylation (or 'benzoylation' in this case) using the Hammett approach, a classic tool in physical organic chemical science. More reactive electrophiles take lower gt/kb ratios and depression o/p selectivity, while less reactive electrophiles accept higher chiliadt/kb ratios and high o/p selectivity. kt/1000b in this case refers to the relative rate of reacting with toluene vs. benzene.Oxygenation (or oxyfunctionalization) of hydrocarbons and aromatics is definitely possible with the right weather condition, as the following ii papers draw. Prof. George Olah has written a serial of papers on the subject field.
  15. Oxyfunctionalization of hydrocarbons. 8. Electrophilic hydroxylation of benzene, alkylbenzenes, and halobenzenes with hydrogen peroxide in superacids
    George A. Olah and Ryuichiro Ohnishi
    The Periodical of Organic Chemical science 1978, 43 (five), 865-867
    DOI:     1021/jo00399a014
  16. Oxyfunctionalization of hydrocarbons. xiv. Electrophilic hydroxylation of aromatics with bis(trimethylsilyl) peroxide/triflic acid
    George A. Olah and Thomas D. Ernst
    The Periodical of Organic Chemical science 1989, 54 (5), 1204-1206
    DOI:     1021/jo00266a041
    In this newspaper, bis(trimethylsilyl)peroxide (TMSOOTMS) is used as the oxidant.