Friedel-Crafts reaction



The Friedel-Crafts reactions are a set of electrophilic aromatic substitution.

Several reviews have been written.[2][3][4][5]

Friedel-Crafts alkylation

Friedel-Crafts alkylation involves the alkylation of an aromatic ring and an alkyl halide using a strong catalyst, the alkyl group attaches at the former site of the chloride ion.

This reaction has one big disadvantage, namely that the product is more carbocation over the secondary and primary carbocations.

Steric hindrance can be exploited to limit the number of alkylations, as in the t-butylation of 1,4-dimethoxybenzene.

Alkylations are not limited to alkyl halides: Friedel-Crafts reactions are possible with any NBS:[6]

In this reaction samarium(III) triflate is believed to activate the NBS halogen donor in halonium ion formation.

Friedel-Crafts dealkylation

Friedel-Crafts alkylation is a Lewis acid.

For example, in a multiple addition of chemical equilibration. The ultimate reaction product is thus the result of a series of alkylations and dealkylations.

Friedel-Crafts acylation

Friedel-Crafts acylation is the carbocation rearrangements, as the carbonium ion is stabilized by a resonance structure in which the positive charge is on the oxygen.


The viability of the Friedel-Crafts acylation depends on the stability of the acyl chloride reagent. Formyl chloride, for example, is too unstable to be isolated. Thus, synthesis of cuprous chloride.

Reaction mechanism

In a simple mechanistic view, the first step consists of dissociation of a chlorine atom to form an acyl cation:

This is followed by nucleophilic attack of the arene toward the acyl group:

Finally, a chlorine atom reacts to form HCl, and the AlCl3 catalyst is regenerated:

Friedel-Crafts hydroxyalkylation

Arenes react with certain carbonyl group:

Scope & variations

This reaction is related to several classic named reactions:

  • The acylated reaction product can be converted into the alkylated product via a Clemmensen reduction.
  • The Gattermann-Koch reaction can be used to synthesize benzaldehyde from benzene.
  • A reaction modification with an aromatic phenyl ester as a reactant is called the Fries rearrangement.
  • In the Scholl reaction two arenes couple directly (sometimes called Friedel-Crafts arylation).
  • In the Zincke-Suhl reaction p-cresol is alkylated to a cyclohexadienone with tetrachloromethane
  • In the Blanc chloromethylation a chloromethyl group is added to an arene with formaldehyde, hydrochloric acid and zinc chloride.
  • The Bogert-Cook Synthesis (1933) involves the phenanthrene [9]
  • The Darzens-Nenitzescu Synthesis of Ketones (1910, 1936) [10] involves the acylation of cyclohexene with acetyl chloride to methylcyclohexenylketone.
  • In the related Nenitzescu reductive acylation (1936) [11] a saturated hydrocarbon is added making it a reductive acylation to methylcyclohexylketone
  • In a 2-bromobutane. This variation will not work with primary halides from which less carbocation involvement is inferred.[12]


Dyes

Friedel-Crafts reactions have been used in the synthesis of several phthalic anhydride:

A reaction of phthalic anhydride with zinc chloride gives the fluorophore Fluorescein. Replacing resorcinol by N,N-diethylaminophenol in this reaction gives rhodamine B:

References

  1. ^ Friedel, C.; Crafts, J. M. Compt. Rend. 1877, 84, 1392 & 1450.
  2. ^ Price, C. C. Org. React. 1946, 3, 1. (Review)
  3. ^ Groves, J. K. Chem. Soc. Rev. 1972, 1, 73. (Review)
  4. ^ Eyley, S. C. Comp. Org. Syn. 1991, 2, 707-731. (Review)
  5. ^ Heaney, H. Comp. Org. Syn. 1991, 2, 733-752. (Review)
  6. ^ S. Hajra, B. Maji and S. Bar (2007). "Samarium Triflate-Catalyzed Halogen-Promoted Friedel-Crafts Alkylation with Alkenes". Org. Lett. 9 (15): 2783-2786. doi:10.1021/ol070813t.
  7. ^ K. Wallace, R. Hanes, E. Anslyn, J. Morey, K. Kilway and J. Siegel (2005). "Preparation of 1,3,5-Tris(aminomethyl)-2,4,6-triethylbenzene from Two Versatile 1,3,5-Tri(halosubstituted) 2,4,6-Triethylbenzene Derivatives". Synthesis (12): 2080-2083. doi:10.1055/s-2005-869963.
  8. ^ R. C. Fuson, H. H. Weinstock and G. E. Ullyot (1935). "A New Synthesis of Benzoins. 2′,4′,6′-Trimethylbenzoin". J. Am. Chem. Soc. 57 (10): 1803-1804. doi:10.1021/ja01313a015.
  9. ^ This reaction with J. Am. Chem. Soc. 58 (6): 1062-1063. doi:10.1021/ja01297a514.
  10. ^ http://www.drugfuture.com/OrganicNameReactions/onr94.htm
  11. ^ http://www.drugfuture.com/OrganicNameReactions/onr277.htm
  12. ^ Sereda, Grigoriy A.; Rajpara, Vikul B. (2007). "A Green Alternative to Aluminum Chloride Alkylation of Xylene". J. Chem. Educ. 2007 (84): 692.
  13. ^ Synthesis of Triarylmethane and Xanthene Dyes Using Electrophilic Aromatic Substitution Reactions James V. McCullagh and Kelly A. Daggett J. Chem. Educ. 2007, 84, 1799. Abstract


FC reactions in Org. Synth.

Friedel-Crafts reactions appear in Organic Syntheses:

  • Alkylations:
    • Diphenylacetone, Organic Syntheses, Coll. Vol. 3, p.343 (1955); Vol. 29, p.38 (1949) Article link.
    • Reaction of p-xylene with chloromethane to durene Organic Syntheses, Coll. Vol. 2, p.248 (1943); Vol. 10, p.32 (1930). Article link
    • Synthesis of tetrachloromethane Organic Syntheses, Coll. Vol. 1, p.95 (1941); Vol. 8, p.26 (1928).Article link
  • Acylations:
    • Dibenzoylethylene Organic Syntheses, Coll. Vol. 3, p.248 (1955); Vol. 20, p.29 (1940) Article link.
    • reaction of succinic acid Organic Syntheses, Coll. Vol. 3, p.6 (1955); Vol. 20, p.1 (1940).Article link
    • Desoxybenzoin Organic Syntheses, Coll. Vol. 2, p.156 (1943); Vol. 12, p.16 (1932). Article link
    • Acylation of a phenanthrene compound Organic Syntheses, Vol. 80, p.227 Link
    • Reaction of bromobenzene with acetic anhydride Organic Syntheses, Coll. Vol. 1, p.109 (1941); Vol. 5, p.17 (1925). Article link
    • beta-methylanthraquinone, Organic Syntheses, Coll. Vol. 1, p.353 (1941); Vol. 4, p.43 (1925). Article link
    • Benzoylation of ferrocene Organic Syntheses, Coll. Vol. 6, p.625 (1988); Vol. 56, p.28 (1977). Article link

See also

  • Darzens-Nenitzescu synthesis of ketones
  • Haworth phenanthrene synthesis
  • Nencki reaction
 
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