Arndt–Eistert reaction

Source: Wikipedia, the free encyclopedia.

Arndt-Eistert reaction
Named after Fritz Arndt, Bernd Eistert
Reaction type Homologation reaction
Identifiers
Organic Chemistry Portal arndt-eistert-synthesis
RSC ontology ID RXNO:0000063

In

α-amino acids.[1]

Conditions

Aside from the acid chloride substrate, three reagents are required: diazomethane, water, and a metal catalyst. Each has been well investigated.

The diazomethane is required in excess so as to react with the HCl formed previously.[2] Not taking diazomethane in excess results in HCl reacting with the diazoketone to form chloromethyl ketone and N2. Mild conditions allow this reaction to take place while not affecting complex or reducible groups in the reactant-acid.[3]

The reaction requires the presence of a

catalyst is required. Usually Ag2O is chosen but other metals and even light effect the reaction.[4]

Arndt-Eistert reaction with ketene intermediate.

Variants

The preparation of the beta-amino acid from phenylalanine illustrates the Arndt–Eistert synthesis carried out with the Newman–Beal modification, which involves the inclusion of triethylamine in the diazomethane solution. Either triethylamine or a second equivalent of diazomethane will scavenge HCl, avoiding the formation of α-chloromethylketone side-products.[5][6][7]

Diazomethane is the traditional reagent, but analogues can also be applied.[8] Diazomethane is toxic and potentially violently explosive, which has led to safer alternative procedures,[9] For example, diazo(trimethylsilyl)methane has been demonstrated.[10][11]

methyl ester.[12]

This method can also be used with primary diazoalkanes, to produce secondary α-diazo ketones. However, there are many limitations. Primary diazoalkanes undergo

1,3-dipolar cycloaddition
products.

An alternative to the Arndt–Eistert reaction is the Kowalski ester homologation, which also involves the generation of a carbene equivalent but avoids diazomethane.[15]

Reaction mechanism

The acid chloride suffers attack by diazomethane with loss of HCl. The alpha-diazoketone (RC(O)CHN2) product undergoes the metal-catalyzed Wolff rearrangement to form a ketene, which hydrates to the acid.[16][17][4] The rearrangement leaves untouched the stereochemistry at the carbon alpha to the acid chloride.[6]

Homologation of N-boc-phenylalanine

Historical readings

  • doi:10.1002/cber.19350680142
    .
  • Org. React.
    1: 38.

See also

References

  1. doi:10.1021/cr00028a010
    .
  2. ^ Lee, V.; Newman, M. S. (1970). "Ethyl 1-Naphthylacetate". Organic Syntheses. 50: 77; Collected Volumes, vol. 6, p. 613.
  3. ISBN 978-81-7709-605-7
    .
  4. ^
    doi:10.1002/1099-0690(200207)2002:14<2193::AID-EJOC2193>3.0.CO;2-D
    .
  5. doi:10.1021/ja01167a101
    .
  6. ^ a b Linder, M. R.; Steurer, S.; Podlech, J. (2002). "(S)-3-(tert-Butyloxycarbonylamino)-4-phenylbutanoic acid". Organic Syntheses. 79: 154; Collected Volumes, vol. 10, p. 194.
  7. doi:10.1039/ct9150701491.{{cite journal}}: CS1 maint: multiple names: authors list (link
    )
  8. doi:10.15227/orgsyn.073.0134
    .
  9. PMID 11485491
    .
  10. doi:10.1016/S0040-4039(00)92200-7
    .
  11. doi:10.1016/S0040-4039(01)01458-7
    .
  12. doi:10.1021/ja01367a040.{{cite journal}}: CS1 maint: multiple names: authors list (link
    )
  13. doi:10.1002/jlac.19576020116
    .
  14. ^ Yates, P. Farnum, D. G. Wiley, D. W. (1958). Chem. Ind.: 69. {{cite journal}}: Missing or empty |title= (help)CS1 maint: multiple names: authors list (link)
  15. doi:10.15227/orgsyn.071.0146
    .
  16. doi:10.1021/ja01264a505
    .
  17. doi:10.1002/anie.197500321
    .
Retrieved from "https://en.wikipedia.org/w/index.php?title=Arndt–Eistert_reaction&oldid=1161090171"