Organic Syntheses Procedure

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Org. Synth. 1953, 33, 1

DOI: 10.15227/orgsyn.033.0001

3-ACETAMIDO-2-BUTANONE

[2-Butanone, 3-acetamido-]

Submitted by Richard H. Wiley and O. H. Borum¹.

Checked by R. S. Schreiber and B. D. Aspergren.

1. Procedure

A mixture of 156.6 g. (159 ml., 1.98 moles) of pyridine (Note 1), 239.9 g. (224 ml., 2.35 moles) of acetic anhydride (Note 2), and 35.1 g. (0.39 mole) of vacuum-dried alanine (Note 3) and (Note 4) is heated with stirring (Note 5) on the steam bath for 6 hours after solution is complete (Note 6). The excess pyridine and acetic anhydride, and the acetic acid, are removed at reduced pressure. The residue is distilled through a 15-cm. column, packed with glass helices, to give 41.5–47.5 g. of crude product, boiling at 110–125°/3 mm. Refractionation gives 41–45 g. (81–88%) of 3-acetamido-2-butanone; b.p. 102–106°/2 mm.; n_D25 1.4558–1.4561 (Note 7).

2. Notes

1. A commercial C.P. grade can be used. The checkers used Merck A.R. grade.

2. A commercial grade, 95% minimum assay, can be used. The checkers used Merck A.R. grade.

3. Any good commercial grade material appears to be satisfactory.

4. Reducing the molar ratio of pyridine or anhydride to the amino acid reduces the yield.

5. Without stirring the yield is 46%.

6. With other amino acids, notably glycine and sarcosine, it is necessary to reflux the reactants 1–6 hours.

7. The checkers found it necessary to heat the column to obtain the maximum available product.

3. Discussion

This method, an adaptation of a previously described procedure,²^,³^,⁴ has been used with a variety of amino acids and anhydrides to give the following products: 1-phenyl-1-propionamido-2-butanone (75%);⁵ acetamidoacetylacetone (60%);⁵ N-methylacetamidoacetone;⁶ 1-phenyl-2-acetamido-3-butanone (79%);⁷ 1-phenyl-2-propionamido-3-pentanone (41%);⁷ 1-phenyl-2-butyramido-3-hexanone (27%);⁷ α-benzamidopropiophenone (42%);⁷ α-benzamido-β-phenylpropiophenone (44%);⁷ 1-phenyl-1-acetamidoacetone (72–90%);⁸^,⁹ 1-phenyl-1-benzamidoacetone (65%);⁸ 1-phenyl-2-benzamido-3-butanone (78%);⁸ 3-benzamido-2-butanone (65–88%);⁸ and 3-acetamido-5-methyl-2-hexanone (73%).¹⁰

This preparation is referenced from:

Org. Syn. Coll. Vol. 5, 27

References and Notes

University of Louisville, Louisville, Kentucky.
Dakin and West, J. Biol. Chem., 78, 91, 757 (1928).
Levene and Steiger, J. Biol. Chem., 74, 689 (1927); 79, 95 (1928).
Wiley, J. Org. Chem., 12, 43 (1947).
Wiley and Borum, J. Am. Chem. Soc., 70, 2005 (1948).
Wiley and Borum, J. Am. Chem. Soc., 72, 1626 (1950).
Cleland and Niemann, J. Am. Chem. Soc., 71, 841 (1949).
Searles and Cvejanovich, J. Am. Chem. Soc., 72, 3200 (1950).
Rondestvedt, Manning, and Tabibian, J. Am. Chem. Soc., 72, 3183 (1950).
Borum, Ph.D. Thesis, University of North Carolina, 1949.

Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

acetic acid (64-19-7)

acetic anhydride (108-24-7)

alanine (56-41-7)

pyridine (110-86-1)

sarcosine (107-97-1)

Glycine (513-29-1)

3-Acetamido-2-butanone,
2-Butanone, 3-acetamido- (6628-81-5)

1-phenyl-1-propionamido-2-butanone

acetamidoacetylacetone

N-methylacetamidoacetone

1-phenyl-2-acetamido-3-butanone

1-phenyl-2-propionamido-3-pentanone

1-phenyl-2-butyramido-3-hexanone

α-benzamidopropiophenone

α-benzamido-β-phenylpropiophenone

1-phenyl-1-acetamidoacetone

1-phenyl-1-benzamidoacetone

1-phenyl-2-benzamido-3-butanone

3-benzamido-2-butanone

3-acetamido-5-methyl-2-hexanone

Notes

References/EndNotes

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