Organic Syntheses Procedure

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Org. Synth. 1941, 21, 71

DOI: 10.15227/orgsyn.021.0071

LACTAMIDE

Submitted by J. Kleinberg and L. F. Audrieth.

Checked by Homer Adkins and William H. Bateman.

1. Procedure

One hundred and twenty-five grams (1.06 moles) of ethyl lactate is placed in a suitable Pyrex container which is subsequently cooled in a Dry Ice-acetone bath. When the ester has been cooled below the boiling point of ammonia (Note 1), 125 ml. of liquid ammonia (Note 2) is added. The mixture is then placed in a specially constructed steel pressure apparatus (Note 3) and permitted to come to room temperature. After 24 hours (Note 4) the excess of ammonia is allowed to escape slowly through the gas outlet of the bomb. The last traces of ammonia are removed under reduced pressure. The reaction product is stirred with 200 ml. of absolute ether to dissolve unchanged ester and ethanol. The residue is filtered, washed with ether, and air-dried. The yield of lactamide melting at 74–75° amounts to 65–70 g. (70–74%) (Note 5).

2. Notes

1. Care must be taken to cool the ester below the boiling point of ammonia before addition of the ammonia, to avoid loss of ester by spattering.

2. For manipulative procedures employing liquid ammonia see Franklin, The Nitrogen System of Compounds, A.C.S. Monograph 68, Appendix, Reinhold Publishing Corporation, New York, 1935; also, Fernelius and Johnson, J. Chem. Education, 6, 441 (1929).

3. The steel bomb in which the reaction is carried out is depicted in Fig. 16. It consists of a cylindrical tube (A) of ordinary steel to which a steel bottom (B) has been welded. A 1-in. flange (C) is welded to the top of the container extending about 3/16 in. above the top of the bomb. The lead gasket (D) is pressed into the groove (E) when the cover of stainless steel is tightened by means of six steel bolts (G). The top (F) is machined to make a tight seal on the gasket (D). A ¼-in. steel Hoke ammonia valve serves as the gas outlet. The cross-sectional dimensions are noted in the diagram. The checkers carried out the reaction in a glass beaker which was set in a steel reaction vessel such as is used for hydrogenations at pressures of 50–500 atm.¹

Fig. 16.

4. Increase in reaction time causes no appreciable increase in yield of amide.

5. This method has been used for the preparation of numerous amides.² However, with many esters it is necessary to heat the reaction mixture to 200–250° for a few hours. Ethyl mandelate is like ethyl lactate in that it gives a good yield (75–80%) of mandelamide at room temperatures.

3. Discussion

Lactamide has been prepared by the action of ammonia on ethyl lactate,³ methyl lactate,⁴ lactic anhydride,⁵ lactide,⁶ and the condensation product of lactic acid with acetone.⁷ In general, amides have been prepared by the reaction of liquid ammonia with esters at temperatures varying from −33° to 250°.²^,⁸^,⁹

This preparation is referenced from:

Org. Syn. Coll. Vol. 2, 85

References and Notes

Adkins, Reactions of Hydrogen with Organic Compounds over Copper-Chromium Oxide and Nickel Catalysts, p. 31, University of Wisconsin Press, Madison, Wisconsin, 1937; Ind. Eng. Chem., Anal. Ed., 4, 342 (1932).
Wojcik and Adkins, J. Am. Chem. Soc., 56, 2421 (1934), Paden and Adkins, J. Am. Chem. Soc., 58, 2497 (1936).
Brüning, Ann., 104, 197 (1857).
Ratchford, J. Org. Chem., 15, 326 (1950).
Wurtz and Friedel, Ann. chim. phys., (3) 63, 108 (1861).
Wislicenus, Ann., 133, 259 (1865).
Oeda, Bull. Chem. Soc. Japan, 11, 385 (1936).
Glattfeld and MacMillan, J. Am. Chem. Soc., 58, 898 (1936).
Audrieth and Kleinberg, J. Org. Chem., 3, 312 (1938).

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

ethanol (64-17-5)

ammonia (7664-41-7)

ether (60-29-7)

acetone (67-64-1)

ethyl lactate (687-47-8)

lactic acid (50-21-5)

Methyl lactate (547-64-8)

Lactamide (2043-43-8)

Ethyl mandelate (4358-88-7)

Mandelamide (4410-31-5)

lactic anhydride

lactide (95-96-5)

Notes

References/EndNotes

Article Compounds

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