Synthesis of Phenylacetyl Chloride

[Rhodium]

This is a useful precursor for the synthesis of P2P, for example in the following methods:

Post 503140

(Rhodium: "P2P by acylation of diethyl malonate", Methods Discourse)

Post 502749

(Rhodium: "Phenylacetyl chloride + (CH3)2Cd -> P2P", Methods Discourse)


The use of Oxalyl Chloride for Producing Acid Chlorides
Roger Adams and L. H. Ulich
J. Am. Chem. Soc. 42, 599-611 (1920)

If aromatic or aliphatic acids are warmed with 2.5 moles of oxalyl chloride, these acids are converted quickly and practically quantitatively into the corresponding acid chlorides. The reaction may even be carried out in the presence of benzene as a solvent and very successful results obtained.

Instead of rising the organic acid and excess of oxalyl chloride to produce acid chlorides, it is also possible to use the sodium salts of the organic acids and oxalyl chloride. When one mole of the sodium salt of the organic acid is added gradually to 1-1.5 moles of oxalyl chloride in benzene, the reaction runs smoothly with the production of sodium chloride and the organic acid chloride.  The method is even more general than the one just described where the free organic acid is used; moreover, it is usually the method to be preferred as a smaller excess of oxalyl chloride may be used to get the maximum yields. This is due partly to the fact that less gas is evolved in the reaction so that less oxalyl chloride is lost by volatilization. The yields and the purity oi the products are high.

The mechanism of the formation of these acid chlorides and acid anhydrides from oxalyl chloride and aliphatic and aromatic acids is cleared up by a consideration of the above reactions. There is no question but that the first step is the formation of a double anhydride, the second a decomposition of the double anhydride into a simple anhydride, and third, the conversion of the simple anhydride into the corresponding acid chloride as follows:

RCOOH + (COCl)₂ -> (RCOOCO)₂ + 2 HCl -> (RCO)₂O + CO₂ + CO
(RCO)₂O + (COCl)₂ -> 2 RCOCl + CO₂ + CO

Experimental

Action of Oxalyl Chloride on Organic Acids - Preparation of Acid Chlorides

The general procedure by which acid chlorides are produced from acids by means of oxalyl chloride is as follows: In a roundbottom flask, equipped with a reflux condenser, is placed one mole of the organic acid and 2 to 2.5 moles of oxalyl chloride. In some cases, an evolution of gas starts immediately, indicating that the reaction is taking place; in other cases slight warming is necessary before gases are evolved. After once starting, the reaction proceeds spontaneously for 15-20 min. or sometimes even longer. After this period of time slight heating is again applied and the mixture refluxed for about 2 hours. The reaction mixture is then distilled under atmospheric pressure till the excess of oxalyl chloride is collected and then generally under diminished pressure (preferably with a fractionation column) to obtain the acid chloride.

From 35g of Phenylacetic acid and 70g Oxalyl Chloride was obtained 30g Phenylacetyl Chloride (74%), bp 100°C/12 mmHg.

Most other acids give yields exceeding 90%, but phenylacetyl chloride is not very stable and extremely reactive, giving certain amounts of tarry material, probably condensation products between several molecules. The yields, however, in both cases, are very much better than are obtained with other acid chloride reagents with the possible exception of thionyl chloride. The preparation of these acid chlorides can be carried out if desired in benzene as a solvent (about 50 ml of benzene being used for a 25g portion of acid).

Action of Oxalyl Chloride on the Sodium Salts of Organic Acids - Preparation of acid Chlorides

In a round-bottom flask with the reflux condenser attached is placed 1.2 to 1.5 moles of oxalyl chloride dissolved in benzene (20 ml of benzene is used when about 10g of oxalyl chloride is needed). One mole of the dry sodium salt of the acid is now added in small portions through the condenser (any salt stuck to the sides can be rinsed down with small amounts of benzene). Upon each addition, gases are evolved. After all of the sodium salt has been added, the mixture is refluxed for 2 hours with occasional stirring to be certain that the reaction is completed. At the end of this time the sodium chloride and any traces of unchanged sodium salt of the organic acid are filtered off, The filtrate is distilled and after recovering the benzene, the acid chloride is vacuum distilled. In this way yields of acid chloride varying from 75% to over 90% are easily produced.

In the experiments carried out to test the method only small amounts (10-20g) of the sodium salts of the acid were used and consequently the loss involved in a distillation or crystallization was proportionately large It is probable that if 100 g lots of acid chloride should be made, the yields would be consistently over 90%. The compounds are practically pure as obtained directly from the benzene, but in the experiments described the products were either recrystallized or once distilled.



Preparation of Acyl Halides under Very Mild Conditions
John. B. Lee
J. Am. Chem. Soc. 88, 3440-3441 (1966)

Acyl halides are valuable intermediates in a variety of reactions and are generally readily prepared from the parent acid. The usual reagents (e.g., thionyl chloride, phosphorus pentachloride) can be replaced by slightly less vigorous ones (e.g., oxalyl chloride, phosgene) when sensitive acids are being halogenated, but more or less vigorous acidic conditions are needed in all these cases.

We considered that a triaryl- or trialkylacyloxyphosphonium halide (I) would probably readily decompose to give the corresponding acyl halide and the phosphine oxide and confirmed this by examination of the reaction of triphenylphosphine and carbon tetrachloride with various acids [Crofts & Downie, J. Chem. Soc. 2559 (1963)].

For example, acetic acid (1 mole) and triphenylphosphine (1 mole) in carbon tetrachloride reacted very rapidly to produce acetyl chloride, triphenylphosphine oxide, and chloroform in good yield. A range of acids was treated in this way and in each case good yields of acyl chloride were obtained. The over-all reaction may be written as:

R-COOH + Ph₃P + CCl₄ -> R-COCl + Ph₃P=O + CHCl₃

It can be seen that, in the absence of hydrolysis, the acid is rapidly converted to the neutral halide with no generation of any strongly acidic material.

The reaction is obviously a several-step process, and it is suggested that initially formation of II (triphenyltrichloromethylphosphonium chloride) occurs, with further reaction yielding chloroform and the ion I.

Examples of successful preparations:
Acetyl Chloride (bp 50-53°C)
Propionyl Chloride (bp 80-84°C)
Phenylacetylchloride (bp 206-211°C)


Other methods include:

* Phenylacetonitrile hydrolysis and thionyl chloride chlorination:

Tetrahedron Letters 34(1), 95-98 (1993) DOI:

10.1016/S0040-4039(00)60066-7

* Radical addition of oxalyl chloride to toluene:

Patent US2326228

Patent US2326229

Chem.Abstr. 553 (1944)
J.Amer.Chem.Soc. 64 1621 (1942)