Preparation of .alpha.-acyloxycarbonyl compounds

Disclosed is a process for the preparation of .alpha.-acyloxycarbonyl compounds by contacting the corresponding .alpha.-dicarbonyl compound with an acyl iodide, which can be employed in an essentially pure form or generated in solution from hydrogen iodide and a carboxylic acid anhydride.

This invention concerns a novel process for the preparation of 
.alpha.-acyloxycarbonyl compounds by the chemical reduction of the 
corresponding .alpha.-dicarbonyl compound with an acyl iodide. 
Acyloxycarbonyl compounds such as .alpha.-acetoxy ketone and 
.alpha.-acetoxy carboxylic acid esters, especially aliphatic 
.alpha.-acetoxy ketones and ester, are useful as flavor and fragrance 
ingredients in a number of foods and beverages. These compounds have been 
synthesized by a variety of methods wherein the precursor hydroxy compound 
is prepared and then acylated. 
The reduction of benzils in the presence of aqueous hydrogen iodide and 
acetic acid to obtain the corresponding benzoin compound is described in 
J. Am. Chem. Soc., 71, 1585 (1949); 85, 1669 (1963); and 86, 3068 (1964) 
and in references cited therein. However, when an aliphatic 
.alpha.-diketone was used in this published procedure, the major product 
was a monoketone which was the result of deoxygenation of one keto group, 
i.e., one of the carbonyl groups was reduced to a methylene group. 
I have discovered a process for preparing .alpha.-acyloxycarbonyl compounds 
from the corresponding .alpha.-dicarbonyl compound and avoiding the 
deoxygenation of the reactant as disclosed in the cited references. The 
process comprises contacting an .alpha.-dicarbonyl compound with a 
carboxylic acyl iodide. 
The .alpha.-dicarbonyl compounds which may be used as the reactant in my 
novel process have the formula 
##STR1## 
wherein R.sup.1 and R.sup.2 each represents an alkyl radical, an aryl 
radical, an alkoxy radical or an aryloxy radical or R.sup.1 and R.sup.2 in 
combination represent an alkylene radical, an oxyalkylene radical or an 
oxyalkyleneoxy radical. The alkyl and alkoxy radicals represented by 
R.sup.1 and R.sup.2 can be the same or different radicals and can be 
straight- or branched-chain, unsubstituted or substituted alkyl and alkoxy 
of up to about 14 carbon atoms. The substituents which can be present on 
the substituted alkyl and alkoxy radicals include alkoxy, aryl, aryloxy, 
halogen and other groups which are inert to the materials used in the 
process. Examples of the aryl and aryloxy groups include phenyl, phenyl 
substituted with alkyl, halogen or alkoxy, naphthyl, naphthyl substituted 
with alkyl, alkoxy or halogen, phenoxy, phenoxy substituted with alkyl, 
alkoxy or halogen, naphthyloxy, naphthyloxy substituted with alkyl, alkoxy 
or halogen. The divalent groups which R.sup.1 and R.sup.2 collectively may 
represent may contain from 2 to about 14 carbon atoms such as 
1,3-propanediyl, 1,4-butanediyl, 3-oxypropyl (--CH.sub.2 CH.sub.2 CH.sub.2 
O--), 2-oxy-1,1-dimethylethyl, 1,3-dioxypropane (--OCH.sub.2 CH.sub.2 
CH.sub.2 O--) and the like. The reactants which are most preferred are 
those in which R.sup.1 is alkyl of up to about 4 carbon atoms and R.sup.2 
is alkyl of up to about 4 carbon atoms, phenyl or tolyl. 
The .alpha.-acyloxycarbonyl compounds obtained in accordance with the 
process of my invention have the formula 
##STR2## 
wherein R.sup.1 and R.sup.2 are defined above and R.sup.3 is a carboxylic 
acyl group, e.g., containing up to about 12 carbon atoms such as acetyl, 
propionyl, butanoyl, etc. When the .alpha.-dicarbonyl reactant is an 
unsymmetrical .alpha.-diketone, i.e., when R.sup.1 and R.sup.2 are 
different alkyl or aryl radicals, the product obtained is a mixture of 
.alpha.-acyloxycarbonyl compounds. 
The process requires that the .alpha.-dicarbonyl reactant be contacted with 
at least 2 moles of carboxylic acyl iodide per mole of reactant. The 
process typically is performed using an excess of acyl iodide of as much 
as 5 moles of acyl iodide per mole of reactant. The process preferably is 
performed using about 2 to 3 moles of acyl iodide per mole of reactant. 
The acyl iodide preferably is acetyl iodide although carboxylic acyl 
iodides of up to about 12 carbon atoms, e.g., propionyl iodide and 
butanoyl iodide, may be used. 
The acyl iodide employed may be essentially pure or it may be prepared and 
used as a solution in its corresponding carboxylic acid, for example by 
mixing hydrogen iodide gas or aqueous hydrogen iodide with a carboxylic 
acid anhydride. To maximize conversions to and yield of the desired 
.alpha.-acyloxycarbonyl product, the process should be carried out under 
essentially anhydrous conditions and thus when aqueous hydrogen iodide is 
used sufficient anhydride normally is used to consume the water of the 
hydrogen iodide solution. The process normally is conducted in the 
presence of a carboxylic acid, e.g., an aliphatic carboxylic acid 
containing up to about 12 carbon atoms, such as is produced when the acyl 
iodide is obtained from anhydrous or aqueous hydrogen iodide as described 
above. 
Temperature is not critical to the successful operation of the process 
provided by this invention. For example, temperatures as low as slightly 
above the freezing point of the acyl iodide or anhydride used and as high 
as 200.degree. C. may be used. However, the process normally will be 
conducted at a temperature in the range of about 0.degree. to 125.degree. 
C. A temperature of about 15.degree. to 25.degree. C. is particularly 
preferred when the .alpha.-dicarbonyl reactant is an .alpha.-diketone and 
about 70.degree. to 80.degree. C. is particularly preferred when the 
reactant is an .alpha.-carbonyl ester, i.e., an .alpha.-oxo carboxylic 
acid, or an .alpha.-dicarboxylic acid diester, e.g., diethyl oxalate. 
Pressures moderately above or below ambient pressure can be used although 
there normally is no advantage in doing so.

My novel process is further illustrated by the following examples. 
PROCEDURE 
In each example 8.2 g of 47% aqueous hydrogen iodide (30 mmol hydrogen 
iodide) was added to 30 mL of ice-chilled acetic anhydride with stirring 
except in Example 10 an equimolar quantity of propionic anhydride was 
substituted for the acetic anhydride. The addition should be made with 
extreme caution since the reaction of aqueous hydrogen iodide is very 
exothermic and can be deceptive since there is a variable induction period 
of several seconds to a couple of minutes. After the addition is complete, 
the reaction mixture is allowed to stir an additional 5 to 10 minutes. 
During the course of the reaction, hypophosphorous acid, an oxidation 
inhibitor commonly used in hydrogen iodide solutions, precipitates and is 
removed from the reaction mixture by filtration through a fine fritted 
glass filter. 
The resulting solution contains acetyl iodide as the predominant iodine 
species and varies in color from grey to orange-red depending on the 
source of the aqueous hydrogen iodide. The solution was transferred to a 
100 mL, round-bottom flask to which 10 mmol of .alpha.-dicarbonyl reactant 
was added. The reduction of the .alpha.-diketones (Examples 1, 2, 3, 4 and 
10) was performed with stirring at room temperature for 15 to 20 minutes. 
The .alpha.-ketoesters were reduced by stirring for 15 to 20 minutes at 
50.degree. to 55.degree. C. (Examples 8 and 9) or at 70.degree. to 
75.degree. C. (Examples 5, 6 and 7). 
Each product was isolated by adding, with caution, 10% aqueous sodium 
bisulfite to the reaction mixture until the orange color of iodine is 
completely dissipated. The resulting mixture was transferred to a 250 mL 
separatory funnel and 100 mL water were added. The aqueous layer was 
extracted three times with 50 mL portions of diethyl ether. The ether 
layers were combined and back-extracted twice with 50 mL portions of 
water, 50 mL of 10% aqueous sodium hydroxide and finally with 50 mL of 
water. The ether phase was dried over potassium carbonate (except in 
Example 9 in which sodium sulfate was used) and then filtered. The ether 
then was removed under reduced pressure. 
The products were identified based upon their spectroscopic properties and 
the yields reported are for isolated products except in Example 1 in which 
yields were determined by gas chromatography analysis and in Examples 4 
and 7 in which the yields of the components of the product mixture were 
determined by integration of the .sup.1 H NMR spectrum of the crude 
reaction product mixture after treatment with sodium bisulfite as 
described above. 
The reactants reduced and the products and yields (percent of theory) 
thereof obtained in Examples 1-10 are shown in the Table. The reactants 
conform to formula (I) and the products conform to formula (II) in which 
R.sup.3 is acetyl except in Example 10 in which R.sup.3 is propionyl. The 
yields reported for Example 1 are a range of yields achieved in a 
plurality of biacetyl reductions. 
TABLE 
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Reactant Products 
Example 
R.sup.1 
R.sup.2 
R.sup.1 
R.sup.2 
Yield 
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1 --CH.sub.3 
--CH.sup.3 
--CH.sub.3 
--CH.sub.3 
93-100 
2 --C.sub.6 H.sub.5 
--C.sub.6 H.sub.5 
--C.sub.6 H.sub.5 
--C.sub.6 H.sub.5 
99 
3 --C.sub.2 H.sub.5 
--C.sub.2 H.sub.5 
--C.sub.2 H.sub.5 
--C.sub.2 H.sub.5 
88 
4 --C.sub.6 H.sub.5 
--CH.sub.3 
--C.sub.6 H.sub.5 
--CH.sub.3 
55 
--CH.sub.3 
--C.sub.6 H.sub.5 
37 
5 --C.sub.6 H.sub.5 
--OCH.sub.3 
--C.sub.6 H.sub.5 
--OCH.sub.3 
95 
6 --CH.sub.3 
--OC.sub.2 H.sub.5 
--CH.sub.3 
--OC.sub.2 H.sub.5 
78 
7 --CH(CH.sub.3).sub.2 
--OC.sub.2 H.sub.5 
--CH(CH.sub.3).sub.2 
--OC.sub.2 H.sub.5 
77 
8 --C(CH.sub.3).sub.2 CH.sub.2 O-- 
--C(CH.sub.3).sub.2 CH.sub.2 O-- 
50 
9 --COOC.sub.2 H.sub.5 
--COOC.sub.2 H.sub.5 
--COOC.sub.2 H.sub.5 
--COOC.sub.2 H.sub.5 
88 
10 --C.sub.2 H.sub.5 
--C.sub.2 H.sub.5 
--C.sub.2 H.sub.5 
--C.sub.2 H.sub.5 
98 
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The invention has been described in detail with particular reference to 
preferred embodiments thereof, but it will be understood that variations 
and modifications will be effected within the spirit and scope of the 
invention.