Acetic formic anhydride acylation reactions

In the course of synthesizing DNA-gyrase inhibitors Hogberg, Mitscher, and coworkers determined that an effective means of constructing the core of their inhibitors was via a K-R reaction. Under mild conditions, keto ethylester 52 was acylated using acetic formic anhydride in the presence of sodium formate to deliver chromone 53 in 75% yield. 

The scope of this reaction is similar to that of 10-21. Though anhydrides are somewhat less reactive than acyl halides, they are often used to prepare carboxylic esters. Acids, Lewis acids, and bases are often used as catalysts—most often, pyridine. Catalysis by pyridine is of the nucleophilic type (see 10-9). 4-(A,A-Dimethylamino)pyridine is a better catalyst than pyridine and can be used in cases where pyridine fails. " Nonbasic catalysts are cobalt(II) chloride " and TaCls—Si02. " Formic anhydride is not a stable compound but esters of formic acid can be prepared by treating alcohols " or phenols " with acetic-formic anhydride. Cyclic anhydrides give monoesterified dicarboxylic acids, for example,... 

Low-valent metal salts have been used to bring about reductive cleavage of oximes. Corey and Rich-man used chromium(II) acetate to convert O-acetyl ketoximes into imines, which were hydrolyzed to ketones. " Aqueous titanium(III) chloride and vanadium(II) salts also reduce oximes again, the imines are usually hydrolyzed in situ, but some hindered imines, such as compound (37), are isolable." A method of preventing hydrolysis is to carry out the reduction in anhydrous conditions in the presence of an acylating agent. The products of such reactions, when applied to oximes of enolizable ketones, are en-amides. For example, these ketoximes are converted into A/-formylenamines when heated in acetonitrile with anhydrous titanium(III) acetate and acetic formic anhydride cyclohexanone oxime gives the en-amide (38 97% Scheme 22)." This type of reduction has been used by Barton and coworkers to prepare enamides from steroidal oximes. They reported that the reaction could be performed by acetic... 

These reactions are most important for the preparation of acyl fluorides.1061 Acyl chlorides and anhydrides can be converted to acyl fluorides by treatment with polyhydrogen fluoride-pyridine solution996 or with liquid HF at -10°C.1062 Formyl fluoride, which is a stable compound, was prepared by the latter procedure from the mixed anhydride of formic and acetic acids.1063 Acyl fluorides can also be obtained by reaction of acyl chlorides with KF in acetic acid1064 or with diethylaminosulfur trifluoride (DAST).1065 Carboxylic esters and anhydrides can be converted to acyl halides other than fluorides by the inorganic acid halides mentioned in 074, as well as with Ph3PX2 (X = Cl or Br), 066 but this is seldom done. Halide exchange can be carried out in a similar manner. When halide exchange is done, it is always acyl bromides and iodides that are made from chlorides, since chlorides are by far the most readily available.1067... 

Reaction of 2-aminobenzaldchyde and 2-aminophenyl ketone oximes 22 with acyl chlorides, 3+6-348 esters, acetic anhydride, or formic acid directly... 

The formation of acrylonitriles from the reaction of dihalogenomethylene-phosphoranes with aroyl cyanides has now been extended to include the use of aliphatic acyl cyanides, although the conditions need to be closely defined. Perfluoroisocyanates with diphenylmethylenetriphenylphosphorane give the expected keten-imines (28) or their rearrangement products (29). Formylation of both reactive and stable ylides has been achieved using the mixed anhydride of formic and acetic acids. ... 

Similarly, 3-amino-4(3//)-quinazolinones (600) are formed in high yields when methyl or ethyl o-acylaminobenzoates are heated with hydrazine in an alcohol. Alternatively, acylation and cyclization of an o-aminobenzoylhydrazine is effected by heating with anhydrous formic acid, ethyl orthoformate, or acetic anhydride. Related is the action of heat on a mixture of anthranilic esters and semicarbazides to yield A3-aminated 2,4(1//,3//)-quinazolinediones (601). Reactions which involve... 

The following conditions have proved their worth by avoidance of side reactions a strongly ammoniacal medium an acid medium (alcoholic hydrochloric acid, or if necessary acetic acid) acylating conditions (presence of acetic anhydride or formic esters as solvent) high dilution. 

Friedel-Crafts Acylation of Cedrene. Let us now look in a little more detail at the Friedel-Crafts acylation of cedrene. This reaction can be carried out using acetic acid or acetic anhydride with an acid catalyst such as formic acid, phosphoric acid or sulfuric acid. The species which attacks the double bond of cedrene is the protonated acid or anhydride molecule. When sulfuric acid is used as a catalyst with acetic anhydride as the reagent, it is thought that the sulfuric acid first sulfonates the acetic anhydride to give sulfoacetic anhydride (6.122) as the acylating species. This results in a faster reaction as the sulfoacetate anion (6.126) is a... 

It is interesting to note that the reaction of the l,2,4-triazin-5-ones 34 with pyrroles in acetic anhydride leads exclusively to l-acyl-3-aryl-6-(pyrrolyl-2)-l,2,4-triazin-5-ones 38 however, when the same reaction is carried out in trifluoroacetic anhydride or formic acid, 3-substituted pyrroles, that is, 1-trifluoroacetyl- or l-formyl-3-aryl-6-(pyrrolyl-3)-... 

N-l-Acyl and N-l-sulfamoyl derivatives are formed by the reaction of appropriate chlorides with ergolines under phase-transfer catalysis (Loncaric and Rucman, 1984, Taimr and KrSpelka, 1987). Dimethyl and diethylcarbamoyl derivatives were prepared in the same manner. N-1-Acetyl ergolines were also prepared by a reaction with acetic anhydride under catalysis with BF3 etherate (Benes, 1989). N-1 Formyl ergolines can be obtained by treatment with formic acid and a tertiary amine under palladium catalysis (Taimr et ai, 1987b). 

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