Formic anhydride

Aldehyde Synthesis. Formylation would be expected to take place when formyl chloride or formic anhydride reacts with an aromatic compound ia the presence of aluminum chloride or other Friedel-Crafts catalysts. However, the acid chloride and anhydride of formic acid are both too unstable to be of preparative iaterest. 

Attempts to use acetic-formic anhydride with Friedel-Crafts catalysts resulted only in acetylation. However, using anhydrous HF as a catalyst, a small amount of aldehyde is also formed in accordance with the fact that acetic—formic anhydride gives both acetyl and formyl fluoride with HF. By continuous removal of the low boiling HCOF, the reaction can be shifted to the formation of this compound (118). 

Formic anhydride is not stable. However, formate esters of alcohols and phenoHcs can be prepared using formic—acetic anhydride (69,70). Anhydrides can also be incorporated into polystyrene backbones which can then be treated with alcohols to afford the corresponding esters and carboxypolystyrene for recycle (71). 

Acetic acid, (3,5,6-trichloro-2-pyridinyloxy)-as herbicide, 2, 513 Acetic formic anhydride... 

Typically, the K-R reaction is run at temperatures that often exceed 160 "C. However, a mild variation has been developed using acetic formic anhydride where the transformation occurs at ambient temperature. Okumara and coworkers smoothly converted hydroxyl ester 25 to chromone 26 in 76% yield with acetic formic anhydride and sodium formate at room temperature.Beckett and Ellis also used these conditions to synthesize two chromones in high yield when 27 and 28 were converted to 29 and 30, respectively. ... 

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,... 

Unsymmetrical as well as symmetrical anhydrides are often prepared by the treatment of an acyl halide with a carboxylic acid salt. The compound C0CI2 has been used as a catalyst. If a metallic salt is used, Na , K , or Ag are the most common cations, but more often pyridine or another tertiary amine is added to the free acid and the salt thus formed is treated with the acyl halide. Mixed formic anhydrides are prepared from sodium formate and an aryl halide, by use of a solid-phase copolymer of pyridine-l-oxide. Symmetrical anhydrides can be prepared by reaction of the acyl halide with aqueous NaOH or NaHCOa under phase-transfer conditions, or with sodium bicarbonate with ultrasound. 

Even though formic anhydride is not a stable compound (see p. 714), amines can be formylated with the mixed anhydride of acetic and formic acids (HCOO-COMe) °°° or with a mixture of formic acid and acetic anhydride. Acetamides are not formed with these reagents. Secondary amines can be acylated in the presence of a primary amine by conversion to their salts and addition of 18-crown-6. ° The crown ether complexes the primary ammonium salt, preventing its acylation, while the secondary ammonium salts, which do not fit easily into the cavity, are free to be acylated. 

Reactions 11-15-11-18 are direct formylations of the ring. Reaction 11-14 has not been used for formylation, since neither formic anhydride nor formyl chloride is stable at ordinary temperatures. Formyl chloride has been shown to be stable in chloroform solution for 1 h at -60°C, but it is not useful for formylating aromatic rings under these conditions. Formic anhydride has been prepared in solution, but has not been isolated.Mixed anhydrides of formic and other acids are known and can be used to formylate amines (see 10-56) and alcohols, but no formylation takes place when they are applied to aromatic rings. See 13-15 for a nucleophilic method for the formylation of aromatic rings. 

Formic anhydride and formyl chloride, which do not exist because of their instability. 

The hydrochloride salt of 4-amino-1-benzylimidazole (83 R = H) was acetylated readily by acetic anhydride to give the acetamide derivative (83 R = COCHj) (55%) (74JMC1168). Treatment with acetic-formic anhydride gave the corresponding formamide (83 R = CHO). 

Acetic anhydride, with 2-hep-tanone to give 3-n-butyl-2, 4-pentanedione, 51, 90 ACETIC FORMIC ANHYDRIDE, 50, 1 Acetone azine, 50, 2 ACETONE HYDRAZONE, 50, 2, 28 Acetophenone, 54, 93 as sensitizer for irradiation of bicyclo[2.2.1]hepta-2,5-diene to give quadricyclane,... 

FORMATION AND PHOTOCHEMICAL WOLFF REARRANGEMENT OF CYCLIC a-DIAZO KETONES D-NORANDROST-5-EN-3 -0L-16-CARB0XYLIC ACIDS, 52, 53 FORMIC ACID, AZIDO—, tert-BUTYL ESTER, 50, 9 Formylation, with acetic formic anhydride, 50, 2 p-FORMYLBENZENESULFONAMIDE, ... 

Fig. 19. Schematic drawing of the arrangement of surface dipoles for formic anhydride adsorbed on Ni(l 10) and Ni(lOO) (ffS). Reprinted with permission of North-Holland Publishing Company, Amsterdam, 1979.

Fig. 21. Plot showing the falloff in CO produced from formic anhydride on a Cu/Ni alloy with changing surface composition (100). Reprinted with permission from Journal of Inorganic Chemistry 17, 1978. Copyright 1978, American Chemical Society.

Reaction of hydroxy lactam 97 with acetic formic anhydride gives the formyl derivative 98 in high yield <20000L99>. 

The hydroxyquinoline (39-2) provides the starting material for a quinolone that incorporates a hydrazine function. Reaction of (39-2) with 2,4-dintrophenyl O-hydroxylamine ether (41-1) in the presence of potassium carbonate leads to a scission of the weak N-O hydroxylamine bond by the transient anion from the quinolone the excellent leaving character of 2,4-dinitrophenoxide adds the driving force for the overall reaction, resulting in alkylation on nitrogen to form the hydrazine (41-2). The primary amine is then converted to the formamide (41-3) by reaction with the mixed acetic-formic anhydride. Alkylation of that intermediate with methyl iodide followed by removal of the formamide affords the monomethylated derivative (41-4). Chlorine at the 7 position is then displaced by A-methylpiperazine and the product saponified. There is thus obtained amifloxacin (41-6) [48]. 

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