Acetic formic anhydride preparation

Formylation of amines and alcohols. Behai,8 discoverer of the reagent, found that it reacts unidirectionally with simple alcohols to produce alkyl formates free from acetates. Hurd et al. J found that acetic-formic anhydride (prepared from formic acid and ketene) reacts quantitatively with aniline to give formanilide. Another study10 established that acetic-formic anhydride mixes endothermally with 2-nitro-2-methyl-l-propanol, exothermally with 2-nitro-2-methyl-l,3-propanediol, and displays no appreciable temperature effect with either 2-nitro-l-butanol or tris-(hydroxymethyl)-nitromethane. Formic esters are favored by avoiding a high reaction temperature and by not using sulfuric acid as catalyst. The mixed anhydride has been used for the preparation of formyl fluoride.11... 

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,... 

Acetic formic anhydride has been prepared by the reaction of formic acid with acetic anhydride2 3 and ketene,4,5 and of acetyl chloride with sodium formate.6 The present procedure is essentially that of Muramatsu.6 It is simpler than others previously described and gives better yields. It is easily adapted to the preparation of large quantities, usually with an increase in yield. Acetic formic anhydride is a useful intermediate for the formyl-ation of amines,3,7 amino acids,8,9 and alcohols,2,10 for the synthesis of aldehydes from Grignard reagents,11 and for the preparation of formyl fluoride.12... 

DiazoaeetaUehyde. Diazoacetaldchydc is prepared conveniently in 46% yield by the reaction of acetic-formic anhydride with diazomethane. The coproduct, methyl... 

Preparation. For a recent preparation, see Acetic-formic anhydride, this volume. O... 

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... 

Formylaminopyrazines have been prepared as follows. 2-Amino-3-dimethoxy-methylpyrazine stirred at 0 with acetic formic anhydride gave 2-dimethoxymethyl-3-formamidopyrazine (27) (1075), and 2-amino-3-methylpyrazine similarly treated gave 2-formamido-3-methylpyrazine (1200). 

The intrinsic low thermodynamic stability of most formyl derivatives of transition metals (with respect to the decarbonylation product) is confirmed by the observation that when these compounds are prepared by an indirect route, they normally undergo decarbonylation. For example, a formyl derivative of iron(O) was synthesized by reacting [Fe(CO)4] " with acetic-formic anhydride [reaction (c)] however the resulting product [reaction (d)], decarbonylated slowly (ti/2 12 days at 25°C) ... 

Formyl fluoride is prepared by reaction of acetic-formic anhydride with hydrogen fluoride at atmospheric pressure with continuous removal of formyl fluoride (b.p. 

The parent compound has been prepared by cyclization of 4-formamidopyridine-3-carbalde-hyde (9), obtained from the corresponding amino aldehyde with acetic formic anhydride, with methanolic ammonia at 100°C.39... 

Diethyl formylphosphonate (24) can be prepared from triethyl phosphite and acetic formic anhydride, but is thermally unstable. It eliminates carbon monoxide at -10 °C giving the phosphate (25)... 

An interesting two-step procedure has been reported which allows the stereospecific synthesis of the racemate (3) in 80% overall yield. AT-Formyl-L-proline, prepared from L-proline and acetic-formic anhydride, is treated with ethyl propiolate in acetic anhydride to give the ester (4), the cycloaddition presumably proceeding via the dipolar intermediate (5). Hydrogenation of (4) in the presence of palladized charcoal affords the stereochemically pure ethyl ( )-isoretrone-canolate (3), which on reduction provides (+ )-isoretronecanol (6). Since the ester (3) can be efficiently epimerized at C-1 this synthesis also affords a convenient route to the pseudoheliotridine series. 

Chloral reacts with many amines to furnish formamido compounds and chloroform" but complexes often result from this reaction" . Formic acid alone will formylate certain anilines such as 3,4-dichloro-aniline" ". The addition of acetic anhydride improves reactivity" , presumably by the formation of acetic formic anhydride, but acetylation may then occur in preference to formylation. Huffman" has improved this method by preparing formic acetic anhydride before adding the amine . Oldh has described the use of formyl fluoride as a formylating agent. 

The selective en matic acylation and deacylation of carbohydrates and related compounds have been reviewed. In another, extensive review on the chemistry of acetic formic anhydride, several examples of its application to the preparation of carbohydrate formates are given. A further review, in Czech, entitled "The Chemistry of Sucrose", which contains material relevant to this Chapter, is referred to in Chapter 3. 

An efficient one-pot procedure for the iV-monomethylation of primary amines has been reported the method involves formylation with acetic formic anhydride followed by borane methyl sulphide reduction. The reaction sequence is applicable to even very weakly basic and sterically hindered amines, and the products are uncontaminated by over-alkylation. In addition, the transition-metal-catalysed j V-monoalkylation of amines by alcohols has been previously reported (c/. Vol. 6, p. 198) as a method to overcome problems associated with over-alkylation. A similar procedure for the preparation of unsymmetrical secondary (and tertiary) amines utilises a ruthenium catalyst, and is particularly suitable for the synthesis of cyclic amines. ... 

Unsymmetric anhydrides that react selectively on one side are useful. Although formic anhydride is unstable above 10°C, acetic formic anhydride can be prepared by stirring sodium formate with acetyl chloride in ether (64% yield, bp 27-28°C) [22]. It is useful for the formylation of alcohols and amines. A stable solid formylating agent is the mixed anhydride prepared in 89% yield from p-methoxybenzoyl chloride and sodium formate catalyzed by a polymeric pyridine oxide [23]. Ethyl chlorofor-mate gives mixed anhydrides with various carboxylic acids which are then susceptible to nucleophilic substitution at the carboxylic carbonyl carbon. 

Mixed anhydrides of formic acid with higher homologous acids anhydride are well known and stable. BehaP prepared acetic-formic anhydride from acetic anhydride and formic acid, yielding a suitable formylating agent for the formylation of A/-formyl derivatives from the corresponding amines (Eq 1.8). 

Formylation Reactions. The problem with Acetic Formic Anhydride, the most commonly used formylating agent, is undesirable side reactions, particularly if there are acid sensitive functionalities in the compound. One of the best alternatives is to use pentafluorophenyl formate (7), an easily prepared and stable compound which reacts with N-nucleophiles in minutes at room temperature to yield the IV-formyl derivative (eq 5) (Table 3). Significantly, no reaction occurs with alcohols, thiols, or sterically hindered amines. 

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). 

Even though formic anhydride is not a stable compound (see p. 723), 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. Dimethyl carbonate can be used to prepare methyl carbamates in a related procedure. A-Acetylsulfonamides were prepared from acetic anhydride and a primary sulfonamide, catalyzed by Montmorillonite KlO-FeO or sulfuric acid. "... 

Mixed anhydrides can be obtained by those of the above methods in which acid chlorides are used. Further, formation of anhydrides from carboxylic acids and acetic anhydride involves mixed anhydrides as intermediates, and in some cases these can be isolated, e.g., the mixed formic acetic anhydride.977 This anhydride can replace the unstable formic anhydride itself, for only the reactive formyl group is transferred in its reactions this fact has been utilized in the preparation of numerous formic esters, which in turn can be transformed into esters of tertiary alcohols that are otherwise difficult of access (see page 376). 

Additional study of the alkaloidal fractions has given rise to a neutral component, periformyline (XIII) (mp 206°-209° pK a < 4) whose physical properties, formula, UV-, IR-, and mass spectra were suggestive of its structure. The NMR-spectrum in particular showed the formyl hydrogen as a doublet at 8.2 ppm. Its structure was established by the formylation of perivine with the mixed anhydride prepared from acetic anhydride and formic acid (84, 88) (Chart VII). 

The formyl derivatives are obtained from the amines by the action of a mixture of 98% formic acid and acetic anhydride. It seems that either formic anhydride or a mixed anhydride of formic and acetic acid is formed as an intermediate and acts as the acylating agent. In some cases formyl derivatives were prepared via the aminolysis of ethyl formate or /-nitrophenyl formate . 

By trans-esterification, the degree of acetylation can be easily controlled allowing polymers to form with a wide range of hydrophobicity. Starch acetate can be prepared by the acetylation of starch with pyridine acetic anhydride mixtures and cast into films from 90% solutions of formic acid. The wet strength of the film is maintained in the aqueous solution with sufficient acetyl content when exposed to buffered amylase solution. But the acetyl content permits degradation by a mixture of a- and /5-amylase in 1 h. These films can be useful as membranes for bioreactors, which are degraded by enzyme addition. 

Anhydride Formation. Among other anhydride-forming reagents, including Acetic Anhydride, Trifluoroacetic Anhydride, and Phosphorus(V) Oxide, DCC is one of the simplest, mildest, and most effective reagents for the preparation of symmetrical anhydrides, including formic anhydride, which is useful in the preparation of formamides (eq 2). 

The desired pyridylamine was obtained in 69 % overall yield by monomethylation of 2-(aminomethyl)pyridine following a literature procedure (Scheme 4.14). First amine 4.48 was converted into formamide 4.49, through reaction with the in situ prepared mixed anhydride of acetic acid and formic acid. Reduction of 4.49 with borane dimethyl sulfide complex produced diamine 4.50. This compound could be used successfully in the Mannich reaction with 4.39, affording crude 4.51 in 92 % yield (Scheme 4.15). Analogous to 4.44, 4.51 also coordinates to copper(II) in water, as indicated by a shift of the UV-absorption maximum from 296 nm to 308 nm. 

These reactions are most important for the preparation of acyl fluorides. " Acyl chlorides and anhydrides can be converted to acyl fluorides by treatment with polyhydrogen fluoride-pyridine solution" or with liquid HF at — 10°C. Formyl fluoride, which is a stable compound, was prepared by the latter procedure from the mixed anhydride of formic and acetic acids. Acyl fluorides can also be obtained by reaction of acyl chlorides with KF in acetic acid or with DAST. Carboxylic esters and anhydrides can be converted to acyl halides other than fluorides by the inorganic acid halides mentioned in 10-77, as well as with PhsPXa (X = Cl or but this is seldom done. Halide exchange can be carried out in a... 

---