Formylation, with acetic formic anhydride

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, ... 

FORMIC ACID, AZIDO-, tert-BUTYL ESTER, 50, 9 Formylation, with acetic formic anhydride, SO, 2... 

The remaining three reaction steps, namely the introduction of Z-Leu with DCC, cleavage of the protecting group and formylation with acetic formic anhydride (AcOCHO), are more or less the same as in the previously described syntheses. The overall yield in the twelve-stage synthesis lies at around 11%. 

N-Formylation with acetic formic anhydride NH NGHO... 

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. ... 

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

Formylation of heterocycles with acetic formic anhydride 90T1081. 

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) ... 

Pyridine (s. a. under POClg) S-Formylation of phenols with acetic formic anhydride... 

Tetra-n-butylammonium octahydrotriborate [(Bu 4NXB,H8)] is a mild reagent which reduces aromatic and aliphatic ketones, aldehydes, and acid chlorides in high yield, and finally the formylation of functionalized primary aromatic and aliphatic amines with acetic formic anhydride followed by borane-methyl sulphide reduction in the same pot affords the corresponding iV-methylamines in excellent isolated yields. ... 

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. 

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). 

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. 

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... 

When the triazole contains both an aliphatic and an aromatic amino group, the former is acetylated preferentially. Thus 4-amino-5-aminomethyl-3-benzyltriazole, stirred with 1 Eq of acetic anhydride in pyridine, gave 4-amino-5-acetamidomethyl-3-benzyltriazole (20 C, 15 hr, 90%). The 1- and 2-methyl analogs were similarly made, but in aqueous pyridine, whereas the use of dry pyridine and 4 Eq of acetic anhydride acetylated both amino groups (75%). Acetic formic anhydride was used similarly to obtain either mono- or di-formylated products, as required [73JCS(P1)1634]. 

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

Formylation. See also Acetic-formic anhydride. Formic acid is a reactive acylal-ing agent for alcohols and amines and sometimes requires no catalyst or other solvent Cholic acid yields the triformyl derivative on being heated with 87% formic acid... 

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... 

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. 

An ice-cooled soln. of formic acid in dry ether satd. with ketene, the excess of which is then removed by a stream of dry air, ether and N-hydroxysuccinimide added to the soln. of the resulting acetic formic anhydride, stirred 3 hrs. at room temp., and allowed to stand overnight -> succinimide formate. Y 85.6%. Also formylation of phenols and f. procedures s. S. Sofuku, I. Muramatsu, and A. Hagi-tani. Bull. Chem. Soc. Japan 40, 2942 (1967). 

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