Dimethylformamide acetic anhydride

The observation of Blume and Swezey (5) that cellulose dissolves extremely rapidly in acetic anhydride-dimethylformamide, containing sulfuric acid catalyst, suggested that we investigate the possibilities of this reaction for hydrolyzing celluloses. The cellulose acetate formed was not degraded, whereas our purpose was complete degradation. Accordingly, the depolymerization of the cellulose derivative in solution had to be examined. 

The selection of solvents for quantitative work is not easy. Nitro-alkanes are sufficiently inert, but nitronium tetrafluoroborate is poorly soluble in them c. 0-3 %). Nitronium salts react rapidly with acetic anhydride, and less rapidly with acetic acid, A, A -dimethylformamide and acetonitrile, although the latter solvent can be used for nitration at low temperatures. Sulpholan was selected as the most suitable solvent ... 

Chromic(VI) acid Acetic acid, acetic anhydride, acetone, alcohols, alkali metals, ammonia, dimethylformamide, camphor, glycerol, hydrogen sulflde, phosphorus, pyridine, selenium, sulfur, turpentine, flammable liquids in general... 

Cellulose dissolved in suitable solvents, however, can be acetylated in a totally homogeneous manner, and several such methods have been suggested. Treatment in dimethyl sulfoxide (DMSO) with paraformaldehyde gives a soluble methylol derivative that reacts with glacial acetic acid, acetic anhydride, or acetyl chloride to form the acetate (63). The maximum degree of substitution obtained by this method is 2.0 some oxidation also occurs. Similarly, cellulose can be acetylated in solution with dimethylacetamide—paraformaldehyde and dimethylformamide-paraformaldehyde with a potassium acetate catalyst (64) to provide an almost quantitative yield of hydroxymethylceUulose acetate. 

In 1970, it was disclosed that it is possible to achieve the conversion of dimethylformamide cyclic acetals, prepared in one step from vicinal diols, into alkenes through thermolysis in the presence of acetic anhydride." In the context of 31, this two-step process performs admirably and furnishes the desired trans alkene 33 in an overall yield of 40 % from 29. In the event, when diol 31 is heated in the presence of V, V-dimethylforrnamide dimethyl acetal, cyclic dimethylformamide acetal 32 forms. When this substance is heated further in the presence of acetic anhydride, an elimination reaction takes place to give trans olefin 33. Although the mechanism for the elimination step was not established, it was demonstrated in the original report that acetic acid, yV, V-dimethylacetamide, and carbon dioxide are produced in addition to the alkene product."... 

Sulfonation of indole with pyridinium-A -sulfonate yields indolyl-3-sulfonic acid, and bromine in pyridine at 0 °C affords 3-bromoindole (Scheme 7.4). Acetylation with a heated mixture of acetic anhydride and acetic acid gives 1,3-diacetylindole. Methylation requires heating with methyl iodide in DMF (A,A-dimethylformamide) at 80-90 C and yields 3-methylindole. This compound reacts further, giving 2,3-dimethylindole and finally l,2,3,3-tetramethyl-3Ff-indoleninium iodide. 

Aluminum foil, Iodine powder. Carbon disulfide, 1,4,6,9-Tetrabromodiamantane, Sodium bisulfite. Hydrochloric acid. Methanol, Acetonitrile, Acetone, Sodium hydroxide. Magnesium sulfate. Potassium permanganate. Toluene Methylene chloride, 2-Bromomethanol, Trioxane, Aluminum chloride. Magnesium sulfate, Nitroform, Acetone, Sodium bicarbonate. Hexane, Silver nitrate. Acetonitrile 1,2-Dichloroethane, HexamethyldisUane, Iodine, Cyclohexane, 1,3-Dioxolane, Nitroform, Methylene chloride, Dimethylformamide, Sodium sulfate. Hydrochloric acid. Magnesium sulfate. Nitric acid. Sulfuric acid Sulfuryl chloride. Acetic anhydride. Nitric acid. Sodium bicarbonate. Sodium sulfate Nitric acid. Sulfuric acid, Malonamide Nitric acid. Sulfuric acid, Cyanoacetic acid Sulfuric acid, Acetasalicyclic acid. Potassium nitrate Nitroform, Diethyl ether, 1-Bromo-l-nitroethane, Sodium sulfuate... 

The reactivity of five-membered rings with one heteroatom to electrophilic reagents has been quantitatively compared. Table 1 shows that the rates of substitution for (a) formylation by phosgene and V,iV-dimethylformamide, (b) acetylation by acetic anhydride and tin(IV) chloride, and (c) trifluoroacetylation with trifluoroacetic anhydride (71AHC(13)235) are all in the sequence furan > tellurophene > selenophene > thiophene. Pyrrole is still more reactive as shown by the rate for trifluoroacetylation, by the relative rates of bromination of the 2-methoxycarbonyl derivatives (pyrrole > furan > selenophene > thiophene), and by the rate data on the reaction of the iron tricarbonyl-complexed carbocation [C6H7Fe(CO)3]+ (Scheme 5) (2-methylindole ss V-methylindole > indole > pyrrole > furan > thiophene (73CC540)). 

Other pyrimidine keto-nucleosides, such as 47a and 47b, could be treated with acetic anhydride-pyridine without glycosylic cleavage.33 The stability of 47a and 47b in this medium permitted elaboration of a new, mild, regioselective synthesis of enol acetates, The reaction of 4 -ketonucleosides of uracil with acetals of N,N-dimethylformamide led,33 after addition of acetic anhydride, to the corresponding enol acetate-nucleosides 77a and 77b. 

The hydroxyl group of ethyl 2-hydroxy-4-oxo-4//-pyrimido[2,l-a]-isoquinoline-3-carboxylate (20) was methylated with methyl iodide in dry boiling acetone for 5 h in the presence of potassium carbonate, with dimethyl sulfate in methylene chloride in methanol in the presence of Triton B at 20°C for 18 h, with methyl fluorosulfonate in 2.5 M sodium hydroxide at 20°C for 5 h, and with diazomethane in a mixture of diethyl ether and methylene chloride at 20°C for 3 h to give the 2-methoxy derivative (89AJC2161). The hydroxy group of 3-hydroxymethyl-4//-pyrimido[2,l-b]-isoquinolin-4-one was alkylated and acylated with 2-(diethylamino)ethyl chloride in dimethylformamide in the presence of sodium hydroxide, and with acetic anhydride in boiling chloroform in the presence of triethylamine and a few drops of 4-dimethylaminopyridine, respectively (86EUP 166439). 

Further improvements in dehalogenation selectivity and yields can be achieved by using dipolar aprotic solvents. Dimethylformamide has mostly been used for this purpose,18,56,84 97 although dimethyl sulfoxide,98,99 especially when combined with sonication at room temperature (vide infra), deserves attention in particular cases.100,101 Other polar and dipolar aprotic solvents have also been used, namely, acetone,4 butan-2-one,4 acetonitrile,102 acetic anhydride,103104 ethyl acetate,61 tetrahydrothiophene 1,1-dioxide (sulfolane)105 and hexamethyl-phosphoric triamide,106 but no details were reported on their advantages over dimelhylform-amide or dimethyl sulfoxide. Better performance of dipolar aprotic solvents, such as dimethyl-formamide, over other solvents has been demonstrated in the recent comparison of the dehalogenation of 4,5-dichloro-4,5,5-trifluoropentan-l-ol (4) with zinc in various solvents.90... 

Seidel28 cyclized compounds (32) derived from the amides (31) with dimethylformamide dimethyl acetal to the 3-substituted 2-oxo-2H-pyrido-[l,2- ]pyrimidines (33) by heating in acetic anhydride. On this basis he corrected the conclusion of Antaki,29 who had assumed that by reacting 2-amino-4-methylpyridine and ethyl ethoxymethylenecyanoacetate, the 2-oxo-2//-pyrido[l,2-a]pyrimidine (33 R = 8-Me, R1 = OEt) was produced. The product was in fact the 4-oxo isomer (36 R = 8-Me, R1 = H, R2 = COOEt). 

Vilsmeier formylation has attracted much attention as a route to cyclazines (see Section III,B,6). Jessep and Leaver have obtained the Vilsmeier salt 263 from 1 by using dimethylformamide and phosphoryl chloride at — 65°C, but the formylpyrrolizine was very unstable, and a second Vilsmeier reaction has not been achieved.128 The salt 263 could be converted to the 3,5-bisaldehyde equivalent 264a by treatment with dimethylthioformamide and acetic anhydride. Flitsch et al. prepared l-chloro-3H-pyrrolizine and treated it in situ at — 60°C with the Vilsmeier reagent to obtain the chloro derivative 259 of compound 263. 7 They also obtained the bis(dimethylaminomethylene) derivative 264b and, at room temperature, the tris(dimethylaminomethylene) derivative 265, which was hydrolyzed to give the dialdehyde 266. Reactions... 

A round bottom flask is charged with dimethylformamide 72.0 g, acetic anhydride 25.0 g, pyridine 2.0 g, and nitrilotriacetic acid (NTA) 38.2 g and the suspension is nitrogen purged for several minutes. The flask is stoppered and the mixture is stirred at room temperature for 3 days. A small amount of unreacted NTA is filtered out. The bulk of the solvent 79 ml is removed in vacuo at a bath temperature of 60°-70°C. The resulting viscous solution is twice roto-vacued after two successive additions of 40 ml dimethylformamide. So the 2,6-diketo-N-carboxymethyl morpholine (NTA anhydride) is prepiared. 

To a solution of 350 mg of methyl 4-[2-endo-hydroxy-l-exo-hydroxymethyl-3a,8b-cis-2,3,3a,8b-tetrahydro-lH-5-cyclopenta[b]benzofranyl]butyrate in 3.5 ml of anhydrous dimethylformamide cooled in an ice bath were added 140 mg of imidazole and 360 mg of t-butyldimethylsilyl chloride, and after the mixture was stirred for 3 hours at room temperature, dimethylformamide was removed under reduced pressure. The residue was dissolved in a mixture of 10 ml of acetic anhydride and 5 ml of pyridine. After the mixture was stirred for 2 hours at room temperature, the reaction mixture was concentrated. 

A mixture of guanosine (355 g, 1.25 M), acetic anhydride (0.750 L), pyridine (0.375 L) and dimethylformamide (1 L) is stirred at room temperature for 2 hours and then heated at 75°C for 4 hours. After the heating, the mixture is cooled to room temperature and stirred overnight. Most of the solvent is then removed by vacuum distillation at 45°C to yield a white precipitate. The solid is isolated by filtration and washed with isopropanol. The solid is suspended in isopropanol, and heated to reflux whereupon most of the solid dissolves. The isopropanol is then allowed to cool to room temperature, and filtered to yield a white solid that is dried overnight in a vacuum oven at 60°C to yield the title compound (358 g, 69.8%). 

A thiazole 56 (0.05 mol) or a methylene base 57 (0.05 mol), a hydroxypyridone (60) (0.05 mol) and dimethylformamide (0.075 mol, 5.5 g) were heated at 90°C in acetic anhydride (20-30 mL) for about 3 h. The solid that precipitated upon cooling to room temperature was filtered off, washed thoroughly with 2 -propanol and/or aqueous ethanol until the color of the filtrate changed from violet to red and subsequently dried in a vacuum-drying cabinet at 50 °C. For physical characterization, the dyes were recrystallized from acetic anhydride, toluene or toluene-hexane mixtures. 

Cyclization of enone (9) in hexane with boron trifluorideetherate in presence of 1,2-ethanedithiol, followed by hydrolysis with mercury (II) chloride in acetonitrile, yielded the cis-isomer (10) (16%) and transisomer (11) (28%). Reduction of (10) with lithium aluminium hydride in tetrahydrofuran followed by acetylation with acetic anhydride and pyridine gave two epimeric acetates (12) (32%) and (13) (52%) whose configuration was determined by NMR spectroscopy. Oxidation of (12) with Jones reagent afforded ketone (14) which was converted to the a, 3-unsaturated ketone (15) by bromination with pyridinium tribromide in dichloromethane followed by dehydrobromination with lithium carbonate and lithium bromide in dimethylformamide. Ketone (15), on catalytic hydrogenation with Pd-C in the presence of perchloric acid, produced compound (16) (72%) and (14) (17%). The compound (16) was converted to alcohol (17) by reduction with lithium aluminium hydride. 

Benzaldehyde, 1,1,1-trichlorotrifluoroethane, and zinc are heated in dimethylformamide (DMF) in the presence of acetic anhydride. What are products H and I ... 

Trichlorotrifluoroethane and zinc in diethyl ether or dimethylfor-mamide (DMF) form an organometallic complex with diethyl ether [773] or dimethylformamide [114. This complex reacts with aldehydes similarly as the Grignard reagents to form primarily the expected alcohols. In the presence of acetic anhydride, the alcohol is converted to the corresponding olefin, predominantly with Z configuration. In the case of benzaldehyde, Z- and E- 2-chloro-l-phenyl-3,3,3-trifluoropropene are the products H and I [114]. 

A reductive acylation of oximes was developed621. Acylated oximes in the presence of excess acetic anhydride in dimethylformamide are readily reduced to imines using... 

Chalcogenopyrylium salts with active methyl or methylene groups react readily with dimethylformamide or thioformamide in hot acetic anhydride to give a- or y-(A, A[-dimethylaminovinyl)chalcogenopyrylium salts as shown in Eq. (6) (76KFZ73 81KGS1195 82JOC5235). 

Azaindoles are readily acylated on the pyrrole nitrogen by warming on a water bath with acid anhydrides or with acid chlorides in the presence of carbonate or pyridine. Good yields were obtained by this procedure for the following compounds l-acetyl-7-azaindole, 1-benzoyl- and l-benzenesulfonyl-7-azaindole, l-benzoyl-2-methyl-7-azaindole, 1-ethoxycarbonyl- and l-chloroacetyl-7-azaindole, l-acetyl-3-cyano-7-azaindole, 1-benzoyl-4-azindole, and 1-acetyl- and l-benzoyl-2,5-dimethyl-4-azaindole. The only reported failure was with 5-methyl-2-phenyl-4-azaindole, which failed to react with acetic anhydride or benzoyl chloride. 2-Methyl-7-azaindole-3-acetic acid was acylated by treatment of its ierGbutyl ester with sodium hydride in dimethylformamide, followed by p-chlorobenzoyl chloride. ... 

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