Acetylation in the Presence of Pyridine

Pyridine is by far the most commonly used catalyst or accessory in the present day acetylations of starch. It is particularly suitable for the laboratory acetylation of starch in those cases where damage to the basic molecular structure is to be minimized. 

Mixtures of acetic anhydride and pyridine, both because of their mild character and the difficulty with which they penetrate starch granules, do not effect more than a minor acetylation of untreated starches even during long contact at 100 . Consequently, the reagents may be applied successfully only to those pretreated starches, starch fractions, or modified starches which are in a non-homy, finely divided state. 

After swelling starch granules in aqueous pyridine, Friese and Smith, as well as other workers, have added acetic anhydride to bring about a smooth acetylation of the wet starch. Since water consumes excessive amounts of acetic anhydride and may produce hydrolysis of the starch, it is not a desirable constituent in the reaction mixture. Pacsu and Mullen have improved the Friese and Smith procedure by distilling the water from the gelatinized starch as a pyridine-water azeotrope and adding acetic anhydride to conduct the acetylation under anhydrous conditions. At 100-115 , the acetylation is complete in one hour. 

No uniform acetylation conditions have been customary for the acetylation of starch by acetic anhydride and pyridine. Suggested reaction temperatures have varied from 15 to over 100 and reaction periods from several hours to a week. Recently, work has been undertaken to clarify these views and to establish information on which a more uniform acetylation procedure can be based. 

---

Treatment of N-acetyl aziridinecarboxylate with acetic anhydride and heating resulted in the aziridine ring-opened product [106], whereas treatment of the aziridine 137 (Scheme 3.49) with acetic anhydride in the presence of pyridine and DMAP as base similarly resulted in the formation of acetate 138 in 90% yield [45]. 

The chiral acetate reagent is readily prepared from methyl mandelate [methyl (A)-hydroxy-phenyl acetate] which is first converted by treatment with phcnylmagnesium bromide into the triphenylglycol783, c (see Section 1.3.4.2.2.2.) and subsequently transformed into the acetate by reaction with acetyl chloride in the presence of pyridine. Thereby, the secondary hydroxyl group of the glycol is esterified exclusively. Both enantiomers of the reagent are readily accessible since both (R)- and (5)-hydroxyphenylacelic acid (mandelic acids) arc industrial products. 

As previously discussed, solvents that dissolve cellulose by derivatization may be employed for further functionahzation, e.g., esterification. Thus, cellulose has been dissolved in paraformaldehyde/DMSO and esterified, e.g., by acetic, butyric, and phthalic anhydride, as well as by unsaturated methacrylic and maleic anhydride, in the presence of pyridine, or an acetate catalyst. DS values from 0.2 to 2.0 were obtained, being higher, 2.5 for cellulose acetate. H and NMR spectroscopy have indicated that the hydroxyl group of the methy-lol chains are preferably esterified with the anhydrides. Treatment of celliflose with this solvent system, at 90 °C, with methylene diacetate or ethylene diacetate, in the presence of potassium acetate, led to cellulose acetate with a DS of 1.5. Interestingly, the reaction with acetyl chloride or activated acid is less convenient DMAc or DMF can be substituted for DMSO [215-219]. In another set of experiments, polymer with high o -celliflose content was esterified with trimethylacetic anhydride, 1,2,4-benzenetricarboylic anhydride, trimellitic anhydride, phthalic anhydride, and a pyridine catalyst. The esters were isolated after 8h of reaction at 80-100°C, or Ih at room temperature (trimellitic anhydride). These are versatile compounds with interesting elastomeric and thermoplastic properties, and can be cast as films and membranes [220]. 

Acylation of the piperazine nitrogen atoms of 47/,87/-bis[l,2,5]oxadiazolo[3,4- 4 -< ]pyrazine 59 with acetyl bromide proceeds smoothly in the presence of pyridine in acetonitrile to give 60 (Equation 9) <1997CHE618>. 

The polysaccharide was acetylated with acetic anhydride in the presence of pyridine. Purification of the acetate consisted in precipitation of a 10% boiling benzene solution with petroleum ether. One hundred and fifty such precipitations were necessary before a constant-rotating product resulted [a]D20 = — 20.1° (c = 1.0, chloroform). Cryoscopic molecular weight determinations in benzene solution gave an average value of 3918. 

Specifically, in reactions of 4 with acetic anhydride in the presence of zinc chloride58 or boron trifluoride17,35 as the catalyst, 1,2,5-tri-O-acetyl-/J-D-glucofuranurono-6,3-lactone (12) is the preponderant product in the presence of pyridine,58 however, acetylation of 4 by acetic anhydride leads to the favored formation of the corresponding a-D anomer. In contrast to acetylations, in benzoylation reactions, the ratio of anomers apparently changes. Thus, on treatment of 4 with benzoyl chloride in pyridine, Momose and coworkers17 isolated... 

The treatment of 5-indazolylaminomethylenemalonate (948, R = H) with acetic anhydride in acetic acid in the presence of pyridine for 1.5 hr gave the 1-acetyl derivative (1502) in 97% yield, while in THF in the... 

The acetylation of carbazole by acetic anhydride in the presence of boron trifluoride produces the 9-acetyl derivative. Further acetylation requires more vigorous conditions, using aluminum trichloride as a catalyst, and yields 2,9-diacetylcarbazole, which, upon base-catalyzed hydrolysis, produces 2-acetylcarbazole (80T3017). Acetylation of 1-phenyl-isoindole under mild conditions in the presence of pyridine yields l-acetyl-3-phenylisoin-dole, whereas the presence of an ester group at the 1-position deactivates the ring sufficiently to prevent acylation (81AHC(29)34l). 

Condensation of 3-nitrophthalic anhydride with 2,4-pentanedione in the presence of pyridine and piperidine followed by acidification gives 2-acetyl-4-nitroindane-l,3-dione in 76% yield. 

Acetylation of benzothiazepine 85 (R = aryl, 2 -styryl) in the presence of pyridine caused a ring contraction, affording 2,2-disubstituted-3-acetylated benzothiazoline derivatives 86 (Equation 7) <1997LA995, 2003ARK19, 2004JHC399>. 

The condensation of 2-nitrobenzenesulfonyl chlorides with 3-amino-2-chloropyridine in the presence of pyridine at 60 °C gave the corresponding sulfonamides, which were reacted with sodium hydride and iodomethane to give the N-methylated products. Catalytic hydrogenation of the N-methylated compounds followed by acetylation, treatment with sodium hydride in DMF, and reaction with arylalkyl chlorides or methanesulfonates resulted in the formation of novel benzo[/]pyrido[]3,2-r-][l,2,5]thiadiazepines <2005JME7363>. 

Acetylation of 6-methylamino-l l-phenoxynaphthacene-5,12-quinone by acetic anhydride in the presence of a catalytic quantity of sulfuric acid and 6-oxy-ll-phenoxynaphthacene-5,12-quinone in the presence of pyridine yields /V-acctyl-,6-methylamino- and 6-acetoxy-ll-phenoxynaphthacene-5,12-quinones (IIIA).46... 

---