Carbonylation acetic anhydride

Several syntheses of carbon-14 labeled taxols have been reported. N-3 -[Carbonyl- " C]-taxol 11.1.1 was prepared by coupling a [carbo-nyl- C]-A -benzoyl- 5-lactam with 7-(triethylsilyl)baccatin III (378), while the same group prepared [3 - " C]-taxol 11.1.2 by using a / -lactam prepared from carbonyl- " C-benzaldehyde (379). [3 - " C]-Docetaxel 11.1.3 was prepared by attachment of a labeled cinnamoyl side chain to 7,10-ditroc-10-deacetylbaccatin III, followed by hydroxyamination of the side chain (380). A slightly different approach was used to prepare [2, 3 - " C2]taxol, in that the required doubly labeled /3-lactam synthon was prepared using a doubly labeled Oppolzer s bromoacylbomanesul-tam intermediate (381). 7-([carbonyl- C]-acetyl)taxol was prepared by simple acylation of 2 -(triethylsilyl)taxol with [carbonyl--acetic anhydride and deprotection (382). The taxol analog PNU-105298 (4.1.3.12) was also prepared in both deuterium and carbon-14 labeled forms in both cases the label was placed on the side chain (383). 

The carbonylation of alkene in AcOH-acetic anhydride in the presence of NaCl affords the /9-acetoxycarboxylic anhydride 242 in good yields and the method offers a good synthetic method for / -hydroxycarboxylic acid 243[222],... 

Unusual cyclocarbonylation of allylic acetates proceeds in the presence of acetic anhydride and an amine to afford acetates of phenol derivatives. The cinnamyl acetate derivative 408 undergoes carbonylation and Friedel-Crafts-type cyclization to form the a-naphthyl acetate 410 under severe condi-tions[263,264]. The reaction proceeds at 140-170 under 50-70 atm of CO in the presence of acetic anhydride and Et N. Addition of acetic anhydride is essential for the cyclization. The key step seems to be the Friedel-Crafts-type cyclization of an acylpalladium complex as shown by 409. When MeOH is added instead of acetic anhydride, /3,7-unsaturated esters such as 388 are... 

Figure 3 shows the production of acetaldehyde in the years 1969 through 1987 as well as an estimate of 1989—1995 production. The year 1969 was a peak year for acetaldehyde with a reported production of 748,000 t. Acetaldehyde production is linked with the demand for acetic acid, acetic anhydride, cellulose acetate, vinyl acetate resins, acetate esters, pentaerythritol, synthetic pyridine derivatives, terephthaHc acid, and peracetic acid. In 1976 acetic acid production represented 60% of the acetaldehyde demand. That demand has diminished as a result of the rising cost of ethylene as feedstock and methanol carbonylation as the preferred route to acetic acid (qv). 

Synthesis gas is obtained either from methane reforming or from coal gasification (see Coal conversion processes). Telescoping the methanol carbonylation into an esterification scheme furnishes methyl acetate directly. Thermal decomposition of methyl acetate yields carbon and acetic anhydride,... 

About half of the wodd production comes from methanol carbonylation and about one-third from acetaldehyde oxidation. Another tenth of the wodd capacity can be attributed to butane—naphtha Hquid-phase oxidation. Appreciable quantities of acetic acid are recovered from reactions involving peracetic acid. Precise statistics on acetic acid production are compHcated by recycling of acid from cellulose acetate and poly(vinyl alcohol) production. Acetic acid that is by-product from peracetic acid [79-21-0] is normally designated as virgin acid, yet acid from hydrolysis of cellulose acetate or poly(vinyl acetate) is designated recycle acid. Indeterrninate quantities of acetic acid are coproduced with acetic anhydride from coal-based carbon monoxide and unknown amounts are bartered or exchanged between corporations as a device to lessen transport costs. 

Fig. 2. Flow sheet for methyl acetate carbonylation to anhydride. To convert kPa to psi multiply by 0.145.

The Eastman acetic anhydride [108-24-7] process provides an extension of carbonylation chemistry to carboxyUc acid esters. The process is based on technology developed independendy in the 1970s by Eastman and Halcon SD. The Eastman acetic anhydride process involves carbonylation of methyl acetate [79-20-9] produced from coal-derived methanol and acetic acid [64-19-7]. 

Butane. Butane LPO has been a significant source for the commercial production of acetic acid and acetic anhydride for many years. At various times, plants have operated in the former USSR, Germany, Holland, the United States, and Canada. Only the Hoechst-Celanese Chemical Group, Inc. plants in Pampa, Texas, and Edmonton, Alberta, Canada, continue to operate. The Pampa plant, with a reported aimual production of 250,000 t/yr, represents about 15% of the 1994 installed U.S. capacity (212). Methanol carbonylation is now the dominant process for acetic acid production, but butane LPO in estabhshed plants remains competitive. 

Acetates. Anhydrous iron(II) acetate [3094-87-9J, Ee(C2H202)2, can be prepared by dissolving iron scraps or turnings in anhydrous acetic acid ( 2% acetic anhydride) under an inert atmosphere. It is a colorless compound that can be recrystaUized from water to afford hydrated species. Iron(II) acetate is used in the preparation of dark shades of inks (qv) and dyes and is used as a mordant in dyeing (see Dyes and dye intermediates). An iron acetate salt [2140-52-5] that is a mixture of indefinite proportions of iron(II) and iron(III) can be obtained by concentration of the black Hquors obtained by dissolution of scrap iron in acetic acid. It is used as a catalyst of acetylation and carbonylation reactions. 

This process is one of the three commercially practiced processes for the production of acetic anhydride. The other two are the oxidation of acetaldehyde [75-07-0] and the carbonylation of methyl acetate [79-20-9] in the presence of a rhodium catalyst (coal gasification technology, Halcon process) (77). The latter process was put into operation by Tennessee Eastman in 1983. In the United States the total acetic anhydride production has been reported to be in the order of 1000 metric tons. 

Acetic Acid. Methanol carbonylation has become the process of choice for production of this staple of the organic chemical industry, which is used in the manufacture of acetate fibers, acetic anhydride [108-24-7] and terephthaUc acid, and for fermentation (see Acetic acid and derivatives). 

A related but distinct rhodium-catalyzed methyl acetate carbonylation to acetic anhydride (134) was commercialized by Eastman in 1983. Anhydrous conditions necessary to the Eastman acetic anhydride process require important modifications (24) to the process, including introduction of hydrogen to maintain the active [Rhl2(CO)2] catalyst and addition of lithium cation to activate the alkyl methyl group of methyl acetate toward nucleophilic attack by iodide. 

The introduction of tritium into molecules is most commonly achieved by reductive methods, including catalytic reduction by tritium gas, PH2], of olefins, catalytic reductive replacement of halogen (Cl, Br, or I) by H2, and metal pH] hydride reduction of carbonyl compounds, eg, ketones (qv) and some esters, to tritium-labeled alcohols (5). The use of tritium-labeled building blocks, eg, pH] methyl iodide and pH]-acetic anhydride, is an alternative route to the preparation of high specific activity, tritium-labeled compounds. The use of these techniques for the synthesis of radiolabeled receptor ligands, ie, dmgs and dmg analogues, has been described ia detail ia the Hterature (6,7). 

By a suitable choice of activating reagents, primary and secondary alcohols can be selectively oxidi2ed to carbonyl compounds in good yields at room temperatures. Typical activating reagents are acetic anhydride, sulfur trioxide—pyridine, dicyclohexyl carbodiimide, and phosphoms pentoxide (40). 

In an integrated continuous process, cellulose reacts with acetic anhydride prepared from the carbonylation of methyl acetate with carbon monoxide. The acetic acid Hberated reacts further with methanol to give methyl acetate, which is then carbonylated to give additional acetic anhydride (100,101). 

Garbonylation Reaction. The carbonylation of methyl acetate is an important industrial reaction for producing acetic anhydride ... 

Isatin (190) is a compound with interesting chemistry. It can be iV-acetylated with acetic anhydride, iV-methylated via its sodium or potassium salt and O-methylated via its silver salt. Oxidation of isatins with hydrogen peroxide in methanolic sodium methoxide yields methyl anthranilates (81AG(E)882>. In moist air, O-methylisatin (191) forms methylisatoid (192). Isatin forms normal carbonyl derivatives (193) with ketonic reagents such as hydroxylamine and phenylhydrazine and the reactive 3-carbonyl group also undergoes aldol condensation with active methylene compounds. Isatin forms a complex derivative, isamic acid (194), with ammonia (76JCS(P1)2004). 

The effect of conformation on reactivity is intimately associated with the details of the mechanism of a reaction. The examples of Scheme 3.2 illustrate some of the w s in which substituent orientation can affect reactivity. It has been shown that oxidation of cis-A-t-butylcyclohexanol is faster than oxidation of the trans isomer, but the rates of acetylation are in the opposite order. Let us consider the acetylation first. The rate of the reaction will depend on the fiee energy of activation for the rate-determining step. For acetylation, this step involves nucleophilic attack by the hydroxyl group on the acetic anhydride carbonyl... 

In similar work, CF3CCI2CO2CH3 yields methyl a-trifluoromethyl-a,(i-un-saturated carboxylates when reacted with a zinc-copper couple, aldehydes, and acetic anhydride [67] (equation 55). This methodology gives (Z)-a-fluoro-a- -un-saturated carboxylates from the reaction of carbonyl compounds with CFCI2CO2CH3 and zinc and acetic anhydride [6 ]. 

Kinetic reactivity can be assessed by examining the lowest-unoccupied molecular orbital (LUMO). This is the orbital into which the nucleophile s pair of electrons will go. Compare the LUMO for acetic anhydride and ethyl acetate. For each, determine on which atom(s) the orbital has the largest lobes Do both reagents appear to be susceptible to nucleophilic attack at the carbonyl carbon ... 

The azlactones of a-benzoylaminocinnamic acids have traditionally been prepared by the action of hippuric acid (1, Ri = Ph) and acetic anhydride upon aromatic aldehydes, usually in the presence of sodium acetate. The formation of the oxazolone (2) in Erlenmeyer-Plochl synthesis is supported by good evidence. The method is a way to important intermediate products used in the synthesis of a-amino acids, peptides and related compounds. The aldol condensation reaction of azlactones (2) with carbonyl compounds is often followed by hydrolysis to provide unsaturated a-acylamino acid (4). Reduction yields the corresponding amino acid (6), while drastic hydrolysis gives the a-0X0 acid (5). ... 

Several improved methods for the preparation of known unsaturated azlactones as well as some interesting new compounds of this type have been reported. Crawford and Little observed that the direct use of 2-phenyl-5-oxazolone (1) in the Erlenmeyer reaction gave much improved yields (35-74%) of unsaturated azlactones with aliphatic aldehydes and with ketones such as acetone and cyclohexanone [Eq, (1)], The usual procedure of mixing a carbonyl compound, hippuric acid, acetic anhydride, and sodium (or lead) acetate affords poor yields in the aliphatic series. 

If mutarotation were not a factor, the threo pair would give the isomer having the phenyl group and nitrogen atom in a cis relationship and the erythro pair the isomer with the phenyl and carbonyl groups cis. Since it is doubtful, at least in some cases, that steric integrity is maintained in acetic anhydride prior to elimination, the subsequent... 

The acylation reaction of PS with organic anhydrides, such as maleic and acetic anhydrides, are very important for synthesizing polyfunctional (carbonyl-, carboxyl-, keto-, olefinic) PS. The incorporation of these groups to PS caused an increase of adhesion capability, physico-mechanical properties, elasticity, and photosensitivity [41-46]. 

These carbonyl chloride-activated carriers are unstable on storage, so ligand coupling to them has to be undertaken immediately after chemisorption of the copolymer. To overcome this drawback, more stable activated carriers have been synthesized by treating aminopropyl-silicas with poly(p-nitrophenyl acrylate) and acetic anhydride. 

Hydroxy-substituted iron-acyl complexes 1, which are derived from aldol reactions of iron-acyl enolates with carbonyl compounds, are readily converted to the corresponding /i-methoxy or /1-acetoxy complexes 2 on deprotonation and reaction of the resulting alkoxide with iodomethane or acetic anhydride (Tabic 1). Further exposure of these materials to base promotes elimination of methoxide or acetate to provide the a,/ -unsaturated complexes (E)-3 and (Z)-3 (Table 2). 

The final step in the process involves reacting purified carbon monoxide from the gas separation plant with methyl acetate to form acetic anhydride, using a proprietary catalyst system and process. Part of the acetic anhydride is reacted with methanol to produce acetic acid and methyl acetate, and the latter is recirculated to the carbonylation step. 

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