Combination step acetic acid production

Processes for Triacetate. There are both batch and continuous process for triacetate. Many of the considerations and support faciUties for producing acetate apply to triacetate however, no acetyl hydrolysis is required. In the batch triacetate sulfuric acid process, however, a sulfate hydrolysis step (or desulfonation) is necessary. This is carried out by slow addition of a dilute aqueous acetic acid solution containing sodium or magnesium acetate (44,45) or triethanolamine (46) to neutrali2e the Hberated sulfuric acid. The cellulose triacetate product has a combined acetic acid content of 61.5%. 

The bromination of 4,5-j -dihydrocortisone acetate in buffered acetic acid does not proceed very cleanly (<70%) and, in an attempt to improve this step in the cortisone synthesis, Holysz ° investigated the use of dimethylformamide (DMF) as a solvent for bromination. Improved yields were obtained (although in retrospect the homogeneity and structural assignments of some products seem questionable.) It was also observed that the combination of certain metal halides, particularly lithium chloride and bromide in hot DMF was specially effective in dehydrobromination of 4-bromodihydrocortisone acetate. Other amide solvents such as dimethylacetamide (DMA) and A-formylpiperidine can be used in place of DMF. It became apparent later that this method of dehydrobromination is also prone to produce isomeric unsaturated ketones. When applied to 2,4-dibromo-3-ketones, a substantial amount of the A -isomer is formed. 

Under certain conditions a combination of Pd(II) and Cu(II) in acetic acid oxidises olefins to saturated products which neither reagent produces alone. Although Cu(II) continues to catalyse the production of vinyl acetate through step (46) by a redox mechanism, the following new reaction can be effected... 

Polyolefin cyclization.1 This Pd(0) catalyst in combination with a phosphine ligand and acetic acid effects cyclization of polyunsaturated substrates to polycyclic products in one step (zipper reaction). However, a triple bond is required for initiation. This polyolefin cyclization has been used to prepare tetra- and pentaspirocycles, as a mixture of only two stereoisomers. 

To make the DERA-catalyzed process commercially attractive, improvements were required in catalyst load, reaction time, and volumetric productivity. We undertook an enzyme discovery program, using a combination of activity- and sequence-based screening, and discovered 15 DERAs that are active in the previously mentioned process. Several of these enzymes had improved catalyst load relative to the benchmark DERA from E. coli. In the first step of our process, our new DERA enzymes catalyze the enantioselective tandem aldol reaction of two equivalents of acetaldehyde with one equivalent of chloroacetaldehyde (Scheme 20.6). Thus, in 1 step a 6-carbon lactol with two stereogenic centers is formed from achiral 2-carbon starting materials. In the second step, the lactol is oxidized to the corresponding lactone 7 with sodium hypochlorite in acetic acid, which is crystallized to an exceptionally high level of purity (99.9% ee, 99.8% de). 

Acetic acid (0.448 ml) was added to a solution of the Step 2 product (873 mg) and tryptamine (640 mg) dissolved in 40 ml THF containing 10 ml 1,2-dichloroethane and stirred 15 minutes. Sodium triacetoxyboron hydride (1.2 g) was introduced and the mixture stirred 3 days at ambient temperature and was then concentrated. The residue was dissolved in 40 ml apiece 1M NaOH solution and diethyl ether, while the aqueous phase was extracted twice with 30 ml diethyl ether. Combined extracts were then dried and concentrated. The residue was purified by chromatography using silica gel with methyl alcohol/(methanol/ammonia), 100 1, and 617 mg product isolated as a white solid, mp = 150-152°C. 

The Step 1 product (133 mmol) was dissolved in 300 ml toluene and glacial acetic acid (173 mmol), then slowly treated with isoamyl nitrite (173 mmol), and refluxed overnight. The mixture was poured into 1300 ml water and extracted twice with 300 ml EtOAc. Combined extracts were washed twice with 200 ml saturated NaHC03 solution, once with 100 ml brine, dried using MgS04, concentrated, and 19.5 g product isolated. 

A mixture consisting of the Step 3 product (0.85 mol), 10% palladium on charcoal (25 g) and 8000 ml 20% acetic acid was hydrogenated 6 hours at 40°C under 2 bar hydrogen pressure. After standing overnight, the mixture was warmed to 70°C, then filtered. The catalyst was washed with 1500 ml 20% acetic acid and the combined filtrates concentrated. The residue was recrystallized in 1000 ml water, then washed with cold water, dried under reduced pressure at 50°C, and the product isolated in 90.6% yield. 

Recently, Sit et al. extended the reaction to isoquinolines in an elegant synthesis of the dopamine agonist, (+)-dinapsoline 210 <02JMC3660>. The key step of the synthesis was a tributyltin hydride mediated cyclisation of aryl bromide 208 to pentacycle 209, a procedure that could be scaled up to 100 g of starting material at a time. The authors commented that the tributyltin hydride and AIBN combination was by far the most efficient reductive system for generating the free radical species for cyclisation. Acetic acid (or trifluoroacetic acid) was added to the reaction medium to aid removal of the tin by-products. No comment was made as to whether the acid played any further role, such as protonation of the heteroaromatic base. 

An HPLC-DAD method was developed for the separation and the determination of flavonoid and phenolic antioxidants in commercial and freshly prepared cranberry juice.Two sample preparation procedures were used with and without hydrolysis of the glycoside forms of flavonoids carried out by the addition of HCl in the step prior to solid-phase extraction (SPE). The flavonoid and phenolic compounds were then fractionated into neutral and acidic groups via a solid-phase extraction method (Sep-Pak Cig), followed by a RP HPLC separation with gradient elution with water-methanol-acetic acid and a detection at 280 and 360 nm. A comparison of the chromatograms obtained for extracts prepared with and without hydrolysis showed that flavonoids and phenolic acids exist predominantly in combined forms such as glycosides and esters. In a freshly squeezed cranberry juice, for instance, 400 mg of total flavonoids and phenolics per liter of sample was found, 56% of which were flavonoids. Quercetin was the main flavonoid in the hydrolyzed products, where it accounted for about 75% of the total flavonoids, while it was absent in the unhydrolyzed products. 

To a solution of 6.59 g di-r-butyl oxalacetate (27.0 mmol) and 2.66 g NaOAc (27.0 mmol) in 40 mL acetic acid at room temperature was added slowly a solution of 1.38 mL Br2 (4.3 Ig, 27.0 mmol) in 14 mL acetic acid by cannula over 10 min. After being stirred at room temperature for 30 min, the reaction mixture was diluted with 150 mL water and extracted with CH2CI2 (100 mL, 50 mL, 50 mL). The combined organic layers were washed with 150 mL saturated NaHCOs. The layers were separated and the aqueous layer was extracted with CH2CI2 (2 x 50 mL). The organic layers were combined, dried over Na2S04, filtered, and concentrated in vacuo to afford 8.64 g unpurified a-bromo di-r-butyl oxalacetate as a yellow oil, in a yield of 99%. This product was used directly for the next step reaction without further purification. 

In a shortened synthesis program one can combine the wash-out of the urea derivative with the subsequent deprotection reaction [61]. The acidic reagents used on that step, such as trifluoroacetic acid/dichloromethane or hydrogen-chloride/acetic acid, are excellent solvents for the urea by-product. Under these circumstances, however, the repetition of the actual peptide synthesis step, which eventually enhances its completion, is no longer possible, since the next cycle of operations is already initiated with the N-terminal deprotection of the just elongated sequence. We utilized this time-saving, shortened program successfully in the synthesis of several uncomplicated decapeptide precursors of the cyclic antamanide from Boc-amino acids. 

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