Esterification with MeOH

H-His-OMe 2HC1 Typical Procedure for Esterification with MeOH/HCl I " ... 

Asymmetric induction in the di-jr-methane rearrangement is also of interest and studies on this have examined the influence of chiral esters. Thus the irradiation of 370 yields a cyclooctatetraene 371 and a diastereoisomeric mixture of the semibullvalenes 372 and 373 in a ratio of 60 40 in solution and 20 80 in the solid phase. The position of attachment is vital and the diastereoselectivity shown by the barrelene 374 is very poor and yields a 1 1 mixture of products . Further examples of the control exercised when dibenzobarrelenes are inadiated in the crystalline phase have used the derivatives 375 and 376 as the acid salts formed with chiral amines. Irradiation affords the products 377 and 378 respectively, obtained after esterification with MeOH, with an ee of >95% . The influence of a chiral crystal lattice on the outcome of the di-jr-methane reaction of achiral 379 has been studied. The irradiation in the crystalline phase gives two chiral di-TT-rnethane products 380 and 381. The former of these is racemic but the latter is obtained in high enantiomeric excess which, under the best conditions, i.e. at —20 °C, approaches 100%. The irradiation of ciystals of 345, as an ethanol complex, affords 382 with an ee of 94%. Carrying out the inadiation at temperatures lower than ambient enhances the specificity of the reaction . 

The reaction of HI with MeOH to regenerate Mel, as well as the esterification of MeOH and AcOH were recognized as interrelated equilibria by the team at Monsanto who first investigated the Rh catalysed carbonylation of MeOH, (Eq. (3)), (Eq. (10)), (Eq. (31))... 

The esterification of 1,2,5-dithiazepine 68 with phenylphosphonic dichloride in benzene and subsequent hydrolysis gave 122, which upon further esterification with chloromethyl pivalate in MeOH afforded 0-(l,l,4,4-tetramethyl-2,3,5,6,9,10-hexahydroimidazo[2,, 2,5]dithiazepin-9-yl )cthy 10-pi valoyloxy methyl phenylphosphonate 123... 

Esterification of FFA in Acid Oil with MeOH under Pressure In the Presence of Sulfuric Acid... 

Hydrolysis of herbaceine yields methanol and epiherbaceinic acid (hydrochloride, mp > 200° decomp.) which upon esterification with diazomethane forms epiherbaceine (mp 142°-150° [a]jj —19° in MeOH). The epi compound can also be produced by refluxing herbaceine in methanolic sodium methoxide for 15 hours. Herbaceine upon reduction with lithium aluminum hydride furnishes herbaceinol (perchlorate, mp 215°-217°). 

Compounds 296 and 297 had previously been synthesized by our group from artemisin (2) by an alternative route [49]. This synthesis required reductive cleavage of the C(6)-0 bond, a transformation that was achieved by epimerization at C(6) in an acidic medium followed by reductive treatment with Zn in acetic acid and esterification of the resulting acid with MeOH/sulfuric acid to give hydroxy ester 299. Hydrogenation and acidic treatment of this intermediate afforded the same compounds (296 and 297). Compound 296 has been used as the starting materid in the synthesis of several 8,12-sesquiterpenolides. 

Preparative Methods prepared by the reaction of [E)-2-(trimethylsilyl)vinyllithium with methyl chloroformate or by carbonation of the corresponding Grignard reagent prepared from (l-bromovinyl)trimethylsilane, giving 2-trimethyl-silylacrylic acid. The methyl ester is prepared from the acid by direct esterification with absolute methanol in the presence of mineral acid, by reaction with diazomethane at low temperature, or by treatment with BF3-MeOH complex. For preparation of various trialkylsilylacrylic acid esters and f-butyl 2-trimethylsilylcrotonate, see the cited references. 

Determination of carboxy groups. Esterification or polyesterification kinetics is usually followed by this titration which is both easy and accurate. Each sample is dissolved in a solvent or a mixture of solvents (CHCI3, QH /EtOH or MeOH, toluene/EtOH or MeOH...) and then titrated with alcoholic KOH. The end point is determined either with an indicator (in most cases phenolphthalein) or with a pH-meter. An accuracy of about 0.1-1% can generally be achieved. 

SA conversion increases with increasing residence time, and with increasing MeOH SA to a maximum of about 98%. It appears that the maximum conversion increases to 99% for the highest MeOH SA studied (30), consistent with an equilibrium limited reaction. The esterification reaction rate was strongly suppressed by lowering MeOH/SA ratio below 10%. 

Another possible termination step that has been utilized for the cycloetherification of alkynols involves CO insertion and esterification of the resulting acyl metal with an exogenous alcohol. This process has typically employed MeOH as solvent and a stoichiometric oxidant since the catalyst is turned over in a reduced form. Following this mechanistic motif, a variety of alkynols have been cyclized under Pd(n) catalysis to five- and six-membered oxacycles with incorporation of methyl esters into the products.294,327-329 For the formation of five-membered ring products, this reaction has been carried out in both exo- and endo-mode to provide 1- and 2-substituted... 

A unique Pd(II)-promoted ortfto-esterification of 2,5-diphenyloxazole has been described [26], When 2,5-diphenyloxazole was heated with 2.5 equivalents of Pd(OAc>2 in acetic acid and CCLt, regioselective palladation took place, giving rise to arylpalladium(n) o-complex 31 in almost quantitative yield. The regioselectivity observed reflects the strong coordination ability of the oxazole nitrogen atom to the palladium atom. Complex 31 was then dissolved in MeOH-THF (1 1) and the solution was stirred at 0 °C to produce 2-(5 -phenylthiazol2-yl)-benzoate 32. A... 

A vial containing ( )-4-phenyl-3-butyn-2-ol (73.0 mg, 0.500 mmol) and catalyst 16 (3.3 mg, 0.005 mmol) in tert-amyl alcohol (1.0 mL) was capped with a septum and sonicated to help dissolve the catalyst. The resulting purple solution was cooled to 0 °C, and Ac O (35.4 pL, 0.375 mmol) was added by syringe. After 49 h, the reaction mixture was quenched by the addition of a large excess of MeOH. After concentration in vacuo, the residue was purified by FC on sihca gel (EtOAc/hexanes, 1/9 — 1/1 then EtOAc/hexanes/ EtjN, 9/9/2) to afford the (l )-acetate (68.6% ee by chiral-GC) and the (5)-alcohol (96.0%ee by chiral-GC on the acetate obtained following esterification). The calculated selectivity value at 58.3% conversion was s = 20.2. 

Before looking in detail at the mechanisms of the various reactions and processes it is worth summarizing some relevant observations about the carbonylation processes as a whole that need to be explained by these mechanisms. It should be noted that, although the overall feedstock is MeOH for an AcOH process, for practical reasons it is usual to operate with relatively high [AcOH] in the reactor and that most of the substrate is present as MeOAc through esterification (Eq. (3)). 

Esterification. The esterification reaction (Figure 3) involves the reaction of a FFA with an alcohol (usually a low molecular weight alcohol, such as MeOH, EtOH, PrOH, and ButOH) to produce an alkyl ester (biodiesel) and water. Either base or acid catalysts can be used for the reaction. However, base catalysts can only be used at high temperatures (or catalyst deactivation takes place by soap formation). More commonly, acid catalysts such as sulfuric acid are employed to carry out the esterification reaction under mild conditions. 

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