Anhydrides, purification

Although all four tocopherols have been synthesized as their all-rac forms, the commercially significant form of tocopherol is i7//-n7i a-tocopheryl acetate. The commercial processes ia use are based on the work reported by several groups ia 1938 (15—17). These processes utilize a Friedel-Crafts-type condensation of 2,3,5-trimethylhydroquinone with either phytol (16), a phytyl haUde (7,16,17), or phytadiene (7). The principal synthesis (Fig. 3) ia current commercial use iavolves condensation of 2,3,5-trimethylhydroquiQone (13) with synthetic isophytol (14) ia an iaert solvent, such as benzene or hexane, with an acid catalyst, such as ziac chloride, boron trifluoride, or orthoboric acid/oxaUc acid (7,8,18) to give the all-rac-acetate ester (15b) by reaction with acetic anhydride. Purification of tocopheryl acetate is readily accompHshed by high vacuum molecular distillation and rectification (<1 mm Hg) to achieve the required USP standard. 

Figure 14.10. ALMA maleic anhydride purification area.

Acetic Acid 85 237-273 114-134 - E - - in acetic anhydride purification. Plus 10 percent acetic anhydride. 5 percent water, acetone, acetonitride. amines, etc. Alloy C 0.1 mpy... 

Form Supplied in yellow solid commercially available. Preparative Methods the most convenient procedure involves the reaction of PhsCCl with SUver(I) Tetntfluoroborate in ethanol. The most economical route employs the reaction of Ph3CCl with the anhydrous Tetraftuoroboric Acid-Et20 complex, or PhsCOH with HBF4 in acetic anhydride. Purification recrystallization of commercial samples from a minimal amount of dry MeCN provides material of improved purity, but the recovery is poor. ... 

The crude phthalic anhydride is heated and held at 260 C to allow some byproduct reactions to go to completion. Purification is by continuous distillation in two columns. In the first column, maleic anhydride and benzoic and toluic acids are removed overhead. In the second column, pure phthalic anhydride is removed overhead. High boiling residues are removed from the bottom of the second column. 

Recovery and Purification. AH processes for the recovery and refining of maleic anhydride must deal with the efficient separation of maleic anhydride from the large amount of water produced in the reaction process. Recovery systems can be separated into two general categories aqueous- and nonaqueous-based absorption systems. Solvent-based systems have a higher recovery of maleic anhydride and are more energy efficient than water-based systems. 

Phthalic Anhydride Recovery and Purification. The accepted method of recovering phthalic anhydride from vapor-phase oxidation... 

The cmde phthaUc anhydride is subjected to a thermal pretreatment or heat soak at atmospheric pressure to complete dehydration of traces of phthahc acid and to convert color bodies to higher boiling compounds that can be removed by distillation. The addition of chemicals during the heat soak promotes condensation reactions and shortens the time required for them. Use of potassium hydroxide and sodium nitrate, carbonate, bicarbonate, sulfate, or borate has been patented (30). Purification is by continuous vacuum distillation, as shown by two columns in Figure 1. The most troublesome impurity is phthahde (l(3)-isobenzofuranone), which is stmcturaHy similar to phthahc anhydride. Reactor and recovery conditions must be carefully chosen to minimize phthahde contamination (31). Phthahde [87-41-2] is also reduced by adding potassium hydroxide during the heat soak (30). 

These precursors are prepared by reaction of fuming nitric acid in excess acetic anhydride at low temperatures with 2-furancarboxaldehyde [98-01-1] (furfural) or its diacetate (16) followed by treatment of an intermediate 2-acetoxy-2,5-dihydrofuran [63848-92-0] with pyridine (17). This process has been improved by the use of concentrated nitric acid (18,19), as well as catalytic amounts of phosphoms pentoxide, trichloride, and oxychloride (20), and sulfuric acid (21). Orthophosphoric acid, -toluenesulfonic acid, arsenic acid, boric acid, and stibonic acid, among others are useful additives for the nitration of furfural with acetyl nitrate. Hydrolysis of 5-nitro-2-furancarboxyaldehyde diacetate [92-55-7] with aqueous mineral acids provides the aldehyde which is suitable for use without additional purification. 

The N-oxide function has proved useful for the activation of the pyridine ring, directed toward both nucleophilic and electrophilic attack (see Amine oxides). However, pyridine N-oxides have not been used widely ia iadustrial practice, because reactions involving them almost iavariably produce at least some isomeric by-products, a dding to the cost of purification of the desired isomer. Frequently, attack takes place first at the O-substituent, with subsequent rearrangement iato the ring. For example, 3-picoline N-oxide [1003-73-2] (40) reacts with acetic anhydride to give a mixture of pyridone products ia equal amounts, 5-methyl-2-pyridone [1003-68-5] and 3-methyl-2-pyridone [1003-56-1] (11). 

An especially interesting case of oxygen addition to quinonoid systems involves acidic treatment with acetic anhydride, which produces both addition and esterification (eq. 3). This Thiele-Winter acetoxylation has been used extensively for synthesis, stmcture proof, isolation, and purification (54). The kinetics and mechanism of acetoxylation have been described (55). Although the acetyhum ion is an electrophile, extensive studies of electronic effects show a definite relationship to nucleophilic addition chemistry (56). 

Further purification is accomplished, if desired, by the original directions. The acid, as prepared above, always contains traces of nitric acid, but is satisfactory for conversion into the anhydride. If the catalyst is omitted, the yield is less by 10 per cent. 

Purification as their N-acetyl derivatives is satisfactory for primary, and to a limited extent secondary, amines. The base is refluxed with slightly more than one equivalent of acetic anhydride for half to one hour, cooled and poured into ice-cold water. The insoluble derivative is filtered off, dried, and recrystallised from water, ethanol, aqueous ethanol or benzene (CAUTION toxic ). The derivative can be hydrolysed to the parent amine by refluxing with 70% sulfuric acid for a half to one hour. The solution is cooled, poured onto ice, and made alkaline. The amine is steam distilled or extracted as above. Alkaline hydrolysis is very slow. 

Propionic acid [79-09-4] M 74.1, b 141 , d 0.992, n 1.3865, n25 1.3843, pK 5-6.8 (Ho scale, aq H2SO4), pK2 4.88. Dried with Na2S04 or by fractional distn, then redistd after refluxing with a few crystals of KMn04. An alternative purification uses the conversion to the ethyl ester, fractional distn and hydrolysis. [Bradbury J Am Chem Soc 74 2709 1952.] Propionic acid can also be heated for 0.5h with an amount of benzoic anhydride equivalent to the amount of water present (in the presence of Cr03 as catalyst), followed by fractional distn. [Cham and Israel 7 C/iem 5oc 96 I960.]... 

The industrial grade of acetic anhydride was used without further purification. 

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