Anhydride synthesis extraction

Methyl anthraquinone has been obtained by the oxidation of /3-methyl anthracene by several investigators 1 and material of the same origin, obtained by the benzene-extraction of crude commercial anthraquinone,2 has been fully described. As regards the synthesis from phthalic anhydride and toluene, both the preparation and properties of />-toluyl-o-benzoic acid 3 and the complete synthesis 4 have been the subject of several papers. This acid has also been prepared from o-carbomethoxy benzoyl chloride and toluene.5 The phthalic anhydride synthesis of anthraquinone derivatives in general has received considerable attention. An account of this work, together with extensive references, is given by Barnett.6... 

Production of maleic anhydride by oxidation of / -butane represents one of butane s largest markets. Butane and LPG are also used as feedstocks for ethylene production by thermal cracking. A relatively new use for butane of growing importance is isomerization to isobutane, followed by dehydrogenation to isobutylene for use in MTBE synthesis. Smaller chemical uses include production of acetic acid and by-products. Methyl ethyl ketone (MEK) is the principal by-product, though small amounts of formic, propionic, and butyric acid are also produced. / -Butane is also used as a solvent in Hquid—Hquid extraction of heavy oils in a deasphalting process. 

The synthesis of key intermediate 12, in optically active form, commences with the resolution of racemic trans-2,3-epoxybutyric acid (27), a substance readily obtained by epoxidation of crotonic acid (26) (see Scheme 5). Treatment of racemic 27 with enantio-merically pure (S)-(-)-1 -a-napthylethylamine affords a 1 1 mixture of diastereomeric ammonium salts which can be resolved by recrystallization from absolute ethanol. Acidification of the resolved diastereomeric ammonium salts with methanesulfonic acid and extraction furnishes both epoxy acid enantiomers in eantiomerically pure form. Because the optical rotation and absolute configuration of one of the antipodes was known, the identity of enantiomerically pure epoxy acid, (+)-27, with the absolute configuration required for a synthesis of erythronolide B, could be confirmed. Sequential treatment of (+)-27 with ethyl chloroformate, excess sodium boro-hydride, and 2-methoxypropene with a trace of phosphorous oxychloride affords protected intermediate 28 in an overall yield of 76%. The action of ethyl chloroformate on carboxylic acid (+)-27 affords a mixed carbonic anhydride which is subsequently reduced by sodium borohydride to a primary alcohol. Protection of the primary hydroxyl group in the form of a mixed ketal is achieved easily with 2-methoxypropene and a catalytic amount of phosphorous oxychloride. 

To synthesize 6-methoxy-3,4-dihydro-beta-carboline (10-meth-oxy-harmalan), add 5-methoxy-tryptamine to acetic anhydride and let stand twelve hours at 10°. Dilute with water, basify and extract with methylene Cl and dry, evaporate in vacuum to get melatonin (I). Reflux (1) in xylene in the presence of P205 to get the title compounds. Other References JMC 7,136(1964) JPS 57,1364 (1968), 59,1446(1970) JACS 70,219(1948) JCS 1602(1921), 1203(1951), 4589,4593(1956) Organic Synthesis 51, 136... 

It is remarkable that better enantioselectivities are achieved when CALB-catalyzed acylations of the alcohol are carried out in organic solvent rather than in water. Excellent enantioselectivities are obtained when the process is carried out with vinyl esters [22]. However, in some cases the use of vinyl or alkyl esters as acyl donors has the drawback of the separation of the ester (product) and the alcohol (substrate). A practical strategy to avoid this problem is the use of cyclic anhydrides [23]. In this case an acid is obtained as product, which can be readily separated from the unreacted alcohol by a simple aqueous base-organic solvent liquid-liquid extraction. This methodology has been successfully used for the synthesis of (-)-paroxetine as indicated in Scheme 10.11 [24]. 

SYNTHESIS (from indoleacetone) To a solution of 1.55 g NaOAc in 5 mL acetic anhydride there was added 2.0 g 3-indoleacetic acid and the mixture was heated at 135-140 °C for 18 h. Removal of all volatiles on the rotary evaporator under vacuum produced a pale yellow residue that was the 1-acetylindole-3-acetone. This was dissolved in MeOH to which 0.93 g MeONa was added, and the solution held a reflux several hours. After removal of the solvent under vacuum, the residue was suspended in H20 and extracted with several portions of Et20. These extracts were pooled, and removal of the solvent under vacuum gave 0.41 g (21%) indole-3-acetone as a white solid, mp 115-117 °C. MS (in m/z) indolemethylene+ 130 (100%) parent ion 173 (16%). IR (in cm-1) 691,753,761,780. 1017, 1110, 1172, and a broad C=0 at 1710. 

SYNTHESIS To a solution of 5.0 g 4-hydroxyindole in 20 mL pyridine there was added 10 mL acetic anhydride and the reaction heated on the steam bath for 10 min. The reaction was quenched by pouring over chipped ice to which was added an excess of NaHC03. After being stirred for 0.5 h the product was extracted with ethyl acetate and the extracts washed with brine and the solvent removed under vacuum. The residue weighed 6.3 g (95%) which, after crystallization from cyclohexane, had a melting point of 98-100 °C. IR (in cm-1) 1750 for the carbonyl absorbtion. 

The gross structural features, presence of a tetramic acid and E-decenoyl side chain, could be inferred from NMR studies. Methanolysis (HCl/MeOH) of 47 and pentane extraction of the quenched reaction mixture gave two compounds that were determined to be the methyl esters of decenoic acid and N-(2-decenoyl)leucine. The nature of the 3-acyl tetramic acid was deduced from the identification of 48 and 49 in the aqueous portion of the methanolysis reaction mixture following treatment with trifluoroacetic acid anhydride. The unusual C-C bond fragmentation under acidic conditions, and the structure of the antibiotic was confirmed by synthesis of racemic 47 [86]. The configuration at the lone chiral centre was established as R by chiral GC. The carbon NMR spectrum of 47 indicated an equilibrium between three tautomers in which the A2-pyrrolin-4-one form is preferred (60%) and the two internal tautomers (50, 51) make equal contributions (20% each). 

Monomers 111 (a -d), were prepared from the common starting material 15 by a potassium phenate displacement of the aromatic nitro group. The yields of the keto-ether amine products ranged from 90 to 100% and were of sufficient purity after extractive work up to be utilized directly in the synthesis of the various maleimide monomers. Imidization of the aminobenzocyclobutenes was accomplished using standard reaction conditions (maleic anhydride to form the amic acid followed by cyclodehydration with acetic anhydride and triethyla-mine) and provided the maleimide products in yields ranging from 60 to 90%. 

Bifunctionally tagged Mitsunobu reagents 21 and 22, quaternary ammonium carbonate resin 65, tetrafluorophthalic anhydride (as a solution-phase linking reagent), and amine-functionalized resin 2 were used in a three-step solution-phase synthesis of a series of substituted hydroxypiperidines.39 No further purification (e.g., liquid-phase extraction or chromatography) was required, and products were isolated in good yields and purities. 

SYNTHESIS (from MDA) To a solution of 3.6 g of the free base of 3,4-methylenedioxyamphetamine (MDA) in 20 g pyridine, there was added 2.3 g acetic anhydride, and the mixture stirred at room temperature for 0.3 h. This was then poured into 250 mL H,0 and acidified with HC1. This aqueous phase was extracted with 3x75 mL CH2C12, the extracts pooled and washed with dilute HC1, and the solvent removed under vacuum. The pale amber residue of N-acetyl-3,4-methylenedioxyamphetamine weighed 5.2 g as the cmde product, and it was reduced without purification. On standing it slowly formed crystals. Recrystallization from a mixture of EtOAc/ hexane (1 1) gave white crystals with a mp of 92-93 °C. 

Dolichotheline (111) is a histamine-derived alkaloid produced by the cactus Dolichothele sphaerica Britton and Rose (Cactaceae) native to southern Texas and northern Mexico. The alkaloid was first isolated in 1969 by Rosenberg and Paul (160). Spectroscopic data suggested structure 111, 4(5)-(iV-isovalerylaminoethyl)imidazole or 7V -isovalerylhistamine. The structure was proved by synthesis. Refluxing of histamine with isovaleric anhydride yielded 111, identical to the natural product (160). In addition to the major alkaloid dolichotheline, five minor alkaloids have been isolated (161). These were identified as A-methylphenethylamine, /i-O-methylsyn-ephrine, vV-methyltyramine, synephrine, and / -0-ethylsynephrine by IR, NMR, and comparison to authentic materials / -0-ethylsynephrine was probably an artifact of synephrine, since it was not found in a second extraction attempt when no ethanol was used. 

In the synthesis, by bacterial extracts, of pantothenate from pantoate, /3-alanine, and adenosine 5-triphosphoric acid, an anhydride between adenosine 5-phosphate and pantoate participates. 

Tilak et described the use of excess mixed carbonic anhydrides to force condensation reactions to completion followed by the destruction of the excess mixed anhydride via the addition of aqueous potassium hydrogencarbonate. Hydrolysis of the nnixed anhydride was rapid and the resulting protected dipeptide could be extracted into ethyl acetate in a high state of purity, leaving the excess amino acid derivative and the salts in the aqueous phase. Without further purification the protected dipeptide was N -deprotected and reacted with the next mixed anhydride, and the process repeated until the desired peptide was obtained. Beyerman et al. substantially expanded the scope of this procedure and named it the REMA method for peptide synthesis (Repetitive Excess Mixed Anhydride).P°1 These reaction conditions provide an excellent method to ensure complete reaction of the amine component as well as rapid reaction rates and minimal side products. However, care must be taken to ensure that the excess carboxylic acid component is soluble in sodium hydrogencarbonate solution, e.g. when Z-Asp(OBzl)-OH is the acid component, it is extracted into the ethyl acetate as the sodium salt along with the product. With the due precautions the yields of small peptides are so high that the method could be applied without purification of the intermediate products, that is, in a repetitive way. 

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