Important Intermediates

The list of important diazo components for the diazotization reaction includes aniline and a number of aniline derivatives, diamino diphenyl derivatives, and aromatic aminosulfonic acids. Important coupling components are acetoacetic arylides, pyrazolones, (3-naphthol, 2-hydroxy-3-naphthoic acid, and their aniline derivatives. 

The following list includes starting materials which have found their way to large-scale production and application in the azo pigment industry. 

Other common intermediates for azo pigment production are 2,4-dinitro-aniline, acetoacet-o-chloroanilide, acetoacet-o-toluidide, phenyl- and p-tolyl-methylpyrazolone, 2-hydroxy-3-naphthoic acid, Naphtol AS and its derivatives, and 2-chloro-4-aminotoluene-5-sulfonic acid. 

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Example 13.1 Phthalic anhydride is an important intermediate for the plastics industry. Manufacture is by the controlled oxidation of o-xylene or naphthalene. The most common route uses o-xylene via the reaction... 

Colourless solid m.p. 132-134 C. An important intermediate for preparing indole derivatives, produced by treating indole under Mannich reaction conditions with methanal and dimethylamine. 

It is an important intermediate in the indigo industry. When phenylglycine is fused with sodamide a good yield of indoxyl is obtained. The indoxyl is easily oxidized to indigo. 

Titaniufn(iy) chloride, T1CI4, m.p. — 25"C, b.p. 136°C, d 1-76. Colourless liquid, important intermediate in Ti production (TiOi plus C plus CI2). Hydrolysed via oxide chlorides to Ti02- Forms many complexes including [TiCUP. ... 

Review Problem 2 This allyl bromide is an important intermediate in the synthesis of terpenes (including many flavouring and perfumery compounds), as the five carbon fi agment occurs widely in nature. How would you make it ... 

We made this important intermediate (A) in a slightly different way (frame 318), but this is how it s made industrially for use in perfumes and flavours (Pure. Annl. Chem.. 1975, 43, 527). How would you extend this synthesis to make TM 324 ... 

Acetylenic Grignard compounds or the corresponding organoalkali metal derivatives are important intermediates in many syntheses of acetylenic compounds. The various methods for their formation in organic solvents and in liquid ammonia have been discussed extensively and we here give only a brief summary. 

Zinc acetylides, prepared in situ by the treatment of lithium acetylides with ZnCF, are widely used. The zinc acetylide 311, prepared in situ, reacts with (Z)-3-iodo-2-buten-l-ol (312) with nearly complete retention of stereochemistry to afford an important intermediate 313 for carotenoid synthesis[227]. 

Acetoxy-l,7-octadiene (40) is converted into l,7-octadien-3-one (124) by hydrolysis and oxidation. The most useful application of this enone 124 is bisannulation to form two fused six-membered ketonesfl 13], The Michael addition of 2-methyl-1,3-cyclopentanedione (125) to 124 and asymmetric aldol condensation using (5)-phenylalanine afford the optically active diketone 126. The terminal alkene is oxidi2ed with PdCl2-CuCl2-02 to give the methyl ketone 127 in 77% yield. Finally, reduction of the double bond and aldol condensation produce the important intermediate 128 of steroid synthesis in optically pure form[114]. 

Acetaldehyde, first used extensively during World War I as a starting material for making acetone [67-64-1] from acetic acid [64-19-7] is currendy an important intermediate in the production of acetic acid, acetic anhydride [108-24-7] ethyl acetate [141-78-6] peracetic acid [79-21 -0] pentaerythritol [115-77-5] chloral [302-17-0], glyoxal [107-22-2], aLkylamines, and pyridines. Commercial processes for acetaldehyde production include the oxidation or dehydrogenation of ethanol, the addition of water to acetylene, the partial oxidation of hydrocarbons, and the direct oxidation of ethylene [74-85-1]. In 1989, it was estimated that 28 companies having more than 98% of the wodd s 2.5 megaton per year plant capacity used the Wacker-Hoechst processes for the direct oxidation of ethylene. 

Butane-Naphtha Catalytic Liquid-Phase Oxidation. Direct Hquid-phase oxidation ofbutane and/or naphtha [8030-30-6] was once the most favored worldwide route to acetic acid because of the low cost of these hydrocarbons. Butane [106-97-8] in the presence of metallic ions, eg, cobalt, chromium, or manganese, undergoes simple air oxidation in acetic acid solvent (48). The peroxidic intermediates are decomposed by high temperature, by mechanical agitation, and by action of the metallic catalysts, to form acetic acid and a comparatively small suite of other compounds (49). Ethyl acetate and butanone are produced, and the process can be altered to provide larger quantities of these valuable materials. Ethanol is thought to be an important intermediate (50) acetone forms through a minor pathway from isobutane present in the hydrocarbon feed. Formic acid, propionic acid, and minor quantities of butyric acid are also formed. 

Aldehydes fiad the most widespread use as chemical iatermediates. The production of acetaldehyde, propionaldehyde, and butyraldehyde as precursors of the corresponding alcohols and acids are examples. The aldehydes of low molecular weight are also condensed in an aldol reaction to form derivatives which are important intermediates for the plasticizer industry (see Plasticizers). As mentioned earlier, 2-ethylhexanol, produced from butyraldehyde, is used in the manufacture of di(2-ethylhexyl) phthalate [117-87-7]. Aldehydes are also used as intermediates for the manufacture of solvents (alcohols and ethers), resins, and dyes. Isobutyraldehyde is used as an intermediate for production of primary solvents and mbber antioxidants (see Antioxidaisits). Fatty aldehydes Cg—used in nearly all perfume types and aromas (see Perfumes). Polymers and copolymers of aldehydes exist and are of commercial significance. 

Alkyl esters of trifluoromethanesulfonic acid, commonly called triflates, have been prepared from the silver salt and an alkyl iodide, or by reaction of the anhydride with an alcohol (18,20,21). Triflates of the 1,1-dihydroperfluoroalkanols, CF2S020CH2R can be prepared by the reaction of perfluoromethanesulfonyl fluoride with the dihydroalcohol in the presence of triethylamine (22,23). Triflates are important intermediates in synthetic chemistry. They are among the best leaving groups known, so they are commonly employed in anionic displacement reactions. 

Resorcinol Derivatives. Aminophenols (qv) are important intermediates for the syntheses of dyes or active molecules for agrochemistry and pharmacy. Syntheses have been described involving resorcinol reacting with amines (91). For these reactions, a number of catalysts have been used / -toluene sulfonic acid (92), zinc chloride (93), zeoHtes and clays (94), and oxides supported on siUca (95). In particular, catalysts performing the condensation of ammonia with resorcinol have been described gadolinium oxide on siUca (96), nickel, or zinc phosphates (97), and iron phosphate (98). 

N—Fe(IV)Por complexes. Oxo iron(IV) porphyrin cation radical complexes, [O—Fe(IV)Por ], are important intermediates in oxygen atom transfer reactions. Compound I of the enzymes catalase and peroxidase have this formulation, as does the active intermediate in the catalytic cycle of cytochrome P Q. Similar intermediates are invoked in the extensively investigated hydroxylations and epoxidations of hydrocarbon substrates cataly2ed by iron porphyrins in the presence of such oxidizing agents as iodosylbenzene, NaOCl, peroxides, and air. 

Ketene trimer can be recovered from the tarry residue of diketene distillation and converted into valuable building blocks like 1,3-cyclobutanedione and squaric acid [2892-51-5] (140,141), an important intermediate in the synthesis of pharmaceuticals and squaryHum dyes used in photostatic reproduction (142,143). 

Isopropylnaphthalenes can be prepared readily by the catalytic alkylation of naphthalene with propjiene. 2-lsopropylnaphthalene [2027-17-0] is an important intermediate used in the manufacture of 2-naphthol (see Naphthalenederivatives). The alkylation of naphthalene with propjiene, preferably in an inert solvent at 40—100°C with an aluminum chloride, hydrogen fluoride, or boron trifluoride—phosphoric acid catalyst, gives 90—95% wt % 2-isopropylnaphthalene however, a considerable amount of polyalkylate also is produced. Preferably, the propylation of naphthalene is carried out in the vapor phase in a continuous manner, over a phosphoric acid on kieselguhr catalyst under pressure at ca 220—250°C. The alkylate, which is low in di- and polyisopropylnaphthalenes, then is isomerized by recycling over the same catalyst at 240°C or by using aluminum chloride catalyst at 80°C. After distillation, a product containing >90 wt % 2-isopropylnaphthalene is obtained (47). 

The principal uses for 2-naphthalenol are in the dyes and pigments industries, eg, as a coupling component for azo dyes, and to make important intermediates, such as 3-hydroxy-2-naphthalenecarboxyhc acid (BON) (28) and its anilide (naphthol AS), 2-naphtholsulfonic acids, aminonaphtholsulfonic acids, and l-nitroso-2-naphthol/77/-5 /-5(/ (29). 

Phthalocyanine sulfonic acids, which can be used as direct cotton dyes (1), are obtained by heating the metal phthalocyanines in oleum. One to four sulfo groups can be introduced in the 4-position by varying concentration, temperature, and reaction time (103). Sulfonyl chlorides, which are important intermediates, can be prepared from chlorosulfonic acid and phthalocyanines (104). The positions of the sulfonyl chloride groups are the same as those of the sulfonic acids (103). Other derivatives, eg, chlormethylphthalocyanines (105—107), / /f-butyl (108—111), amino (112), ethers (109,110,113—116), thioethers (117,118), carboxyl acids (119—122), esters (123), cyanides (112,124—127), and nitrocompounds (126), can be synthesized. 

Aromatic amines form addition compounds and complexes with many inorganic substances, such as ziac chloride, copper chloride, uranium tetrachloride, or boron trifluoride. Various metals react with the amino group to form metal anilides and hydrochloric, sulfuric, or phosphoric acid salts of aniline are important intermediates in the dye industry. 

Primary aromatic amines react with aldehydes to form Schiff bases. Schiff bases formed from the reaction of lower aUphatic aldehydes, such as formaldehyde and acetaldehyde, with primary aromatic amines are often unstable and polymerize readily. Aniline reacts with formaldehyde in aqueous acid solutions to yield mixtures of a crystalline trimer of the Schiff base, methylenedianilines, and polymers. Reaction of aniline hydrochloride and formaldehyde also yields polymeric products and under certain conditions, the predominant product is 4,4 -methylenedianiline [101 -77-9] (26), an important intermediate for 4,4 -methylenebis(phenyhsocyanate) [101-68-8], or MDI (see Amines, aromatic amines, l thylenedianiline). 

Amino-4,6-dinitropheno1 is an important intermediate in the manufacture of colorants, especially mordant dyes. It has also been used as an indicator dye in titrations (yellow with acid, red with alkali) and as a reagent for albumin deterrnination. 

Synthesis of P-Methylheptenone from Petrochemical Sources. p-MethyUieptenone (1) is an important intermediate in the total synthesis of terpenes. Continuous hydrochlorination of isoprene [78-79-5] produces prenyl chloride [505-60-6] which then reacts with acetone with a quaternary ammonium catalyst and sodium hydroxide to give P-methyUieptenone (6-methyIhept-5-en-2-one [110-93-0]) (eq. 1) (16—19). 

Geranyl acetone is an important intermediate in the synthesis of isophytol [505-32-8], famesol [106-28-5], and neroHdol [40716-66-3]. Isophytol is used in the manufacture of Vitamin E. 

Petrochemical-based methods of citral manufacture are very important for the large-scale manufacture of Vitamin A and carotenoids. Dehydrolinalool and its acetate are both made from the important intermediate, P-methyUieptenone. 

Phytol [505-06-5] (111) and isophytol [150-86-7] (112) are important intermediates used in commercial synthesis of Vitamins E and K. There is a variety of synthetic methods for their manufacture. Chlorophyll [479-61-8] is a phytyl ester. 

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