Amination of phenols

A recent patent describes the synthesis and catalytic use of Al-containing TUD-1 materials. Some of the reactions demonstrated inclnde hydrogenation of mesitylene (Pt as active metal) and dehydration of 1-phenyl-ethanol to styrene. Several other conceptnal reactions were also described, amongst others the Diels-Alder reaction of crotonaldehyde and dicyclopentadiene and the amination of phenol with ammonia. 

The reduction of azo compounds using sodium hydrosulfite (Na2S204) and NaOH is an important reaction, as it provides an indirect method for the amination of phenols and naphthols (Fig. 13.49). The reduction of nitro groups in anthraquinone compounds works best when a mild reducing agent (e.g., sodium hydrosulfide, NaSH) is used. In this way one avoids reducing the quinoid system. 

Piperidinophenol 13 was prepared by two different ways [Eqs. (1) and (2)] first by reacting p-anisidine with 1.5-dibromopentane and treating the resulting 4-piperidino-anisole with HBr, and second by the homolytic aromatic amination of phenol with N-chloropiperidine83. ... 

Aniline can also be prepared by the amination of phenols under a pressure of 15 to 16 atm at a temperature of 380 to 385°C in the presence of a silica- alumina catalyst (Halcon process). 

Catalytic amination of phenol (7) at 425 °C and around 200 atmospheres has been developed by Mitsui Petrochemical Industries of Tokyo. The nature of the catalyst is unspecified, though various metallic oxides and cocatalysts have been described. One Mitsui process employs a low alkali, weakly acidic alumina catalyst. Mild conditions, high yield and selectivity are claimed. Mitsui operates both the four-step phenol (starting from benzene) and two-step nitrobenzene processes12. 

In the Halcon process, the amination of 7 takes place in the vapor phase with a silica-alumina catalyst (Scheme 3). Amination of phenol has the advantage of reduced capital costs, long catalyst life and high quality product. Excess ammonia favors high conversion of the mildly exothermic (AH = —544 kcal ruol 1) and reversible reaction, and also minimizes formation of byproducts. Generally, however, the price of phenol makes this process more expensive than the nitrobenzene routes. The last plant in the US to produce aniline from phenol by amination was operated by Sunoco Chemicals. It produced 140 million lbs./year-1, with diphenylamine, or DPA (8) as a coproduct, at Haverhill, Ohio, and ceased production in 200213,14. Aristech Chemical Corporation at one time operated a phenol-to-aniline process in the US. 

Table 6.3.8 Amination of phenols and tri-n-butyltin phenoxides with bis(trichloroethyl) azo-di carboxyl ate carried out in 5 mol dm solution of UCIO4 in Et20...

Similarly, anodic oxidation of 2,4,6-tri(ferr-butyl)phenol (73) in MeCN containing n-propylamine provided the corresponding cyclohexa-2,5-dienone 80 (47% yield). Furthermore, electrochemical oxidation of 73 in MeCN-pyridine (1 1) yielded two pyridinium salts 81 and 82 in 44 and 23% yields, respectively (Scheme 15). Here, pyridine works as a nucleophile. Anodic amination of phenols has been also studied. ... 

Amination of phenols with ammonia is a simple route to aromatic amines. Transformation of 2,6-dimethylphenoI in a continuous fixed-bed reactor at 210 °C over Pd/C yielded 90% 2,6-dimethylaniline after only 6 s contact time [17]. 2,6-Dimethylcyclohexanone and 2,6-dimethylcyclohexylamine were identified as key intermediates at low contact times the concentration of the latter reached 25 %. Compared with the performance of other metals, Pd-based catalysts have outstanding activity and selectivity in the amination of phenols [4]. 

Table 3. Homol3 ic amination of phenols, phenol ethers and anilides...

Benzene, CH2CI2, or THF is used as the solvent. Since the products are reduced by benzenethiol to aminophenols, the reaction can be used for amination of phenols. The products can also be rcductivcly acctylated to aminophenol diacetates. 

Diels-Alder reaction of crotonaldehyde and dicyclopentadiene Amination of phenol with ammonia Hydrotreating of FCC clarified slurry oil... 

Traditional processes are still used for the nitration of benzene and toluene, and the hydrogenation of the nitro-derivatives to amines. Some aniline is also produced by amination of phenol. The production of polyurethanes, for foams or coatings, is a major outlet for aniline (c. 60%) and virtually the sole use for 2,4/2,6-toluenediamines. 

The chief outlets are for polyurethane (di-isocyanates) 40%, rubber chemicals, herbicides minor users include dye makers (approx. 5%) and pharmaceutical manufacturers. Benzene is the feedstock and the traditional route is to nitrate this and then to reduce the nitrobenzene to aniline. Catalytic hydrogenation has displaced iron/ferrous chloride reduction in this and analogous reductions e.g. in the manufacture of toluidines. Amination of phenol manufactured from cumene (Vol. I, p. 366) has been patented (Figure 2.8). The yield claimed is 99% though the economic viability is uncertain. 

Itoh, M., Hattori, H., and Tanabe, K. (1974) The acidic properties of Ti02-Si02 and its catalytic activities for the amination of phenol, the hydration of ethylene and the isomerization of butene. /. Catal., 35 (2), 225-231. 

Yu, J. Wang, Y Zhang, R Wu, J. Direct amination of phenols under metal-free conditions. Synlett 2013, 24,1448-1454. 

R often Me) formed by oxidative polymerization of phenols using oxygen with copper and an amine (pyridine) as catalysts. The products are thermoplastics used in engineering applications and in electrical equipment. 

Organic sulfur compounds such as sulfurized spermaceti oil, terpene sulfides, and aromatic disulfides have been used. Encumbered phenols such as di-tertiary-butylphenols and amines of the phenyl-alphanaphthylamine type are effective stopping the kinetic oxidation chain by creating stable radicals. 

The most noteworthy reaction of azo-compounds is their behaviour on reduction. Prolonged reduction first saturates the azo group, giving the hydrazo derivative (C NH-NH C), and then breaks the NH NH linkage, with the formation of two primary amine molecules. If method (1) has been employed to prepare the azo-compound, these two primary amines will therefore be respectively (a) the original amine from which the diazonium salt was prepared, and (6) the amino derivative of the amine or phenol with which the diazonium salt was coupled. For example, amino-azobenzene on complete reduction gives one equivalent of aniline, and one of p-phenylene diamine, NHaCeH NH benzene-azo-2-naphthoI similarly gives one equivalent of aniline and one of... 

Colorations or precipitates given by phenols and many derivatives of phenols by neutral salts of acids by some amines. (The FeCl, solution can be added directly to a small quantity of the phenol or to its aqueous solution free acids must first be neutralised.)... 

Dissolve 1 g. of the secondary amine in 3-5 ml. of dilute hydrochloric acid or of alcohol (in the latter case, add 1 ml. of concentrated hydrochloric acid). Cool to about 5° and add 4-5 ml. of 10 per cent, sodium nitrite solution, and allow to stand for 5 minutes. Add 10 ml. of water, transfer to a small separatory funnel and extract the oil with about 20 ml. of ether. Wash the ethereal extract successively with water, dilute sodium hydroxide solution and water. Remove the ether on a previously warmed water bath no flames should be present in the vicinity. Apply Liebermann s nitroso reaction to the residual oil or solid thus. Place 1 drop or 0 01-0 02 g. of the nitroso compovmd in a dry test-tube, add 0 05 g. of phenol and warm together for 20 seconds cool, and add 1 ml. of concentrated sulphuric acid. An intense green (or greenish-blue) colouration will be developed, which changes to pale red upon pouring into 30-50 ml. of cold water the colour becomes deep blue or green upon adding excess of sodium hydroxide solution. 

Some reference to the use of nitrous acid merits mention here. Primary aromatic amines yield diazonium compounds, which may be coupled with phenols to yield highly-coloured azo dyes (see Section IV,100,(iii)). Secondary aromatic amines afford nitroso compounds, which give Liebermann a nitroso reaction Section IV,100,(v). Tertiary aromatic amines, of the type of dimethylaniline, yield p-nitroso derivatives see Section IV,100,(vii). ... 

Triflates of phenols are carbonylated to form aromatic esters by using PhjP[328]. The reaction is 500 times faster if dppp is used[329]. This reaction is a good preparative method for benzoates from phenols and naphthoates (473) from naphthols. Carbonylation of the bis-triflate of axially chiral 1,1 -binaphthyl-2,2 -diol (474) using dppp was claimed to give the monocarboxy-late 475(330]. However, the optically pure dicarboxylate 476 is obtained under similar conditions[331]. The use of 4.4 equiv. of a hindered amine (ethyldiisopropylamine) is crucial for the dicarbonylation. The use of more or less than 4.4 equiv. of the amine gives the monoester 475. 

Unusual cyclocarbonylation of allylic acetates proceeds in the presence of acetic anhydride and an amine to afford acetates of phenol derivatives. The cinnamyl acetate derivative 408 undergoes carbonylation and Friedel-Crafts-type cyclization to form the a-naphthyl acetate 410 under severe condi-tions[263,264]. The reaction proceeds at 140-170 under 50-70 atm of CO in the presence of acetic anhydride and Et N. Addition of acetic anhydride is essential for the cyclization. The key step seems to be the Friedel-Crafts-type cyclization of an acylpalladium complex as shown by 409. When MeOH is added instead of acetic anhydride, /3,7-unsaturated esters such as 388 are... 

The most important synthesis of phenols m the laboratory is from amines by hydrolysis of their corresponding diazonmm salts as described m Section 22 17... 

Although acetyl chloride is a convenient reagent for deterrnination of hydroxyl groups, spectroscopic methods have largely replaced this appHcation in organic chemical analysis. Acetyl chloride does form derivatives of phenols, uncompHcated by the presence of strong acid catalysts, however, and it finds some use in acetylating primary and secondary amines. 

H2O2 in the presence of HE/BE acts as an effective and economical reagent for aromatic hydroxylation (163). Hydroxylations of phenols and amines in similar high acidity media are very effective (163). Xylenes were hydroxylated by bis(trimethylsilyl) peroxide and AlCl in poor yields (164). 

Special resoles are obtained with amine catalysts, which affect chemical and physical properties because amine is incorporated into the resin. For example, the reaction of phenol, formaldehyde, and dimethylamine is essentially quantitative (28). 

Reductive amination of cyclohexanone using primary and secondary aHphatic amines provides A/-alkylated cyclohexylamines. Dehydration to imine for the primary amines, to endocycHc enamine for the secondary amines is usually performed in situ prior to hydrogenation in batch processing. Alternatively, reduction of the /V-a1ky1ani1ines may be performed, as for /V,/V-dimethy1 cyclohexyl amine from /V, /V- di m e th y1 a n i1 i n e [121 -69-7] (12,13). One-step routes from phenol and the alkylamine (14) have also been practiced. 

Aromatic amines can be produced by reduction of the corresponding nitro compound, the ammonolysis of an aromatic haUde or phenol, and by direct amination of the aromatic ring. At present, the catalytic reduction of nitrobenzene is the predominant process for manufacture of aniline. To a smaller extent aniline is also produced by ammonolysis of phenol. 

Although aminyl radicals are stable towards oxygen, they can oxidi2e other aromatic amines, phenols and thiols (10), and regenerate the diarylamine. Thus, mixtures of phenols and diarylamines frequendy show better antioxidant activity than either one alone. This is called synergism. 

Sulfonic acids are prone to reduction with iodine [7553-56-2] in the presence of triphenylphosphine [603-35-0] to produce the corresponding iodides. This type of reduction is also facile with alkyl sulfonates (16). Aromatic sulfonic acids may also be reduced electrochemicaHy to give the parent arene. However, sulfonic acids, when reduced with iodine and phosphoms [7723-14-0] produce thiols (qv). Amination of sulfonates has also been reported, in which the carbon—sulfur bond is cleaved (17). Ortho-Hthiation of sulfonic acid lithium salts has proven to be a useful technique for organic syntheses, but has Httie commercial importance. Optically active sulfonates have been used in asymmetric syntheses to selectively O-alkylate alcohols and phenols, typically on a laboratory scale. Aromatic sulfonates are cleaved, ie, desulfonated, by uv radiation to give the parent aromatic compound and a coupling product of the aromatic compound, as shown, where Ar represents an aryl group (18). 

Phenols. Phenols are unreactive toward chloroformates at room temperature and at elevated temperatures the yields of carbonates are relatively poor (< 10%) in the absence of catalysis. Many catalysts have been claimed in the patent Hterature that lead to high yields of carbonates from phenol and chloroformates. The use of catalyst is even more essential in the reaction of phenols and aryl chloroformates. Among the catalysts claimed are amphoteric metals or thek haUdes (16), magnesium haUdes (17), magnesium or manganese (18), secondary or tertiary amines such as imidazole (19), pyridine, quinoline, picoline (20—22), heterocycHc basic compounds (23) and carbonamides, thiocarbonamides, phosphoroamides, and sulfonamides (24). 

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