Hydrolysis of aniline

Reductive hydrolysis of anilines, which may occur as an unwanted side reaction when anilines are reduced in aqueous media, can be turned to synthetic advantage. Reductive cleavage is facilitated by substitution on the nitrogen and by acidic media. Palladium is the preferred catalyst (33), Reductive hydrolysis of substituted anilines carrying chiral N-substituents gives chiral cyclohexanones (34),... 

An amorphous 2,3,4-tribenzoyl-D-ribose has been reported as a product of the hydrolysis of aniline D-ribopyranoside tribenzoate29 as well as of the hydrolysis of tribenzoyl-/3-D-ribopyranosyl bromide with moist acetone in the presence of silver carbonate.110 In the latter case the structure of the product was demonstrated through methylation to the known methyl /9-D-ribopyranoside tribenzoate. Recently Ness, Fletcher and Hudson111 have succeeded in obtaining a 2,3,4-tribenzoyl-D-ribose in crystalline form. 

Reductive Hydrolysis. Reductive hydrolysis of anilines to cyclohexanones, assumed to go through an imine-type intermediate, clearly involves isomerization (18). 

TABLE LXVIII. HYDROLYSIS OF ANILINE HYDROCHLORIDE FROM DISTRIBUTION... 

In the following table Denham s figures are given for the percentage hydrolysis of aniline hydrochloride, and the hydrolytic constant for a senes of dilutions—... 

Tabus I. Hydrolysis of Aniline Hydrochloride at 25°, determined from Conductance Measurements. 

Hydrogenation of A, Af-dimethylaniline in dilute aqueous HCl produces cyclohexanone and cyclohexanol (90% yield). Reductive hydrolysis of anilines that are properly substituted with a chiral ligand on the nitrogen atom affords chiral cyclohexanones with 30% optical yield ... 

In a very early study Patat (1945) investigated the hydrolysis of aniline to phenol in a water-based acidic solution in near-critical and supercritical water (Tc = 374.2°C, Pc = 220.5 bar). Phosphoric acid and its salts are used as the catalyst for this reaction. The reaction proceeds extremely slowly under normal conditions and reaches equilibrium at low conversion levels. For these reasons, Patat chooses to study the reaction in supercritical water to temperatures of 450°C and to pressures of 700 bar in a flow reactor. He finds that the reaction follows known, regular kinetics in the entire temperature and pressure space studied and the activation energy of the hydrolysis (approximately 40 kcal/mol) is the same in the supercritical as well as in the subcritical water. He suggests that the reaction is catalyzed by hydrogen ions formed from dissolution of phosphoric acid in supercritical steam. Very small amounts of phosphoric acid and the salts of the phosphoric acid are dissolved in the supercritical steam and are split into ions. Patat lists several dissolution constants for primary ammonium phosphates in supercritical steam. In this instance, the reaction performance is improved when the reaction is operated homogeneously in the mixture critical region and, thus, in intimate contact between the reactants and the catalyst. 

Several other chemists were active in the field of supercritical fluid reactions at the beginning of the twentieth century. For example, Briner studied the decomposition and reactivity of supercritical fluids such as scNO and scCO (e.g., eq 1.1-6) [119-122]. He also investigated the system N2-H2 and reported that N2 and H2 do not combine at room temperature and 900 bar [122]. At the Chemical Institute of the University of Berlin, Arthur Stabler studied the reactions of alkyl halides such as chloroethane with SCNH3 (eq 1.1-7) [123]. One of the earliest attempts to utilize SCFs for the selective synAesis of low molecular weight organic products dates to the early 1940s, when Patat at the University of Innsbruck studied the hydrolysis of aniline under supercritical conditions (eq 1.1-8) [124]. 

The hydrolysis of aniline to phenol in supercritical water by Patat [14] is accredited as the earliest reported study of a simple reaction in a supercritical medium. The reaction is catalysed by hydrogen ions formed from dissociation of phosphoric acid. Close to the critical point of water aniline has limited solubility, but as the conditions of the flow reactor were raised towards 450°C and 710 bar, the reaction rate was observed to increase by an order of magnitude. In his view, mechanism was unaffected by the phase change it was from the enhanced solubility of aniline and thus better contact between reactants and catalyst that the rate improvement was derived. 

Experiment.—Determine the Degree of Hydrolysis of Aniline Hydrochloride in Aqueous Solution at 25°. 

A portion of the monophenylurea then reacts with the aniline (formed by the hydrolysis of the aniline hydrochloride or cyanate) to give diphenyl-urea and ammonia, a reaction which probably proceeds through the... 

Mono-substitution products of primary amines cannot easUy be prepared by direct action of the appropriate reagent for example, bromination of aniline yields largely the 2 4 6-tribomo derivative and nitration results in much oxidation. If, however, the amino group is protected as in acetanilide, smooth substitution occurs. Thus with bromine, />-bromoacetanilide is the main product the small quantity of the ortlio isomeride simultaneously formed can be easily eliminated by crystallisation. Hydrolysis of p-bromoacetanilide gives/ -bromoaniline ... 

Hydrolysis of benzanilide. Place 5 g. of benzanilide and 50 ml. of 70 per cent, sulphuric acid in a small flask fitted with a reflux condenser, and boU gently for 30 minutes. Some of the benzoio acid will vapourise in the steam and solidify in the condenser. Pour 60 ml. of hot water down the condenser this will dislodge and partially dissolve the benzoic acid. Cool the flask in ice water filter off the benzoic acid (anifine sulphate does not separate at this dilution), wash well with water, drain, dry upon filter paper, and identify by m.p. (121°) and other tests. Render the filtrate alkaline by cautiously adding 10 per cent, sodium hydroxide solution, cool and isolate the aniline by ether extraction. Recover the ether and test the residue for anifine (Section IV,100). 

Similarly aniline CgHjNHj is converted into benzonltrlle C3H5CN. Hydrolysis of the nitrile with so um hydroxide solution, followed by acidification, 3uelds the corresponding acid, for example ... 

Conversion of aniline to acetanilide [103-84-4] by reaction with acetic anhydride, is a convenient method for protecting the amino group. The acetyl group can later be removed by acid or base hydrolysis. 

The direct conversion of aniline into aminophenols may be achieved by hydrogen peroxide hydroxylation in SbE —HE at —20 to —40° C. The reaction yields all possible aminophenols via the action of H20" 2 on the anilinium ions the major product is 3-aminophenol (64% yield) (70,71). This isomer may also be made by the hydrolysis of 3-aminoaniline [108-45-2] in dilute acid at 190°C (72). Another method of limited importance, but useful in the synthesis of derivatives, is the dehydrogenation of aminocyclohexenones (73). 

Its production was 621 t and the average price 0.75/kg in 1987. Direct YeUow 44 (64) is prepared by phosgenation of an equimolar mixture of metanilic acid coupled to o-anisidinomethanesulfonic acid (with subsequent hydrolysis of the methanesulfonic acid group) and nitro aniline coupled to sahcychc acid (with subsequent reduction of the nitro group). 

The reaction of substituted chloronitrobenzenes with arylamines to form substituted diphenyl amines is typified by 4-rutrodiphenylamine-2-sulfoiiic acid where 4-chloronitrobenzene-3-sulfonic acid (PN salt) is condensed with aniline ia an aqueous medium at 120°C and 200 kPa (2 atm) ia the presence of alkaline buffer at low pH to avoid the competing hydrolysis of the PN salt. 

P-amino acid products. Treatment of oxazoline 53 with 7V-lithiopiperidine followed by alkylation with iodomethane affords aniline derivative 54 in 94% yield and 99% de. Hydrolysis of the oxazoline group provided amino acid 55 in 92% yield and >99% ee. 

Reaction of aniline derivatives with 4-chlorobutyroyl chloride followed by cyclization with sodium ethoxide and subsequent thionation promoted by sonication gave the corresponding A -arylpyrrolidine-2-thiones 126. Zinc-mediated condensation of diethyl bromomalonate with 126 using iodine as activator gave the vinylogous urethanes 127 whose cyclization with PPA gave the tricyclic compound 128 which upon hydrolysis afforded the acid 129 (96TL9403). 

In a departure from the prototype molecule, the benzylpiperi-done is first converted to the corresponding aminonitrile (a derivative closely akin to a cyanohydrin) by treatment with aniline hydrochloride and potassium cyanide (126). Acid hydrolysis of the nitrile affords the corresponding amide (127). Treatment with formamide followed by reduction affords the spiro oxazinone... 

It is prepd by the action of methylamine on 4-chloro-l-nitrobenzene (Ref 5) by the action of methyl iodide (Ref 6), or methyl sulfate on 4-nit roaniline (Ref 7) or by the hydrolysis of 4-nitro-N-methylformanilide with hot coned aq HC1 (Ref 8). In a study of the effect of nitric acid concn on the prods of the nitration of N,N-dimethylaniline to form Tetryl, it was isolated in low yield by the action of nitric acid, d 1.046g/cc, plus Na nitrite on N,N-dimethylaniline (Ref 10). A eutectic mixt with N-ethyl-4-nitroaniline has been patented as a stabilizer for NC (Ref 12). Studies at NPF indicate that 4-nitro-N-methyl-aniline is superior to Centralite, 2-nitrodiphenyl-amine, or Acardite in stabilizing. NC Refs 1) Beil 12, 586, (295) 1125 ... 

Meerwein reactions can conveniently be used for syntheses of intermediates which can be cyclized to heterocyclic compounds, if an appropriate heteroatom substituent is present in the 2-position of the aniline derivative used for diazotization. For instance, Raucher and Koolpe (1983) described an elegant method for the synthesis of a variety of substituted indoles via the Meerwein arylation of vinyl acetate, vinyl bromide, or 2-acetoxy-l-alkenes with arenediazonium salts derived from 2-nitroani-line (Scheme 10-46). In the Meerwein reaction one obtains a mixture of the usual arylation/HCl-addition product (10.9) and the carbonyl compound 10.10, i. e., the product of hydrolysis of 10.9. For the subsequent reductive cyclization to the indole (10.11) the mixture of 10.9 and 10.10 can be treated with any of a variety of reducing agents, preferably Fe/HOAc. 

Chlorinated anilines are produced by the hydrolysis of a range of acetanilide, urea, and carbamate herbicides, and are therefore widely distributed in agricultural soils. Mechanisms for their loss... 

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