From Anilines

2 From BenzU-a-aryttmino Oximes and a-Nitroketene N, S-Anittnoacetals 

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CaHjNCO, PhNCO. A pungent lachrymatory almost colourless liquid m.p. — 33 "C, b.p. 162°C. Used as a dehydrating agent and for characterization of alcohols. Prepared from aniline and phosgene in the presence of hydrogen chloride. 

Pheiiyl iso-thiocyanate may be prepared in quantity directly from aniline. Aniline, carbon disulphide and concentrated aqueous ammonia react to form the sparingly soluble ammonium phenyldithiocarbamate this is decomposed by lead nitrate to produce phenyl iso-thiocyanate ... 

Gassman and co-workers developed a synthetic route from anilines to indoles and oxindoles which involves [2.3]-sigmatropic rearrangement of anilinosul-fonium ylides. These can be prepared from Ai-chloroanilines and ot-thiomcthyl-ketones or from an aniline and a chlorosulfonium salt[l]. The latter sequence is preferable for anilines with ER substituents. Rearrangement and cyclizalion occurs on treatment of the anilinosulfonium salts with EtjN. The initial cyclization product is a 3-(methylthio)indole and these can be desulfurized with Raney nickel. Use of 2-(methylthio)acetaldehyde generates 2,3-unsubstituled indoles after desulfurization[2]. Treatment of 3-methylthioindoles with tri-fiuoroacetic acid/thiosalieylie acid is a possible alternative to Raney nickel for desulfurization[3]. 

INDOLES FROM ANILINES via o-CHLOROACETYLATION-THE SUGASAWA SYNTHESIS... 

Outline syntheses of each of the following from aniline and... 

Many substituted quinolines are intermediates for antimalarials. The 2,4-di-substituted quinolines are produced from aniline and 1,3-diketones by the Combes quinoline synthesis (28). The reaction of aniline with nitrobenzene in the presence of dry sodium hydroxide at 140°C leads to formation of phenazine [92-82-0] and by-products (Wohl-Aue synthesis) (29). 

Most derivatives of aniline are not obtained from aniline itself, but ate prepared by hydrogenation of their nitroaromatic precursors. The exceptions, for example, /V-a1ky1ani1ines, /V-ary1ani1ines, sulfonated anilines, or the A/-acyl derivatives, can be prepared from aniline and have been discussed. Nitroanilines are usually prepared by ammonolysis of the corresponding chloronitroben2ene. Special isolation methods may be requited for some derivatives if the boiling points are close and separation by distillation is not feasible. Table 6 Hsts some of the derivatives of aniline that are produced commercially. 

The formation of quinoline [91-22-5] (51) from aniline and acrolein involves formation of two bonds during the ring synthesis. 

Nitro-l-diazo-2-naphthol-4-sulfonic acid prefers the 2-position in spite of the nitro group, and increasing alkalinity favors ortho coupling with diazophenols. 1-Naphthalenesulfamic acid [24344-19-2] (ArNHSO H) and N-nitro-1-naphthylamine [4323-69-7] (ArNHNO ) couple exclusively in the para position. The substitution of resorcinol [108-46-3] and y -phenylenediamine [108-45-2] is compHcated and has been discussed (29,30). The first azo dyes from aniline, eg. Aniline Yellow [60-09-3] (19) (Cl Solvent Yellow 1 Cl 11000) were manufactured in 1861 and Bismark Brown [10114-58-6] (20) (Cl Basic Brown 1 Cl 21000) appeared in 1863. The reaction is as follows ... 

A significant group of carbonamides are the Naphtol products formed by condensation of 2-hydroxy-3-naphthoic acid (via its acid chloride) with a wide range of arylamines. The simplest example, Naphtol AS from aniline, is typical, and manufacture is accompHshed by suspending the acid ia a solvent such as toluene, preforming the acid chloride by addition of phosphoms trichloride, and then adding the aniline. 

COMBES Quinoline Synthesis Quinoline synthesis from anilines and p-diketones... 

DUTT - WORMALL Azide formation Synthesis of aromatic azides from anilines via diazonium salts. 

HINSBERG - STOLLS Indoie-OxindoiaSynthesis indoie synthesis Irom anilines and glyoxal (Hinsberg), oxindola synthesis from anilines and a haloacyi hafides (Stolie). 

S K R A U P Quitxiline synthesis Quinoline synthesis from anilines and acrolein or glycerol... 

ULLMANN - FEOVAOJAN Acridine synthesis Synthesis ot polynuciear pyridines from anilines, phenols and formaldehyde... 

W 0 H L - A U E Phenazine synthesis Synthesis of phenazine N-oxide from anilines and nitrobenzene... 

Non-basic materials, including nitro compounds were removed from aniline in 40% H2SO4 by passing steam through the soln for Ih. Pellets of KOH were added to liberate the aniline which was steam distd, dried with KOH, distd twice from zinc dust at 20mm, dried with freshly prepared BaO, and finally distd from BaO in an allglass apparatus [Few and Smith J Chem Soc 753 7949]. Aniline is absorbed by skin and is TOXIC... 

N-2-cyanoethylaniline has been prepared (accompanied by much of the N,N -bis-2-cyanoethyl compound) by heating aniline, acrylonitrile and acetic acid either in an autoclave, or at refluxing temperature for 10 hours in the presence of various inorganic catalysts. The substance has also been obtained, free of the N,N -bis-2-cyanoethyl compound, from aniline salts and /3-diethylaminopropionitrile. ... 

The Goodyear vulcanization process takes hours or even days to be produced. Accelerators can be added to reduce the vulcanization time. Accelerators are derived from aniline and other amines, and the most efficient are the mercaptoben-zothiazoles, guanidines, dithiocarbamates, and thiurams (Fig. 32). Sulphenamides can also be used as accelerators for rubber vulcanization. A major change in the sulphur vulcanization was the substitution of lead oxide by zinc oxide. Zinc oxide is an activator of the accelerator system, and the amount generally added in rubber formulations is 3 to 5 phr. Fatty acids (mainly stearic acid) are also added to avoid low curing rates. Today, the cross-linking of any unsaturated rubber can be accomplished in minutes by heating rubber with sulphur, zinc oxide, a fatty acid and the appropriate accelerator. 

The isosteric relationship of benzene and thiophene has often led medicinal chemists to substitute the sulfur containing heterocycle for benzene drugs in biologically active molecules. That this relationship has some foundation in fact is attested by the observation that the resulting analogs often possess full biologic activity. Alkylation of the diamine, 71 (obtained from aniline and the chloroethylamine), with 2-chloromethylthiophene affords the antihistamine methaphenylene (72) The correspond-... 

The cymidin is now sulphonated, 100 parts by weight of cymidin being slowly added to 69 parts by weight of sulphuric acid (sp. gr. 1 84), contained in a shallow dish, and the solid crystalline mass of cymidin sulphate thus obtai ed is then converted into cymidin sulphonic acid by an identical method to that tised in the so-called baking process for the preparation of stilphanilic acid from aniline sulphate. 

A different diisocyanate used in polyurethane synthesis is methylene diisocyanate (MDI), which is prepared from aniline and formaldehyde. The diamine product is reacted with phosgene to get MDI. 

Another useful aniline derivative is acetanilide, which is simply the amide formed from aniline and acetic arid ... 

Pure samples are best prepd by the methylation of acetanilide or benzanilide to the N-methyl compds followed by acid hyd. It has been prepd commercially by the action of methyl ale on aniline in an autoclave under press and by the action of methyl amine on halobenzenes. For a summary of prepns see Refs 6 9. It may be separated from aniline and dime thy laniline by treatment of the mixt with benzenesulfonyl chloride. Dimethylamline fails to react and is extd out with dil acid. Aniline forms benzenesulfonanilide which is acidic and is removed by washing with dil base, leaving the N-methylbenzenesulfonanilide. Purified N-methylaniline is obtd by acid hyd (Ref 8). N-Methylaniline is used as an additive to raise the octane no of motor fuels (Ref 6), as a dyestuff intermediate (Ref 3), in the prepn of Tetryl (see below), and in the prepn of Methylcentralite (Encycl, Vol 2, C137-R)... 

Hydro-de-diazoniation seems to be an unnecessary reaction from the synthetic standpoint, as arenediazonium salts are obtained from the respective amines, reagents that are normally synthesized from the hydrocarbon. Some aromatic compounds, however, cannot be synthesized by straightforward electrophilic aromatic substitution examples of these are the 1,3,5-trichloro- and -tribromobenzenes (see below). These simple benzene derivatives are synthesized from aniline via halogenation, diazotization and hydro-de-diazoniation. Furthermore hydro-de-diazoniation is useful for the introduction of a hydrogen isotope in specific positions. 

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