Glycerol reaction with anilines

EXPLOSION and FIRE CONCERNS combustible liquid NFPA rating Health 3, Flammability 2, Reactivity 1 moderate explosion hazard reacts explosively with solid or concentrated sodium hydroxide and heat, potassium hydroxide and heat, aluminum chloride and phenol ( at 120°C), sulfunc and nitric acid and heat, and sulfuric acid and aniline and glycerol violent reaction with aniline and glycerin, silver perchlorate, and dinitrogen oxide forms explosive mixtures with aluminum chloride, fluorodinitromethane, tetranitromethane, sodium chlorate, nitric acid, nitric acid and water, dinitrogen tetraoxide, phosphorus pentachloride, potassium, and sulfuric acid products of combustion include oxides of nitrogen use carbon dioxide, dry chemical, foam, or water spray for firefighting purposes. 

On acetylation it gives acetanilide. Nitrated with some decomposition to a mixture of 2-and 4-nitroanilines. It is basic and gives water-soluble salts with mineral acids. Heating aniline sulphate at 190 C gives sulphanilic add. When heated with alkyl chlorides or aliphatic alcohols mono- and di-alkyl derivatives are obtained, e.g. dimethylaniline. Treatment with trichloroethylene gives phenylglycine. With glycerol and sulphuric acid (Skraup s reaction) quinoline is obtained, while quinaldine can be prepared by the reaction between aniline, paraldehyde and hydrochloric acid. 

Quinoline may be prepared by heating a mixture of aniline, anhydrous glycerol and concentrated sulphuric acid with an oxidising agent, such as nitrobenzene. The reaction with nitrobenzene alone may proceed with extreme violence, but by the addition of ferrous sulphate, which appears to function as an oxygen carrier, the reaction is extended over a longer period of time and Is under complete control. 

Benzanthrone has been prepared by three general methods, the first of which is generally regarded as the best (i) by heating a reduction product of anthraquinone with sulfuric acid and glycerol,1 or with a derivative of glycerol, or with acrolein. The anthraquinone is usually reduced in sulfuric acid solution, just prior to the reaction, by means of aniline sulfate, iron, , or copper. It has also been prepared (2) by the action of aluminum or ferric chloride on phenyl-a-naphthyl ketone, and (3) from i-phenylnaphthalene-2-carboxylic acid. ... 

A somewhat different approach is used for the preparation of the analogue that contains a trifluoromethyl group. The scheme involves first the conversion of ort/zo-trifluoromethyl aniline (27-1) to a quinolol. The compound is thus condensed with EMME and cyclized thermally (27-2). That intermediate is then saponified the resulting acid is decarboxylated and finally converted to the 4-chloroquinoline (27-3) by reaction with phosphorus oxychloride. The displacement of chlorine with methyl anthranilate (27-4) then affords the coupled intermediate (27-5). An ester interchange of that product with glycerol leads to the glyceryl ester. There is thus obtained the NSAID flocatfenine (27-6) [31]. 

The classical Skraup synthesis of quinolines is exemplified by the reaction of aniline 6.3 with glycerol 6.4 under acidic/oxidative conditions to produce quinoline 6.1. 

Perhaps the most generally useful method for preparing substituted quinolines is the Skraup synthesis. In the simplest example, quinoline itself is obtained from the reaction of aniline with glycerol, concentrated sulfuric acid, nitrobenzene, and ferrous sulfate. 

Quinolines are commonly synthesized by a method known as the Skraup synthesis, which involves the reaction of aniline with glycerol under acidic conditions. Nitrobenzene is added to the reaction mixture to serve as an oxidizing agent. The first step in the synthesis is the dehydration of glycerol to propenal. 

EXPLOSION and FIRE CONCERNS a flammable liquid NFPA rating Health 2, Flammability 2, Reactivity 1 explosive reactions with barium peroxide, boric acid, hydrochloric acid + water, potassium permanganate incompatible with 2- amino ethanol, aniline, glycerol, hydrogen fluoride, permanganates, sodium hydroxide, sodium peroxide, sulfuric acid, water when heated to decomposition it emits toxic fumes such as acetic acid and carbon monoxide use carbon dioxide, dry chemical, water mist, or alcohol foam for firefighting purposes. 

Quinoline was discovered in coal tar by Friedlieb Ferdinand Runge in 1834 it is present in concentrations of approximately 0.3%. Quinoline is recovered by extraction with sulfuric acid from the methylnaphthalene fraction of coal tar, followed by springing with ammonia and rectification of the crude base mixture. Quinoline can be synthesized by the Skraup method, by the reaction of aniline with glycerol (or acrolein produced from glycerol) and catalytic gas-phase reaction of aniline with acetaldehyde. Since the supply of the tar-derived material has been adequate for a long time, synthetic production is not warrented. 

When anilines reacted with (R)-citronellal in glycerol, octahydroacridines 171 were formed (Scheme 100) and easily isolated by decantation of the product immiscible with glycerol [143]. The recyclability of the solvent was explored using model reaction of aniline with (R)-citronellal. The yield of the product (R=H) did not change much after four nms, but in the fifth one, it dropped to 72%. 

When a mixture of aniline, nitrobenzene, glycerol and concentrated sulphuric acid is heated, a vigorous reaction occurs with the formation of quinoline. It is probable that the sulphuric acid first dehydrates the glycerol giving acrolein or acraldehyde (A), which then condenses at its double bond with the amino group of the aniline to give acrolein-aniline (B), The latter in its enol... 

Dijbner-von Miller Synthesis. A much less violent synthetic pathway, the Dn bner-von Miller, uses hydrochloric acid or 2inc chloride as the catalyst (43). As in the modified Skraup, a,P-unsaturated aldehydes and ketones make the dehydration of glycerol uimecessary, and allow a wider variety of substitution patterns. No added oxidant is required. With excess aniline the reaction proceeds as follows ... 

Quinoline.—The formation of c[uinoline by Skratip s reaction may be explained as follows - The sulphuric acid converts the glycerol into aciolein, which then combines w-ith the aniline to form acrolein-aniline. The latter on o.xidation with nitrobenzene yields quinoline. 

By reaction of a primary aromatic amine—e.g. aniline 1—with glycerol 2, and a subsequent oxidation of the intermediate product 4, quinoline 5 or a quinoline derivative can be obtained.As in the case of the related Friedlander quinoline synthesis, there are also some variants known for the Skraup synthesis, where the quinoline skeleton is constructed in similar ways using different starting materials. ... 

The key intermediate for the preparation of the 8-aminoquin-oline antimalarial agents is obtained by condensation of the substituted aniline, 90, with "dynamite-grade" glycerol in concentrated sulfuric acid. (The reaction may well follow some scheme such as that depicted below.) Ihe nitroquinoline obtained from... 

The traditional unpredictably violent nature of the Skraup reaction (preparation of quinoline and derivatives by treating anilines with glycerol, sulfuric acid and an oxidant, usually nitrobenzene) is attributed to lack of stirring and adequate temperature control in many published descriptions [1], A reaction on 450 1 scale, in which sulfuric acid was added to a stirred mixture of aniline, glycerol, nitrobenzene, ferrous sulfate and water, went out of control soon after the addition. A 150 mm rupture disk blew out first, followed by the manhole cover of the vessel. The violent reaction was attributed to doubling the scale of the reaction, an unusually high ambient temperature (reaction contents at 32°C) and the accidental addition of excess acid. Experiment showed that a critical temperature of 120°C was attained immediately on addition of excess acid under these conditions [2],... 

Of the above methods, the only ones which need be considered are those in which a mixture of aniline, glycerol and sulfuric acid is heated with an oxidizing agent. With the use of nitrobenzene, the reaction, according to the original method, takes place with extreme violence. 

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