Paraldehyde, reactions

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. 

It is convenient to replace the volatile free acetaldehyde by paraldehyde, which by dissociation in the reaction-mixture generates acetaldehyde in situ. 

Acetaldehyde, b.p. 21°, undergoes rapid pol5unerisation under the influence of a little sulphuric acid as catalyst to give the trimeride paraldehyde, a liquid b.p. 124°, which is sparingly soluble in water. The reaction is reversible, but attains equilibrium when the conversion is about 95 per cent, complete the unreacted acetaldehyde and the acid catalyst may be removed by washing with water ... 

Quinoline derivatives may be synthesised by heating aii aromatic amine with an aldehyde or a mixture of aldehydes in the presence of concentrated hydrochloric or sulphuric acid this synthesis is known as the Doebner - Miller reaction. Thus aniline and paraldehyde afford 2-methylquinohne or quinaldine. 

Reactions with Ammonia and Amines. Acetaldehyde readily adds ammonia to form acetaldehyde—ammonia. Diethyl amine [109-87-7] is obtained when acetaldehyde is added to a saturated aqueous or alcohoHc solution of ammonia and the mixture is heated to 50—75°C in the presence of a nickel catalyst and hydrogen at 1.2 MPa (12 atm). Pyridine [110-86-1] and pyridine derivatives are made from paraldehyde and aqueous ammonia in the presence of a catalyst at elevated temperatures (62) acetaldehyde may also be used but the yields of pyridine are generally lower than when paraldehyde is the starting material. The vapor-phase reaction of formaldehyde, acetaldehyde, and ammonia at 360°C over oxide catalyst was studied a 49% yield of pyridine and picolines was obtained using an activated siHca—alumina catalyst (63). Brown polymers result when acetaldehyde reacts with ammonia or amines at a pH of 6—7 and temperature of 3—25°C (64). Primary amines and acetaldehyde condense to give Schiff bases CH2CH=NR. The Schiff base reverts to the starting materials in the presence of acids. 

Examples include acetaldehyde, CH CHO paraldehyde, (CH CHO) glyoxal, OCH—CHO and furfural. The reaction is usually kept on the acid side to minimize aldol formation. Furfural resins, however, are prepared with alkaline catalysts because furfural self-condenses under acid conditions to form a gel. 

Acetaldehyde can be used as an oxidation-promoter in place of bromine. The absence of bromine means that titanium metallurgy is not required. Eastman Chemical Co. has used such a process, with cobalt as the only catalyst metal. In that process, acetaldehyde is converted to acetic acid at the rate of 0.55—1.1 kg/kg of terephthahc acid produced. The acetic acid is recycled as the solvent and can be isolated as a by-product. Reaction temperatures can be low, 120—140°C, and residence times tend to be high, with values of two hours or more (55). Recovery of dry terephthahc acid follows steps similar to those in the Amoco process. Eastman has abandoned this process in favor of a bromine promoter (56). Another oxidation promoter which has been used is paraldehyde (57), employed by Toray Industries. This leads to the coproduction of acetic acid. 2-Butanone has been used by Mobil Chemical Co. (58). 

In a 2-1. three-necked, round-bottomed flask fitted with a liquid-sealed mechanical stirrer, a dropping funnel, and an efficient reflux condenser are placed 720 g. (226 cc., 4.5 moles) of bromine (Note i) and 1.5 g. of sulfur (Note 2). A glass tube is connected to the top of the condenser to carry the evolved hydrogen bromide to a gas trap (Org. Syn. 14, 2). Sixty-nine grams (69 cc., 0.52 mole) of dry paraldehyde (Note r) is added slowly, with stirring, over a period of about four hours. The reaction proceeds under its own heat during the addition of the paraldehyde subsequently the mixture is heated externally for two hours at 60-80°. The solution is distilled and a fraction collected over the range 155-175° (Note 3). 

A. ot-Chloroelhyl ethyl ether. A mixture of 200 g. (201 ml.) of redistilled paraldehyde, b.p. 121-122.5° (equivalent to 4.54 moles of acetaldehyde), and 200 g. (254 ml., 4.34 moles) of absolute ethanol is placed in a 1-1. three-necked flask fitted with a mechanical stirrer and a gas inlet tube reaching to the bottom of the flask. The mixture is cooled to —5° in a mixture of Dry Ice and acetone, and dry hydrogen chloride (Note 1) is passed into the stirred reaction mixture maintained at about —5° until 200 g. (5.48 moles) has been absorbed. During this operation, which requires about 2 hours, the reaction mixture separates into two layers. The upper layer of crude a-chloroethyl ethyl ether is re-... 

Tetrahydroharman, m.p. 179-80°, has been prepared by a number of workers by a modification of this reaction, viz., by the interaction of tryptamine (3-)5-aminoethylindole) with acetaldehyde or paraldehyde and Hahn et al. have obtained a series of derivatives of tetrahydronorharman by the use of other aldehydes and a-ketonic acids under biological conditions of pH and temperature, while Asahina and Osada, by the action of aromatic acid chlorides on the same amine, have prepared a series of amides from which the corresponding substituted dihydronorharmans have been made by effecting ring closure with phosphorus pentoxide in xylene solution. 

Paraldehyde, a sedative and hypnotic agent, is prepared by treatment of acetaldehyde with an acidic catalyst. Propose a mechanism for the reaction. 

Oxidation of the trioxane ( paraldehyde ) to glyoxal by action of nitric acid is subject to an induction period, and the reaction may become violent if addition of the trioxane is too fast. Presence of nitrous acid eliminates the induction period. 

The decomposition of gaseous paraldehyde into gaseous acetaldehyde, which may be represented by the equation, A => 3B, has been followed at 260°C by observing the change in total pressure with time, t in hrs, 7r in Torr. Find the order of the reaction. 

Experiment 8.—To 5 c.c. of freshly distilled acetaldehyde in a moderate-sized conical flask one drop of concentrated sulphuric acid is added with cooling. When the vigorous reaction is over, the paraldehyde produced is shaken in a small separating funnel with water in order to remove the sulphuric acid, and the polymeride, which is insoluble in water, is separated if necessary by extraction with ether. After being dried with a little calcium chloride the substance is distilled from a small distilling flask. Boiling point 124°. 

Experiment 9.—Pure paraldehyde is tested by the previously described aldehyde reactions with ammoniacal silver nitrate, fuchsine-sulphurous acid, and bisulphite solutions. All are negative. 

A second similar synthesis, due to Doebner and Miller, leads to the formation of substituted quinolines. The simplest example is the production of quinaldine from aniline and paraldehyde by heating with concentrated hydrochloric acid. The course of the reaction is closely related to that of the Skraup synthesis by route II. There the aniline reacts with acrolein, here with crotonaldehyde, which is easily formed under the conditions which prevail ... 

The Skraup-type reactions proceed by the use of acrolein or 2-bromo-acrolein in the presence of mineral acids or with glycerol and sulfuric acid [52CI(L)562 60NKZ509], The quinaldine-type products are afforded by acetaldehyde, crotonaldehyde, or paraldehyde in the presence of hydrochloric acid (54JCS286). 

Sulfuric acid cannot be used for the synthesis of acetals and so bis(2,2-dinitropropyl)acetal (179) is prepared from the reaction of paraldehyde with 2,2-dinitropropanol (25) in the presence of boron trifluoride.333 323 50 50 eutectic mixture of bis(2,2-dinitropropyl)formal (175) and bis(2,2-dinitropropyl)acetal (179) has found use as an energetic liquid plastisizer for nitrocellulose. 

The determination of 17-ketosteroids is most often determined in the clinical laboratory by the Zimmerman reaction, in which the ether-extracted material is allowed to react with m-nitroaniline to yield a colored product. Thus, any compound with the 17-keto basic structure such as reserpine, morphine, ascorbic acid, or their metabolites will interfere. The Porter-Silber reaction used in the determination of 17,21-dihydroxysteroids is also not specific, and the reaction requires a di-hydroxyacetone side chain. Paraldehyde, chloral hydrate, meprobromate, and potassium iodide have been found to interfere, and patients should be maintained free of these drugs for 24-48 hours before the urine collection (Bll). 

The yield may be increased to 60-70% by use of an 8 1 molar ratio of ammonium hydroxide to paraldehyde, but this is generally inconvenient because of the greatly increased volume of the reaction mixture. 

Two hundred and sixty-seven grams (296 ml., 4.38 moles) of 28% aqueous ammonium hydroxide, 207.5 g. (209 ml., 1.57 moles) of paraldehyde, and 5.0 g. (0.065 mole) of ammonium acetate are heated to 230° with continuous agitation in a 2-1. steel reaction vessel (Note 1), and the temperature is maintained at 230° for 1 liour (Note 2). The autoclave is then allowed to cool, and the two layers of the reaction mixture are separated (Note 3). To (lie non-aqueous layer is added 60 ml. of chloroform, causing separation of water which is combined with the aqueous layer. I he aqueous layer is extracted with three 50-ml. portions of chloroform, and the extracts are combined with the main portion of the chloroform solution. After removal of the chloroform by distillation at atmosiiheric pressure, fractional distillation under reduced pressure through a 30-cm. Fenske-type column gives a fore-run of water, paraldehyde, and a-picoline, b.p. 40-60°/17... 

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