Paraldehyde Ethanol

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-... 

Pure formaldehyde, prepared by vacuum depolymerisation of paraldehyde, was collected as a solid at — 189°C. When the flask was transferred to a Cardice-ethanol bath, the contents began to repolymerise exothermally and ignited. 

This technique has been applied [47] to the determination of ethanol, methylethyl ketone, paraldehyde and acrolein in soils. Following extraction of the soil with methanol and gas purging the purge gas is trapped on a Tenax column. The purgate obtained by heating the Tenax column is analysed by gas chromatography and/or mass spectrometry. 

Accdg to Davis (Ref 23, p 407), MF can also be ptepd by replacing ethanol with acetaldehyde, paraldehyde, metaldehyde or dimethyl-and ethylacetal. Another method consists of... 

Similar constancy is shown by other covalent bond distances (with certain exceptions that will be discussed later). For the carbon— oxygen single bond, for example, the value 1.43 A has been reported for methanol,4 ethanol, ethylene glycol, dimethyl ether, paraldehyde, metaldehyde, and many other molecules this value is accepted as standard for the C—O bond. 

The chemical structures of some older and less commonly used sedative-hypnotics, including several barbiturates, are shown in Figure 22-3. Glutethimide (a piperidinedione) and meprobamate (a carbamate) are of distinctive chemical structure but are practically equivalent to barbiturates in their pharmacologic effects, and their clinical use is rapidly declining. The sedative-hypnotic class also includes compounds of simple chemical structure, including ethanol (see Chapter 23 The Alcohols), chloral hydrate, trichloroethanol, and paraldehyde (not shown). 

Disposition in the Body. Acetaldehyde is a major intermediate metabolite of ethanol and is also a metabolite of metaldehyde, paraldehyde, and phenacetin. It undergoes further metabolism by oxidation to acetic acid and, eventually, to carbon dioxide and water. A minor pathway involves condensation with pyruvic acid to form acetoin. 

Disposition in the Body. Acetic acid occurs as a metabolite of ethanol and also of paraldehyde after its depolymerisation to acetaldehyde. It is further oxidised to carbon dioxide and water. 

Thiram and other dithiocarbamates are metabolic poisons. The acute effects of thiram are very similar to that of carbon disulfide, supporting the notion that the common metabolite of this compound is responsible for its toxic effects. The exact mechanism of toxicity is still unclear, however it has been postulated that the intracellular action of thiram involves metabolites of carbon disulfide, causing microsome injury and cytochrome P450 disruption, leading to increased heme-oxygenase activity. The intracellular mechanism of toxicity of thiram may include inhibition of monoamine oxidase, altered vitamin Bg and tryptophan metabolism, and cellular deprivation of zinc and copper. It induces accumulation of acetaldehyde in the bloodstream following ethanol or paraldehyde treatment. Thiram inhibits the in vitro conversion of dopamine to noradrenalin in cardiac and adrenal medulla cell preparations. It depresses some hepatic microsomal demethylation reactions, microsomal cytochrome P450 content and the synthesis of phospholipids. Thiram has also been shown to have moderate inhibitory action on decarboxylases and, in fish, on muscle acetylcholinesterases. 

Preparation (b). The reaction sequence is shown in the formulation. Treatment of paraldehyde and absolute ethanol with hydrogen chloride gas at —5° produces a-chloroethyl ethyl ether (1), which on bromination affords a,j8-dibromoethyl ethyl ether (2). Coupling with allylmagnesium bromide gives (3), which on reaction with zinc dust in n-butanol generates 1,4-pentadiene. Thus one double bond is that of allyl bromide, and the other is generated by elimination of BrOCjH, from the bromohydrin ethyl ether (3). 

Benzaldehyde, salicylaldehyde, semicarbazide hydrochloride, paraldehyde, 1 % solutions of Na2C03, NaOH, AgN03, NH3, 4 % solutions of Bi(N03)3 and Seignette salt KNaC4H40fi 4 H2O, concentrated H2SO4, ethanol, formaldehyde solution (highly diluted), NaHS03, parafuchsine. 

I) 40 mL of the silver nitrate solution is treated with the same amount of sodium hydroxide solution in an Erlenmeyer flask ammonia is added until the precipitate of (AgOH)aq which is initially formed redissolves completely. Samples are now placed in 4 test tubes as follows 4 mL of formaldehyde solution (test tube 1), a mixture of 2 mL of benzaldehyde and 5 mL of ethanol (test tube 2), 3 mL of pure paraldehyde (test tube 3) and a mixture of 3 mL of freshly distilled acetaldehyde with 3 mL of water (test tube 4). 5 mL of the [Ag(NH3)2] solution are added to each test tube in the cold. The solutions in test tubes 1, 2 and 4 are colored black by the silver precipitate, while paraldehyde shows no reaction. A beautiful silver mirror is formed on the lower part of test tube 3 if it is warmed slightly. 

The treatment of anxiety throughout human history has involved a variety of natural agents which were administered to relieve tension and induce a state of altered consciousness, with ethanol in its various forms the most widely used [4]. Within the last century, general CNS depressants such as barbiturates, bromide salts, and ethanol surrogates such as chloral hydrate and paraldehyde have been employed to treat anxiety. Because of side-effects of the other drugs, barbiturates were used predominantly in the first half of this century as anxiolytics, but their clinical utility was limited by tolerance and dependence liability. Propanediolcarbamates such as meprobamate were also used to treat anxiety but displayed many of the barbiturate side-effects. 

Dibromoethyl ethyl ether 531 Dry HC1 is led cautiously into a mixture of paraldehyde (100 g) and ethanol (100 g) which is cooled in a freezing mixture. Two layers are formed, the upper of which is dried over CaCl2 and fractionated (69% b.p. 93-96°). To this 1-chloro-ethyl ethyl ether is added the theoretical quantity of bromine, portionwise (with time for decolorization in each case), with cooling in ice HC1 is evolved. When the crude dibromo product is distilled in a vacuum it has b.p. 92-95°/17 mm, the yield being 88-91 %. 

Schiff (135) reported a synthesis of coniine involving the action of alcoholic ammonia on butyraldehyde, but it was later shown that the resulting tertiary amine was not identical with coniine. The first synthesis of coniine and the first sjm thesis of an alkaloid is that of Laden burg (136) who condensed 2-methylpyridine with paraldehyde at 250° and reduced the resulting 2-allylpyridine (XCVIII) with sodium in ethanol, thereby obtaining an inactive base (XCIX) very similar to coniine in properties. The... 

Chlorination of Acetaldehyde. In some commercial processes for chloral, acetaldehyde, or its condensation product, paraldehyde is chlorinated under hydrous conditions. In some cases this has an advantage over the chlorination of ethanol as only 3 moles of chlorine are required as compared with the 4 moles used in the ethanol process ... 

Chloral hydrate, paraldehyde, meprobamate and glutethimide cause sedation, but are neither benzodiazepines or barbiturates. Chloral hydrate is used most often for the sedation of children. It is reduced in the body to trichloroethanol, a potent ethanol. Like ethyl alcohol, the side effects of chloral hydrate include mucosal irritation, light-headedness, malaise and ataxia. Paraldehyde, meprobamate and glutethimide are seldom used and their mechanism of action is unknown. The non-barbiturate/non-benzodiazepine sedatives are not listed in a table. 

The first lipophilicity-activity relationship was published by Charles Richet in 1893, exactly 100 years ago. From his quantitative investigations of the toxicities of ethanol, diethyl ether, urethane, paraldehyde, amyl alcohol, acetophenone, and essence of absinthe ( ) he concluded plus Us sont solubles, mains Us sont toxiques (the more they are soluble, the less toxic they are). One year later Emil Fischer derived the lock and key model of ligand-enzyme interactions from his results on the stereospecificity of the enzymatic cleavage of anomeric glycosides. 

Gessner Shakarjian MP. Interactions of paraldehyde with ethanol and chloral hydrate. J Pharmacol Exp Ther ( 9%5) 235, 32-6. 

Carbonyl reactions— Their aldol reactions with carbonyl compounds are perhaps the most important undergone by primary or secondary alkyl groups attached to the pyridine ring. Ladenburg first observed the reaction of 2-picoline with paraldehyde, which gave, at 250 -260 , 2-propenylpyridine. At lower temperatures, a-(2-picolyl)ethanol is formed, but in low yield 3a, 6-4, Formaldehyde is more reactive. jS-(2-Pyridyl)ethanol has been prepared by heating 2-picoline and formalin or formaldehyde under pressure and this reaction and that with 4-picoline has... 

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