Reaction with paraldehyde

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. 

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. 

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. 

In a reaction which is mechanistically related to the Skraup reaction an a,/ -unsaturated carbonyl compound, generated by way of an acid-catalysed aldol condensation, reacts with a primary aromatic amine in the presence of acid to yield a quinoline derivative (Doebner-Miller reaction). For example, when aniline is heated with paraldehyde (which depolymerises to acetaldehyde during the reaction) in the presence of hydrochloric acid the final product is 2-methyl-quinoline (101) (quinaldine, Expt 8.40). Retrosynthetic analysis for the 1,2-dihydroquinoline reveals crotonaldedhyde as the unsaturated carbonyl component which is in turn formed from acetaldehyde (see Section 5.18.2, p. 799). 

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). 

Several examples have been reported of the preparation of 4,7-phenanthrolines from substituted 6-aminoquinolines by the Skraup and related reactions. In this way, 5-methoxy-, 5-chloro-, 3-methyl-6-methoxy-, l-methyl-, and l,2,3,4-tetrahydro-4-methyl-4,7-phenanthrolines have been synthesized while improvements have been made to the synthesis of the 3-methyl derivative. The Skraup reaction has also been applied to quaternary salts of 6-aminoquinolines. For example, 5-chloro-4-methyl-4,7-phenanthrolinium iodide (36) was obtained from the methiodide of 6-acetamido-8-chloroquinoline (35). Cyclizations starting from aminocarbostyrils have also been reported. Thus, 6-amino-1-methylcarbostyril (37) was condensed with paraldehyde in the presence of concentrated hydrochloric acid to afford 3,4-dihydro-4,8-dimethyl-3-oxo-4,7-phenanthroline (38), while under Skraup conditions, with glycerol as condensing agent, 6-amino-4-methylcarbostyril afforded 3,4-dihydro- l-methyl-3-oxo-4,7-phen-... 

This compound, 223, a potent and selective iXj-adrenoceptor agonist used also in studies of vasoconstriction , has been obtained according to the reaction sequence of equation 93. This involves oxidation of high-specific-activity paraldehyde-with selenous acid to ethanedial-l,2- C2 which was condensed directly with 1,2,4-benzenetriamine dihydrochloride to 6-quinoxalin-2,3- C2-amine in 56% yield, bromi-nation of 224 and conversion of 225 to its isocyanate 226 by reaction with thiophosgene, and finally the reaction of 226 with ethylenediamine in refluxing 1 1 methanol-toluene. The overall radiochemical yield of 223 was 11% starting from paraldehyde-The radiochemical purity of the tartrate 227 was 98.2%, specific activity 101.5 mCi mmor ... 

Scheme 7.20 Enantioselective polystyrene-supported diatylprolinol catalysed cross-aldol reaction of paraldehyde with aromatic idehydes.

Production is carried out by liquid-phase synthesis from acetaldehyde and ammonia. Acetaldehyde is first trimerized to paraldehyde. The subsequent reaction with aqueous ammonia, which gives a 70% yield of 5-ethyl-2-methylpyridine, is performed in the liquid phase at 230 °C and at a pressure of around 150 bar with ammonium-salt catalysts. 

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... 

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. 

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 ... 

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