Aldimines drying

Into a 500 ml. three-necked flask, provided with a mechanical stirrer, a gas inlet tube and a reflux condenser, place 57 g. of anhydrous stannous chloride (Section 11,50,11) and 200 ml. of anhydrous ether. Pass in dry hydrogen chloride gas (Section 11,48,1) until the mixture is saturated and separates into two layers the lower viscous layer consists of stannous chloride dissolved in ethereal hydrogen chloride. Set the stirrer in motion and add 19 5 g. of n-amyl cyanide (Sections III,112 and III,113) through the separatory funnel. Separation of the crystalline aldimine hydrochloride commences after a few minutes continue the stirring for 15 minutes. Filter oflF the crystalline solid, suspend it in about 50 ml. of water and heat under reflux until it is completely hydrolysed. Allow to cool and extract with ether dry the ethereal extract with anhydrous magnesium or calcium sulphate and remove the ether slowly (Fig. II, 13, 4, but with the distilling flask replaced by a Claisen flask with fractionating side arm). Finally, distil the residue and collect the n-hexaldehyde at 127-129°. The yield is 19 g. 

Decant the ethereal solution from the yellow aldimine stannichloride which has separated, rinse the solid with two 50 ml. portions of ether, and transfer the solid to a 2-5 litre flask fitted for steam distillation and immersed in an oil bath at 110-120°. Pass steam through a trap (compare Fig. 11,40, 1,6) to remove condensed water, then through a superheater heated to 260° (Fig. I, 7, 2), and finally into the mixture (2). Continue the passage of y steam until the aldehyde is completely removed (4-5 litres 8-10 hours). Filter the white soUd at the pump, and dry in the air. The resulting p-naphthaldehyde, m.p. 53-54°, weighs 12 g. It may be further purified by distillation under diminished pressure (Fig. II, 19, ) -, pour the colourless distillate, b.p. 156-158°/15 mm., while hot into a mortar and powder it when cold. The m.p. is 57- 58°, and the recovery is over 90 per cent. 

Aldehydes, general procedure (3). A solution of nilnie 1 (1 mol) in EtOAc saturated with HO gas al 0°C is added to a solution ol SnCl2 (1.1 mol) in EtOAc previously saturated wlh HCI at 0°C. After several hours at 0°C the aldimine complex (R.CHNH2 3 SnCle separated as pale yellow prisms. The complex was filtered, washed with EtjO and dried over KOH under vacuum to afford a pure sample of 2. Steam distillation of 2 gave aldehyde 3 in the distlRate if the aldehyde was volatile. Alternatively, the aldehyde was extracted from the residue of the steam distillate... 

The inlet tube is replaced by a dropping funnel, and a solution of 30.6 g. (0.2 mole) of jS-naphthonitrile, m.p. 60-62° (Note 2), in 200 cc. of dry ether is added rapidly. Hydrogen chloride is again passed into the mixture until it is saturated, and the mixture is then stirred rapidly for one hour and allowed to stand overnight while the yellow aldimine-stannichloride separates completely. 

To a stirred solution (0 °C) of 10 mmol of (- )-(S)-a-(methoxymethyI)benzenccthanamine dissolved in 30 mL of benzene (previously washed with concentrated sulfuric acid and distilled) are added 10 mmol of the pure aldehyde. An immediate cloudiness usually results on addition of the aldehyde. The mixture is allowed to warm to r.t. and 15 g of anhyd Na2S04 are added. After stirring the mixture an additional 30-40 min, it is filtered and the Na2S04 washed thoroughly with dry diethyl ether. The solvent is removed by evaporation, first with aspirator pressure and then with the vacuum pump (0.5 Torr) to generally furnish 9.5-10 mmol of the aldimine as a colorless oil. The aldimines are dissolved in THF (0.4 M) and stored at — 20 to — 30 °C. Attempts to store the aldimines as neat liquids results in deterioration. As solutions, the aldimines can be conveniently transferred via syringe to reaction vessels. 

The physical constants of several other imines prepared by a similar procedure are shown in Table X. The aldimines listed in the Table can be obtained only if certain precautions are strictly observed [4b]. The method of Emerson, Hess, and Uhle [4c] could not be extended satisfactorily and the method described in Preparation 2-2 is a modification of the one described by Chancel [4d] for propylidenepropylamine. The reaction is best carried out by adding the aldehyde to the amine, without a solvent, at 0°C. When the order of addition is reversed, the yields are much lower. Potassium hydroxide is added at the end in order to remove the water formed during the reaction. The use of other drying agents such as potassium carbonate or magnesium sulfate failed to yield aldimines on distillation. The aldimines should always be distilled from fresh potassium hydroxide to yield water-white products. The aldimines are unstable and should be used within a few hours after their distillation otherwise polymeric products are obtained. 

To a solution of aldimine 1 (0.01 mol) in acetone, added ethyl-a-mercapto/a-cya-noacetate (0.01 mol) followed by basic alumina (20 g) with constant stirring. The reaction mixture taken in a beaker, was thoroughly mixed and the adsorbed material was dried in air. The adsorbed reactant in the beaker was placed in an alumina bath and subjected to microwave irradiation for 1-2 min. On completion of the reaction as followed by TLC examination, the mixture was cooled to room temperature and the product was extracted into acetone (3x15 mL). Recovering of solvent under reduced pressure yielded the product, which was purified by recrystallization from the mixture of ethanol-acetone. 

The reduction of a nitrile is achieved with anhydrous tin(n) chloride dissolved in ether or ethyl acetate saturated with dry hydrogen chloride (the Stephen reaction). The resulting aldimine hydrochloride (probably in the form of a complex with tin(iv) chloride) is then hydrolysed with warm water. 

In the laboratory of N. Suzuki, the synthesis of several heterocyclic condensed 1,8-naphthyridine derivatives with potential antimicrobial activity was executed. The preparation of pyrazolo[3,4-b][1,8]naphthyridines required 7-chloro-6-formyl-3-ethyl ester as the precursor that was obtained by the Stephen reduction of the corresponding aromatic nitrile. The solution of the aromatic nitrile in chloroform was added to the solution of SnC /dry HCI gas in ether. After two days of stirring, the aldimine hexachlorostannane product was treated with warm water to obtain the desired aromatic aldehyde in modest yield. Heating of the aldehyde with methyl hydrazine afforded the pyrazole derivative. 

Perfluoro-c -2,3-dialkyloxaziridines (64) are prepared in good yield (68-77%) by MCPBA oxidation of the corresponding perfluoroazaalkenes (188) (Equation (46)) <93JOC4754>. To be successful, the peracid needs to be > 80% pure, well-dried, and the solvent needs to be acetonitrile. Interestingly, oxidation does not proceed in CH2C12. A series of 3-/-butyl-3-( 1 -haloalkyl)oxaziridine were prepared by oxidation of the corresponding a-chloro, a-bromo, a,a-dichloro, and a,a-dibromo aldimines with MCPBA <92T7345>. 

Hydroxy-6-methoxyaeetophenone added to an ice-salt cooled soln. of anhydrous A1C12 in dry ether, anhydrous HCN and HC1 passed in for 1 % hrs. at 0°, and worked up, whereby the aldimine is hydrolized by heating with water on a steam bath for 15 min. —> 2-hydroxy-6-methoxy-3-formylacetophenone. Y 68%.—The Gattermann reaction with Zn(CN)2 gives a yield of 36%. (W. Baker and G. F. Flemons, Soc. 1948, 2138.)... 

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