Aldimines—

Condensation of RR CHCHO (R = H or alkyl R = H, alkyl, CH2=CH, Ph or PhCHj) with Me3CNHj, followed by the reaction of the resultant aldimine with phosgene and thermal elimination of Me3CCl and HCl from the acid chloride, gave a, 3-unsaturated isocyanates [1150a]  

When R is unsaturated and in the presence of base, however, 2,3-unsaturated alkenylcarbamoyl chlorides were formed [1105]  

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GattermaDD synthesis A method for the synthesis of aromatic hydroxyaldehydes. E.g. AICI3 is used to bring about the condensation of phenol with a mixture of gaseous hydrochloric acid and hydrocyanic acid an aldimine hydrochloride is formed and on hydrolysis gives p-hydroxybenzaldehyde... 

From nitriles by treatment with anhydrous Stannous chloride dissolved in ether saturated with hydrogen chloride the resulting crystaUine aldimine stannichloride, [(RCH=NHj)2] SnCl, or (RCH=NH,HCl)2SnCl4, is hydrolysed by warm water, and the aldehyde is isolated by distillation with steam or by extraction with a solvent (Stephen reaction), for example, for R = CH3(CH2)4, i.e., n-amyl ... 

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. 

Anilines react with ct-haloacetophenones to give 2-arylindoles. In a typical procedure an W-phenacylaniline is heated with a tw o-fold excess of the aniline hydrobromide to 200-250°C[1]. The mechanism of the reaction was the subject of considerable investigation in the 1940s[2]. A crucial aspect of the reaction seems to be the formation of an imine of the acetophenone which can isomerize to an aldimine intermediate. This intermediate apparently undergoes cyclization more rapidly (path bl -> b2) than its precursor (Scheme 7.3). Only with very reactive rings, e.g, 3,5-dimethoxyaniline, has the alternative cydiz-ation (path al a2) to a 3-arylindole been observed and then only under modified reaction conditions[3],... 

Aldimines (azomethines) C=N—R, r/ 1673-1639 1405-1400 (s) Dialkyl substituents at higher frequency diaryl substituents at lower end of range... 

If, however, hydrogen is present in the a-position of the iV-alkyl substituent, 2-alkyl-oxaziridines are easily decomposed by alkali. Base attack on this H atom effects 1,2-elimination at the C—N bond. From (86) and aldimine (87) forms, and a mixture of ammonia and two carbonyl compounds is finally obtained, one of them containing the carbon atom of the original oxaziridine ring, the other originating from the IV-alkyl group (57JA5739). 

By working in anhydrous solvents even aldimines like (296) could be prepared (79TL3201). 

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... 

Several blocked diamines or amino-alcohols are commercially available. The aldimine is an aldehyde-blocked diamine. The ketimine is a ketone-blocked diamine. The oxazolidine is a five-membered ring containing oxygen and nitrogen. The oxazolidine ring shown below is an aldehyde-blocked amino alcohol. The basic synthetic concepts of an aldimine, a ketimine, and an oxazolidine are shown below ... 

Halogen-free A/-acyl aldimines and N-acyl ketiimnes tautomenze readily to give enamides [J6] In contrast, perfluonnatedyV-acylimines are stable compounds These electron-deficient itnmes not only exhibit high thermal stability but also show umque properties both as electrophiles and as strongly polanzed hetero-1,3-dienes... 

Iminium salts can be made in a number of ways such as protonation of enamines (7), alkylation of aldimines and ketimines (5,9), cleavage of a covalent bond in a... 

The alkylation of aldimines and ketimines as a method for obtaining iminium salts is now useful only for the preparation of iminium salts not accessible by any of the newer methods. The preparation of and 8 illustrates the conversion of ketimines to iminium salts (9,21). 

It is not known whether the amine assists the elimination of the nitrogen, but that the iminium salt retains its stereochemistry has been demonstrated (709). When a mixture of 68 and 69of 1 5 ratio is treated with diazomethane, the ratio of 70 71 obtained in 75% yield and determined spectroscopically was still 1 5. The traw-N-isopropyl-N-methylisobutylidinium perchlorate (69) was prepared by alkylation of an aldimine salt with diazomethanc and... 

Petrow described the formation of 3-iminoketones from 3-keto-aldehydes and aniline. Cyclization in the presence of aniline hydrochloride and ZnCh smoothly provides the desired quinoline 26. Bis-imine 24 is the proposed intermediate that undergoes cyclization. The aldimine is more reactive than the ketimine toward cyclization thus, cyclization on the aldimine occurs. When the bis-imine is not formed, partial aniline migration can occur which results in mixtures of cyclized products. 

We have previously discussed that keto-aldehydes react with anilines first at the aldehyde carbon to form the aldimine. Subsequent condensation with another aniline formed a bis-imine or enamino-imine. The aniline of the ketimine normally cyclizes on the aldimine (24 —> 26). Conversely, cyclization of the aldimine could be forced with minimal aniline migration to the ketimine using PPA (30 —> 31). The use of unsymmetrical ketones has not been thoroughly explored a few examples are cited below. One-pot enamine formation and cyclization occurred when aniline 48 was reacted with dione 49 in the presence of catalytic p-TsOH and heat. Imine formation occurred at the less-hindered ketone, and cyclization with attack on the reactive carbonyl was preferred. ... 

COCH=CHPh) have been formulated as enols (79LA965 81CC118). In some cases mixtures of enol and oxo forms have been observed (84CCC603). Aldimines of type 67 exist predominantly as keto tautomers 68 (74JPR971). 

The spectra of aldimines 74 and X-ray investigations on hydrazones of type 75 demonstrate the existence of these eompounds in the eorrespond-ing keto forms (74JPR971 92IZV917). 

Whereas vicinal hydroxy, mercapto, and hydroselenoaldimines of azoles strongly prefer the aminomethylene tautomeric form (Section II,E,2), their metal chelates 380 are characterized by.pronounced equalization of bond lengths within the chelate ring, which makes their structures similar to those expected for the aldimine tautomeric type. 

The [4-1-3] cycloaddition has also been realized in acceptors containing a nitrogen atom. While a,/ -unsaturated aldimines, and structurally flexible ketimine such as (87), generally only undergo [3-1-2] cycloadditions (see Scheme 24), the ketimine (112), which is rigidly held in a cisoid conformation, does give exclusively the [4-1-3] adduct azepine (113). On the other hand, the steroidal imine (114) produces a quantitative yield of a 1 1 mixture of the [4-1-3] and [3-1-2] cycloadducts (115) and (116), respectively (Scheme 2.31) [36]. 

The effect of the metals used was then examined (Table 5.4). When the group 4 metals, titanium, zirconium, and hafnium, were screened it was found that a chiral hafnium catalyst gave high yields and enantioselectivity in the model reaction of aldimine lb with 7a, while lower yields and enantiomeric excesses were obtained using a chiral titanium catalyst [17]. 

In general the reaction of an aldehyde with a ketone is synthetically useful. Even if both reactants can form an enol, the a-carbon of the ketone usually adds to the carbonyl group of the aldehyde. The opposite case—the addition of the a-carbon of an aldehyde to the carbonyl group of a ketone—can be achieved by the directed aldol reaction The general procedure is to convert one reactant into a preformed enol derivative or a related species, prior to the intended aldol reaction. For instance, an aldehyde may be converted into an aldimine 7, which can be deprotonated by lithium diisopropylamide (EDA) and then add to the carbonyl group of a ketone ... 

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