Schiff bases from amines

1 Enamines from amines and acetone or other ketones [31] 

The amine hydrochloride (0.5—1 mg) was dissolved in 0.05 ml of dimethylformamide (DMF). Solid K2CO3 or KHCO3 (2 mg) was added, followed by 0.5 ml of acetone (or other ketone). The mixture was shaken at room temperature for 3 h. Samples were injected directly into the gas chromatograph 10% F-60 or 7% F-60 -h 1% EGSP-Z on Gas-Chrom P was used. 

For enamines from amines containing OH groups, to 0.5-1 mg amine in 0.05 ml DMF was added 0.15 ml of hexamethyidisilazane (HMDS), and the mixture was allowed to stand for 30 min at room temperature. 

A ketone—HMDS mixture was prepared by adding 1 ml of HMDS to 10 ml of acetone (or other ketone), heating to boiling and cooling. A 0.4 ml portion of the ketone-HMDS mixture was added to the DMF solution and the reaction mixtures was allowed to stand for 12 h. Precipitates were separated by centrifugation. The reaction products were stable for several days at — 5 C. Analyses were effected by GC or GC-MS. 

2 Pentafluorobenzaldehyde derivatives from water-soluble primary amines [36] 

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As has been outlined for the Strecker synthesis, the Ugi reaction also proceeds via initial formation of a Schiff base from an aldehyde and an amine. The imine intermediate is attacked by the isocyanidc, a process which is supported by protonation of the imine by the carboxylic acid component. The resulting a-amino nitrilium intermediate is immediately trapped by the carboxylate to give an 6>-acyl imidiate. All steps up to this stage are reversible. Only the final oxygen to nitrogen acyl shift is irreversible and delivers the A-acyl-a-amino amide as the thermodynamically favored product which contains two amide groups. 

Structures have been determined for [Fe(gmi)3](BF4)2 (gmi = MeN=CHCF[=NMe), the iron(II) tris-diazabutadiene-cage complex of (79) generated from cyclohexanedione rather than from biacetyl, and [Fe(apmi)3][Fe(CN)5(N0)] 4F[20, where apmi is the Schiff base from 2-acetylpyridine and methylamine. Rate constants for mer fac isomerization of [Fe(apmi)3] " were estimated indirectly from base hydrolysis kinetics, studied for this and other Schiff base complexes in methanol-water mixtures. The attenuation by the —CH2— spacer of substituent effects on rate constants for base hydrolysis of complexes [Fe(sb)3] has been assessed for pairs of Schiff base complexes derived from substituted benzylamines and their aniline analogues. It is generally believed that iron(II) Schiff base complexes are formed by a template mechanism on the Fe " ", but isolation of a precursor in which two molecules of Schiff base and one molecule of 2-acetylpyridine are coordinated to Fe + suggests that Schiff base formation in the presence of this ion probably occurs by attack of the amine at coordinated, and thereby activated, ketone rather than by a true template reaction. ... 

Schiff bases from substituted and unsubstituted benzaldehyde and aliphatic or aromatic amines are more stable [6-8]. Benzaldehyde substituents such as nitro, dialkylamino, hydroxyl, methoxyl, or halo have been used [7a-c]. Benzalaniline, m.p. 51°-52°C, is prepared in 87% yield by adding 1.0 mole of aniline to 1.0 mole of benzaldehyde at room temperature in the absence of a solvent. The crude product is added to alcohol [5] in order to induce crystallization [6]. 

FIGURE 18-5 Pyridoxal phosphate, the prosthetic group of aminotransferases. (a) Pyridoxal phosphate (PLP) and its aminated form, pyri-doxamine phosphate, are the tightly bound coenzymes of aminotransferases. The functional groups are shaded, (b) Pyridoxal phosphate is bound to the enzyme through noncovalent interactions and a Schiff-base linkage to a Lys residue at the active site. The steps in the formation of a Schiff base from a primary amine and a carbonyl group... 

Aryl amines, 403 4-Aryl-2-aminothiazoles, 178-182 mercuration of, 81 nitration of, 72 reduction of, 86 Schiff bases from, 99 Aryl diazonium salts, reaction with, rho-danine, 419... 

The alkylation of Schiff bases and hydrolysis of the resulting quaternary salts is an excellent method for obtaining certain secondary amines, RR NH, particularly where R = CHj. The procedure is less satisfactory for the introduction of large alkyl groups. The Schiff base is usually a derivative of benzaldehyde. It is readily prepared, and, without isolation, is alkylated furthermore, the salt is seldom isolated. An example is the treatment of the Schiff base from allylamine and benzaldehyde. Methyla-tion is accomplished by the action of methyl iodide at 80° for 16 hours subsequent hydrolysis furnishes methylallylamine in 71% yield. ... 

Side reactions which may occur during their formation have been studied. On the other hand, Schiff bases from substituted benzaldehydes and amines, aliphatic and aromatic, are more stable and have been prepared in large numbers. The benzaldehyde entity may carry a halo, hydroxyl, methoxyl, dialkylamino, or nitro group. Usually, an immediate reaction occurs upon mixing the two reactants either without a solvent or in dilute alcohol, as illustrated by the synthesis of benzalaniline, C,H,CH=NC,H, (87%). ... 

Unsymmetrical secondary amines are readily prepared in good yields by the catalytic reduction of Schiff bases at moderate temperatures in high-or low-pressure equipment. Many examples have been cited. The intermediate imines are prepared from primary amines and aldehydes—very seldom from ketones—and may be used without isolation (cf. method 431). For the preparation of aliphatic amines, e.g., ethyl-w-propylamine and n-butylisoamylamine, a prereduced platinum oxide catalyst is preferred with alcohol as the solvent. Schiff bases from the condensation of aromatic aldehydes with either aromatic or aliphatic amines are more readily prepared and are reduced over a nickel catalyst. In this manner, a large number of N-alkylbenzylamines having halo, hydroxyl, or methoxyl groups on the nucleus have been made. Reductions by means of sodium and alcohol and lithium aluminum hydride have also been described,... 

The pyridinium ring in PLP provides a highly optimized electron sink for stabilizing the pair of electrons released by the decarboxylation step. Consequently, the decarboxylation step is irreversible. Beginning the reaction with a Schiff base, rather than with a free aldehyde, also provides an additional catalytic advantage (705), as Schiff base interchange is faster than formation of a Schiff base from an aldehyde and an amine. Precise conformational control is also an... 

Recently an interesting result has been reported which may be useful for understanding the formation of Schiff bases from aldehydes and amines. On crystallization from ethanol and chlorobenzene of the Schiff base (a) derived from 4-aminopyridine and salicylaldehyde (Figure 10), crystals containing the two hydrolysis products (b) and (c) (Figure 10) were obtained. These crystals, after heating above 45 °C, yielded a powder which exhibits photochromic behaviour, suggesting the formation of (a) in the solid state. 

Acetone, butanone, cyclobutanone and similar ketones have been used to prepare Schiff bases from long-chain amines, aromatic amines, diamines, anriino-phenols and catecholamines in biological media [29-34], and from hydrazines in air [35], prior to separation by GC. When electron capture detection was used, penta-fluorobenzaldehyde was the chosen reagent. This procedure was applied to the analysis of traces of amines in water samples [36] and biological extracts [37,38], as well as hydrazine in tobacco smoke, technical maleic hydrazide and pyrolysis products [39]. 

Palladium II)-Schiff base complex Amines from nitro compds. s. 44, 54... 

Aldehydes and ketones serve as useful precursors to amino acids when they are converted to a Schiff base (from aldehydes) or an imine (from ketones). Reduction of the imino C=N moiety, usually in situ, generates the amine. When 1.83 (m = 1, 2) was treated with ammonia, for example, the resulting iminium salt (1,84) was hydrogenated to give either 8-aminooctanoic acid (7.[Pg.18]

For the formation of 45, nitrobenzene would be reduced to aniline by CO/H2O (see Chapter 4.2.). By aldol condensation, an a,p-unsaturated aldehyde is formed. Michael addition of aniline to the unsaturated aldehyde followed by ring closure with dehydration would form 1,2-dihydroquinoline. Oxidation of this last product by nitrobenzene would yield 45. This sequence of reactions is similar to what proposed in Scheme 15. For the formation of 46, an intermediate nitrene was suggested (Scheme 16). Addition of the nitrene to the aldehyde would give an oxaziridine and, correspondingly, an isomeric nitrone. The nitrone would then be reduced by CO to the Schiff base and this, in turn, would be reduced to the amine. Final reaction with one more molecule of aldehyde would lead to 46. Some previously made comments on the formation of Schiff bases from nitroarenes and aldehydes vide supra and Chapter 4.5.) also apply to the first part of this scheme. 

A DFT mechanistic study of the formation of Schiff bases from acetaldehyde in water has looked at two amines of biological importance glycine and phosphatidylethanolamine, with an amine-phospholipid monolayer model being incorporated in the latter. The rate-determining step was found to be dehydration of the carbinolamine intermediate in both cases. Relative free energies of the intermediates and transition states were lower (compared to butylamine as a reference amine), these effects being ascribed to the carboxylic group and phospholipid environment, respectively. 

Schiff, for example, had included carbohydrates in his studies on the formation of Schiff bases from aldehydes and amino compounds. He heated D-glucose with aniline or withp-toluidine in substantia [11], and described that these components, under loss of water, formed yellow glass-like condensation products. These supported his suggestions on the formation of Schiff bases from aldehydes and suitable aromatic amines [12]. 

Binuclear Schiff bases from hydroxy aryl-aldehydes and aliphatic hydroxy amines ... 

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. 

Primary amines form Schiff bases, (CH3 )2C=NR. Ammonia induces an aldol condensation followed by 1,4-addition of ammonia to produce diacetone amine (from mesityl oxide), 4-amino-4-methyl-2-pentanone [625-04-7] (CH2)2C(NH2)CH2COCH2, and triacetone amine (from phorone),... 

Pentafluoroaniline. Pentafluoroaniline [771 -60-8] i2is been prepared from amination of hexafluoroben2ene with sodium amide inbquid ammonia or with ammonium hydroxide in ethanol (or water) at 167—180°C for 12—18 h. It is weakly basic (p = 0.28) and dissolves only in concentrated acids. Liquid crystals have been prepared from Schiff bases derived from pentafluoroaniline (230). 

Primary aromatic amines react with aldehydes to form Schiff bases. Schiff bases formed from the reaction of lower aUphatic aldehydes, such as formaldehyde and acetaldehyde, with primary aromatic amines are often unstable and polymerize readily. Aniline reacts with formaldehyde in aqueous acid solutions to yield mixtures of a crystalline trimer of the Schiff base, methylenedianilines, and polymers. Reaction of aniline hydrochloride and formaldehyde also yields polymeric products and under certain conditions, the predominant product is 4,4 -methylenedianiline [101 -77-9] (26), an important intermediate for 4,4 -methylenebis(phenyhsocyanate) [101-68-8], or MDI (see Amines, aromatic amines, l thylenedianiline). 

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