Amination reactions carbonyl compounds

SchifT s bases A -Arylimides, Ar-N = CR2, prepared by reaction of aromatic amines with aliphatic or aromatic aldehydes and ketones. They are crystalline, weakly basic compounds which give hydrochlorides in non-aqueous solvents. With dilute aqueous acids the parent amine and carbonyl compounds are regenerated. Reduction with sodium and alcohol gives... 

Secondary amines cannot form imines, and dehydration proceeds to give carbon-carbon double bonds bearing amino substituents (enamines). Enamines were mentioned in Chapter 7 as examples of nucleophilic carbon species, and their synthetic utility is discussed in Chapter 1 of Part B. The equilibrium for the reaction between secondary amines and carbonyl compounds ordinarily lies far to the left in aqueous solution, but the reaction can be driven forward by dehydration methods. 

The Leuckart-Wallach reaction is the oldest method of reductive amination of carbonyl compounds. It makes use of formamide, formic acid or ammonium formate at high temperature. The final product is a formamide derivative, which can be converted to an amine by reduction or hydrolysis. The method has been applied to the preparation of 1,2-diamines with a norbornane framework, which are interesting rigid analogues of 1,2-diaminocyclohexanes. As a matter of fact, starting from N-acetyl-2-oxo-l-norbornylamine 222, the diamide 223 was obtained with excellent diastereoselectivity and then converted to the M-methyl-N -ethyl derivative 224 by reduction with borane [ 104] (Scheme 34). On the other hand, when the reac-... 

A one pot samarium-catalyzed three-component reaction of aldehydes, amines, and nitroal-kanes leads to pyrroles. The reaction proceeds via imines, generated from the amine and carbonyl compound, followed by the Michael addition of the nitro compound (Eq. 10.10).12a In... 

Four-component condensation (4CC) of carboxylic acids, C-isocyanides, amines, and carbonyl compounds to afford diamides. Cf. Passerini reaction. 

In the reduction of imines and enamines with hydrogen telluride and sodium hydrogen telluride, hydrolysis leading to primary amines and carbonyl compounds is frequently competitive with the reduction. This undesired side reaction is minimized by the addition of triethylamine, in the case of hydrogen telluride. ... 

This chapter on electrophilic amination using O-substituted hydroxylamines 1-5 and oximes 7 is focused on the various methods that have been reported for the amination of carbon nucleophiles. Synthetic aspects and applications of the methods for C—N bond formation are accompanied by a brief discussion of the reaction mechanisms. The preparation of O-substituted hydroxylamines and oximes has not been considered in detail. This review covers the literature up to August 2007 and is partly based on reviews on the electrophilic amination of carbanions and a-amination of carbonyl compounds. ... 

CONDENSATION REACTIONS A. Condensation of Amines with Carbonyl Compounds... 

All three compounds (WF6 and MoF6 are best) will bring about a reaction (not a fluorination) that may have synthetic utility at 0CC in l,l,2-trichloro-l,2,2-trifluoroethane (Freon 113) or chloroform they will cleave N,TV-dimethyl- and N-tosylhydrazones and oximes back to the parent carbonyl compounds12,14 (UF6 converts any first-formed aldehydes into acid fluorides1213). All three hexafluorides will convert1215 tertiary amines into carbonyl compounds and carboxylic acids into acid fluorides.16 They also dope polyacetylene to the metallic regime.17... 

The position of the equilibrium between imine and carbonyl may be perturbed by interaction with a metal ion. We saw in Chapter 2 how back-donation of electrons from suitable orbitals of a metal ion may stabilise an imine by occupancy of the jc level. It is possible to form very simple imines which cannot usually be obtained as the free ligands by conducting the condensation of amine and carbonyl compounds in the presence of a metal ion. Reactions which result in the formation of imines are considered in this chapter even in cases where there is no evidence for prior co-ordination of the amine nucleophile to a metal centre. Although low yields of the free ligand may be obtained from the metal-free reaction, the ease of isolation of the metal complex, combined with the higher yields, make the metal-directed procedure the method of choice in many cases. An example is presented in Fig. 5-47. In the absence of a metal ion, only low yields of the diimine are obtained from the reaction of diacetyl with methylamine. When the reaction is conducted in the presence of iron(n) salts, the iron(n) complex of the diimine (5.23) is obtained in good yield. 

Probably one of the commonest reactions encountered in the template synthesis of macrocycles is the formation of imine C=N bonds from amines and carbonyl compounds. We have seen in the preceding chapters that co-ordination to a metal ion may be used to control the reactivity of the amine, the carbonyl or the imine. If we now consider that the metal ion may also play a conformational role in arranging the reactants in the correct orientation for cyclisation, it is clear that a limitless range of ligands can be prepared by metal-directed reactions of dicarbonyls with diamines. The Tt-acceptor imine functionality is also attractive to the co-ordination chemist as it gives rise to strong-field ligands which may have novel properties. All of the above renders imine formation a particularly useful tool in the arsenal of preparative co-ordination chemists. Some typical examples of the templated formation of imine macrocycles are presented in Fig. 6-12. 

Reductive amination of carbonyl compounds. Sodium cyanoborohydride has been the reductant of choice for this reaction, even though it is highly toxic (4, 448-449). Borane-pyridine is recommended as a nontoxic substitute. The reactions are conducted in acetic acid, in which this borane is fairly stable, and a co-solvent such as CH2CI2 or THE... 

A A -Disulfonamides are decomposed with sodium hydrogencaibonate in DMSO to give ketones. Imines formed from the reaction of primary amines with carbonyl compounds can be oxidized to ox-aziridines with MCPBA which hydrolyze to aldehydes or ketones with acid. When acetone is used, the final by-products are ammonia and acetone (equation 37). The use of 2-pyridinecarbaldehyde is preferred since it gives an acid-soluble by-product which aids work-up (equation 38)." ... 

Reductive amination of carbonyl compounds with ammonia or amines in the presence of a reducing agent has been discussed (method 431). When the reducing agent is formic acid or a derivative, the products are the formyl derivatives of primary or secondary amines or the formates of tertiary amines. These intermediates readily furnish the amines, A critical discussion of the reaction along with experimental conditions and procedures and a tabular survey of compounds has been presented. ... 

The mechanisms illustrate why the reaction of 1° amines with carbonyl compounds forms imines, but the reaction with 2° amines forms enamines. In Figure 21.10, the last step of both mechanisms is compared using cyclohexanone as starting material. The position of the double bond depends on which proton is removed in the last step. Removal of an N—H proton forms a C=N, whereas removal of a C-H proton forms a C=C. 

In 1958, the isocyanides 10 became readily availablehl and shortly afterwards the four-component reaction (4CR) was introduced, in which an amine 6 (e.g., ammonia, hydrazine, hydroxylamine, or a primary or secondary amine), a carbonyl compound 1, and an acid 7... 

Secondary amines. The reductive amination of carbonyl compounds with MeNHj HCl is easily accomplished. Triediylamine is present in the reaction mixture. 

Leuckart-Wallach reaction. Reductive alkylation of ammonia or of primary or secondary amines with carbonyl compounds and formic acid or formamides as reducing agents. 

Reductive amination of carbonyl compounds. Method A. N-octylbenzylamine (typical procedure). AAMF (30 mL) suspension of benzylamine (1.67 g, 15 mmol), octanal (1.55 g, 15 mmol), EtjN (7.0 mL, 50 mmol) and Al2Te3 (6.1 g, 14 mmol) is refluxed. The reaction is monitorized by GLC and H2O (3 mL, 168 mmol) is added at 15°C after 30 min. The het-erogeneons mixtnre is refluxed for another 30 min. The black solid is removed by filtration and the filtrate dried (CaCOj) and evaporated. The residne is distilled, giving the prodnct (2.7 g (80%) b.p. 108-112°C/1 torr). 

Acyloxaziridines are easily obtained from compounds unsubstituted at nitrogen by reaction with acid chlorides or isocyanates. Acylation proceeds so smoothly that, in the amination of carbonyl compounds, oxaziridine compounds are obtained in better yields on addition of acid chlorides than in the absence of the acylating agent. With aliphatic aldehydes, amination does not succeed at all except in the presence of benzoyl chloride. Proof of structure comes from reduction by iodide to give the acid amide and carbonyl compound. 

Accordingly, the Ugi reaction is closely related to the Mannich reaction and may be classified as an a-aminoalkylation. However, at the same time, a special type of Ugi reaction, the formation of a-acylami-nocarboxamides (42g) by 4CC of carboxylic acids and primary amines with carbonyl compounds and isocyanides, resembles the Passerini reaction (see Section 4.6.2). 

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