Secondary amines, addition with

In addition to carbonyl substrates, imines have been used extensively with phosphorus-halogen reagents for the preparation of a variety of phosphonates and phosphinates. Combined in a reaction medium, secondary amines react with formaldehyde and phosphorus trichloride134 135 or alkyldichlorophosphines136 to produce N,N-disubstituted aminomethylphosphonates or -phosphinates. These reactions occur under mild conditions with good yield. Similarly, aliphatic carboxylic amides react with aldehydes to generate imines, which can be used in situ with diphenylchlorophosphine to produce... 

Secondary amines react with aldehydes and ketones via addition reactions, but instead of forming imines, produce compounds known as enamines. Initially, there is the same type of nucleophilic attack of the amine onto the carbonyl system, followed by acid-catalysed dehydration but, since the amine is secondary, the product of dehydration is an iminium... 

Secondary amines react with ketones that contain an H atom in the a-position through an addition and subsequent El elimination to form enamines (Figure 9.29). In order for enamines to be formed at all in the way indicated, one must add an acid catalyst. In order for them to be formed completely, the released water must be removed (e.g. azeotropically). The method of choice for preparing enamines is therefore to heat a solution of the carbonyl compound, the amine, and a catalytic amount of toluenesulfonic acid in cyclohexane to reflux in an apparatus connected to a Dean-Stark trap. Did someone say Le Chateher ... 

Other C-electrophiles besides iminium salts and carbonyl compounds have not yet extensively been tested for C-C-forming cyclopropane ring cleavage. However, whereas acyl or tertiary alkyl halides do not give addition products, benzaldimine at least provides the expected secondary amine 194 with good yield and diasteroselectivity 61). 

The mechanism for the formation of secondary amine, proposed by von Braun et al., is supported by the fact that the formation of secondary amine decreases with addition of ammonia.11,12 Ammonia may add to the aldimine 1 competitively with primary amine, forming a,a-diamine 6 (eq. 7.12), and thus may suppress the condensation reaction leading to secondary amine formation (eqs. 7.5 and 7.6). Further, in the presence of ammonia, the intermediates 2 and 3 may be decomposed to give one mole of aldimine and one mole of primary amine by the reversal of the reactions in eqs. 7.5 and 7.613,14 and may thus effectively depress the formation of secondary amine. 

The kinetics of the addition of ketene dimer to aromatio amines havo been mvostigated. The dimers of the higher alkylketenes do not react with secondary amines or with phmiyUiydraiine, but their quantitative reaction with ethylamine hae been used for their determination, 2,3-J)ihydro-A, A diiii thyl-p-tketene dimer to form 7.8-dihydio-2,6 dimethy1-chromone. 

With just a few exceptions, active platinum antitumor agents contain Pt(II) in a square-planar configuration with two cis primaiy or secondary amines, together with two other more weakly bound ligands such as chlorides or carboxylates 13—17) (Table V). Related Pt(IV) complexes with additional chloro or hydroxo axial ligands are often also active and are believed to be reduced to Pt(II) in vivo with removal of the axial ligands. 

Three different types of curing mechanism can be distinguished Primary and secondary amines react with epoxy resins by an addition mechanism. 

Aliphatic primary and secondary amines react with C q and C70 rather efficiently, typically forming multiple addition products [76,115,116], One of a few examples in which the reaction products are well characterized is the nucleophilic additions of morpholine and piperidine to Cjo in the presence of oxygen, resulting in the formation of products 11-13 [76],... 

All reactions are reversible and proceed at high temperatures and pressures. In fact the reactions run a multistep course with formation of a range of by-products, particularly dialkyl (secondary) amines. Addition of ammonia in the last stage would suppress the formation of secondary amines. 

Besides addition to double bonds to give dihalocyclopropane derivatives—the most important reaction of dihalocarbenes—many other reactions of these active electrophilic species can be performed using PTC methodology, such as insertion into C-H bond, reactions with primary and secondary amines and with many other nucleophiles ... 

The N-chloramines 12 are conveniently obtained by addition of aliphatic primary amines to acceptor-substituted olefins and N-chlorination of the resulting secondary amines 11 with trichloroisocyanuric acid. 

As substituted ureas result from the reaction of a secondary amine with an isocyanate, a great variety of latent initiators may be generated by dissolving a convenient amount of a secondary amine in the epoxy resin and adding a stoichiometric amount of an isocyanate. By adjusting the addition rate of the isocyanate, the evolution of reaction heat may be kept under control. Moreover, as the isocyanate reacts very much faster with secondary amines than with any secondary OH present in the epoxy molecule, and no reaction is observed between NCO and epoxides at moderate temperature [74], the substituted ureas are the only products generated in the reaction medium. 

Method 2. Place a 3 0 g. sample of the mixture of amines in a flask, add 6g. (4-5 ml.) of benzenesulphonyl chloride (or 6 g. of p-toluenesulphonyl chloride) and 100 ml. of a 5 per cent, solution of sodium hydroxide. Stopper the flask and shake vigorously until the odour of the acid chloride has disappeared open the flask occasionally to release the pressure developed by the heat of the reaction. AUow the mixture to cool, and dissolve any insoluble material in 60-75 ml. of ether. If a solid insoluble in both the aqueous and ether layer appears at this point (it is probably the sparingly soluble salt of a primary amine, e.g., a long chain compound of the type CjH5(CH2) NHj), add 25 ml. of water and shake if it does not dissolve, filter it off. Separate the ether and aqueous layers. The ether layer will contain the unchanged tertiary amine and the sulphonamide of the secondary amine. Acidify the alkaline aqueous layer with dilute hydrochloric acid, filter off the sulphonamide of the primary amine, and recrystaUise it from dilute alcohol. Extract the ether layer with sufficient 5 per cent, hydrochloric acid to remove all the tertiary amine present. Evaporate the ether to obtain the sulphonamide of the secondary amine recrystaUise it from alcohol or dilute alcohol. FinaUy, render the hydrochloric acid extract alkaline by the addition of dilute sodium hydroxide solution, and isolate the tertiary amine. 

In the above reaction one molecular proportion of sodium ethoxide is employed this is Michael s original method for conducting the reaction, which is reversible and particularly so under these conditions, and in certain circumstances may lead to apparently abnormal results. With smaller amounts of sodium alkoxide (1/5 mol or so the so-called catal3rtic method) or in the presence of secondary amines, the equilibrium is usually more on the side of the adduct, and good yields of adducts are frequently obtained. An example of the Michael addition of the latter type is to be found in the formation of ethyl propane-1 1 3 3 tetracarboxylate (II) from formaldehyde and ethyl malonate in the presence of diethylamine. Ethyl methylene-malonate (I) is formed intermediately by the simple Knoevenagel reaction and this Is followed by the Michael addition. Acid hydrolysis of (II) gives glutaric acid (III). 

There also exists an acidregioselective condensation of the aldol type, namely the Mannich reaction (B. Reichert, 1959 H. Hellmann, 1960 see also p. 291f.). The condensation of secondary amines with aldehydes yields Immonium salts, which react with ketones to give 3-amino ketones (=Mannich bases). Ketones with two enolizable CHj-groupings may form 1,5-diamino-3-pentanones, but monosubstitution products can always be obtained in high yield. Unsymmetrical ketones react preferentially at the most highly substituted carbon atom. Sterical hindrance can reverse this regioselectivity. Thermal elimination of amines leads to the a,)3-unsaturated ketone. Another efficient pathway to vinyl ketones starts with the addition of terminal alkynes to immonium salts. On mercury(ll) catalyzed hydration the product is converted to the Mannich base (H. Smith, 1964). 

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