Synthesis of Secondary Amines

The methodology is extended to number of functionalized 3-substituted 2-azanorbornenes [15] (Table 12.5). The data reveal that exo substitution provides modest yield of cyclopentenylamines, whereas the endo-substituted azanorbornenes give poor yields of the amines. The low yield of endo-substituted substrate may be attributed to severe steric crowding on the endo face. In addition, the substituent at C-3 retains its geometry (Eq. 12.6). 

McCarty CG (1970) In Fatal S (ed) The chemistry of the carbon-nitrogen double bond. In-terScience, New York, p 363 

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Synthesis of secondary amines can be achieved by replacement of a pyridinium moiety with hydrogen. Two examples are given in Reaction (21),... 

The sulphonyl chloride 23 is proposed as a protecting group for the Gabriel synthesis of secondary amines from primary amines. At the deprotecting stage, carbon-sulphur bond cleavage is achieved using zinc and acid as the electron source [109]. 

For the synthesis of secondary amines, Beak, Basha and Kokko used iV-alkyl-0-methylhydroxylamines li and Ij. The method of treating 1 equivalent of amination reagent with 1 equivalent of methyllithium, followed by reaction with 1 equivalent of organo-lithium to be aminated, was found more effective than reacting 1 equivalent of amination reagent with 2 equivalents of the organoUthium (Scheme 8). ... 

Reduction ofimines using formates Ammonium formates and formic acid have been employed as reducing agents in the synthesis of secondary amines from imines. By simple mixing of the reagents and microwave irradiation without solvent, the amines were produced in good yields within 2.5-10 min (Scheme 4.28)51. 

The synthesis of secondary amines from azides is efficient in terms of chemos-electivity [57] and has found valuable applications in the preparation of diamines [58,59], m-alkylaminoboronic esters [60], and in Diels-Alder-based amination reactions [61]. A convenient general route to open-chain polyamines, which play major roles in cellular differentiation and proliferation, has also been developed using the reductive alkylation of aliphatic aminoazides by (co-halogenoalk-yi)dichloroboranes as a key step [62] (Scheme 21). 

The reaction of trialkylboranes with iV-chloroalkylamines can be used to synthesize a wide variety of functionally substituted dialkylamines in good yields [66,67], and it complements the synthesis of secondary amines via the reaction of trialkylboranes with organic azides. The reaction is analogous to the reaction of chloramine with organoboranes, and presumably occurs via an anionotropic migration of an alkyl group from boron to nitrogen (Scheme 24). 

Following the demonstration of catalytic hydroboration-amination employing hydroxylamine-O-sulfonic acid as the electrophile, extension to the synthesis of secondary amines was considered. 

Ring formations by nucleophilic substitution at saturated carbon atoms with primary amines as nucleophiles have rarely been carried out because the resulting secondary amines as a rule are more nucleophilic than the primary ones, and therefore competition reactions are favored. The synthesis of secondary amines often starts from toluene sulfonamides which can easily be deprotonated and alkylated. A large number of methods for detosylation exists especially the acidic cleavage with H2SO4 or with HBr/phenol have proved to be reliable. 

Auxiliary-Induced Stereoselective Synthesis of Secondary Amines... 

Stereospecific synthesis of secondary amines. Phenyidichloroborane (I) reacts with an azide, for example cyclohexyl azide (2). in benzene solution, first at 20" and... 

Brown and coworkers have reported chiral organoboron reagent mediated asymmetric synthesis of primary amines of high optical purity (Scheme 32). Stereospecific synthesis of secondary amines and N-substituted aziridines by the use of organoboron reagents has also been reported. ... 

In contrast to the anion of diethyl phosphoramidate or trifluoromethanesulfonamide, which cannot be cleanly monoalkylated, - the anion of trifluoroacetamide (100) was monoalkylated by alkyl halides or alkyl methanesulfonate. The resulting A -alkylamides (101) were converted into primary amines by alkaline hydrolysis or reduction (NuBHa Scheme 42). Various primary amines were prepared from (100) with primary alkyl iodides or methanesulfonate, benzyl and allyl halides, a-bromocarbonyl compounds and 2,4-dinitrochlorobenzene. However, competitive elimination is a serious side reaction for less reactive primary alkyl chlorides and secondary halides or methanesulfonate. The synthesis of secondary amines from (100) has also been reported. ... 

The ubiquitous role of amines in both nature and in a vast variety of biologically important synthetic molecules gives this functionality a place of special prominence and interest in organic chemistry. Therefore, much effort and attention has been exerted toward developing methods for the selective synthesis of primary, secondary, and tertiary amines.4 In particular, the selective synthesis of secondary amines and orthogonally protected primary amines is quite important as these are often featured as valuable synthetic intermediates.5... 

The hydrogenation of C=N double bonds is an important synthetic strategy for the synthesis of secondary amines. Chiral iridium catalysts allow the hydrogenation of prochiral imines to be carried out with high enantioselectivity in conventional liquid solvents. Such a process has already found industrial application in the preparation of (S)-metolaclor, a herbicide produced by Novartis in Switzerland [40]. Recent research at the Max Planck Institute for Coal Research has demonstrated that reactions of this type can be carried out in SCCO2 with the same level of enantioselectivity and with enhanced catalyst efficiency [12]. 

Deallylation of amines. A practical method for the synthesis of secondary amines... 

Reductive amination. Imines formed in situ from amines and carbonyl compounds are subject to reduction. This method constitutes a convenient synthesis of secondary amines. 

A very similar equilibration was conducted as shown in Scheme 6 for the synthesis of secondary amine terminated siloxane oligomers. The amine terminated disiloxane here is a secondary... 

Although Forster initially reported this reaction, it was Decker and Becker who investigated it in more depth and made this reaction an applicable route for the preparation of secondary amines. Therefore, this reaction is known as the Decker-Becker method or Forster reaction, but it is named the Decker-Becker secondary amine synthesis in this book. It is the synthesis of secondary amine by the condensation of primary amines with aldehydes to form an imine intermediate, which then reacts with alkyl halides via alkylation to Anally afford secondary amines after hydrolysis. This reacAon gives good results when methyl halides are used but works poorly and unstably when larger alkyl halides are applied. ... 

Figure 4.22 Synthesis of secondary amines of methyl dehydroabietate.

Simultaneous GLC Determination of Zimelidine and Norzimelidine. Synthesis of Secondary Amines as Closely Related Internal Standards Acta Pharm. Succ. 16(5) 299-308 (1979) CA 92 174085w... 

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