Condensations with secondary amines

If a molecule contains both aldehydic and ketonic functions, reaction with a secondary amine occurs at the former115-117. Acyloins (a-hydroxyketones) condense with secondary amines to give a-aminoketones rather than enamines118. 

An interesting reaction is the o-aminophenol rearrangement of acylfuran-enamines described by Birkofer and Daum.340 2-Acylfurans condense with secondary amines in the presence of a small quantity... 

Enamination. Ketone condensation with secondary amines using BSA [or bis(trimethylsilyl)urea] as dehydrating agent is quite advantageous. lodomethane is also present. 

The above mentioned methods for preparation of cyclic bis-amides were patterned after peptide chemistry reactions where amide bonds dominate. Also in peptide chemistry, DCC, and DCC plus 1-hydroxybenzotriazole (HOBT) have been used in amide formation reactions. Using this procedure, 16-membered peraza-crowns have been prepared in 50-55% yields for the cyclization step (Vellacio et al., 1977). The carboxyl group can also condense with secondary amines in DMF in the presence of 1.1 mol of DCC and 1.2 mol of HOBT per mole of the dicarboxylic acid (Krakowiak et al., 1989). 

Condensations with secondary amines give enamines... 

The condensation of aldehydes or ketones with secondary amines leads to "encunines via N-hemiacetals and immonium hydroxides, when the water is removed. In these conjugated systems electron density and nudeophilicity are largely transferred from the nitrogen to the a-carbon atom, and thus enamines are useful electroneutral d -reagents (G.A. Cook, 1969 S.F. Dyke, 1973). A bulky heterocyclic substituent supports regio- and stereoselective reactions. 

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). 

Enamines from the Condensation of Aldehydes and Ketones with Secondary Amines. ... 

The most versatile method for preparing enamines involves the condensation of aldehydes and ketones with secondary amines [Eq. (1)]. Mannich and Davidsen (/) discovered that the reaction of secondary amines with aldehydes in the presence of potassium carbonate and at temperatures near 0° gave enamines, while calcium oxide and elevated temperatures were required to cause a reaction between ketones and secondary amines, although usually in poor yield. The introduction by Herr and Heyl 2-4) of the removal of the water produced in the condensation by azeotropic distillation with benzene made possible the facile preparation of enamines from ketones and disubstituted aldehydes. 

Sodium alkylamides can also be generated in situ by reacting the amine with sodium naphthalene in THF [207, 208]. This procedure has been used for the condensation of secondary amines with different 1,3-dienes to give high yields of monoalky-lated products without formation of 1 2 telomers. In the case of primary amines, mixtures of mono- and dialkylated products are obtained together with unidentified... 

The course of the condensation of ethylene glycol with secondary amines (Me2NH, Et2NH, pyrrolidine or morpholine) depends on the catalyst used. Triphenylphosphine complexes of ruthenium, e.g. RuCl2(PPh3)3, give hydroxyalkylamines while hydrated ruthenium(III) chloride yields diamines (equation 24)62. 

CONDENSATION REACTIONS A. Condensation of Secondary Amines with Aldehydes and Ketones... 

In addition to the condensation of secondary amines with aldehydes or ketones (Eq. 2), the other important methods [24] of synthesizing enamines are briefly outlined in Eq. (4). 

One of the most general methods of preparing urea derivatives in the laboratory involves the condensation of primary amines with urea. The reaction does not proceed well with secondary amines. The availability of urea gives this method an advantage (Eq. 3). 

Bis(bromomethyl)quinoxaline (126) is better prepared by the condensation of o-phenylenediamine and l,4-dibromobutane-2,3-dione than by side-chain bromination of 2,3-dimethylquinoxaline. It reacts with secondary amines, forming quinoxalino[2,3-c]pyrrolidine salts, e.g. (127).134 Reaction with thiols yields 2,3-bis(thiomethyl)quinoxalines,135... 

The reduction of the nitrile proceeds stepwise with formation of a primary aldi.nine which then is hydrogenated to the primary amine (pentyl ami ne). Part of the aldimine condenses with primary amine already formed to produce the unstable aminal. This intermediate looses ammonia to yield a secondary aldimine (dipentylimine) which ultimately leads to secondary amine (dipentyl amine). The reaction of the same primary imine with the secondary amine gives rise to the tertiary amine (tripentylamine), after hydrogenation. 

Thioindoxyl condenses with various primary aliphatic and primary and secondary aromatic amines to give 3-aminobenzo[6]thio-phenes 539,541, 553,554 condensation with secondary aliphatic amines... 

Cyclomethine Dyes can be prepared by condensing N-heterocyclic carbonyl compounds with secondary amines. Intensely colored products such as 4 are obtained by condensing 3-phenylpyrazoline with compounds such as /V-cthyl-naphtholactam. This compound dyes polyacrylonitrile a brilliant, lightfast yellow. Orange-red dyes are obtained by condensing acridone with secondary amines [6],... 

Condensation of aldehydes and ketones with secondary amines in the presence of dehydrating agents (often potassium carbonate69-71) represents a general method of enamine preparation. By this procedure ketones afford the enamines directly, whereas aldehydes are converted in the first step into diamino derivatives which decompose on distillation to give the enamine and a molecule of the secondary amine. In the case of ketones and disubstituted acetaldehydes, the water formed by the reaction can be removed by azeotropic distillation with benzene, toluene, or xylene.27,31,72-75 In the case of derivatives of aromatic aldehydes, the formation of intermediary carbinolamines 76 is sometimes observed. 

Substituted bicyclo[ . 1.0]alkanes may also be obtained by condensation of secondary amines with 2-haloketones. A variety of nucleophilic reactions can be carried out on the intermediate cyclopropaniminium salt 116251 (Scheme 108). Competing alkene scission and cyclopropanation occurs on reaction of enamines with pentacarbonyl-chromium carbene complexes252 (Scheme 109). N-Silylated allylamines and their derived N-silylated enamines undergo rhodium or copper catalysed cyclopropanation by methyl diazoacetate253 (Scheme 110). 

Enamines of steroids formed in situ by condensation of the corresponding ketones with secondary amines, followed by treatment with formic acid, gave the 3/ -saturated amine derivatives as the main products206. 

As depicted below, 2-furaldehyde reacted with secondary amines in a lanthanide-catalyzed condensation/ring-opening/electrocyclization process to provide trans-4,5-diaminocyclopenten-2-ones <07CC3759>. The formation of the ring-opened intermediate (deprotonated Stenhouse salt) was proposed as the rate-determining step. 

Even if the a hydrogen of an amine is not highly acidic, its activation is possible by condensation with a special type of carbonyl compound. Grigg s idea (86CC602) is given in Eq. (12), in which carbonyl compounds bearing a conjugated C=X moiety (X = heteroatom) are condensed with secondary... 

The simplest ylide generation method among the deprotonation route (Section II,D) consists of the condensation of N-substituted a-amino esters with carbonyl compounds. This procedure must be especially useful for utilization in intramolecular cycloadditions because the substrates for the cycloadditions are simply prepared in situ by reacting the carbonyl compounds (or secondary amines) bearing a trapping chain with secondary amines (or carbonyl compounds). 

In a paired electrolysis, amines have been A -alkylated in alcoholic solution. At the Pt(Pt) anode the alcohol was oxidized to an aldehyde that condensed with the amine to an imine the imine was reduced at the cathode to a secondary amine. Benzylamine was thus electrolyzed to benzylethylamine in 96% yield (65% current yield) in ethanol containing 10 vol% of water [14]. 

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