N- benzyl amines

The benzyl—nitrogen bond is not so easily cleaved as the benzyl—oxygen bond, unless the O-benzyl group is sterically hindered. This difference in activity allows the selective removal of the O-benzyl function in a molecule containing both N-benzyl and O-benzyl protecting groups. The selectivity can be reversed if the amine is protected by the Cbz group. If a small amount of amine (e g., butylamine) is added, then the selective removal of N-benzyl amines can be achieved.292... 

Carried out on a small multi-gram scale, the overall yield over the four recycle loops in the unoptimized process was 49% (based on the amount of racemate added throughout the investigation) compared to a traditional single-step resolution yield of -30% of the N-benzyl amine, demonstrating some improvement from an early stage. The product was isolated in 80-90% ee over each loop and required a final crystallization of the combined material from acetone to bring it up to the required specification. The main losses were to the imine, and, in a separate experiment, treatment of this under the SCRAM racemization conditions in the... 

An early example of this strategy is the palladium black catalyzed conversion of (Z)-2-buten-l,4-diol with primary amines (cyclohexyl amine, 2-aminoethanol, n-hexyl amine, aniline) at 120 °C to give iV-substituted pyrroles in 46-93% yield [119]. Trost extended this animation to the synthesis of a series of N-benzyl amines 169 from the readily available a-acetoxy-a-vinylketones 168 [120]. This methodology allowed for the facile preparation of pyrrolo-fused steroids. 

Friedel-Craft acetylation of385 followed by bromination yields 5-(2-bromoacetyl)-1,3-dibenzyl-1H, 3H-2,1,3,-benzothiadiazole-2,2-dioxide (387). Reaction of 387 with N-benzylated amines followed by reduction with hydrogen produces (388). No significant increase in heart rate, blood pressure, left ventricular pressure and bronchodilator activity was observed when the thiadiazoles 388 were tested in dogs. 

Palenzuela and coworkers explored the reaction of vinyl allenes with imines under the influence of Lewis acids, and found that reacting the trisubstituted allene (119) with N-benzyl amine under BF3 OEt2 catalysis provides the octahydroquinoline derivative (120) as a single isomer (Equation 73) [76]. 

In 1999, WulfF and coworkers reported that catalyst (140), based on vaulted biaryls, catalyzes the asymmetric aziridination reaction of N-benzyl amines. The catalyst was prepared by treatment of S-VAPOL (141) with three equivalents of borane-THF complex followed by heating (Figure 5.9) [87]. The use of one equivalent of borane-THF also gives the same selectivity but requires longer time for the generation of the catalyst. 

Catalyst (140) promotes the reaction between various N-benzyl amines and ethyldiazoacetate (142) at room temperature to give aziridination products (143) in good yields and excellent enantioselectivity (Equation 85) [87]. The corresponding aziridines could be transformed into valuable D-phenyl alanine ethyl ester by treatment with palladium black in acidic conditions [87]. 

Pyridinium salts, l-aryl-4-methoxy-2,6-dimethyl-synthesis, 3, 762 Pyridinium salts, N-aryloxy-rearrangements, 2, 354 Pyridinium salts, 1-benzyl-covalent amination, 2, 239 Pyridinium salts, N-benzyl-reactions... 

Pyrimidin-4-amine, N-benzyl-2-chloro-dehalogenation, 3, 91 Pyrimidin-4-amine, 2-benzyIthio-6-chloro-reactions... 

The benzene was distilled from the extract and the residue of d-N-methyl-N-benzyl-)3-phenyl-isopropylamine was distilled at reduced pressure. The thus obtained free base, distilling at 127°C at a pressure of 0.2 mm of mercury and having an np of 1.5515, was dissolved in ethyl acetate and a molar equivalent of ethanolic hydrogen chloride was added thereto. Anhydrous ether was added to the mixture and d-N-methyl-N-benzyl-)3-phenylisopropyl-amine hydrochloride precipitated from the reaction mixture as an oil which was crystallized from ethyl acetate to give crystals melting at 129° to 130°C. 

BORIC ACID CATALYZED AMIDE FORMATION FROM CARBOXYLIC ACIDS AND AMINES N-BENZYL-4-PHENYLBUTYRAMIDE... 

Manche Hydroxylamine, z. B. N-Benzyl-hydroxylamin, werden durch Basen zum Amin und Oxim disproportioniert. In solchen Fallen hydrolysiert man unter sauren Bedingun-gen. 

The process is not limited to amines. Amides can also be dealkylated. N-Benzyl amides are debenzylated in the presence of NBS and AIBN. ... 

Note The following solvent systems were tried but gave no separation dioxane/water (7 3, v/v) n-butanol saturated with water amyl alcohol/ace-tone/water/benzyl amine (40 35 20 5, v/v) 2,6-lutidine/water/ethnol/diethylamine (55 25 20 1, v/v). 

Belleau and Malek47 introduced the use of this reagent (EEDQ) to couple acylamino acids with amino acid esters, and Dunstan and Hough46 were able to couple the peracetates of maltosyl-, lactosyl-, and cello-biosyl-amine (55, 47, and 57, respectively) with 1-benzyl N-(benzyl-... 

It was found in the case of O-benzyl systems that palladium oxide is much more effective than palladium metal. No such effect was observed with the N-benzyl system.8 It is possible that the N-compounds can poison the electrophile metal ions, and the hydrogenolysis of the N-benzyl bond can take place only by the hydrogenolytic cleavage instead of the insertion mechanism. This is supported by the experimental finding that the product amine can inhibit the catalyst, and this can be minimized by buffering at a pH less than 4. 

Sortais J-B, Pannetier N, Holuigue A, Barloy L, Sirlin C, Pfeffer M, Kyritsakas N (2007) Cyclometalation of primary benzyl amines by ruthenium(II), rhodium(III), and iridium(III) complexes. Organometallics 26 1856-1867... 

Cooke and coworkers reported on the synthesis of the amino acid N-benzyl-4-acetylproline (2-889) (Scheme 2.198) [453], as this might represent an interesting synthon for the preparation of bioactive compounds. These authors also used a domino iminium ion formation/aza-Cope/Mannich protocol. Thus, treatment of the secondary amine 2-885 with glyoxylic acid (2-888) primarily provided the corresponding iminium ion, which led to 2-889 in 64% yield as a mixture of diastereom-ers. 

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