Benzylamine derivative

The chelated complex of the benzylamine derivative 505 underwent a remarkable oxidative transformation by treatment with thallium trifluoroace-tate to give narwedine (506) in one step by biomimetic oxidation[459]. 

A -disilylamines, precursors of benzylamine derivatives, in high conversion and chemoselectivity (Scheme 18 and Table 6). 

The reaction of racemic Sb-chiral l-phenyl-2-trimethylsilylstibindole with the optically active ortho-palladated benzylamine derivative, di-p-chlorobis (S)-2-[l-dimethylamino)ethyl]phenyl-C,N dipalladium, leads to diastereomeric complexes which were used for the separation of the enantiomers of the stibindoles.65 The molecular structures of the diastereomeric palladium complexes are depicted in Fig. 4. 

The addition of 95 onto 2m-Me in THF at ambient temperature (89% yield) was not stereoselective [53]. All attempts to add the chiral cyclic benzylamine derivative 96 and 97 onto the spirocyclopropanated chloro ester 2c-Me were unsuccessful [21b]. Although it was possible to add heterocycles (S)-4-phenyloxa-zolidine-2-one (98) and its thio analog 99 onto the chloro esters 1-Me and 2j-Me (Scheme 30) [10b, c] and to substitute or reductively remove the chlorine atom in the adducts 101, all attempts to deprotect the amino functions in 101 and the products of their transformations under various conditions were unsuccessful. 

Table 1. Kinetic constants of fluorine-substituted benzylamine derivatives for oxidation by monoamine oxidases (MAO) B (pH 9.0, 25 °C) [31]. Adapted by permission of Harwood Academic Publishers GmbH. Copyright 1995.

Cfiemical Class Benzylamine derivative I Ciinicai Pharmacology ... 

Table 3.9. Acidolytic cleavage of resin-bound A-benzylamine derivatives.

V-Benzylamines derived from di-O-protonated glyceraldehydes react with phenyl-magnesium bromide to give protected aminodiols with total diastereoselectivity the nature of the O-protecting group determines the direction of the selectivity.40... 

The Lobry de Bruyn reaction can be carried out on the paper, followed by chromatography of the products.167 168 The procedure of Bayly and Bourne22 for forming benzylamine derivatives of oligosaccharides on filter paper has been mentioned previously. Enzymic hydrolysis of phosphate esters, in conjunction with paper chromatography, aids detection of the spots.126... 

Similar results were obtained with the benzylamine-derivative 399, which can be lithiated by s-BuLi-(-)-sparteine to lead to a methylated product in good ee via a configurationally stable organolithium.82 The reaction of 400 proves again that the presence of (-)-sparteine during the electrophilic substitution step plays no part in determining the enantioselectivity of this reaction. 

Section 5.4 describes the enantioselective deprotonation of a deuterated benzylamine derivative 431 to give a configurationally unstable organolithium 432.75 Over a period of minutes, in the presence of (-)-sparteine, the organolithium 432 gave products of increasing ee as the organolithiums equilibrated under thermodynamic control to the more stable 432-(-)-sparteine complex, a process that could be accelerated by the precipitation of the complex. 

Chiral polymer-supported thiiranes 401 were prepared by free radical copolymerization of TMA ((3)-thiiranylmethyl-methacrylate) and ethylene glycol dimethacrylate (EDMA) (Equation 60) <2006TA1944>. These chiral thiiranes were transformed into polymer-supported aminothiols by the facile ring opening of the thiirane group with benzylamine and methylamine. These derivatives, complexed with [RuCl2(p-cymene)]2, were used in assymmetric reduction of acetophenone to gave (A)-l-phenylethanol (39% ee from methylamine and 50% ee from benzylamine derivatives). 

KP-363, a benzylamine derivative, is used in creams and solutions in concentrations of 0.1 and 0.6%. It is reported to cause less irritation than bifonazole and tolciclate (SEDA-14, 235). 

The Bobbitt modified Pomeranz-Fritsch reaction allows the preparation of enantiopure tetrahydroisoquinolines. During the studies directed toward the total synthesis of ET 743 and its analogues, S.J. Danishefsky and co-workers utiiized this transformation for the preparation of a key tetrahydroisoquinoline intermediate. The cyclization precursor was efficiently synthesized from the enantiopure benzylamine derivative by A/-alkylation with excess diethylbromoacetal. The resulting compound was subjected to QN hydrochloric acid at 0 °C and slowly warmed to ambient temperature overnight. The desired tetrahydroisoquinoline was formed as a 4 1 mixture of diastereomers. 

Most cyclometallations occur with nitrogen donor ligands benzylamine derivatives and palladium offer some examples of this ... 

A migration of an aryl group from carbon to nitrogen takes place also in the Stieglitz rearrangement. For example, the benzylamine derivatives 234 were converted into anils 235 in a reaction induced by p-nitrobenzenesulfonyl peroxide (p-NBSP)337 (equation 94). 

Over-the-counter antifungus (fungistatic or fungicidal) medications typically include active ingredients such as allylamines (e.g., butenafine [benzylamine derivative], terbinafine), azoles (e.g., clotrimazole, micon-... 

Yamamura, S., Oda, K., Mizoguchi, X, Saito, S., Iwasawa, Y., Kiyomoto, A. Study on the structure-activity relationships of adrenergic, beta-mimetic benzylamine derivatives. V. 9-aryl-l/7-2,3,7,8,9,10-hex-ahydro-benzo[d,e]quinoUnes. Chem. Pharm. Bull. 1979, 27, 858-869. 

Scheme 4.45 Different types of fluorine-containing herbicide. From top to bottom carotenoid biosynthesis inhibitors, aryloxyphenoxypropionates, pyridyloxyacetic acids, sulfonylureas, trifluoromethane sulfonanilides, benzylamine derivatives [3 — 14].

Synephrine, the N-methylated analog of OA, completely blocked uptake at this concentration. The two imidazolines, naphazoline and XAMI, were somewhat effective as uptake blockers (20-30% inhibition), comparable to DCDM and DDCDM. The tricyclic antidepressant desipramine, a known amine uptake blocker in vertebrates, showed good potency in the cockroach system, as originally described by Evans (21). Finally, the N-chloroethyl benzylamine derivative, xylamine, has been described as a potent, specific and irreversible inhibitor of norepinephrine uptake in mammals (25). It was an active inhibitor of uptake in the cockroach preparation. 

Da Settimo A, Primofiore G, Da Settimo F, Marini AM, Novellino E, Greco G, Martini C, Giannaccini G, Lucacchini A. Synthesis, structure-activity relationships, and molecular modeling studies of A-(Indole-3-ylglyoxylyl)benzylamine derivatives acting at the benzodiazepine receptor. J Med Chem 1996 39 5083-5091. 

Butenafine hydrochloride (mentax) is a benzylamine derivative with a mechanism of action and spectrum of antifungal activity similar to those of terbinafine, naftifine, and other allylamines. 

An active carbonate resin 2a has also been prepared from Wang resin and used to anchor a multifunctional benzylamine derivative for a combinatorial application. Final products were cleaved using TFA-CH2CI2 (1 1)... 

Hydrogenation of nitro compounds is rather straightforward, and palladium, platinum, and nickel catalysts have been used. Palladium is the most common catalyst for both aromatic and aliphatic nitro compounds. The poor results obtained for reduction of aromatic nitriles with hydride reagents (sec. 4.2.C.iii) make catalytic hydrogenation the preferred method. Reduction of 407 involved conversion of the aromatic nitrile moiety to the benzylamine derivative when palladium and a trace of platinum oxide was used. Hydrogenation using platinum oxide converts aromatic nitro compounds to aniline derivatives, even in the presence of other reducible groups. OS... 

V-Boc allylic amines are readily obtained by CuCN-mediated coupling of enol triflates with the a-lithiated carbamates. This method offers regio- and stereocontrol with respect to the double bond. However, it cannot be extended to the preparation of benzylamine derivatives. 

Synthesis of repaglinide involves condensation of an appropriately substituted and chi-rally pure benzylamine derivative with an appropriately substituted phenylacetic acid derivative (7) followed by saponification. The reported process for the key intermediate (7) described a five-step process with an overall yield of about 30% of theory (Scheme 23.4) We undertook development of an alternative synthetic strategy to prepare 7 and developed an efficient and commercially feasible synthesis starting from 2-hydroxy-4-methylbenzoic acid (9) in two steps. Thus, 9 was first alkylated with ethyl bromide in a polar aprotic solvent and in the presence of an inorganic base to afford ethyl 2-ethoxy-4-methylbenzoate... 

The aforementioned Na-auxiliary-mediated ubiquitination methods all employed substituted benzylamine-derived auxiliaries. Recently, Chatterjee et al. reported an auxiliary-mediated ubiquitination method employing 2-mercaptoethoxyl group as the auxiliary [16]. The 2-mercaptoethoxyl auxiliary was introduced to the a-amine of Gly76 which had been attached to the lysine side chain during SPPS. The ubiquitination was achieved through the reaction between... 

The group of Gong and coworkers explored a biomimetic 1,3-dipolar cycloaddition between a-ketoester 79 and benzylamine derivatives 80 with electron-deficient olefins 81a,b to devise a straightforward route to proline derivatives 82 in high yields and enantioselectivities [49]. The proposed biomimetic three-component 1,3-dipolar cycloaddition proceeds as illustrated in Scheme 2.22a. The azomethine ylide B is formed, via a transamination from ketimine ester A, which is in turn prepared from a-ketoesters 79 and benzyl-amine derivatives 80 then, the 1,3-dipolar cycloaddition with electron-poor olefins 81a takes place. For this purpose, the bisphosphoric acid 83 was found to be the catalyst of choice to promote such transformation (Scheme 2.22b). Replacing dimethyl maleate (previously used as deficient olefins) by methyleneindolinones, the same approach could be extended to spirooxindoles synthesis in high yields and... 

Santia reported a microwave-promoted, chemodiveigent four-component reaction that afforded either spiro pyrrolidines 13 or 2,5-diketopiperazines 14 from the reaction of ethyl hydrogen fumarate, aldeltydes, benzylamine derivatives and isonitriles. The product selectivity of this reaction depends mainly on the substituent on the amine component, since it affords compounds 13 for the case X=OH and 14 for X=OMe [10], Its mechanism involves an initial Ugi four-component reaction that gives intermediate 15, which undergoes either an intramolecular Michael reaction to give 13 (pathway a) or, for less reactive aromatic rings, an intramolecular aza-Michael reaction that affords 14 (pathway b Scheme 1.6). 

Building on this chemistry, the same authors developed a novel four-component reaction of p-hydroxybenzaldehyde derivatives, benzylamine derivatives, fumaric acid monoethyl ester and isonitriles in water under microwave irradiation to give natural product-like 5,5,6-fused azaspiro tricycle systems 16 as the main products [11]. This transformation can be assmned to proceed through addition of a final aza-Michael step to the previously developed Ugi/Michael domino sequence, and generates six contiguous bonds and fonr stereogenic centres, including one... 

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