5-Amino-2-benzyl-4-phenyl

Amino-2-phenyl-2//-benzotriazole reacted with epichlorhydrin in chlorobenzene at 140-145°C to give the A-benzyl-7-hydroxy-6,7,8,9-tetrahydrotriazolo-quinoline derivative 194. This was benzylated and rearranged by heating in DMSO to give the isomeric 7-benzyloxy derivative 195 (Scheme 59) (77MI2). 

This approach (Scheme 3) has been applied (53JCS1636) to the synthesis of 4(5)-aminoimidazole derivatives with potential antihistamine or anthelmintic properties. For example, 4(5)-amino-2-thymyloxymethylimidazole (47) was obtained from benzyl-thymyloxy acetothioimidate hydrochloride (42) (75%). Similarly, 4(5)-amino-2-phenylimidazole (48) and 4(5)-amino-2-(thiophen-3-yl)imidazole (49) were prepared (72CA19645) from benzyl-phenyl acetothioimidate hydrochloride (43) and benzyl-(thiophen-3-yl) acetothioimidate hydrochloride (44), respectively. 

Phenylalanine (Phe or F) (2-amino-3-phenyl-propanoic acid) is a neutral, aromatic amino acid with the formula HOOCCH(NH2)CH2C6H5. It is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. Tyr and Phe play a significant role not only in protein structure but also as important precursors for thyroid and adrenocortical hormones as well as in the synthesis of neurotransmitters such as dopamine and noradrenaline. The genetic disorder phenylketonuria (PKU) is the inability to metabolize Phe. This is caused by a deficiency of phenylalanine hydroxylase with the result that there is an accumulation of Phe in body fluids. Individuals with this disorder are known as phenylketonurics and must abstain from consumption of Phe. A nonfood source of Phe is the artificial sweetener aspartame (L-aspartyl-L-phenylalanine methyl ester), which is metabolized by the body into several by-products including Phe. The side chain of Phe is immune from side reactions, but during catalytic hydrogenations the aromatic ring can be saturated and converted into a hexahydrophenylalanine residue. ... 

B. 2-(N-Benzyl-N-mesitylenesulfonyl)amino-1-phenyl-1-propanol, 3. A mixture of 2 (16.7 g, 50 mmol), benzyl chloride (6.90 mL, 60 mmol) (Note 1), tetrabutylammonium iodide (200 mg) (Note 1) and potassium carbonate (8.4 g, 60 mmol) in acetonitrile (100 i L) is heated under reflux for 17 hr (Note 4). The cooled mixture is filtered and the salt is washed with diethyl ether (100 mL). The combined organic layers are concentrated and the residue is crystallized from dichloromethane (25 mL) and hexane (100 mL) to give 3 (17.0 g. 80%) (Notes 5, 6). 

C. 2-(N-Benzyl-N-mesitylenesulfonyl)amino-1-phenyl-1-propyl propionate, 1. To a solution of 3 (15.0 g, 35.4 mmol) and pyridine (3.7 mL, 46 mmol) in dichloromethane (200 mL), propionyl chloride (3.8 mL, 44 mmol) (Note 1) is added dropwise at 0°C. The reaction mixture is stirred at room temperature for 13 hr and diluted with diethyl ether (300 mL). The mixture is washed successively with 100 mL each of water, 1 M HCI, water, saturated sodium hydrogen carbonate solution, and brine, and dried with anhydrous sodium sulfate. The filtered organic solution is concentrated to give a crystalline residue, which is triturated with hexane to give 1 (16.8 g, >99%) (Note 7). 

N-Benzyl-N-mesitylenesulfonyl)amino-1 -phenyl-1 -propyl propionate Benzenesulfonamide, 2,4,6-trimethyl-N-[1 -melhyl-2-(1 -oxopropoxy)-2-phenylethyl]-N-(phenylmethyl)-, [R-(R, S )]- (14) (187324-66-9)... 

N-BENZYL-N-MESITYLENESULFONYL)AMINO-1-PHENYL-1-PROPYL PROPIONATE 109... 

In analoger Weise lassen sich konfigurativ einheitliche, 2-substituierte 1-Amino-cy-clohexan-Hydrochloride herstellen. Man erhiilt so in ahnlich hohen Ausbeuten und mit hohen ee-Werten die Hydrochloride von optisch-aktivem 2-Amino-1-methyl-, 2-Amino-1-ethyl-, 2-Amino-1-benzyl- und 2-Amino-l-phenyl-cyclohexan2. 

N-Benzyl-N-mesitylenesulfonyl)amino-1 -phenyl-1 -propyl Propionate. A. Abiko, Venture Laboratory, Kyoto Institute of Technology,... 

Anilino-propyl)-methyl- E2, 143 (2-Arylaminocarbonyl-alkyl)-organo- E2, 140 (a-Bcnzylamino-benzyI)-ethyI- E2, 131 ( -Benzylamino-benzyl)-phenyl- E2, 131 (l-Benzylamino-eihyl)-phenyl- E2, 131 (l-Benzylamino-pentyl)-phenyl- E2, 131 Benzyl-butyl- -ethylester XII/1, 255 [(Bcnzyl-carboxymethyl-amino)-methyl]-ethyl- ... 

Alkoxy- -2-sulfid E2, 739 2-Amino-3-phenyl- -2-oxid E2, 643 2-(a-Anilino-benzyl)-3-isopropyl- -2-oxid E2, 394 2-Anilino- -2-oxid... 

Dimethylamino-2,2-dimethyl-2//-azirine (23) and methyl 2-amino-3-phenyl-propionate gave 3-benzyl-5-dimethylamino-6,6-dimethyl-3,6-dihydro-2(17/)-... 

Niwa K, Yamada K, Shudo N, Seto K, Matsumoto T, Takao S, Akiyama SI, Shi-madzu H (1992) Effect of a dihydropyridine analogue, 2-[benzyl(phenyl)amino]ethyl l,4-dihydro-2,6-dimethyl-5-(5,5-dimethyl-2-oxo-l,3,2-dioxaphosphorinan-2-yl)-l-(2-morpholinoethyl)-4-(3-nitrophenyl)-3-pyridinecarboxylate on reversing in vivo resistance of tumor cells to adriamycin. Cancer Res 52 3655-3660... 

As an example, the temperature dependent NMR spectra of 5-benzyl-l -[(4-nitrophenyl)-amino]-4-phenyl-l, 3-dihydro-2H-imidazole-2-thione 26 (R = Ph, Z = NO2) are reproduced in Figure 3. With increasing temperature the signals of the AB quartet of the diastereotopic methylene... 

Figure 3 Temperature dependent H NMR spectra of 5-benzyl-l-[(4-nitrophenyl) amino]-4-phenyl-l,3-dihydro-2H-imidazole-2-thione 26.

Amino-benzyl)- VIII, 185 (4-Aminomethyl-phenyl)- VIII, 185 Malonsaure... 

Ethanol 2-[2-(Dimethylamino-ethyl)-methyl-amino]-l-phenyl- E21f, 5795 (CO-NR2 -> CH2-NR2) Hydrazin l-(3-tert.-Butyl-4-hydroxy-5-methyl-benzyl)-l-methyl- E16a, 477 (N-Benzylier.)... 

SYN S a-(l -(N-METHYL-N-NITROSOAMINO)ETHYL). BENZYL ALCOHOL 2-(N-METHYL-N-NITROSO-AMINO)-l-PHENYL-l-PROPANOL... 

SYNS a-(l-AMINOETHYL)BENZENEMETHANOL HYDROCHLORIDE a-(l-AMINOETHYL)BENZYL ALCOHOL HYDROCHLORIDE ( )-2-AMINO-l-PHENYL-l-PROPANOL HYDROCHLORIDE O-HYDROXY-P-AMINOPROPYLBENZENE HYDROCHLORIDE MONHYDRIN MUCORAMA MYDRIATINE dl-NOREPHEDRINE HYDROCHLORIDE dl-l-PHENYL-2-AMINO-l-PROPANOL MONOHYDROCHLORIDE PHENYLPROPANOLAMINE HYDROCHLORIDE... 

Using the same procedure, phenyl-substituted alkenes can be aminated. For example, the photochemically promoted reaction of l,2-dihydro-4-phenylnaphthalene (3) with an amine in the presence of 1,4-dicyanobenzene (/ -DCNB) afforded the corresponding 2-amino-1 -phenyl derivatives 4, albeit in relatively low yield after 64-71% conversion of the alkene30. The stereochemistry of the product is dependent on the steric bulk of the amine, since the intermediate benzylic carbanion should undergo protonation from the less hindered face, that is, opposite to the amino group. The stereochemical assignment of 4 was based on chemical shifts and coupling constants for the methine protons in the H-NMR spectra. 

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