A-Phenethyl amine

Ishibashi and Iwao have reported [37] a novel route (Scheme 13) to lamellarin G trimethyl ether that utilizes a much different strategy than the one outlined in Scheme 8. The synthesis begins with the dialkylation of a phenethyl amine with ethyl a-bromoacetate to yield an aminodiester (67). 

The scheme used to produce a somewhat more complex 5-a-reductase inhibitor relies on a chiral auxiliary to yield the final product as a single enantiomer. The first step in a sequence similar to that above starts with the reaction of bromotetralone (23-1) with R-a-phenethyl amine (23-2) to afford the enamine (23-3). Reaction with methyl iodide adds the methyl group at what will be a steroid-like AB ring junction... 

Miscellaneous reactions. The starting point of a practical route to P -amino acids is the proline-catalyzed Mannich reaction of aldehydes with a chiral iminium salt derived from A-benzyl-A-(a-phenethyl)amine. Condensation of aldehydes with A-Boc imines furnishes mainly i yn-adducts. "... 

In a glass flask, 90 gm of chlormethylated styrene (2% crosslinked, 200-400 mesh) was stirred with 200 gm of l-( - )-A, A -dimethyl-a-phenethyl-amine ([o S - 70.3°]) at room temperature for 1 hr. Then the mixture was heated in a thermostated oil bath at 100°C for 2 hr. After allowing the mixture to remain at room temperature for 24 hr, the resin was separated on a dry, sintered-glass funnel. The excess amine in the filtrate had [ ] D - 70.7°. The resin was... 

There is a relatively large number of alkaloids which maybe considered as simple phenethyl amine [64-04-0] (59, R = H), CgH N, or tyramine [51-67-2] (59, R = OH), CgH NO, derivatives. These iaclude mescaline (61) from the small wooly peyotyl cactus l ophophora mlliamsii (L emaire) Coult. anhalamine (62) and lophocerine (63) from other Cactaceae, and the important antamebic alkaloids (—)-protoemetiae (64), (—)-ipecoside (65), and (—)-emetine (66) from the South American straggling bush Cephaelis ipecacuanha (Brotero) Rich. AH of these bases appear to be derived from tyrosiae (25,... 

The A-substituted derivatives of 4-oxo-4//-pyrido[l,2-n]pyrimidine-3-carboxamides and -3-acetamides and l,6-dimethyl-4-oxo-1,6,7,8-tetrahy-dro-4//-pyrido[l,2-n]pyrimidine-3-carboxamide were prepared by treatment of the appropriate 3-carboxylic acids and acetic acid, first with an alkyl chloroformate in the presence ofNEt3 in CHCI3 below — 10°C, then with an amine (98ACH515). A-Phenethyl and A-[2-(3,4-dimethoxyphenyl)ethyl] derivatives of 6-methyl-6,7,8,9-tetrahydro-4//-pyrido[l, 2-n]pyrimidine-3-acetamide were obtained in the reaction of 6-methyl-6,7,8,9-tetrahydro-4//-pyrido[l,2-n]pyrimidine-3-acetic acid and phenethylamines in boiling xylene under a H2O separator. Hydrazides of 4-oxo-4//- and 4-oxo-6,7,8,9-tetrahydro-4//-pyrido[l, 2-n]pyrimidine-3-acetic acid were prepared from the appropriate ester with H2NNH2 H2O in EtOH. Heating 4-oxo-4//- and 6-methyl-4-oxo-6,7,8,9-tetrahydro-4//-pyrido[l, 2-n]pyrimidine-3-acetic hydrazides in EtOH in the presence of excess Raney Ni afforded fhe appropriafe 4-oxo-6,7,8,9-fefrahydro-4//-pyrido[l,2-n]pyrimidine-3-acefa-mide. In the case of the 4-oxo-4// derivative, in addition to N-N bond... 

A 4-foot coiled column is packed with SP-2100 and maintained at 240°C. The temperature of the 63Ni electron capture detector is 250°C. The retention time of the pentafluoropropionate derivative is 1.6 minutes. Plasma levels as low as 50 ng/ml are readily measured using this method. 3-Hydroxy-N-3-(4-hydroxyphenyl)-l-methyl-N-propyl)phenethyl-amine hydrobromide is used as an internal standard. 

Note The above formula is obviously a rapid, convenient procedure, and eliminates the need to isolate intermediates and other time consuming operations. The procedure above is described for the p-methoxy derivative, a potent but toxic drug. If you wish to avoid the toxic quality of the p-methoxy derivative the formula may be used to make other phenethyl amines without substantive modification. 

Me and coworkers reported a novel oxidation reaction of Af-Boc-phenethyl amines 21a and 21b to the corresponding cyclic carbamate 22 and aldehydes 23a and 23b (equation 21). ... 

This is a rare transformation. A rather direct method was reported whereby a primary amine reacted with KOH in diethylene glycol at 210°C. The reaction of 5-phenethylamine and the bis(sulfonyl chloride) of 1,2-benzenesulfonic acid, followed by KNO2 and 18-crown-6 gave (R)-phenethyl alcohol in 70% yield and 40% enantiomeric excess (ee). ... 

Figure 3 shows the menu obtained when requesting the graphics model builder option. A list of 9 "frequently used" substructures is provided to speed the selection of appropriate subunits. Also shown in Figure 3 is the "rough" joystick-assisted construction of a simple, sample compound, phenethyl-amine. The sequence of steps required to construct this molecule is as follows ... 

The SAR for norepinephrine uptake inhibition by amphetamine analogs is similar to that for inhibition of 5-HT reuptake. The protypical unsubstituted derivative, 2-phenethyl-amine, is a weak uptake inhibitor in isolated rat heart membranes (IDgo = 1.1 jM) (143). Introduction of a methyl group at the Cl position adjacent to the amino group results in a 10-fold increase in potency (i.e., dexamphetamine, (8), 1D = 0.18 pAO (143). Sibutra-mine, a tertiary amine, shows moderate NE uptake activity iK = 350 nAO, but its des-methyl and di-desmethyl metabolites, (JD-BTS 54 354 (44) and (R)-BTS 54 505 (46), exhibit potent activity values <20 nM) (see Table 15.10) (71). 

Possibly as a result of the social implications of the hallucinogenic j5-phenethyl-amines and simple isoquinoline alkaloids, a large number of new plant species suspected to contain these structural types have been closely scrutinized with the aid of sensitive analytical methods. Thus, extensive screening of a large variety of cactus species has been carried out. G.c. analysis has indicated the presence of trace amounts of dimers and trimers of phenethylamine and tetrahydroiso-quinoline types " while combination g.c.-mass spectrometry has enabled rapid identification of alkaloids of 120 cactus species." High voltage electrophoresis has been used for quantitative alkaloid determination.Useful structural information may be obtained from the technique of chemical ionization mass spectrometry. ... 

FIGURE 9.13 Gas chromatograms of (a) primary amines and (b) secondary amines, BSC derivatives on a 12 m X 0.2 mm i.d. U-1 fused silica column, carrier gas helium 2 ml/min, oven programmed from 70 to 300°C at 10°C with MS detection. Peaks 1. methylamine 2. ethylamine 3. /t-butylamine 4. propylamine 5. isobutylamine 6. n-butylamine 7. isopentylamine 8. pentylamine 9. hexylamine 10. phenethyl-amine 11. dimethylamine 12. methylethylamine 13. diethylamine 14. ethylpropylamine 15. dipropylamine 16. pyrrolidine 17. morpholine 18. piperidine 19. dibutylamine 20. methylbenzylamine. (Reproduced with permission from Pfundstein, B., Tricker, A. R., and Preussmann, R. J. Chromatogr., 539, 141-148, 1991. Copyright 1991, Elsevier Science.)... 

The advantage of a fluoride leaving group was clear in reaction of a hydroxy-carbamate anion with (fluorobenzene)FeCp complex, where the yield was 72% for F and 41% for Cl [79]. The (l,2-difluorobenzene)FeCp complex underwent smooth double substitution with phenethyl amine, whereas a dichloro complex led to monosubstitution. Replacement of a nitro group in q -nitrobenzene-FeCp" is possible with O, S, and N-nucleophiles [70,80,81]. The nitroarene complexes, which are not known in the Cr(CO)3 series, are prepared by oxidation of the corresponding aniline complexes. 

There have been recorded a number of other syntheses of hydrohydrastinine, some of which are in the patent literature, but most of them depend upon the formation of the isoquinoline ring from /3-3,4-methylenedioxy-phenethylamine or of its V-methyl derivative (47, 48) or upon the N-methylation of norhydrohydrastinine (49). When the above phenethyl-amine as its hydrochloride is heated with aqueous formaldehyde in a sealed tube for three hours at 130° it generates hydrohydrastinine in 88 % yield (50). There takes place not only the now well-known ring closure of the isoquinoline, but also the V-methylation reaction studied in detail by Hess, Merck, and Uibrig (51, 52). 

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