1 -Phenylethylamine reagent

The present procedure was developed from those of Wallach and Freylon, based upon the general method discovered by Leuckart. a-Phenylethylamine also can be prepared satisfactorily by the reduction of acetophenone oxime with sodium and absolute alcohol or sodium amalgam, but the reagents are more expensive and the processes less convenient. The amine has been obtained by reducing acetophenone oxime electro-lytically, by reducing acetophenone phenylhydrazone with sodium amalgam and acetic acid, from a-phenylethyl bromide and hexamethylenetetramine, and by the action of methyl-magnesium iodide upon hydrobenzamide, as well as by other methods of no preparative value. 

Fig. 1 Comparative recordings of the reflectance scans of a mixture of phenylethylamine (1), tyramine (2), serotonin (3) and histamine (4) A. ninhydrin reagent (q.v.), B. ninhydrin — collidine reagent.

Fluorodediazoniation of 2-fluoro-2-phenylethylamines with sodium nitrite m Olah s reagent (70% anhydrous hydrogen fluoride-30% pyridine) gives high yields of 1,1-difluoro-2-phenylethanes arising from 1,2 migration of phenyl fJ] (equation 2)... 

Fig. 7-6). Two unichiral amides which have been known capable of this reaction are 1-phenylethylamine [15] and l-(l-naphthyl)ethylamine [16]. Marfey s reagent [N-a-(2,4-dinitro-5-fluorophenyl)-L-alaninamide] was introduced as a reagent to deriva-tize amino acids with cyclopentane, tetrahydroisoquinoline or tetraline structures [17]. Simple chiral alcohols such as 2-octanol can also be used to derivatize acids such as 2-chloro-3-phenylmethoxypropionic acid [18]. 

Asymmetric reactions have also been developed. The reactions of allyltitaniums with chiral aldimines derived from optically active 1-phenylethylamine afford optically active homoallylic amines with excellent diastereofacial selectivities. Thus, the Cram syn addition products are obtained highly predominantly when using crotyltitanium reagent 33, as exemplified in Scheme 13.30 [61]. 

Alternatively, a P-methoxy-P-phenylethylamine can be used to circumvent the oxidation step after the conventional Bischler-Naperialski cyclization. Here, when treated with the phosphorus reagent the amide (R = OMe) undergoes both cyclization and the elimination of methanol to give the isoquinoline (R = H) directly. This is known as the Pictet-Gams modification of the Bischler-Napieralski synthesis. 

Monoamine oxidase (MAO) (E.C. 1.4.3.4) is an enzyme found in all tissues and almost all cells, bound to the outer mitochondrial membrane. Its active site contains flavine adenine dinucleotide (FAD), which is bound to the cysteine of a -Ser-Gly-Gly-Cys-Tyr sequence. Ser and Tyr in this sequence suggest a nucleophilic environment, and histidine is necessary for the activity of the enzyme. Thiol reagents inhibit MAO. There are at least two classes of MAO binding sites, either on the same molecule or on different isozymes. They are designated as MAO-A, which is specific for 5-HT (serotonin) as a substrate, and MAO-B, which prefers phenylethylamine. Similarly, MAO inhibitors show a preference for one or the other active site, as discussed below. 

P-Phenylethyl alcohol, 812,816 Phenylethylene, 1015,1024 a-Phenylethylamine, 560, 566 P-Phenylethy,amine, 560, 567,569 Phenylethylbarbituric acid, 1003,1005 P-Phenylethyl bromide, 283 P-Phenylethyl iodide, 288 Phenylglycine-o-carboxylic acid, 980 Phenylglyoxal, 866 Phenylhydrazine, 635, 636 hydrochloride, 636, 637 Phenylhydrazine acetate reagent, 343, 721 ... 

Several alkaloids of the phenylethylamine, morphine and Ipecacuanha classes can be detected directly with DNS-C1 [121-124]. This reagent reacts with the primary and secondary amino groups or phenolic hydroxyl groups of the alkaloids to form highly fluorescent derivatives, nanogram amounts of which may be detected after chromatographic separation. 

Pereira [38] separated enantiomers of sec.-alcohols on Carbowax 20M after their conversion into carbamates by treatment with optically pure / -(+)-N-l -phenylethyl isocyanate. This reagent is prepared from commercially available R-(+)-1 -phenylethylamine and phosgene. 3(3-Acetoxy-As-etienic acid esters [39] were used for the same purpose. 

The generality of the method was demonstrated by the preparation of various oxisuran bioisosters where the pyridyl moiety was replaced by phenyl, furyl, and thienyl moieties. The optical purities of these products were determined by proton NMR spectroscopy using the chiral shift reagents Eu(hfc)3140 and (-)-A-(3,5-dini-trobenzoyl)-a-phenylethylamine,141 following conditions established by the study of racemic mixtures of the P-ketosulfoxides. 

Thus, in terms of stereochemical theory, the minimal requirement for the differentiation of enantiomers by a chiral reagent is a one-point approach rather than a three-point attachment . This idea is illuminated by the data cited earlier for the heats of neutralization between the base, a-phenylethylamine, and mandelic add. Here the reaction does not involve a covalent bond formation rather it is an ionization leading to an electrostatic situation. For the neutralization of (R )-base with (/ )-acid, — AH = 7.630 0.013 kcal/mol for (/ )-base with (S)-acid, —AH = 7.431 0.014 kcal/mol—a significant difference of approx. 0.2 kcal/mol. 

Chiral imines have proved to be useful reagents in the synthesis of cyclic systems. For example, imines derived from (S)-( — )- and (R)-( + )-l-phenylethylamine 412 have been used in the preparation of optically pure polysubstituted cyclopentanone derivatives 414 (equation 87)252 and in enantioselective steroid synthesis (equation 88)253. 

The addition of chiral amines to a,/(-unsaturated sulfoximines has been employed for the resolution of racemic sulfoximines 3 utilizing 0.5 equivalents of a chiral amine in chloroform 117. After completion of the reaction, the unreacted starting material is isolated by column chromatography and its optical purity determined by comparison with the reported optical rotation, or by HNMR using a chiral shift reagent. While (—)-(l/f,2.S,)-2-mcthylamino-1-phenyl-l-propanol [(l/ ,2S)-ephedrine] affords material of moderate optical purity, racemic products are isolated from addition reactions with (—)-l-phenyl-2-propanamine [(—)-am-phetamine] or ( + )-( )-l-phenylethylamine. 

It is best to ran a series of spectra with increasing concentrations of the chiral shift reagent, as demonstrated by the unusual behavior of the orffio-hydrogen resonance of 2-phenyl-2-butanol with Eu(hfc)3. This resonance showed increasing enantiomeric discrimination up to a lanthanide-substrate ratio of about 0.5. At higher lanthanide-substrate ratios the nonequivalence diminished until the resonances recoalesced and then reversed their order in the spectrum. Such behavior likely reflects the dominance of a 2 1 substrate-lanthanide complex at low lanthanide concentration and a 1 1 complex at higher lanthanide concentrations. The chiral discrimination in the 2 1 and 1 1 complexes is markedly different . A similar behavior was observed for 1-phenylethylamine with Eu(dcm)3 . 

A general method for the preparation of primary amines, free from secondary and tertiary amines, involves the interaction of Grignard reagents and O-methylhydroxylamine. The yields range from 45% to 90% for many amines including ethylamine (81%), t-butylamine (70%), n-amyl-amine (65%), and /3-phenylethylamine (68%)/ ... 

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