2- Phenylethylamine synthesis

Isobutylamine and 2 phenylethylamine can be prepared by the Gabriel synthesis ten butyl amine N methylbenzylamine and aniline cannot... 

Deamination, Transamination. Two kiads of deamination that have been observed are hydrolytic, eg, the conversion of L-tyrosiae to 4-hydroxyphenyUactic acid ia 90% yield (86), and oxidative (12,87,88), eg, isoguanine to xanthine and formycia A to formycia B. Transaminases have been developed as biocatalysts for the synthetic production of chiral amines and the resolution of racemic amines (89). The reaction possibiUties are illustrated for the stereospecific synthesis of (T)-a-phenylethylamine [98-84-0] (ee of 99%) (40) from (41) by an (5)-aminotransferase or by the resolution of the racemic amine (42) by an (R)-aminotransferase. 

In an attempted synthesis of papaverine based on Rugheimer s preparation of 6 7-dimethoxyisoquinoline from veratrylaminoacetal (McO)2—CjHg—NH—CH2(OEt)2, Allen and Buck reduced deoxy-veratroin oxime, (MeO)2—CgHg—C(NOH)—CHj—C6H3(OMe)2, to a 3-di-(3 4-dimethoxy)-phenylethylamine,... 

A synthesis of possible biological significance was effected by Spath and Berger, who ozonised eugenol methyl ether to 3 4-dimethoxyphenyl-acetaldehyde (Villa), which was then condensed with 3 4-dimethoxy-phenylethylamine (Vlllb), and the resulting Schiff s base (IX) treated wit hot 19 per cent, hydrochloric acid, whereby it was transformed into... 

Condensation of adipic acid derivative 17 with phenylethylamine in the presence of carbo-nyldiimidazole affords the bis-adipic acid amide 18. The synthesis is completed by reduction of the carbonyl groups with diborane followed by demethylation of the aromatic methoxy groups with hydrogen bromide the afford dopexamine (19) [3]. 

Figure 13.7 Synthesis and structure of the trace amines phenylethylamine, /)-tyramine and tryptamine. These are all formed by decarboxylation rather than hydroxylation of the precursors of the established monoamine neurotransmitters, dopamine and 5-HT. (1) Decarboxylation by aromatic L-amino acid decarboxylase (2) phenylaline hydroxylase (3) tyrosine hydroxylase (4) tryptophan hydroxylase...

The stereochemistries of the reactions between 0-aryl 0-methyl phosphonochloridothioates and nucleophiles have been studied in relation to the synthesis of 1,3,2-oxazaphospholidines. No displacement of chlorine takes place on treatment of O-methyl 0-4-nitrophenyl phosphonochloridothioate with 2-methoxyethanol, and in the presence of 1-phenylethylamine, it is only the latter which reacts. In addition, when the same phosphonochloridothioate is treated with sodium ethoxide, it is the 4-nitrophenoxy group, rather than chlorine, which is displaced. Both displacements were shown to occur with inversion of configuration at phosphorus. The use of such an acid chloride as a two-step 1cyclophosphorylating1 agent of 2-aminoalcohols to give 1,3,2-oxazaphospholidines (209), is illustrated. ... 

Nitroalkenes prepared from aromatic aldehydes are especially useful for natural product synthesis. For example, the products are directly converted into ketones via the Nef reaction (Section 6.1) or indoles (Section 10.2) via the reduction to phenylethylamines (Section 6.3.2). The application of these transformations are discussed later here, some examples are presented to emphasize their utility. Schemes 3.3 and 3.4 present a synthesis of 5,6-dihydroxyindole66 and asperidophytine indole alkaloid,67 respectively. 

Similarly, heterogeneous amide synthesis can be elegantly achieved in cartridges filled with silica functionalized with carbodiimide. The process outlined in Figure 3.16 yields quantitative conversion and 98.8% purity by reacting benzoic acid with phenylethylamine. 

The same group also demonstrated an efficient, two-step asymmetric synthesis of (S)-2-phenylpiperidine as an extension of the N-heterocycUzation of primary amines with diols the results are illustrated in Scheme 5.25. First, the reaction of enantiomerically pure (R)-l-phenylethylamine and 1-phenyl-1,5-pentanediol was conducted to produce a diastereomeric mixture of the corresponding N-(l-phenyl-ethyl)-2-phenylpiperidines 32 and 33 with 92% diastereomeric excess (de). Hydrogenation of this diastereomeric mixture of 32 and 33 with Pd/C catalyst then gave (S)-2-phenylpiperidine in 96% yield (78% ee). 

It is important to mention again at this point that a general feature of the solid-state ionic chiral auxiliary approach to asymmetric synthesis is that not all chiral auxiliaries lead to high enantiomeric excesses. A case in point is found in the work of Natarajan et al. on the a-oxoamide-containing salts 43 (Scheme 10) [29]. Like the nonionic a-oxoamides discussed previously (Sect. 2.2), these compounds undergo photocyclization to p-lactam derivatives, and while the prolinamide salt behaves perfectly, leading to p-lactam 44 in 99% ee at 99% conversion, the corresponding 1-phenylethylamine salt affords nearly racemic photoproduct (3% ee at 99% conversion). The reason for this difference is... 

Tyramine is derived by using 4-hydroxybenzaldehyde as the starting material. Vanillin and 0-vanillin can also be used in this synthesis to make the tyramine analogs 2-hydroxy-3-methoxy-B-phenylethylamine and 3-methoxy-4-hydroxy-B-phenylethylamine, respectively. Vanillin is less suspicious to purchase and the potency and elfects of the vanillin made drug are about the same as Tyramine. 

In addition to his extensive freelance work on psychedelic compounds, Shulgin has also served as a member of the faculty at San Francisco State University and the University of California at Berkeley. He is perhaps best known to the general public as the author, with his wife Ann, of two books on psychedelic drugs, PiHKAL Phenethylamines I Have Known and Loved A Chemical Love Story), and TiHKAL [Tryptamines I Have Known and Loved The Chemistry Continues). The two books provide not only a fascinating autobiographical sketch of the authors lives and works but a detailed introduction to the chemical synthesis, characterization, and properties of the chemicals belonging to major psychedelicfamilies, the phenylethylamines and the tryptamines. 

This approach to the isoquinoline ring, albeit a reduced isoquinoline, is mechanistically similar to the Bischler-Napieralski synthesis, in that it involves electrophilic attack of an iminium cation on to an aromatic ring. In this case, the imine intermediate is formed by reacting a phenylethylamine with an aldehyde. 

Phenylethylamines. The properties of phenylethylamines have been investigated in some detail as stimulators of cAMP synthesis in homogenates of the CNS of the American cockroach (54 55), in the crayfish behavioral assay (31) and as inhibitors of the myogenic contraction of the locust ETi muscle (56) as shown in Table III. 

Bicyclic ester 100 forms in analogy to isomeric ester 65 (Section 2.4.1.1) (07JOC5608). /l-Phenylethylamine 101 undergoes palladium-catalyzed direct aromatic carbonylation, thus providing another synthesis of benzo-lactam 78b (06JOC5951). A stereoselective nitro-Mannich/lactamization cascade of y-nitro ester and cyclic imine affords polysubstituted lactam 102 (08OL4267). 

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. 

For the synthesis of the benzosulfonamide subclass of 1,2-thiazines, introduction of the sulfonyl chloride has been effected by treatment of electron-rich aromatic compounds with chlorosulfonic acid. Such is the case for 1,2-benzothiazine 1,1-dioxides 181 which have been accessed from phenylethylamines 182 in 67-92% yields via intermediate 183 (Scheme 23) <1998SC2137>. 

Solid-phase library synthesis of triazolopyridazines via a [4+2] cycloaddition strategy has been accomplished <99TL619>. Intramolecular bis-Mannich reaction of 3-aryl-5-mercapto-13,4-triazole, formaldehyde and a-phenylethylamine yields chiral 5-aryltriazolo[3,4-ft]-[133]thiadiazine derivatives. These compounds have been screened for antibacterial activities and some of them show potent biological activity <99SC2027>. 

The most versatile lithium amides in regard to accessibility and asymmetric induction in deprotonation and elimination reactions arc lithium bis(l-phenylethyl)amide, lithium 2,2-dimethyl-A -[1 -pheny 1-2-0-piperidinyliethyljpropylamide and lithium 2,2-dimethyl-A-[2-(4-methyl-l-piperazinyl)-l-phenylethyl]propylamide. 1-Phenylethylamine and phenylglycine, which serve as educts for the synthesis of these bases, are commercially available at modest prices in both enantiomeric forms. Relevant preparative procedures can be found in the Appendix. 

Cyclic mew-configurated 1,2-dicarboxylic acid dimethyl esters are excellent substrates for pig liver esterase90. Cyclopropanedicarboxylales have been studied not only for synthetic reasons, but also so that an active-site and/or substrate model of pig liver may be developed13 5. The results obtained, compounds 11-17, are a good demonstration of the scope and limitation of PLE in asymmetric synthesis. Enantiomeric excesses of the monoesters can be determined by conversion into the amides with (S)-l-phenylethylamine and analysis either by GC or H-NMR spectroscopy, whereas the absolute configuration rests on chemical correlation. 

This was first experimentally verified for the [2.2]metacyclophane-4-carboxylic acid (55) which had to be prepared by an elaborate 7-step synthesis 771 in order to avoid an electrophilic substitution which might have led to a transanular ring closure (as had been observed in so many cases of [2.2]metacyclophanes)12). The resolution of 55 was accomplished via salt formation with (-t-)-l-phenylethylamine and gave the levorotatory acid ([a]D —9° in CHC13) which then was transformed into several optically active derivatives. The enantiomeric purity of 55 (and therefore of all compounds correlated with it) was confirmed by nmr spectroscopy of the diastereo-meric esters with (—)-l-phenylethanol77) as well as by HPLC of its diasteromeric naphthylamides 55). 

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