N-Phenylisopropylamine

Reasonable conversions of NPBA were observed when using ketones as solvents however, product analysis showed increased byproducts formation with the use of ketones. When acetone is used as solvent, GC/MS analysis identified 2-methylindoline and N-phenylisopropylamine as the two major byproducts, which are produced via a secondary reaction between aniline (product), acetone and hydrogen (reductive amination). Similar byproducts were observed when using methyl ethyl ketone (MEK) as a solvent. In a parallel experiment, about 13% of aniline reacted with acetone under the same reaction conditions except in the absence of a catalyst. Most of the reaction product, about 11%, is non-hydrogenated product 2-methylindoline (C9H11N). These results clearly demonstrate that ketones are the least preferred solvents for N-debenzylation due to the secondary reaction between the desired product and the ketones. 

Synonyms/Trade Names N-IPA, Isopropylaniline, N-(1-Methylethyl)-benzenamine, N-Phenylisopropylamine... 

Alternative Names/Abbreviations Benzeneamine, N-phenylisopropylamine, NIPA... 

Anderson, G. M., Ill, Castagnoli, N., Jr., and Kollman, P. A. (1978) Quantitative structure-activity relationships in the 2,4,5-ring substituted phenylisopropylamines. In NIDA Research Monograph Series 22, edited by G. Barnett, M. Trsic, and R. Willette, pp. 199-217. U. S. Govt. Printing Office, Washington, D. C. 

O. 016 mole of the amine and then 3.6 g of formaldehyde (ca. 10 ml of formalin) and reflux for 5 hours. Cool to room temperature, add 7 ml concentrated HCI and evaporate in vacuum. The resulting oily dimethylamine can be purified by dissolving in 25 ml water, extracting with 2X25 ml CHCI3. Basify the aqueous layer with 2N NaOH and extract with 3X25 ml ether, and proceed as described above for the N-methylamines. This procedure should work for both phenethylamines and phenylisopropylamines, and should affect the trip similarly to N-monomethylation. 

The benzene was distilled from the extract and the residue of d-N-methyl-N-benzyl-p-phenylisopropylamine was distilled at reduced pressure. The thus obtained free base, distilling at 127°C at a pressure of 0.2 mm of mercury and having an nD19 of 1.5515, was dissolved in ethyl acetate and a molar equivalent of ethanolic hydrogen chloride was added thereto. Anhydrous ether was added to the mixture and d-N-methyl-N-benzyl-p-phenylisopropylamine hydrochloride precipitated from the reaction mixture as an oil which was crystallized from ethyl acetate to give crystals melting at 129° to 130°C. 

Similarly, (V-ethyl-l-naphthylamine was prepared in 88% yield, and (V-ethyl-, N-bu-tyl- and (V-benzyl-2-naphthylamine, and (V-ethyl- and (V-butyl-/ -toluidine were prepared in 50-64% yields.34 In the alkylation of / -toluidine and / -anisidine with butyraldehyde, N,N-dibutyl derivatives were also produced in 19 and 25% yields, respectively. The Emerson-Waters procedure was also applied to the reductive alkylation of 2-phenylpropylamines and 2-phenylisopropylamines with C1-C3 aldehydes (amine aldehyde ratio = 1 3).35 With higher aldehydes the monosubstituted products were isolated in good yields (in 48-94% yields with acetaldehyde), while with formaldehyde (V.N-dimethyl derivatives were obtained in 51-85% yields. 

SYNS ADIPEX 1-DESOXYEPHEDRlNE HYDROCHLORIDE (-)-N-o-DIMETHYLPHENETHYLAXnNE HYDROCHLORIDE METH 1-N-METHYL-p-PHENYLISOPROPYLAMINE HYDROCHLORIDE ... 

Parts of racemic N-methyl-B-phenylisopropylamine are introduced into a solution of 100 parts of tartaric acid in 1000 parts of methyl alcohol. After protracted standing, about 100 parts of the precipitated salt are aspirated off, and extracted with hot ethyl alcohol. Since the c -tartrate of dextrorotatory N-methyl-B-phenylisopropylamine is readily soluble in both methyl and ethyl alcohol, whereas the rf-tartrate of/e o-rotatory N-methyl-B-phenylisopropylamine is sparingly soluble, both in methyl alcohol and hot ethyl alcohol, an extremely simple separation of the c -tartrates of the optical antipodes of the base. 

Bupropion (amfebutamone) is a phenylisopropylaminoketone that is structurally related to the phenylisopropylamine CNS stimulant, methamphetamine, and the phenylisopropylaminoketone, cathinone (a constituent in khat), and the anorexiant, diethylpropion (Fig. 21.21). Although structurally similar to the CNS stimulants, bupropion exhibits distinctive different pharmacologic and therapeutic effects. The absence of the tricyclic ring system in bupropion results in a better adverse-effect profile than with the TCAs. The tertiary butyl group in bupropion prevents its N-dealkylation to metabolites that could possess sympathomimetic and/or anorexigenic properties. 

When optical isomers have been examined, activity resides primarily with the R-(-)-isomer the S-(+)-isomers typically are less active, inactive, or have received little study. For example, although not well investigated, it appears that R-(-)-DOM and R-(-)-DOB show activity at total human doses of less than 4 and less than 1 mg, respectively. N-monomethylation reduces potency or abolishes activity for example, the N-monomethyl analogues of DOM and DOB are approximately 10% as potent as their primary amine counterparts. The SARs for the DOM-like actions of phenylisopropylamines are summarized in Table 23.3 and Figure 23.2. 

A closely related agent is PMMA, or N-methyl-1-(4-methoxyphenyl)-2-aminopropane. PMMA is a hybrid structure of two phenylisopropylamine stimulants PMA, and methamphetamine (Fig. 23.6) Surprisingly, PMMA lacks significant central stimulant actions, and unlike PMA and methamphetamine, PMMA is not recognized by (+)-amphetamine-trained animals. Because PMMA is structurally related to metabolites of MDMA, it was examined in MDMA-trained animals and found to be several-fold more potent than MDMA. Animals have been trained to discriminate PMMA from vehicle, and PMMA stimulus generalization occurred to ( )-MDMA and S-(+)-MDMA, but not to DOM,... 

CAS 768-52-5 EINECS/ELINCS 212-196-7 Synonyms N-(l-Methylethyl) benzenamine Phenylisopropylamine... 

Phenylisopropylamine. See N-lsopropylaniline N-Phenyl isopropyl carbamate. See Propham 4-(2-Phenylisopropyl) phenol. See Cumyl phenol... 

If the racemic compound is reacted with half an equivalent amount of resolving agent, the enantiomeric mixture remained after crystallization can be separated by distillation. Such a method was accomplished at the resolution of N-methyl-phenylisopropylamine (MA) by (R,R)-dibenzoyl-tartaric acid ((R,R)-DBTA). In this case the (S)-MA was distilled off beside of crystalline (R)-MA(R,R)-DBTA salt. 25... 

When the racemic phenylisopropylamine (A) is resolved with (S)-N-phthaloyl-phenylethylamine (PPEA) according to the abover mentioned method, further separation can be accomplished starting from the residue of the first distillation. When the temperature is increased, the residual crystalline diastereoisomeric salt decomposes and the liberated enantiomer ((R)-A), constituting the diastereoisomeris salt) can also be distilled off while the resolving agent is transformed into a phthalimide derivative. ... 

Monoamine oxidase plays a critical role in the regulation of monoamine neurotransmitters such as serotonin, noradrenaline, and dopamine. MAO isoenzymes are classified on the basis of their substrate preference, sensitivity toward spiecific inhibitors, and tissue distribution into MAO-A and MAO-B. Selective MAO-A inhibitors have been used clinically in the treatment of depression and anxiety, while MAO-B inhibitors have been used in the treatment of Parkinson s and Alzheimer s diseases. Many plant-derived and synthetic compoxmds such as isoquinolines and xanthones have been identified as MAO inhibitors. In (Deeb and dare, 2008b) the monoamine oxidase (MAO)-inhibitory activity of 46 phenylisopropylamines expressed as pICSO is modeled with the orientations of nodes in n -like orbitals of the phenyl ring and some other descriptors using flip regression analysis. The... 

From equation (6), it can be predicted that the phenyl moiety of phenylisopropylamines is involved in electronic interactions with the enzyme. Lowest unoccupied n energy was identified to be an important descriptor. Adding classical variables, improves the correlation. The classical variables found to be significant are LUP and LDl which were found to be favorable to high activity. This is based on the concept that the stability of stacked aromatic systems is highly orientation-dependent, and is also dependent on the energies of those orbitals in the two aromatic systems that resemble the degenerate HOMO... 

Cho, A.K., Lindeke, B., Hodshon, B.J. (1972). The N-hydroxylation of phentermine (2-methyl-l-phenylisopropylamine) by rabbit liver microsomes. Res. Commun. Chem. Pathol. Pharmacol. 4, 519-528. 

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