The enzymatic oxidative deamination and effect on cat behavior of mescaline and structurally-related β-phenethylamines was written by Clark, L. C. Jr.;Benington, F.;Morin, R. D.. And the article was included in Alabama J. Med. Sci. in 1964.Synthetic Route of C10H16ClNO2 The following contents are mentioned in the article:
The dosage used for all the β-phenethylamines was 25 mg./kg.; injections were intramuscularly into the cat. When rapid deamination of the β-phenethylamines was prevented by pretreating the cat with monoamine oxidase (MAO) inhibitors, the rage response of the phenethylamine was usually intensified. Some compounds, e.g., 4-methoxy-β-phenethylamine (I), that were nearly inactive prior to MAO blockade had powerful rage-producing effects after blockade. The β-phenethylamines that caused a pos. rage response also caused hyperthermia, and the degree of hyperthermia was apparently correlated with the intensity of rage. Pretreatment with MAO inhibitors greatly enhanced the pyretogenic activity of weakly active compounds E.g., I caused a rise of >8°F. after 5 mg. pheniprazine/kg. The activity of nondeaminated amines, e.g., 2,6-dimethoxy-β-phenethylamine, was not affected by pheniprazine. The pyretogenic effects did not occur in pentobarbital-anesthetized cats or in cats treated with curarelike drugs. The phenethylamines were deaminated by incubating them with semicarbazide (or other amine oxidase inhibitors used) in phosphate buffer at pH 7.4. Incubation was stopped with 5% Cl3CCO2H in 0.1 N HCl. Compounds Containing 2,6-dimethoxy groups or having >3 MeO groups interfere with or block deamination. None of the nondeaminated compounds interferes with the deamination of tyramine (II) or mescaline (III). Preliminary studies indicate that the deamination systems, as to which substrate can be metabolized, are similar in cat, dog, turtle, and man. Human brain rapidly metabolized phenethylamine, II, 2-methoxyphen-etheylamine, and 2,3-dimethoxy-β-phenethylamine and slowly deaminated several other III analogs, but not III. The deamination rate was dependent on the O tension, indicating that some of the physiol. effects of tissue anoxia result from the “unwanted” amines being uncatabolized and participating in neurophysiol. systems. Deamination was completely arrested by adding glucose and glucose oxidase to the enzyme substrate mixture Apparently, the deamination enzymes in rabbit liver do not contain Cu, since Cu-chelating compounds had little effect on deamination. None of the β-phenethylamines which were not deaminated inhibited II and (or) III oxidase, indicating that these structures cannot enter the specific deamination site. A structural analog of III capable of acting as a III antagonist is probably unlikely. Criteria given for deciding which structural analogs of III may be tested in the human are: the analog is deaminated by rabbit liver but not by cat or human liver; the deamination by rabbit liver is inhibited by semicarbazide but not by MO-911 (mescaline oxidase); and the analog is not a powerful excitant or pyretogenic. Only 6 compounds fulfilling these criteria were found: the 3,4,5-substituted phenethylamines having MeO, Me, EtO, or OH groups, and 3,4,5-trimethoxy-γ-phenylpropylamine. Three new substituted β-phenethylamines and one intermediate were synthesized. 2,6-Dimethoxybenzoic acid (54.6 g.) was refluxed with 17 g. LiAlH4 in C6H6 for 4 hrs. and the mixture kept overnight to give 2,6-dimethoxyloxybenzyl alc., which was treated with 3.6 ml. pyridine and 49 ml. SOCl2 under ice cooling and the mixture stirred at room temperature to yield 2,6-dimethoxybenzyl chloride. The acid chloride in acetone was stirred with 39 g. KCN in 300 ml. H2O at room temperature for 20 hrs. to yield 41% 2,6-dimethoxyphenylacetonitrile, m. 94-5°. The nitrile (21.7 g.) was autoclaved in MeOH containing 19 g. NH3 and 10 ml. Raney Ni catalyst. The vessel was charged with H to 1050 psig. and heated for about 1.5 hrs. at 100-20° to yield 2,6-dimethoxy-β-phenethylamine (IV), b28 165-71°, m. 56-9°; HCl salt m. 214-15°. Propylbenzene (200 g.), 30 g. paraformaldehyde, and 20 g. ZnCl2 were treated with dry HCl gas for 4 hrs. at 60° to yield 50% 4-propylbenzyl chloride, which (84 g.) in 120 ml. EtOH was added to 32.5 g. NaCN and 37 ml. H2O and refluxed for 4 hrs. to yield 76% 4-propylphenylacetonitrile, b7.5 137-9°. The nitrile (60 g.) was added dropwise to an ice-cooled mixture of 20 g. LiAlH4 in 500 ml. Et2O and refluxed 1 hr. to give 4-propyl-β-phenethylamine-HCl, m. 190-1°. 2,4,5-Trimethylacetophenone (66 g.), 53 g. morpholine, and 19.5 g. S was refluxed 10 hrs. to yield 60% 2,4,5-trimethylphenylacetothiomorpholide, m. 110-11°. The morpholide (75 g.) was added to 165 ml. AcOH, 24 ml. concentrated H2SO4, and 37 ml. H2O and refluxed 5 hrs. to yield 60% 2,4,5-trimethylphenylacetic acid, m. 128-9°. The acid (30 g.) and 35.4 g. PCl5 was warmed for 10 min., POCl3 removed, and the crude product poured in concentrated NH4OH to yield 90% 2,4,5-trimethylphenylacetamide, m. 183-3.5°, which was reduced with LiAlH4 to yield 85% 2,4,5-trimethyl-β-phenethylamine-HCl, m. 224-5°. 55 references. This study involved multiple reactions and reactants, such as 1-(2,6-Dimethoxyphenyl)ethanamine hydrochloride (cas: 1087707-43-4Synthetic Route of C10H16ClNO2).
1-(2,6-Dimethoxyphenyl)ethanamine hydrochloride (cas: 1087707-43-4) belongs to ethers. Volatile esters with characteristic odours are used in synthetic flavours, perfumes, and cosmetics. Certain volatile esters are used as solvents for lacquers, paints, and varnishes. Liquid esters of low volatility serve as softening agents for resins and plastics. Esters also include many industrially important polymers. Polymethyl methacrylate is a glass substitute sold under the names Lucite and Plexiglas; polyethylene terephthalate is used as a film (Mylar) and as textile fibres sold as Terylene, Fortrel, and Dacron.Synthetic Route of C10H16ClNO2
Referemce:
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Ether | (C2H5)2O – PubChem