Yes! Very interested!
BTW, the correct Ramirez & Burger ref is J. Am. Chem. Soc.; 1950; 72(6); 2781-2782. (https://www.thevespiary.org/rhodium/Rhodium/chemistry/lah.phenolic.nitrostyrenes.html)
(https://www.thevespiary.org/rhodium/Rhodium/chemistry/lah.phenolic.nitrostyrenes.html)
The ones I have posted has been verified through http://pubs.acs.org (http://pubs.acs.org)
Clark Leland C. Jr. was the man who wrote the above article on the polymethoxy mescaline analogs. He and his group did a lot of researchs on this subject, here is a quick compilation of their work. Link in red are articles that didn't show in TFSE, link in green are posted or downloadable.
Mescaline analogs.
Part I of this paper is on the 2,4,6-trimethoxy pattern, and was posted in Post 480428 (https://www.thevespiary.org/talk/index.php?topic=11438.msg48042800#msg48042800)
(merbst: "Mescaline analogs - 10 part article series", Novel Discourse):
Mescaline analogs. I. 2,4,6-Trialkoxyphenethylamines.
Benington, F.; Morin, R. D.; Clark, Leland C., Jr.
Journal of Organic Chemistry (1954),19 11-16.
Part II was the paper Vitus posted at the top of the thread Post 413367 (https://www.thevespiary.org/talk/index.php?topic=11812.msg41336700#msg41336700)
(Vitus_Verdegast: "tetra- and penta-methoxy-beta-phenethylamines", Novel Discourse) and the PDF was posted in Post 480428 (https://www.thevespiary.org/talk/index.php?topic=11438.msg48042800#msg48042800)
(merbst: "Mescaline analogs - 10 part article series", Novel Discourse):
Mescaline analogs. II. Tetra- and pentamethoxyphenethylamines.
Benington, F.; Morin, R. D.; Clark, Leland C., Jr.
Journal of Organic Chemistry (1955), 20 102-8.
Part III was posted by Vitus there Post 414105 (missing)
(Vitus_Verdegast: "preparation of adrenochrome analogs", Chemistry Discourse) and the PDF was posted in Post 480428 (https://www.thevespiary.org/talk/index.php?topic=11438.msg48042800#msg48042800)
(merbst: "Mescaline analogs - 10 part article series", Novel Discourse):
Mescaline analogs. III. 2,4,6-Trialkyl- and 3,4-dihydroxy-5-methoxyphenethylamines.
Benington, F.; Morin, R. D.; Clark, Leland C., Jr.
Journal of Organic Chemistry (1955), 20 1292-6.
Part IV was posted in Post 480428 (https://www.thevespiary.org/talk/index.php?topic=11438.msg48042800#msg48042800)
(merbst: "Mescaline analogs - 10 part article series", Novel Discourse):
Mescaline analogs. IV. Substituted 4,5,6-trimethoxyindoles.
Benington, F.; Morin, R. D.; Clark, Leland C., Jr.
Journal of Organic Chemistry (1955), 20 1454-7.
Part V was posted in Post 480428 (https://www.thevespiary.org/talk/index.php?topic=11438.msg48042800#msg48042800)
(merbst: "Mescaline analogs - 10 part article series", Novel Discourse):
Mescaline analogs. V. p-Dialkylamino-b-phenethylamines and 9-(b-aminoethyl)julolidine.
Bennington, F.; Morin, R. D.; Clark, L. C., Jr.
J. Org. Chem. (1956), 21 1470-2.
Part VI was posted in Post 480428 (https://www.thevespiary.org/talk/index.php?topic=11438.msg48042800#msg48042800)
(merbst: "Mescaline analogs - 10 part article series", Novel Discourse):
Mescaline analogs. VI. Mescaline homologs.
Bennington, F.; Morin, R. D.; Clark, L. C., Jr.
J. Org. Chem. (1956), 21 1545-6.
Part VII use a Willgerodt-Kindler reaction and was cited by vitus in Post 414469 (https://www.thevespiary.org/talk/index.php?topic=11616.msg41446900#msg41446900)
(Vitus_Verdegast: "alternative routes to mescaline", Novel Discourse) and PDF posted in Post 480428 (https://www.thevespiary.org/talk/index.php?topic=11438.msg48042800#msg48042800)
(merbst: "Mescaline analogs - 10 part article series", Novel Discourse):
Mescaline analogs. VII. 3,4,5-Trimethyl-b-phenethylamine.
Benington, F.; Morin, R. D.; Clark, Leland C., Jr.
Journal of Organic Chemistry (1957), 22 332-3.
Part VIII was posted in Post 480428 (https://www.thevespiary.org/talk/index.php?topic=11438.msg48042800#msg48042800)
(merbst: "Mescaline analogs - 10 part article series", Novel Discourse):
Mescaline analogs. VIII. Substituted 5-methoxy- and 5,6,7-trimethoxyindoles.
Benington, F.; Morin, R. D.; Clark, Leland C., Jr.
Journal of Organic Chemistry (1958), 23 19-23.
Part IX was posted in Post 480428 (https://www.thevespiary.org/talk/index.php?topic=11438.msg48042800#msg48042800)
(merbst: "Mescaline analogs - 10 part article series", Novel Discourse):
Mescaline analogs. IX. Tetra- and pentamethyl-b-phenethylamines.
Benington, F.; Morin, R. D.; Clark, Leland C., Jr.
Journal of Organic Chemistry (1958), 23 2034-5.
Part X is the last one, and was posted in Post 480428 (https://www.thevespiary.org/talk/index.php?topic=11438.msg48042800#msg48042800)
(merbst: "Mescaline analogs - 10 part article series", Novel Discourse):
Mescaline analogs. X. 3,4-Dimethyl-, 3,4-dichloro-, and 3,5-dimethoxy-4-methyl-b-phenethylamines.
Benington, F.; Morin, R. D.; Clark, Leland C., Jr.
Journal of Organic Chemistry (1960), 25 2066-7.
Pharmacostuff:
Effects of psychotomimetic compounds on certain oxidative and hydrolytic enzymes in mammalian brain.
Clark, Leland C., Jr.; Fox, R. Phyllis; Morin, Richard; Benington, Frederick.
J. Nervous Mental Disease (1956), 124 466-72.
Abstract
The effect of 19 b-phenethylamines (I), related to mescaline, and 30 closely related analogs on alk. phosphatase activity (AP) and pyruvate (II) utilization by homogenates of rat brain tissue, or supernatant fluids from such homogenates, was studied. The position of substitution in I was more important than the nature of the substituent in effect on AP. In general, compds. substituted in the 3,4,5 positions had only slight effects on AP, whereas unsubstituted I exerted a definite inhibition. Compds. having alkyl or alkyloxy substituents in the 2 and 6 positions were more inhibitory than 3,4,5-substituted amines. In 2,4,6-substituted compds. inhibition was related to the groups as follows: CH3 > C2H5O > C2H5 > CH3O. The same compds. had quite different effects on II utilization; increasing the no. of substituents caused increased inhibition, and the nature of the substituent had a great influence, e.g. replacement of OH- by CH3O- or CH3- by CH3O- increased inhibition. Max. AP in glycine buffer (0.05M) at pH 10.4 was 54% of that in 0.1M 2-amino-2-methyl-1-propanol (III). In 1MM III, AP was about 20% higher than in 0.1M III. The effect of 10 compds. with psychotomimetic or tranquilizing activity on AP and lactic and malic dehydrogenase (IV) activities of brain prepns. was studied. Bufotenin and the tranquilizers (e.g., reserpine, chlorpromazine, frenquel), significantly increased AP. IV was relatively resistant to the compds. tested.
Synthesis of 5,6,7-trimethoxyindole, a possible intermediary metabolite of mescaline.
Morin, R. D.; Benington, F.; Clark, L. C., Jr.
Journal of Organic Chemistry (1957), 22 331-2.
Posted in Post 480583 (https://www.thevespiary.org/talk/index.php?topic=11812.msg48058300#msg48058300)
(Rhodium: "More from Leland C. Clark", Novel Discourse)
Abstract
Psychotomimetic substances may owe physiol. activity to the presence of an indole nucleus. Similar activity of b-phenethylamines such as mescaline could be explained on the same basis provided they are capable of oxidative cyclization in vivo to the corresponding indole. 5,6,7-Trimethoxyindole was synthesized as a possible intermediary metabolite of mescaline. Only one of seven alternate routes explored was practical. The critical step was introducing a nitro group in 2-position of a suitably 1-substituted 3,4,5-trimethoxybenzene. 2-Nitro-3,4,5-trimethoxy-b-nitrostyrene (I), m. 177-8°, was obtained in 9% yield by the nitration of 3,4,5-trimethoxy-b-nitrostyrene in Ac2O with red fuming HNO3. Reductive cyclization of I to 5,6,7-trimethoxyindole (II), m. 71-2°, was accomplished with Fe powder and HOAc (cf. Ek and Witkop, C.A. 49, 12437i). The ultraviolet spectrum of II in MeOH-PrOH showed l 268 (log e 3.52), 287 mm(3.34).
Psychopharmacological activity of ring- and side chainsubstituted b-phenethylamines.
Benington, F.; Morin, R. D.; Clark, Leland C., Jr.; Fox, R. Phyllis.
Journal of Organic Chemistry (1958), 23 1979-84.
Abstract
Synthesis of a no. of ring substituted b-phenethylamines contg. alkyl, halogen, and alkoxy substituents by various methods is described. The influence of these ring substituents on the psychotomimetic activity of substituted b-phenethylamines was examd. by observing the effect of these compds. on cat behavior. Addnl. information was thus required on the influence of both the nature and position of substituents on the psychotomimetic activity. The procedure developed for the synthesis of 4-ethyl-b-phenethylamine (I) is representative of that used to obtain related compds.
A link to the full text was provided by Rhodium in Post 433309 (https://www.thevespiary.org/talk/index.php?topic=5463.msg43330900#msg43330900)
(Rhodium: "3,5-Dimethoxyphenethylamine Activity", Chemicals & Equipment).
The effects of ring-methoxyl groups on biological deamination of phenethylamines.
Clark, Leland C., Jr.; Benington, Frederick; Morin, Richard D.
Journal of Medicinal Chemistry (1965), 8(3), 353-5.
Posted in Post 480583 (https://www.thevespiary.org/talk/index.php?topic=11812.msg48058300#msg48058300)
(Rhodium: "More from Leland C. Clark", Novel Discourse)
Abstract
The oxidative deamination of all :P the possible ring-methoxylated b-phenethylamines by the amine oxidase systems present in rabbit liver has been investigated. The effects of the no. and position of the methoxyl groups on ease of deamination of this series of mescaline congeners were detd.
The enzymatic oxidative deamination and effect on cat behavior of mescaline and structurally-related b-phenethylamines.
Clark L. C., Jr.; Benington, F.; Morin, R. D.
Alabama J. Med. Sci. (1964), 1(4), 417-29.
The paper was posted by Vitus (again ;) ) in Post 458113 (missing)
(Vitus_Verdegast: "mescaline: deamination & effect on cat behaviour", General Discourse).
Structure-activity relation studies on mescaline. III. The influence of the methoxy groups.
Smythies, John R.; Bradley, Ronald J.; Johnston, Victor S.; Benington, Frederick; Morin, Richard D.; Clark, Leland Charles, Jr.
Psychopharmacologia (1967), 10(5), 379-87.
Abstract
Psychotomimetic activity of a series of mescaline analogs was examd. in rats; 2 behavioral indexes were used to elucidate the probable role of methoxy group configuration in the mescaline mol.: discrete trial avoidance technique in a shuttle box and a continuous avoidance schedule in a Skinner box. Of 18 compds. tested, only an i.p. injection of 2,3,4,5 - tetramethoxyphenylethylamine and 2,3,4,5,6 - pentamethoxyphenylethylamine (12.5 and 3.125 mg./kg., resp.) produced an effect similar to mescaline (25 mg./kg.). All the mono-, di-, and trisubstituted compds. tested, except mescaline, were inactive; since none of these inactive compds., nor the inactive tetrasubstituted compds. possessed the 3,4,5-configuration, this is required for activity; the addn. of other methoxy groups to this configuration further increased the activity. The greater activity of the pentamethoxy compd. may be due to its not being metabolized by mescaline oxidase. 18 references.
New behavior-disrupting amphetamines and their significance.
Smythies, John R.; Johnston, Victor S.; Bradley, Ronald J.; Benington, Frederick; Morin, Richard D.; Clark, Leland Charles, Jr.
Nature (London) (1967), 216(5111), 128-9.
Abstract
The effect of a series of 12 amphetamines on hallucinogenic behavior was investigated in rats. A typical Bovet-Gatti hallucinogenic profile, with activity in decreasing order, was obtained for 2,4,5-, 3,4,5-, and 2,4,6-trimethoxyphenylisopropylamine, while 2,3,4-trimethoxyphenylisopropylamine was almost inactive. 2,3-, 2,5-, and 3,5-Dimethoxyphenylisopropylamine were inactive, but 3,4-dimethoxyphenylisopropylamine was highly active, 12.5 mg./kg. being roughly equiv. to 25 mg. of mescaline/kg. o-Methoxyphenylisopropylamine was moderately active but p-methoxyamphetamine (PMA) proved to be the most potent hallucinogen so far tested with the exception of LSD. At 3.1 mg./kg., it produced a typical "low dose hallucinogenic" Bovet-Gatti profile, quite distinct from that for amphetamine; at 6.2 mg./kg. it disrupted bar-pressing behavior completely and induced bizarre behavior. Substitution in the para position apparently is the essential feature for hallucinogenic properties. Behavior was completely disrupted and toxic effects appeared rapidly after the pretreatment of an animal with 50 mg. of iproniazid/kg. 3 hrs. before the injection of 6.2 mg. of p-methoxyphenylethylamine/kg. but not when either drug was given alone.
Related:
New synthesis of trichocereine.
Benington, F.; Morin, R. D.; Clark, L. C., Jr.
J. Org. Chem. (1957), 22 227-8.
Posted in Post 480583 (https://www.thevespiary.org/talk/index.php?topic=11812.msg48058300#msg48058300)
(Rhodium: "More from Leland C. Clark", Novel Discourse)
Synthesis of O- and N-methylated derivatives of 5-hydroxytryptamine.
Benington, F.; Morin, R. D.; Clark, Leland C., Jr.
Journal of Organic Chemistry (1958), 23 1977-9.
Posted in Post 480583 (https://www.thevespiary.org/talk/index.php?topic=11812.msg48058300#msg48058300)
(Rhodium: "More from Leland C. Clark", Novel Discourse)
Abstract
Several new methylated derivs. of serotonin (I) and bufotenine (II) having potential physiol. interest were prepd. Convenient syntheses of 1-methylbufotenine (III), 5-methoxy-N,N-dimethyltryptamine (IV), and 1 methyl-5-methoxy-N,N-dimethyltryptamine (V) from 5-benzyloxyindole (VI) are described. The wide study made on I and II in relation to mental disorders prompted the present work.
Synthesis of 2,3-dihydro-5,6,7-trimethoxyindole and 6,7-dimethoxyindole.
Benington, F.; Morin, R. D.; Clark, L. C., Jr.
Journal of Organic Chemistry (1959), 24 917-19.
Also describe the synthesis of 2-Bromo-Mescaline, a link to the article is in Post 470662 (https://www.thevespiary.org/talk/index.php?topic=10446.msg47066200#msg47066200)
(Rhodium: "2,6-Dichloromescaline", Newbee Forum).
Synthesis of 5- and 6-chloro, 5-methyl, and 5,6,7-trimethyl derivatives of tryptamine.
Benington, F.; Morin, R. D.; Clark, L. C., Jr.
Journal of Organic Chemistry (1960), 25 1542-7.
Posted in Post 480583 (https://www.thevespiary.org/talk/index.php?topic=11812.msg48058300#msg48058300)
(Rhodium: "More from Leland C. Clark", Novel Discourse)
Abstract
cf. CA 53, 11342c. Ring-chlorinated indoles, RC6H3.NH.CH:CH (I), were converted through the corresponding glyoxalyl chlorides and glyoxalamides, RC6H3.NH.CH:CCOCONR'2 (II), to ring-substituted tryptamines, RC6H3.NH.CH:CCH2CH2NR'2 (III), to obtain compds. with psychopharmacol. activities comparable to the corresponding substituted b-phenethylamines.
Synthesis of vicinal trimethoxyphenyl derivatives of heterocyclic nitrogen bases.
Benington, F.; Morin, R. D.; Clark, L. C., Jr.
Journal of Organic Chemistry (1960), 25 1912-16.
Posted in Post 480583 (https://www.thevespiary.org/talk/index.php?topic=11812.msg48058300#msg48058300)
(Rhodium: "More from Leland C. Clark", Novel Discourse)
Abstract
v-Trimethoxy analogs of compds. possessing psychopharmacol. activity were synthesized to exam. the influence of v-trimethoxy groups on this type of activity.
Pharmacological activity of phenylisopropylhydroxylamine and its O-methyl ether.
Benington, F.; Morin, R. D.; Clark, L. C., Jr.
Nature (London, United Kingdom) (1964), 202(4934), 813.
Abstract
N-(2-Phenylisopropyl)hydroxylamine (I) and its O-Me ether (II) were prepd. by the method of Vavon and Krajcinovic (CA 22, 2745) and injected into cats as the HCl salts. I at concns. of 25 mg./kg. by muscle induces rage and other symptoms in cats similar to amphetamine and is inhibited by chlorpromazine. II does not have an observable effect in cats. I has an E.D.200 = 20 mg./kg. in mice compared with amphetamine with E.D.200 = 100 mg./kg. II was inactive for 0.5 hr. after injection into mice but spontaneous motor activity developed in 2 hrs., producing death. I antagonized hexabarbital but II increased the action of hexabarbital. In cats I resembles b-phenylethylamine and II does not.
5-Methoxy-N,N-dimethyltryptamine, a possible endogenous psychotoxin.
Benington, F.; Morin, R. D.; Clark, L. C., Jr.
Alabama J. Med. Sci. (1965), 2(4), 397-403.
Abstract
A review of plant sources of substituted tryptamine alkaloids, their use as hallucinogens, and the occurrence of tryptamines as urinary metabolites. The possible role of the title compd. as an endogenous psychotoxin in schizophrenia is discussed. 25 references.
There are a bunch of very interesting articles in the references above, feel free to post them. ;)
Notes - New Synthesis of Trichohocereine
F. Benington, R. Morin, L. Clark, Jr.
J. Org. Chem. 22, 227-228 (1957) (https://www.thevespiary.org/rhodium/Rhodium/pdf/archive/leland.c.clark/trichocereine.pdf)
(https://www.thevespiary.org/rhodium/Rhodium/pdf/archive/leland.c.clark/trichocereine.pdf)
Notes - Synthsesis of 5,6,7-Trimethoxyindole Possible Intermediary Metabolite of Mescaline
R. Morin, F. Benington, L. Clark, Jr.
J. Org. Chem. 22, 331-332 (1957) (https://www.thevespiary.org/rhodium/Rhodium/pdf/archive/leland.c.clark/567-meo-indole.pdf)
(https://www.thevespiary.org/rhodium/Rhodium/pdf/archive/leland.c.clark/567-meo-indole.pdf)
Synthesis of O- and N-Methylated Derivatives of 5-Hydroxytryptamine
F. Benington, R. D. Morin, Leland C. Clark, Jr.
J. Org. Chem. 23, 1977-1979 (1958) (https://www.thevespiary.org/rhodium/Rhodium/pdf/archive/leland.c.clark/o-n-methylated.5ht.pdf)
(https://www.thevespiary.org/rhodium/Rhodium/pdf/archive/leland.c.clark/o-n-methylated.5ht.pdf)
Synthesis of Some Vicinal Trimethoxyphenyl Derivatives of Heterocyclic Nitrogen Bases
F. Benington, R. D. Morin, L. C. Clark, Jr.
J. Org. Chem. 25, 1912-1916 (1960) (https://www.thevespiary.org/rhodium/Rhodium/pdf/archive/leland.c.clark/trimethoxyphenyl.derivs.pdf)
(https://www.thevespiary.org/rhodium/Rhodium/pdf/archive/leland.c.clark/trimethoxyphenyl.derivs.pdf)
Synthesis of Some 5- and 6-Chloro, 5-Methyl, and 5,6,7-Trimethyl Derivatives of Tryptamine
F. Benington, R. D. Morin, L. C. Clark, Jr.
J. Org. Chem. 25, 1542-1547 (1960) (https://www.thevespiary.org/rhodium/Rhodium/pdf/archive/leland.c.clark/chloro.methyl.tryptamines.pdf)
(https://www.thevespiary.org/rhodium/Rhodium/pdf/archive/leland.c.clark/chloro.methyl.tryptamines.pdf)
The Effects of Ring-Methoxyl Groups on Biological Deamination of Phenethylamines
Leland C. Clark, Jr. Frederick Benington, Richard D. Morin
J. Med. Chem. 8, 353-355 (1965) (https://www.thevespiary.org/rhodium/Rhodium/pdf/archive/leland.c.clark/pea-biological.deamination.pdf)
(https://www.thevespiary.org/rhodium/Rhodium/pdf/archive/leland.c.clark/pea-biological.deamination.pdf)
This is very far from the first topic of this thread but is on topic of the latest two posts due to the authors of this old paper (this one is missing from the above Clark's bibliography). Besides I thought somebee might bee interested in the pharmacological activity (in animal tests) of phenylisopropylhydroxylamines and related stuff:
Behavioral and Neuropharmacological Actions of N-Aralkylhydroxylamines and their O-Methyl Ethers.
Benington F., Morin R.D., Clark L. C. Jr.
J. Med. Chem. 8, 100-104 (1965) (https://www.thevespiary.org/rhodium/Rhodium/pdf/archive/leland.c.clark/n-aralkylhydroxylamine.ethers.pdf)
(https://www.thevespiary.org/rhodium/Rhodium/pdf/archive/leland.c.clark/n-aralkylhydroxylamine.ethers.pdf)
Abstract: The syntheses of a number of ring-substituted l-aryl-2-hydroxyamino- and l-aryl-2-methoxyaminopropanes are described. These compounds are compared pharmacologically with the corresponding 1-aryl-2-arnino-propanes. The hydroxyamino compounds are, in general, central stimulants, and O-methylation diminishes this activity. Two compounds within this series were found to be monoamine oxidase inhibitors.
Here is another forgotten article by Benington & Clark, dealing with the synthesis of Escaline and Homosyringylamine from syringaldehyde:
Synthesis of 4-Hydroxy- and 4-Ethoxy-3,5-dimethoxy-?-phenethylamines
F. Benington, R. D. Morin, Leland C. Clarke, Jr.
J. Am. Chem. Soc.; 1954; 76(21); 5555-5556 (1954) (https://www.thevespiary.org/rhodium/Rhodium/pdf/escaline.homosyringylamine.pdf)
(https://www.thevespiary.org/rhodium/Rhodium/pdf/escaline.homosyringylamine.pdf)