Derivatives of Alpha, Alpha-Dimethyl-Beta-Phenethylamine

77 Pages·03.318 MB·English

by  Platau, Gerard O

PURDUE UNIVERSITY
THIS IS TO CERTIFY THAT THE THESIS PREPARED UNDER MY SUPERVISION
5Z______fcerard 0. Platan ________ — ---------
entitled Derivatives of alpha, alpha—Dimethffl-beta*»
________phenethylamine.__________________________
COMPLIES WITH THE UNIVERSITY REGULATIONS ON GRADUATION THESES
AND IS APPROVED BY ME AS FULFILLING THIS PART OF THE REQUIREMENTS
FOR THE DEGREE OF
Doctor of 1 obotdIiv
Professor in Charge of Thesis
4
Head of School, or Department
3 / 19 J
TO THE LIBRARIAN:------
is vxo'tr
THIS THESIS IS NOT TO BE REGARDED AS CONFIDENTIAL.
PROFESS OB rsr CHARGE
GRAD. SCHOOL FORM 0—3-49—1M

DERIVATIVES OF ALPHA, ALPHA-DIMETHÏL-BETA-PHENETHrLAllINE
A Thesis
Submitted to the Faculty
of
Purdue University
by
Gerard 0. Flatau
In Partial Fulfillment of the
Requirements for the Degree
of
Doctor of Philosophy
June, 1950
ProQuest Number: 27714145
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ACKNOWLEDGMENT
This work was begun under Dr. H. B. Hass; but the major
portion of this work was directed by Dr. G. B. Bachman to whom
the author is indebted for many helpful suggestions and for
stimulating enthusiasm given during the course of the research.
The author wishes to acknowledge assistance received
from Abbott Research Laboratories and the Purdue Research
Foundation which made this investigation possible.
TABIE OF GOST ENTS
Page
ABSTRACT.................................................. i
INTRODUCTION.............................................. 1
DISCUSSION.............................................. . 7
EXPERIMENTAL................................................ 2?
Preparation of p-Nitro b enzy 1C hloride ........... 27
Preparation of 2,U-DinitrobenzylC hloride . . . . . . . . . 27
Preparation of o-Nitrob enzyl Chloride .........
Action of Chlorine on o—Nitrotoluene . . . . . . . . . 28
Action of Sodium Hypochlorite on ^-Nitrotoluene • » • • • 28
Oxidation of o-Nitroto lue ne to o-Nit roben z aldehyde ... 29
Reduction of o-Nitrobenzaldehyde to o-Nitrobenzyl
Alcohol . .. . . . . . . . . . . . . . . . . . . . 30
Conversion of o-Nit robenzyl Alcohol to o-Nitrob enz yl
Chloride . . . . .. .. . . . . . . . . . 30
Formation of Anth r anilic Acid in an Attempted
Brominatinn of o-Nitroto lue ne . . . . . . . . . . . . . . 31
Preparation of 1-(g-Nitrophe nyl)-2—methyl-2-
nitropropane . . . . . . . . . . . . . . . . . . . . . . . 32
Preparation of 1-(2*,U1 —Dinitropheny^-2-methyl-2-
nitropropane . . . . . 32
Preparation of 1-( o-Nitrophenyl )-2-methyl-2-
nitropropane......... 33
Preparation of 1—(g-iAniinophenyl )-2-methy1 -2-
propyl amine Hydrochloride . . . . . . . . . . . . . . . 3U
Preparation of l-( o-Aminophenyl )-2-methyl- 2-
propylardne Hydrochloride ......... 35
Preparation of 1-( p-Aminophenyl )-2-methyl-2-
nitropropane......... 36
Page
Preparation of 1—( 21 ,L* -Diamincphenyl )—2-me thyl- 2-
propylamLne Tril^drochl oidude......................... 37
Preparation of l-(21 -Nitro-U1 -aminophenyl)-2-
iaethyl-2-nitropropane ................. .
Selective Reduction . ................... 38
Proof of Structure by Deamination............. . . 38
Preparation of l-(Chlorophenyl)-2-methyl-2-propylamine
hydrochloride . . . . . ............... . 39
Preparation of 1- ( o-Chlorophenyl )-2— metlryl- 2-
propylamine hydrochloride . . . . . . . . . . . . UO
Preparation of l-(]>-Hydroxyphenyl)-2-methyl-2—
propylamine Hydrochloride ................... IpL
Preparation of l-t^-Methoxyphenyl)-2-methyl-2-
proiylamine hydrochloride . . . . . .......... 1*2
Preparation of l-( 2 ^Nitro-U^hydroxyphenyl)-2-
methy 1-2-nitropropane . . . . . ... . . . ........... 1*3
Preparation of l-( 21 -Amino-U1 -hyclrcccyphe nyl )-2-
methyl-2-propylamine Dihydr och loride ........... • • • 1*1*
Attempted preparation of 1-(£-Fluorophenyl )-2-
met hy1 - 2- pr opylandn e ...........
Action of KLuoboric Acid...... • • • • .............1*5
Action of Anhydrous hydrofluoric Acid.............. 1*6
Preparation of Ch-Nitrobenzyl Bromide............... 1*7
Reaction of o-Hitrobenzyl Bromide and the Sodium
Salt of 2-Witropr opane . . . . . . . . . . . . . . . . . 1*8
SUMMARY.................................................... U9
BIBLIOGRAPHY.............................................. $Q
V I T A ....................................................
LIST OF FI GORES
Figure Page
I Reactions of Nitrobenzyl Chlorides and the Sodium
Salt of 2-Nitropropane....................... • U
II Reduction of l-(o- or ]>-Ni trophenyl )-2-me thyl- 2—
nitropropane and of 1- ( 2 *, U1 -Dinitro phenyl )- 2-
iaethyl-2-nitropropane ......... 5
III Selective Diazotizations of l-(o- and £- Amino—
phe ryl ) -2-met hyl- 2-pro pylamine .......... 5
IV and Synthesis of a Series of Derivatives of alpha, 8
V alpha-Dimetbyl-beta-phenethylamine and oft heir 9
Intermediates . . . . . . . . . . . . . . . .
VI Preparation of o-Nitrobenzyl Chloride from
0-Nitrotoluene by Oxidation, Reduction and
Chlorination ............................. 11
VII Preparation and Proof of Structure of
1-( 2 * -Nitro-IV - aminophenyl )-2-methyl-2-
nitropropane......... 17
VIII Preparation of l-(o- and p-Chloro phenyl )-2-
me thyl- 2-propylamine.......................... 19
IX Preparation of 1~(£~hYdroxyphenyl)-2-methyl-2-
propylamine ............. 20
X Preparation of 1-(jo-Methoxyphenyl )-2-methyl-2-
propylanriLne ....................... 21
XI Preparation of l-( 2 * -Nitro-U1 -hydr oxyphenyl )-
2-methyl—2—nitropropane and reduction of the
product to the corresponding diamine • • • • • • . 23
LISTS OF TABLES AND GRAPHS
last of Tables Page
I New Intermediates Isolated in the Investigation ..21*
II Derivatives of alpha, alpha-Dimethyl—beta-
phenethylaznine Hydrochloride ......... 26
List of Graphs
I Selective Reduction of 1 - (p-Nitro phenyl ) - 2-
metly 1-2-nitropr opane . . . . . . . . . . . . . 16
(Contribution from the Purdue Research Foundation
and the Department of Chemistry of Purdue University)
DERIVATIVES OF ALPHA, ALPIiA-DIMETHYL-BETA-PHENETHYIAIlINE^*
(1) An abstract of a thesis by Gerard 0* Platan, submitted to the
Faculty of PuÈdue University in partial fulfillment of the
requirements for the degree of Doctor of Philosophy, June,
1950.
By G. Bryant Bachman, Hemy B. Hass**, and Gerard 0. Flatau^
(2) Present address: General Ainiline and Film Corp., New York,
N.Y.
(3) Abbott Laboratories Research Fellow, 19U8-50.
AN ABSTRACT
Derivatives of beta-phenethylamine with the amino group
on a tertiary alkyl carbon have received little attention. They
are especially interesting since they should strongly resist
the enzymatic deamination reaction shown to limit the duration
of sympathomimetic activity. They cannot be deaminated by living
organisms in the usual manner, that is, by oxidation to the
corresponding imine followed by hydrolysis, since there is no
tydrogen on the carbon atom to which the amino group is attached.
This investigation deals with the synthesis of a series of