^' ''-.'-^Hi

UNIVERSITY
OF FLORIDA
LIBRARY

PHENANTHRIDINE DERIVATIVES

PART I

AND THE
CATALYTIC ALKYLATION OF AMINES

PART II

By

GERSHON JOSEPH SHUGAR

A DISSERTATION PRESENTED TO THE GRADUATE COUNQL OF

THE UMVERSITY OF FLORIDA

IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE

DEGREE OF DOCTOR OF PHILOSOPm'

UNIVERSITY OF FLORIDA

Fekruarv, 1Q43

LIBRARY

rosivfOBO

This disaartatlon deals with two problems. The first is con-
eernod with the dorolopaent of a new synthesis of phenanthridine
derivatiTvs and the reaction of those cofflpounds with the Srignard
Reagent.

The second prohlea involves the catalytic alkylation of amines
with alcohols.

1^0529

f&BLB or COHTEBTS

PART Z PHBB&HTHHIDIBK SIRIYATITXS

1. Introduction to Fh«nanthrldine 1

2. Thaoratical Discus sion 5

3. The Sehiff •• Bates lU

(a) B«asal>2-«aiinoph«nol 13

(b) Tottr->«thoz7l)«nzal-2'-aminophenol l6
( e ) 2~h7drozy-3-B«thox3rb«nBal-2-«uiino-

phaasl 17

(d) 3-nitro1>«nzal->2-ajBinopheael IS

(•) 2-h]rdroxyl>«aBal->2-«Binophenol 19

(f ) 2-3 dimethoz3rb«nsal-2-aainophenol 20

(g) 2->h7droxy-3-aetho3grbonzal-4-B«tb-
oxjaAllina 21

(h) 2-h7drozyb«afal-«Ailin« 22

(1) 2-hydrory-3-«sthoxyben2al-anilin* 23

(i ) M-aethox7b«nzal-2-ajainophenol 2k

(k) U-h/droZ7b«nzal-2-aBinophenol 2^
(1) 2-h9rdroT7-3-aethox7b«nzal-l|-aaino->

bansoic aeiA 26

(a) M-«B«th3rlb«nKal-2-aainophenol 27

(n) 2-ohlorob«nial-2-afflinoph«nol 28
( 0 ) 2-h7drox7-3-««thoz3rbenzal-U-amlno-

phenol 29
11

Dftf*

h, G«B«ral Procedure for Syalhoais of the

PheiuuEithridinos JO

(a) phenacthrldiao 5t

1. tabulatioB of data Jt

(b) 9-*thox]r^pheBanthrldlno 33
( 2. tal>ulatlon of data ^

(e) ^h]rdrox]r«-104i«thox7-phoaaBthrldiB« 55

3. talmlatloa of data Jf

(d) 7'^*Bzo7^o^-'*^Be^^o^-ph«z>*athridlii« 38
(•} T'^^yA^^-S-Bethoxy-phenaathridino 39

(f) ostalillshaoat of the atracture of
2-h]rdroxy-10-Beth03qr-pheBanthrldliie ^

(g) T-Hydroxy-pheaanthridlae Ml

1. talmUtion of data III
(h) eatabliehaeat of the straetore of

J.faydrozy-phenaathridiae 1|3

(i) 9')B«thoxypheaaathrldlae H^

1. Uhulatioa of data Hi

(j) 9-meth9rl-^eaanthrldlae kf

1, tabulatioa of data kt

3« The arigaard Beactioa k9

(a) pheaaathridlae k^

(b) heasal-S-aaiaopheaol <PL

(e) beazal-2~beaxo7lox3r-anlllae yi

ill

(d) »-b«izo7l-2-«aliioph«Bol \^

6. L^Udae-2-laphthel->l-Salfonle Add 59

7. S]rmth«si8 of the Ph«iiyI-I)l%«nso-XaBth«aa ^6

(*) 9-'Ph«B7l, 1-2, 7-8 dibenso-xftnthaa 56
(b) 9(U-«ethyl)-ph«nyl, 1-2, 7-g dlbtnzo-

xaathsn 57

(e) 9(U-aethox3r)-.ph«n7l, 1-2, 7-g dibsaso-
xaathea 37

8. StuBoiar7 Bart I ^

9. Bibliography Bart Z ^
BLBT ZZ CkfkLinC AIXTUTIOH 07 AMZHBS

1. Zatrodxietioa 60

2. Suonary of Problra (k

3. Xzporiaoatal

(a) latoraedlatei

1. proparatloa of cyelohoxoao 71

2. preparation of 2-chloro-c7clohexanol 72

3. preparatioa of c/clohezene oxide fk
H« preparation of the copper chroaate

eatalyat 73

(b) STatheaie of H(betah7drox7eth3rl)-o-
pheaylene-diaaine 76
1. tabulatioa of date 80

(c) Syatheaia of »-»• dKbetahydroxy-ethyl)-

e-phenylene-diaaina 81

It

1. toVaUtioB of data 8k
(d) Syn«the8i« of H-CorthohydrezTC/dohoxyl)-

•thylcn* di*mlB« S^

1. taVxilatlon of data tf
(o) Synthooit of H-N* di(orthoh7droz7.

cyclohoxjrl) othjleno dlamlao M

1. talnilatioa of data 9$

(f) Syathool* of doea-hydroquiaoxallao 90

1, table of •xporlmontal remits 9^

2. tabulation of data 9^
(f) STBthotit of quinoxaliao 9^

1. Ubulatioa of daU 97
(h) Syntheiis of l-2->-U>totrah3rdro>

quiaoxallne 99

1. Ubulatioa of daU lOt

k, Suonarjr Fart IZ 103

^. Bibliography Fart XI lOU

ACIXOWLEDOMEBf 10$

BZOGBAPHICAL ITEMS lOS

COKMITTES BSPORT 107

XIKBOOUCTIOH TO PHXlOkllTHRISIXB

The realisatioB that (lainlae has certain tozioological effacts on
th« fauaan nervous ayston has atiaalatod tha aynthaaia of antl-aalarlala
with Bora deairal>le prepartiaa. Aa a raaolt tha litaratara eoataina tha
deaeriptlon of nnaaroua ooapoonda which hara bean aymthaaizad aa potaa-
tial anti-aalariala.

Of the rinc syatema eaployed aa a baala for theae coiqponnda, probab-
ly none haa Iraan ao widely uaad aa the qulnollna and laoqulnollne
anclaaa. Atabrlne, a benzo^nollne, haa bean one of the acre effeotlra
recant dlacoyariea and haa net with a eonaiderable medical use. Its baais
la acridina, an iaonar of phenanthridina.

COO

Acrldlne Phenanthridine

The aynthaaia in I926 of plaaaoquine, a promising anti-malarial.

CH^C

CO

haa oalmixAted in the preparation of a aariaa of acrldlne derlTatires
iriUlch are quite potent anti-malarial a. Tha therapeutic slgalflcance of
each part of the Atabrlne noleoale eaxmot be gauged, but the olesa ra-
lationahip between phenantlurldine and acrldlne saggesta that darlTatlTea
of this type in the phenanthridine aariaa might possaaa valuable

1

properties.

Phenanthridlne has been syathesised. by a number of different methods.
Its structure has been proven repeatedly by different methods of prep-
aration, Ihifortunately, the nomenclature used throughout the literature
Is not constant. The British use one system and the Americans, another.
In order to eliminate confusion, the latest system of num^ erlng the
atoms employed by Chemical Abstracts will be used throu^ this Alsserta-

2.

tlon.

T C

Phenanthridlne

A rerlevr of the literature glres the following syntheses of phenan*
thrldlne and Its derlTatlyes.

1. Plctet and Ankersmlt's (ll) classical synthesis of phenanthri-
dlne luTolved the pas sin of the Tapers of bensylldene aniline through
a hot tube filled with pumice heated to redness.

a„.

/v

o

Benzyl Idene aniline Phenanthridlne hydrogen

2. Plctet and Ankersnlt (12) prepared ortho-phenyl benzole add,
nitrated and then reduced It. Ttaus they obtained by this method hy-

drosjr phMtunthridlna aa on* of th« isoaert. Oa distillation with liao
test phonanthrldino was obtained.

o-Phonjl bonsele acid

IHJ

3. Starting with phenanthrone. Pictet and Aakemit (lU) obtained
pheaaathridine by the following reactions:

C<„ H^ «^M

) II

IPj

Ct, M

jD.sr.l»,r.o~ C, M»

<= »^«f

C, M.

/.vi,

Lj,hv Of,4e

c =c

FhMMM throne

Phenanthrone
qulnone

I I

13) N

— M^C

Cfc Ml A/*;,

C M^ C«OM

C^ M^^

a9

U. Plettt and Habnar (10) used o-aalao bipheayl as their lMia«,
■ad* the acyl derlratlTe, and then conda&sed the aailide to glre aa
alkyl phenanthridla*.

-»?

3. Morgan and Walls (22) liq>roTed Fletet's method of dehydratlne
the aoyl o-zenyl aaine by rofluziag the anllld* with POOXk instead of
heating with sine chloride. This reaction proceeds saoothly and has been
used vaecessfolly in the preparation of alkyl, chloroalkyl, phenyl and
nitrophenyl phenanthridines. The colorless acyl derifatires are converted
to quaternary salt* by Ulaaa** sethed, (7) «*ing hot aitroobMiiMM a* th«
*olT*nt.

/■"^ ^~~

6. The idettl synthesis froa separate bensene nnclei was doTaloped
by Kondo (7) ^i^ heated o-bromobenxald*hyd* with e-broaoanilin* in th*
pr***nc* of Betallic copper.

a:.^50

^ ' ' ' :2(^r2^

7. Pictet and Oonset (13) di*till*d *q[aiBol*calar amotints of caloitui
foraat* and oalciua o-phenyl bensoate and prepared o-phenyl bensaldehyd*.

Troa this they obtained the oxiae vhich was heated with U-5 tines its
weight of ZnCl2 at 280-30o'*C. ead obtained phenanthridine.

((i7Co«),C«

r4HtoM.

8. nie Becknen rearrangement of floorenone ozljie by Pictet and
GoQset (16) led to the foraation of phenanthridoae with a 30J( jield.

C =: Z^CH

9. The diasotization of an aromatic amine with subsequent ring
closure and the simultaneous evolation of nitrogen and hydrogen chloride
was used by Pictet and Gonset (16) to bbtain an H-methyl phenanthridine.

\Ac/

\A/

10. Pletet (15) 1>7 pTTolysis method* heated K-aethyl earbsiole and
obtained phenanthridine la a Uo^ yield.

Ikf- C.H-,

Cm

11. The Cortius degradation of diphenic aeid hydraiides hae been
etudled b7 Labriolu (9). He found that yiamn. diphenic aeid dihjrdrazide
«a» treated with one mole of nitrous aeid, the atide-hydrazide was formed.
Thie was unstable and reacted in alcohol^ether mixture to gire phenan-
thridone.

IP. He? and Buehley (3) heated 2-aaiao biphenyl hydrochloride «rith
methanol in an autoolaTO for 12 hours at 2$0-300^C. and obtained dimethyl
phenaathridine .

2-amimo biphenyl hydrochloride - CH3OH dimethyl

AutoelaTe, phenaathridine
12 hours

13. Phenaathridine has been found to be present in coal tar by
Siebishh and Sandke (19), who isolated it and checked its constants
with theae reported in the literature. They were fotmd to be identical.

lU. Baployine the pyrogeneous technique derised by Pietet and An-

ktraslt, Etard (2) pr«par*d a aathyl phszianthrldlne by petsing Beaial-o-
TeluldlB* throo^ a glowing tube.

a?'

^*"J

15. Omaba (3) raported the tmrallabillty of Plctat** ayflthaala b]
pjrogaBaoaa satheda. Ha ahowad that tha eoapoo&da producad from beai]p>-
lidaaa alpha-aaphthylaaliia and beniylidaaa bata-naphthylaalna ware la
raality aeridina darivatiTaa. Pletat reported that beni/lidene alpha*
oaphthylaalae yielded a beasophenanthridine, ris:

a

//

CM

Bat, whan Oraabe ayatheaisad this baniophaBaathridiaa by an aaaabiguous
aethod, he found that the two conpooada were aot identical. Heace, he
ahowed that Pictet'a ooapounds were aeridiae derlTatiTei formed in the
following manner.

OXO) — ocoo

16. Pictet and Habner (I7) attempted the synthesia of Phenanthridine
by dehydration reaction using aalhydranilide as the starting material.
It aeaaed that the reactioa ahould proceed smoothly to give pheaaathridoae.

but actually, they obtained acridone. Instead of proceeding as they had
predicted

a aeleealar rearrangement was inyolved giving aotidone:

o

The talhydxvnilide was eubjected to a dry distillation, and the residue
extracted with alcohol. Analysis gare the fonmla to be CixS^'SKi corres-
ponding to that of phenanthridone. Zinc dust diltillatioa on the other
hand yielded acridine, instead of the expected pjieaanthridine .

17. Xordo and Ulzeo (8) obtained a weak base by the sine dust dis-
tillation of lycorine, an alkaloid. The crystalline conpound melted
at 10U.5°C. , and analysis shoved it to be phenanthridlne.

THB0RE9IC1L DISCUSS ZOI

Plek«t*B and Aakertmlt'B paper (lU) ws of Bpecltd interest to ua,
for they reported that all atteapts to synthoelie pheaanthridlne froa
hons/lldene o-aainopheaol vere uasuceetsfol. They stated tl^t when
this compound, which is eoimaonly known as an anil or Sehiff's base, was
heated with dehydrating agents such as P2^« ZnCl^ or solfaric acid, no
phenanthridine was obtained. Howerer, they never isolated the reaction
product except as the ■ercurie chloride double salt, whose melting point
they reported was higher than that of phenanthridine 's double salt.
Therefore they coxusluded that aeridine had Been f omed instead of phenan-
thridine. They also used the salicylidene a&iline as their starting
natorial, and again their results were negatire. Tron a structural
standpoint it seen* rery probable that the benial-o-aaine phenol should
dehydrate and gire phenanthridine.

If Mter is formed by the splitting out of the hydroxyl group in the
ortho position of one ring and the hydrogen atom on the o^kbe position
in the other ring, a sizmeaberod ring should be produced. They, how-
ever, stated that they had obtained aeridine by the following method:

10

It •eoKS that th« reaction should procsed aqually as UMothly to yield
phtnathridiiM a« aeridine. A ooaiplete anxrrey of the literature shows
that in no case has phenanthridine been prepared by this aethod. When-
ever a reference is aade to the effect that this reaction does not go
as predicted, the vrorkers ali<ays refer to this original article. The
work, as far ■• we hare been able to fine, has nerer been repeated.

Since these men nerer analysed their product, which they believed
to be aeridine, we decided to repeat their work. Using an apparatus
for working under reduced pressure, we heated bensal o-^Lsiinophenol with
phosphorous pentozide and obtained a base which nelted at lOU^C. Analysis
shoved it to hare the aiolecular foroola of phenanthridine, and no amount
of purification by steam distillation, vacuum distillation, recrystallisa-
tioa, or decomposition of the hydrochloride would raise the melting
point of the compound above lOU^C. It, therefore, was assumed that the
dehydration of this anil had yielded phenanthridine. Various amounts
of pho>ix>horou8 pentoxide were used with the anil and a range of tempera*
tures were employed. In all oases the final compo\ind melted at 10U**C.
The melting point of aeridine is listed in the literature as from 107^
to 112°C., while the majority of articles give the melting point of phenan-
thridine as loUoc.

As a result of this work ve have shown that phenanthridine could
be synthesized from bensal o-aminophenol by using phosphorous pentoxide
as the dehydrating agent.

Hsving proved that synthesis by this method tras feasible, a series

•f dey4v4tiTee were prepared using the tame general procedure. In all

1 •#

11

easts ths straetnrs of the rssoltla^ phsnanthridlBe mis aeceptsd on tha
tests of STnthssls. ?er exuple. If the bsnsal portion of the noleeole
is suhstitated in the para position, there can be only one phenanthridina
fonsed.

Since the luhstltuted phenyl ring is attached to the carbon atoa by «
single bond, the phenyl ring is trmn to rotate. Hence it can be seen
that the hydrozyl group has an equal opportunity to split off hydrogen
fron either of the t»o ortho positions of the other ring. Regardless of
irtilch hydrogen it reacts with, the resxatiag phenanthridine will be the
saae, since the substituted group is in the para position on that phenyl
ring.

When two possible phenanthridines could be foroMd, the structure was
prered by iaplication. That is, if salicylidene o-aminophenol were the
starting anil, thsn two possible phenanthridines could be fomed.

cN

OM

12

Xb this c&te one of th« postibilitlea «a* •llalnatod by syathosizlag
th« othor phoaanthridlnc aad ooBi>Brlai£ the phTtieal conttaata with
those of the phenanthrldiae obtained by using salicylidene o-aainophenol
as the starting aaterial.

The presence of an ortho-hydrogen atom on one ring and am ortho-
hydroxyl group on the other ring should lead to the foraation of the
same phenanthridlne regardless of which ring the hydroxyl group is
attached. A noaber of different anile were prepared in which erery
anil aade had either one or Bore hydroxyl groups in the ortho position
on the ring. All of these were treated under mrying conditions of
temperature, pressure, and concentration with regard to the dehydrating
agent, phosphorous pentoxlde, in order to determine whether or net they
would yield the corresponalag phenanthridlne compound.

Erery anil compound of o-«uainophenol yielded a phenanthridlne. How-
erer, those anils in which there was no hydroxyl group on the ortho
position of the aniline portion of the molecule failed to cycllse. A
series of anils vas prepared by coupling 2-hydroxy-3-Bethoxy bensaldehyde
•td substituted anilines. The anils formed very easily, by adding the
aldehyde and amine together in alcohol and warming. TM.» reaction may
be exemplified by the synthesis of bensal aniline from bentaldehyde aad
aniline :

These anils crystallised out in orange needles harlng the proper nitrogen

13

6Mli«Bt. Bi>w«T«r, theas aalla, y&Mn heattd with phosphorous pontozido
la the roactioa tostoI nndorwont a pocullar doooapositioa. At a
dafiaito taaperatare tho lailaato alxtura of aail aad aahydrida started
glrlBg off broia fnaos haviag a eharaetsrlstic odor. Tha first siga
of decoapositioa was tho foraatloa of a dark char on tho sorfaco of tho
■ixturo which spread rapidly aod fiaallj consuaed the entire batch of
■aterial. Daring this time Toliminoas clouds of brown rapors were enTolred
which were not condensable at a teaperature of -20°C. Even when the source
of heat was reaoTod froa the Tsssel, the decoapositioa proceeded in all
eaeea. Vhea the reaction was carried out in the dark, the flaae of
eoabustion was plainly risible. All of the anhydride was consuaed by
this reaction; the reaction aizture had practically doubled its size la
the flask. There was ao reaction of the final product with %fater,
showing that all of the anhydride had been consuaed. Ixtraotion of the
■aas yielded a fluorescent solution, but in no case could definite products
be identified.

This charring did not take place when o-aainophenol was used in
place of aniline or other substituted anilines. When the ortho-aainoi-
phenol MIS the aniline portion of the aolecule, the two possibilities
products were identified by synthesis, as in the ease of the salicylidene-
o*«Bino phenol. There has been no reference to such a reaction in the
literature and personal inquiry prorided no further infomation. It is
•apposed that certain phosphine or phosphine-like coapounds were foraed,
but ho atteapts were aade to identify the gases other than by their odor.

ih

THE SCHlirF«S BASIS

The preparatioaa of the anils or Schlff t Bates, which were aaed
»■ iatemediatee in the esmtheeie of the phenanthridiae derivatiree,
are deeoribed in the following pages. Seren new anils were prepared,
and six preTiousl/ reported anils were resynthesifed.

19

BEIZAL-S-JUailOPHSBOL

qm

CH=-M

Xquiaolar qtumtltl** (0.2 aole) of beas&ldahyd* and 2-aalnopheiioX
w»r« dl«iolT«d in bolllne alcohol. On cooling l>ro>« crystals soparated
froB the aolutioa, and thty wore roorjstalllxed soYeral tines fron 9^^
ethanol and aetlimtad charcoal.

ftipirleal Tonnla
Nolocular Voight
Color
Soluhilitsr

Mitor

alcohol

Keltlng Point

Analysio

nitrogen
Yield

Cl3 % " 0

197
white

insoluble

soluble in hot, fairly insoluble
in cold

89*3-90 ezperinental

89-90®C. reported (lU)

found oalculated

7.0)1 T.IOJJ

7^ theoretical

u

^Ao

U.ETH0XTB2H2AL-2-AMI10P]T''30L
(Hev Compound)

en ^ /v

XqulBOlar q^uAatltlet (O.l mole) of ^ethoxj baas«ld«h7d« and 2-aalno-
phcnol were dlesolTed in boiling alcohol &nd heated seTer&l ainutee.
Aeti^tad charcoal «ae added and the eolution filtered. Water was added
%e the hot filtrate until tarhidity beffan and the solution allowed to
cool. Crystals were filtered off and recrystallized froa ^yyft alcohol and
Mtter.

fiopirioal forsnla
Molecular weight
Color
Solubility

Alcohol
Melting PoUt
Analysis

aitroeea
Yield

/'
•15 %5 ®2 "

2ta ^^*^

light ereaa

Tory soluble in hot alcohol

S2.5-«3®C.

found calculated

69^ theoretical

17

(Hew CoBpmmd)

oil

CM- —f>t

Ths co^>ound femed Innedlatel/ vhma melted (0.2 aelc of) Z-hydroxT-
5-Bethoz]r1>enBaldeh7de w»s pexired oa 0.2 aole of 2-«ialiiepheiiol. The aall
MtLB yry Inaoluble in boiling 3'S/f^ ethanol, but repeated leeching with
boiling alcohol left the pore base ai a residue.

Dnpirlcal Formula
Meleealar weight
Color
Solublllt7

water

ethanol
Melting Point
Aaal/sis

nitrogen
Tield

ClU «13 " °3
2^3

orange red

insoluble

Insoluble in boiling ethanol

lg7-l«8«C.

found calculated

5.71^ 5.775^
€yfL theoretical

IM

ySl TRQBMZUf-2«ANIB0PHEH0L

A/0

oH

CH='^

Equimolar quantitls* (0.2 aol*) of 3-Aitre-beaiald.«h7de and 2-amino->
phenol woro Added together In boiling alcohol. On cooling greenish
needles separated out. It was recrjstallized froa 3^% ethanol.

XiiQ)islcal Fonmla

Molecular Weight

Color

form

Solubility

ethanol

«ater
Meltiis Point
Analysis

nitrogen
TieU

^3 ^10 *2 ^

greenish

needles in cluster*

soluble in hot ethanol
insoluble in water
133°C recorded in literature (21)
found calculated

11 M 11.56jt

Ti% theoretical

19

a-HTOROXIBSNZAL-S^AMZIilOPHEBOL

lq[aiB»lar q[aMititie« of (0.2 aola) salieylie aldehyde and 2-aaliu>>
phanol v«r9 dlBtolred la boiling aleehol. On cooling bloodp-rod er/atalt
aopamtod. Tarthor rocrystalliaatloas frtm alcohol and actiratod clmr-
ooal jrioldod the par* anil.

Sqpirical Foraola

Molecular voight

Color

Tora

Soluhilitj

wator

aleohel
Molting Point

Aaalyais

nitrogon
Tiold

»l3"ll

I 0.

213

blood rod
ezyotallino

laoolublo

■olublo in hot alcohol

186»7^C. experioental

186-7^C. rocordod in litatetoro (U-20)

fooAA caleolatod

6.5JS 6.655t

70)( thoorotioal

ao

2-3 mvimmajBmzAL-2'JMimpmsmT4

(l«w Conpound)

CCM

Xqulawlar qaaatitUi (0.2 ■»!«) of 2-3 dlHethoxy-beafaidohTAc and
2-«alBophonol were dlssolrod In boiling alcohol. On cooling crystals
separated out. Bacrystallisation fron 93^ ethanol and activated char-
coal yielded the pure base.

Xb^lrleal Fonsola
Molecolar Vels}it
Color
Solubility

etbanel

water
Melting Point
Analysis found calculated

nitrogen 5.231 5'^1^

Yield 36^ theoretical

°15 "15 ^

"3

257

buff

soluble In hot

ethanol

insoluble

In water

92-93*0

(Hew Coapound)

OH

CM = /V

OCMj

Iqulaolar quuitltlM (0»2 aole) of 2-h7droz7-3-a«thox7l)«&zald«lqrd«
•od >^^«thoz7a&lline were Added together and the aixtore heated gently
for lereral ■iantea. The naes erysti llized on cooling and was reerystal-
liied froa 9^^ ethanol and aetiirated charcoal.

aQ>lrioal 7onnla

Molecular Weight

Color

Solubility

ethanol

vater
Melting Peiaft
Analysis

nitrogen
Yield

'15 "15

■ 0.

257

light orange

soluble in hot ethaael

insoluble

9U-95»C.

found calculated

5.35t 5Mi

J2iL theoretical

2.HTI}R0XrBG!!ZiLL*ASZLISI

Ie[ulBolftr qtiaatltles (0.2 sole) of lAlieylie aldthyde and anilia*
wars heated together to boiling. When the eolution cooled, alcohol was
added and a precipitate formed. It «at recrye tall i zed from 951^ ethanol
and activated charcoal.

Ikpirical Fonmla

Kolec\\lar welf^t

Color

7oni

Solubility

alcohol

water
Melting Point

Analyeio

nitrogen
Yield

«13^1

197

jrellew
eryttalline

■oluble in hot e';lHUMl

inaolnhle

50-50. 5®C. experimental

50-51^C. reported (lU)

found ealcnlated

^2/f> theoretical

23

2.SXI2ROXT.3>KITIDrrBZIZU. ANIL I M

Iq[aiBOlar qtumtitlei (0.2 aole) of 2-h3rdrozy«3<Hiethpz]r beauildahyd*
and Milllaa w«re heated In a beak«r for sororal ■limtea, and 99^ aleobol
addod. The solutioa beoaae dark red In eolor, 1>ui would not erjetallize
on eeoliag. The aelutlon waa imt tuder a preeature of ahoat 1 ano. of aer-
eury trnd the alcohol distilled off with caatle waniiB«. Crxetallizatioa
took place inaediately, giriag practicall/ a qiiantitatiTo yield. The
emde aaterial was reerystallised frea alcohol, and a crude seed crystal
used to ii^duee crystallisation. lo aaouat of scratching of the beaker
would induce the anil to crystallise without the seed.

Iqpirieal Tonaila C^^ M^r > Og

Molecular weight 227

Color Oraa«;e-red

Solubility

alcohol soluble

Meltins Point
Analysis

ni trogen
Yield

«2-«3®0.

found

calculated

5.9Jt

6.16)(

9ffk

^METHOXTBi:irZM:,-2^MI]IOPHEIiOL

CM

<^H = t<i

IqulBol&r quantitie* (0.2 aol*) of U-aethoxy bensaldthyde and
2-aaiBopheBol w«r« dlsaolyed in boiling alcohol. When the solution
cooled, eryetale sepaz^ted out. These were reerystallised fron 95^
ethanol and activated charcoal.

Sapirieal Fersnla
Molecular Weight
Color
Solubility

alcohol

water
Melting Point

Aaalysit

nitrogen
Yield

227
light-buff

Soluble in hot ethamel

insoluble

90-91*0, experinental

Vy^O, reported in literature (U)

fOTUd calculated

7U^ theoretical

25

U-ETI)It0XTBISZAL-2-AMXV0PRES0l
(I«w Coapouad)

He

oH

€H- /V

IquiaolAr q^oMitititt (0.2 sole) of U->hydrez7 beiiiald«h/d« and 2<
laophsBol vere add«d to boiling alcohol. Gto eooliag the rlseoua oil
voTild not crystallizo. Qm aass «es freson solid with ieo plus HOI
aizturo and then ivaeaaa distillod. The distillate was reerjrstallized
froa alcohol, to which water was rdded until the eolation beeaae turbid

Aipirical ^raal*

Molecular Woi|^t

Celer

form

Solubilitj

ethanol

water
Melting Point
Aaaljreie

nitrogen
Yield

C13 Hii 1 O2

213

orange

cryitals

soluble

insoluble

2U7.5-2»«.5«0.

found calculated

^Sii theoretical

26

2-HnjROXT-3-METaOXTBSNZAL-U-AMIHO BEHZOIC ACID
(H«w Cexpotmd)
^CH3

CH — /V

CeOM

Squiaolar cLXuaatltles of (0.2 sole} 2<>hydrox7^3-aethoz7 banzaldehyd*
and t^wtmino'benzolc add were diasolred in boiling aleohel. On cooling
erystali separated oat. These were recrystallized from 93^ ethanol and
activated charcoal.

Sapirical Foraola

Moleeolar Weight

Color

fern

Soluhilltf

ethanol

water
Melting Point
Analjsis

nitrogen
Yield

Ci5 \^TS%
271

orax^e
flocealent

seloble in hot ethanol

insoluble

232-233°C

found calculated

5.0J6 5.2Jt

79Jf theoretical

tr

U-MirrHILBl!»ZlL-?.^iMIIK)PHEaroL

CM

CM

CH •= /V

Iqulaolar fOMitltlea (0.2 sol*) of U-neth/l beazaldelgrd* «nd 2-aalBe-
phsBol ««re dl««olT«d In boiliag alcohol. On eooling the solution and
•eratehln^ the tides of the beaker, orystale separated out.

lapirleal Vonula

Noleeular Weight

Color

'om

Solubllltj

ethanol

water
Neltln« Point

iMOjale

nitrogen
Tleld

°1U\3"°
ai

light buff
erystalllna

yrj soluble

Insoluble

108.5-109*0. experlaental

108.5°C. reported In literature (21)

found oaleulated

^M 6.63Jt

T^i theoretical

2-CHlOBOBEHZAL-2-AMll!roPHEN01

f

HqulBolar quaatitit* (0.2 anl*) of 2«>ehloro1)eas»ld«h]rde and
2-«iilnephenol ware dlssolred in boiling alcohol. On cooling, tha solu-
tion was agitated and the sides of the beaker scratched to induce erysfcal-
lization. The anil precipitated and vols reerystalliaed from 93^ ethanol.

Inpirieal Toranla

Moleculnr Wei^t

Color

For*

Solubility

ethanol

water
Melting Point

Abaljsis

nitrogen
Yield

0,3 H,o I 0 CI

yellow
crystals

soluble

insoluble

9>4^C. experimental

9H^C. reported in literature (20)

found calculated

5.91^ 6.0H5I

7U^ theoretical

29

^— <^

0>^

IfniaolAr <^atiti«« (0.2 a»la) of 9*}qfdUr«i!7-5-acth«]i7 b«acAld«l)yA«
•aA >»-«uk1imiA«m1 Wit* MunMd toc«th«r, aaA thaa • aaall voltM* of 95^
otliMMl addod. ¥ho solvtioa «»• hoatod to bolIUc •»& o«olod. Tho dark
rod Ttseouo oil woold aot oiyatftlliio %f aerotehlac tlw taokar. v%t4Hr
«»■ oddod to llio hot Bolutlem omtll tmrbldltj ool la oad thoa tho tolu-
tioB «oo ■oo>»aieall7 stirrod for 19 Blaotoo. A floecaleat procipltato
foraod which t«K roorystaUlffod fro« othor aad thoa dUaio oleohol.

lifiriMil KonHla
NolooaUr Mol^ht
OoUr
7oni

Solium tj

•thor
othaaol

Nol%la« PoUt
Aaaljrolo

aitro4(«a
TioU

I 0,

•taai^o raA

•olablo

oolttblo

T2.5-73-5*C.

ftaad ealealatoA

9^ thooroliool

30

aUNZHAL PROCXOUHS TOR SYXTHB8XS OT TRR PHSaSAHTHRXDllTES

A reaction vett«l fitted with a ground glass Joint vas attached
by means of a standard tapered stillhead to a distillation fXask
vhieh serred as a receirer. Connected to the side arm of the receirer
imM a Taeuum pump fitted with a fapor trap and a oanometer. The re*
action vessel vas heated by means of an oil bath in which a thenraaeter
was immersed.

The anil was mixed intimately with an eqtud Tolme of phosphoreas
pentoxlde and the pressure reduced to ^-20 mm. The reaction ressel was
then lowered into the oil bath and a definite temperature was established
for a certain time interval. After the required time interval the re-
action vessel was disconnected from the set-up and allowed to cool.
After cooling, the reaction mixture was treated by different procedures
in order to Isolate the resulting phenanthridlne.

A IhnoTia, quartz tube, ultraviolet-ray lamp was used to determine
whether reaction had taken place. The anils do not fluoresce under the
influence of the ultra-violet li^t. The phenanthridines fluoresce with
colors varying from bright blues to brilliant greens and yellows, depend-
ing on the substituent groups in the molecule. The yields in all cases
were lew, never exceeding 10^ of the theoretical.

MC

V^c^/"

Phenanthridlne

B«nsal-2->amlnopheiiol was mixed with an equal roluae of phosphorous
poBtozido and hoatod at a proscuro of ^ am. of Borcur/ at 330*0. for 25
■iautes. Crystals subliaad on the cool portion of the still-head. After
the reaction aass was eooled, alcohol mis added and a red solution resul-
ted. The solution was poured Into a large excess of water and a reddish
precipitate separated. After chilling, the precipitate was filtered
and nixed veil with 23^ XnOH solution. The unreacted anil formed the
sodium salt. Sther extraction followed by evaporation of the ether and
su1>seq[uent recrystallisatlons from dilute alcohol and activated charcoal
yielded the phenanthridine. In order to get the last trace of color out
of the bateh for specimen purposes, a small amount of it was steam dis-
tilled, yielding white micaceous flakes melting at 10>»OC. This melting
point checks with the Talues accepted in the literature (IU-I5-7-8-I7.16-
15-11)* The vapors of the compound are irritating to the nose and eyes.
The hydrochloride is decomposed hy water. In alcoholic or ethereal
solution it fluoresces blue in ultra-violet light. The per cent N found
was 7*70 i^^le the calculated value was 7.83j( H.

32

PSSlbURHRIDIKI

BDiplrleal fonmla
Molecular W«lght
Crystalline Form
Color
Solubility

alcohol

Muter

dilute hydrochloric aield
Melting Point

Aaalysle

nitrogen

m

■Ic&ceous flakes
vhlte

fairly soluble In cold

insoluble

soluble

104° recorded in literature

10U° e^qperioental

found calculated

Vr% 7.835J

53

9-X'fHOXr PHSmNTHRIDIIK

C-,Ko

foxu>^thoz3rbenialo2-uiliioph«Bol was Bixtd iatlmately with phosphorous
pontoxldo and heatod for two hotirs at 210^0. nndor a prossoro of 8 ■».
of aorcurr. Repeated ether oxtractlons of the reaction mixture followed
by evaporation of the ether jlelded a residue. The residue was reerystal-
llied from dilute alcohol and activated charcoal several times and yielded
\ihit9 alcaoeous flakes aeltlng at 118-1190C. The percentage nitrogen oal^
culatod froB the forsmla was 6.27)(, that found was 6,1%, The coapoond
fluoresces blue under the ultra-violet light.

^

9.STHOXT PHSN^NTHRIDIlil

aq>irleal fonnla
Molecular V.'elght
HAlting Point
Crystalline form
Color
Solubility

witor

alcohol

other

HCl (dilute. 111)
Analysis

nitrogen

0^5 %5 I 0

223

118-119*C.

flakes

white

insoluble

▼ery soluble in hot

soluble in cold

soluble in cold

found ealoulabed

»

\

U-HTimOXT-lO-METaOXT PHEnLHTHRIDIBI

Two-h7drox]r-3<-aethox3r b«iiial-2-aainophenol was mixed intlaately with
phosphorous psntozids and heatsd under iraeaoM for 1/2 hotxr at 250*0.
Vapors were giren off which condensed on the upper portion of the still
head. The reaction aixture uas decomposed with alcohol, heated to boil-
ing and filtered. The filtrate was treated with activated charcoal and
filtered. Water %ias added dropwise to the filtered solution and an aoor-
pheus precipitate resulted. Ether extraction followed by subsequent re-
crystallisation frosi dilute alcohol and activated charcoal yielded creaa
colored cyrstals melting 131-151*5 C. The compound fluoresced brilliant
yellow under the ultra-rielet light. The calculated percentage of nitro-
gen was 6.209(, that found was 6,0%,

The structure of U-hydroxy-10-methoxy phenanthridine ie prored by
the following considerations. Two-hydroxy-3-methoxy-bensaldehyde and
bensoyl chloride in equivalent quantities were treated with a dilute
solution of alkali as directed in Cummings et al. (27). The 2-benzoyloxy-
5-oiethoxy benzaldehyde was isolated in the font of white flocks meltiac
at 91-91*5 C. The benzoate was then heated in boiling alcohol with an
equimolar qtiantity of 2-aminophenol, and a precipitate of 2-brnsoyloxy-^
methoxy-bensal>2-aminophenol formed on cooling. Its asltixig point was
131-131.5°C. The calculated percentage of nitrogen was 5* 6^* that found

^** 5'3l^» '^^ rMtctiom involved naybe shovn as follows:

OH

This now anil, 2<»benzo7loxy-3''>Bethoxybensal-2>affiinophonel was tho ball*
for the synthesis of 7-^«i^oyloxy->S>aethox7-phenanthridine, which is
discussed in the following pace*.

U-HTSROXY-lO-MSTaOXT PHEaULNTUEXDZn

37

CH,

bqplrical romola
Molecular Weight
Melting Point
Color
Solul)ilit7

wator

alcohol

ether

HCl (dil. 1:1)
Analysis

nitrogen

225
151-151.5*0.

insoluble

Tory soluble in hot

soluble in cold

soluble in cold

found calculated

6.0jt 6.20jt

7-BZNZOTLOXT-8-HeTHOXT PHEHOTHRIDIXX

CHJD

«

The 2-benzo7lox7->3-aetho3qr-l)«neal>2<HUBlnophenol va* heated under
reduced pressure for two hours at 2U0^C. The reaction Bass was deae»-
posed with alcohol, cuid water added. The resulting solution was ex-
tracted sereral times with ether, followed by OTaperation of the co»>
bined ether extracts. The residue was recrystallised sereral tiaes
with alcohol which yielded white crystals and a gam. The crystals and
gam were 'vaouua distilled, and the distillate on recrystallisation from
alcohol melted 99.^100. 3°C. The distillate had the smU of rotten
cabbage. The compound fluoresces yellow under the ultra-riolet light.
The calculated percentage of nitrogen was 6.11^, that found 6.0^.

35

7-HnmOXT-8-MS9HOXT PHndHTHBIDIHZ

Ths 7-*^«BM7loxj-8-B«thox]r phsnaathrldine was dii«elT«d in hot
glyosrin* and Bolld KOH added. The solution was heated for a short
time. The solution was extracted sereral tines with ether, the ether
extracts combined, and then evaporated to dryness. Reerystallization
ef the residue sereral times with dilate alcohol yielded a white mica-
ceous compound, melting at l^^l^^^C. This compound has a slight
greenish fluorescence under the ultra-riolet light.

%plrioml Tormal*

Noleoalar Wei^t

Color

Ibrm

Solubility

ether

alcohol
Analysis

nitrogen

\khl^^2

225

white

■icaeeous

soluble

soluble

fotand

calculated

5.n

6.205t

no

BSfABLISHMBHT OF THE STRUCTDBE OF 2-HIDBDXT-lO-MBTHDXr PHKHANTHRIDIHE

From an •nualoation of the prsrious fire i)age8 it is erident that
2-hjrdrox]r>10-acthoxy phenanthrldien was fornwd by the dehydration of th«
2-h]rdroz7-3-methox7-bensal-2<-&inlnepheaal by the followiag reaction:

C^H.o

for, the syatheslt of the 7-hydrozy-8>aetho3gr phenanthrldlne carried out
is tmambigaous. One hydroxyl group %«& blocked, the reaction carried out,
and then the hydrozyl groxxp restored.

If the two coapounds are identical, they should have the same mel-
ting point and shotdd not giro a depression when a mixture melting point
is taken. A mixture melting point of the two compounds prepared abore
softens at 120°C. and finally melts at 137°C. On this basis it was con-
cluded that the two compounds were not identical.

kl

T-HTDROXT PHEMLNTHRIDIITE

^ M, o

OH H

The 2-h7drox7l>enzal-2-aaixiophenol v«8 alxcd intioatcly with phos-
phorous pontoxldo and was ho&tod for ^ hoar at 300^0. On cooling, the
reaction aixtaro was dacoBq>os«d with alcohol, and after boiling soveral
■inutes, water was added. Sereral recrystallizations from alcohol with
activated charcoal jrielded white laioaceoas crystals melting at 102-103^0.
This coiq>ouiid fluoresces brilliantly under the ultra-violet light. The
ni|r«gen percentage calculated from the foraula was 7*18^» that feund was

Itt

7-HTDHOXT PHEIUHTHRIDIHI!

bplrioal 7ormala
Molecular Weight
Melting Point
Color

Crystalline Tom
Solubility

vater

alcohol

ether
iaalyii*

nitrogen

C«

Ql-^ H^ H 0

195

IO2-IO3OC.

white

■icaceous flake*

Ineoluble

soluble in hot alcohol
soluble in cold ether
found calculated
T.OJt 7.1811

>»3

ESTIBLZSHMENT 01^ THE STRUCTURS OF J-HTHtOXY PEKHAHTHRIOISI

Tve hydroxy bcnzaldehyda mis shaken with an sqiiliiolar quantity
of bonsoyl chlorido in the presence of excess dilate sodiua hydroxide.
▲ Tiseous oil was obtained which was 2-l>ensoyl«benBaldebyde.

oW

A/>tO» .

c cc

This oil was then mixed with an equiaolar quantity of 2-aminophenol in
boiling alcohol. When the solution was cooled, a quantity of crystals
separated out, which aelted at lU3-U4°0 after recrystalliiation Aroa di-
lute alcohol. This coapound was 2-bensoyloxybenBal<-2-aainopheaol.

CC<.M^

C,/=N

This anil was then heated with phosphorous pentoxide f»r two hours at 2Uo°C.
uider reduced pressure. The reaction aixture was decomposed with alcohol
and then poured into water. After standing oTernlght the tarry mass and
brown powder were extracted with ether. Following the evaporation of
the ether and recrystallitfition of the residue from alcohol, there were
obtained white crystals. These crystals melted at 102-3**C. and gaTO no
aixture aeltiag point degression with the 7'bydroxy phenanthridien pre-
pared by the other method. ObTieusly the benzoyloxy phenanthrldine hydro-
lyies Tery easily to yield the J-hydroxy phenanthridine as every attemitl
yielded the same coa^ound aelting at 102-3°C., The reaction may be ex-

]nr«si«d by the following eqiiatlons:

Mk

J

Therefor* the phenanthridlne synthesised froa S-hydroxybensal-E-aminophenol
has the formala shown by the following equation:

CH-

CPh

9-Ml^THDXT PHiaULNTHRlDIHE

The U-aethoxy b«nsal-2-aBinophenol was nixed intimately with an
eqttfkl ToliuM of phosphorous pentoxide and heated under reduced preesure
at 2^^C. for three hours. The reaction oass was deco^>OBed with 9^
ethanol and heated for a few aionents. Water was added and then sodiua
hydroxide solution was added until the solution was basic to litmus.
Ether extraction of the solution followed by evaporation of the ether
yielded a residue. The residue, when reorystallised froa dilute alco-
hol and activated charcoal, yielded clusters of white needles aelting
*^t 99.5-lOO^C. The coapoond fluoresced blue under the ultra-rlolet
light. The analysis gave 6.^^ nitrocea, the percentage calculated froa
the fenmla was 6.69^.

kS

f iioifixT yflMtBOPna

Mtl««iiUr M«l#it
Iteltlac i^U%
(hrraWlIiaa ^on
CoX«r
8«tabtlliy

aXeehol
•%hm9
Aailyslt

«l»l Hi » 0

209

oUw%«r« of «Midl««
vhit«

IttMlMbU

MXtihU la |w« *le«lwl
Mlnkli ia o«ld stlMr

t»lettlat«d tvami
6,m 6.5^

>»7

9-MBfIII> nMUffBIISIll

CH

Thm tMMthl^lM«wl-?UMiiB»ph«Ml «M aly^d lBiiaftt«ly with aa •qml
ynhmm of j^ti^imNms pwitoxid* aad h«a%«d iiaa«r r«dn0«d pr«»«iir« at
890*K!. fbr OM Mid oiM»h»lf hoars. Tho r«(Mtloa •Ixtoro w»« doeoapoMMI
with f9^ •thonel and pourod lalo Mior, fho retaltlai; wlulloB wat
•Um dIotiUod maA ola«%or« of sMdloii Mlttag m% lll-U2«C. won oh*
taiaod yAmk the dlatillato had e«ol«d. IRm OBap—aA Cteeroteod bX««
«adar tha «lti»->Tlol«t lii^t. Tha p«r««Bta«a of nitrai^ oaleolatad
fVM tha fonnla wao 7*32^» tha peroantaca fooad «a« 7.D(,

HI

9-METIITL PHEaumTHRIDZin!

r

BgqplrioAl Fonmila
Molecular Wel^t
Mtltine Point
Crystalline Fom
Solubility

«»ter

alcohol

ether
Analysis

nitrogen

\\ hi ■
193

111-112®C.
clusters of needles

insoluble in cold water
soluble in hot alcohol
soluble in cold ether
found ealculated
7.1^ 7.32JI

THE ORIGNURD RBiLCTIOH

Th« possibilit7 of attaching allgrl and tubstitutod alkyl side
chains on a pheaanthridine naclous «&■ the next consldoration. PhoBa»>
thrldiao can be considorod an untatvirated •lx>>B«Bborod hotoroc/clie
rlnc; theroforo, thero «at a possibility that the double b«ad attached
to the nitrogen tSon would react with a Grignard reagent:

If such a reaction would take place, then a new series of ditaydro-phenaa-
thridinee with Tarlous side chains could be prepared, and by siaple oxi-
dation with silrer oxide, the alkylated phenaathridine could be synthesised.

Experimental

One-tenth sole of freshly cleaned na^esiua turalags and 2^0 cc. of
absolute ether were placed in a ^00 cc. 3-necked flask fitted with a re-
flux condenser, mercury- sealed stirrer, and a dropping funnel. The
stirrer was started and 0.1 mole of methyl iodide dissolved ia 25 ec. of
absolute ether was added dropwise. There was aa evolutioa of heat and
the solution ia the flask turaed gray in color. The reaction mixtTire
be^a to reflux and, whea additioa of the methyl iodide was completed,
the mixture was refluxed for ten minutes. Then 0.03 boI* of phenanthri-

50

din* dlaaelT«d in absolute athsr was pat into the sfparaterj funnsl and
addod dropwiss until addition was complete. After reflnxing for 2 houre,
the reflux eondonser was replaced hy a Liebig condenser and all of the
ether distilled off. Than the residue was warned with 200 ce. of water
acidified with 20 cc. of concentrated sulfuric acid for one hour. The
resulting solution waa made baaic, and extracted sereral tinea with ether.
Tht combined ether extracta were efaporated to dryneaa and the residue
taken up in alcohol. Recryatallization from dilute alcohol yielded whit*
micaceous crystals melting at 104 C. A mixture melting point with phen-
anthridine shovkA no depression. From these results we concluded that
BO reaction had taken place.

The next method to be tried involTOd the addition of the Orignard
reagent to the uncyclized anil. After addition the ring could be closed
by the previous methods usf d for the ayntheaia of phenanthridine. It
haa been r'^perted in the literature that the Grignard reagent will react
with bensal-aniline in the folle%ring manner:

Therefore in an analogous maxmer, the Orignard reagent should react
irith benBal-o<-aminophenol to gire a secondary amine which could be cycle-
iied giTing a substituted phenanthridine:

51

One* the reaction had l>««n ihown to work la a satisfactory Banner, then

different side chains would be substituted. First, howerer, the Grignard
reagents used were nethyl magnesium iodide, and ethyl magnesium bromide.

Xzperimental

One-tenth mole of methyl magnesium iodide was prepared according to
accepted methods with standard apparatus involying a 3->necked flask fit-
ted with a reflux condenser, stirrer and a dropping funnel. After com-
pletion of the reaction, 0.1 mole of bens»l-o-aainephenol dissolved in
absolute ether was added dropwise to the Orignard reagent, a riolent
reaction took ^lace, and the solution tamed red. An orange-red conQ>eund
precipitated out. After the addition of the anil was completed, the re-
sulting reaction mixture was stirred for one hour under reflux. Then a
solution of 200 CO. of water and 20 cc. of concentrated sulfuric acid
was added, and the resulting solution stirred for one hour. The solution
was made basic with excess sodium carbonate and ether extracted ssTeral
timet. The combined ether extracts were evaporated to dryness, the resi-
due was recrystallised from aldohol. White micaceous crystals melting
89-900q^ were obtained. These eare no depression when a mixture melting

point with bencal^-o-anlnophcnal %*■ tak«n. The rcaetion vhich did eeev
waa probabl/ an addition which decomposed on acidification refclating the
original conpoond.

Another attempt to aake the Origoard reagent react with the anil
was tried, but this tine the bensoate of the anil was used instead of the
free anil. Theoreticall/, the reaction should proceed in the following
Banner:

Xxpe risen tal

Methyl oagnesiun iodide was prepared according the the accepted pro-
eedure. Ilhe benxal-2~benB07lox7 aniline suspended in dry ether was added
dropwise to the Grignard resigent with stirring. A riolent reaction took
place on mixing, causing the Other to reflux rery rapidly. After all of
the anil had been added, the reaction mixture was refluxed for one hour.
IHien 200 oc. of water containing 20 grams of concentrated sulfuric acid
was added and the ether eraporated. A brown precipitate remained in
the flask.

Concentrated sodium hydroxide solution was added to the flask until
the reaction mixture was basic, to litmus then an excess ym.» added.

»

After r«fli»la« Um eoat«it« f«r en* hitnr^ %bm r*aeti«n ■lz1nr« im« fil*
UmA to movt th» tar. nw filtmt* Mt Midlfl«d with dlXai* mlfturle
Mid aad filt«r»A l»»t* th* r««ldxui «»• rverystalllsed frsa aleohol mA
|rt«Id«A iriitt* aleateAoa* «r9r«tftl« Mltla< «t ITl-a C. A mixvar* aeltUx
p»lat with a-MiUi^i«Ml ffkf a bic d«iMr«t«loa. A atstor* Mltin.' poist
with ywM S»b«BS«y]L»2««uiiwiphm^ »how«d to to b« S»b«u«yl«>2»MiU«ph«aol,
«• w» dopmaolMi «•• obotmod.

Iha flltr»t# obtAlmd bj fUtorla^ th* h»t «i«ldlfi«A •elatlM /t'^IdaA
b«»i«ie aeld on eoollac*

SlATO, im Ml fl*M voro wo raveooofyil Im c*ttlM< tho Oripuiitd ro*«on%
to r«ftet with tho jdMNMHthridliM or tho anil, wo eosiiidorod %ho foXlowiac
rooetioBa. If it woro pooslblo to appl/ owr ojmthooio of phouAthridiao
t4 fHoanothridtiOt %ro oould attoiqiii to rooot tho phoaoAthridoso with ttio
Orisaard roogont. IMo, of eonroo. woold jiold o torftiary aloohol whioli
eonld bo dohyd^tod to (iro tho fhoooateridiao dorimtivo.

•m« J<?olus « J

SzptrlnBiitel

B-beiiB07l-2-aalnoph«nol froo the sto^ room was aixed intimately
with phosphorous pentoxido In the reaction vetsol and heat applied for
one hour, the qceten heing under 3 ■■• ot mercury. A white crystalline
coopouad «ae distilled into the receirer, and vh.9n recrystallised gare a
BMlting point of 102-3°C* Analysis showed that the coBQ>ound was not
phenanthridone, which aelts at 293 C. (28), but 2<-phenyl-benfozaiole (29).
The reaction isrolved aay he shown by the following nethod:

Befardless of the conditions used in the attenipted foraation of phenan^
thridene, only the 2-phenyl>bencoxasole was formed.

55

L-aalno-2-iMkphthol->4~8ulfoiiic acid

Attenpts w«ra aadc to apply our synthaaia of phaoanthridiaa to tha
banzophenanthridine aulfonic acida. la this way, by having one hydro>
phylie group attachad to the molacula, the phenanthridixiaa adght possaea
desirable properties.

The l-Bmino-2->aaphthal*^8ulfoBic acid should condeaaa with bea-
saldehyde to give the corresponding Schiff baaa. A rariew of the liter»>
tare shoved that so far none of the aaila had been prepared from the
aaino~naphthol-8ulfonic aoid:

rfHx

The following aethods for condensing the aljlehyde and aaiae were used,
bat ae coadeasation products could be detected:

1. Refliuciag the pore coa^ouad with beazaldehyda.

2. Haatiag the pure coapound with bensaldehyde in an open flask.

3. Heating the hydrochloride of the base with benzaldehyde.

\, Shaking a suspension of the hydrochloride in a concentrated
solution of sodiua acetate with benzaldehyde.

5, Shaking the di-sodiua salt of the baee with bensaldehyde in
a coaceatrated sodiuii acetate solutioa.

56

STFFHKSIS OF THF. PHBHTL-DIBSNZO-X&IITHSNS

When benzaldehyde was heated in abstnee of the solTent with heta-
naphthol, a pxmetioally qtiantltative yield of 9'>pb«i>7l-'l'2, 7->8 dlbeii-
zozanthen was formed.

CM

The crystalline conpound was isolated and foxmd to check with constants
listed in Bellstein. It had preriously been prepared by heating beta-
naphthol with benzal chloride, by heating beta-aaphthol with bensalde«
hyde in acetic acid solution in the presence of concentrated hydrochlorlo
acid.

Sxperioental
An excess of bentaldehyde was added to beta-naphthol and the resul-
ting solution was boiled for ten minutes. After cooling alcohol was
added to the solidified mass and crystals besan to form. IThe compotind
was rery insoluble even in boiling 95/^ alcohol, so leaching with hot al-
eteel remoTed the unreacted phenol and aldehyde. The 9-pb«a7^-l->2, 7-*^
dibenso-xanthea was extremely soluble in cold chloroform, and its mel-

ting point was 189-190°C.

57

9 (U-m«th3rl)-ph«a/l, 1-2, 7-^ dibenzo-zanthen

Th« Muie proeadnre was employed as used for ths synthesis of 9-'P^*Byl,
1-2, 7-S dll>enio-xanthe]i except that p-tolulc aldehyde instead of hen-
saldehyde was used. It is a light gray coiQ>ound neltin^ 203-6^C. , and
is very soluble in ehlorofem, hut inaolnhle in hoiling alcohol.

9 (4-nethozy)-phenyl, 1-2, 7**^ dihenso-xanthan

The sane procedure was followed as used for the synthesis of 9~ph*nyl(
1-2, 7-S dibenso-xanthen, except that p-anisic aldehyde was used in-
stead of henzaldehyde. The eoapound is light gray in color and nelts
222-223^0. It is Tery soluble in ehloroBom, but is net soluble in
boiling alcohol.

u

SUMMILRT PART I

1. The n«w lynthasls of pheaanthridlne has been r«port«d.

2. The following new phen&nthridlnes have been eyntheslKCd.

a. 9-«thox3rph«iianthridlne

h. 4>hydroxy-lo-methoz3rpheaanthrldine

e. 7**^^^ox7-8-methox7phenanthridlae

d. f~hjAroxf phenanthridine
•. 9-Bethox7phenanthrldlne

f. 9~>Bth7lph«nanthridiii«

g. 7*'^«i^soylo^'~^>Q*thox3rphenanthrldlixe

3. The following new Schiff's Bases have been synthesized.

a. U-ethox7bensal-2-aBinophenol

b. 2-hjdroxy-3«Bethox7benzal aniline

e. 2-hydroz7-3-methoz7be&i&l->2->aminephenol
d. 2>3diaethex7benial-2-«fflinophenol

e • 2-h7dro z7'-3>ae thox7bensal-^Be thozjrani 1 ine

f. 2->h]rdrozy-3-iBBthox)i^-U-«minopheiM>l

g. ^h7droz7benuil«2-«miiiophenol

U. The failure of l-aBino-2-naphthol-U~8alfonic acid te condense with
with benzaldehyde under the conditions tried is noted.

5. The \mreaetlTlty of the bensal-2-aBinophenol toward the Orignard

reagent has been inyestigated.

6. Two new phenjrl-dibenso-zanthens have been prepared.

59

Bililiesxmphy "Pftrt ^H*

1. Coamings, Hopper, and Wh««l«r, SystMatlo Org. Chea. , pag* 362.

2. Btard, Co«pt. Rend., gfi. 730.

3. Ontebe, Ann. JjJS^ 122 (190U).
U. Hkegele. Ber. 25^ 2755.

5. He7 and Backley, J. C. S,, e*5-6»»9 (193^).

6. Oibner, Ann. 210. 3^5.

7. Kondo, Ber. JO. 1087-109^ (1937).

8. Kondo and Dl««o. Ber. 68. I756 (1935).

9. Labrlota, J. Org. Chea. #5. 329-33 (19»*0).

10. Morgan and Walls, J. C. S., 2UU7. Zk^ (1931).

11. Plctet and Ankersait, Ber. 22, 3339, 33^*.

12. Pietet and Ankermit, Arch. Sei. Phjre. Nat. Oenere, ^ 606.

13. Plctet and Ankeremit, Arch. Sol. Phyc. lat. Oeaev*, 3, 37 (1897).
Ik. Plctet and Ankersalt, Ann. 266, I38.

15. Plctet, Ber. J8. I9U6, 1951.

16. Plctet and Gonset, C. 21. (D ^13.

17. Placet and Kibner, Ber. 1182, (I892).

18. Pietet and Batry, Ber. 26, 1962.

19. Sleblaeh and Sandke, Ber. 66-B, U33-3U (1933).

20. Singleton, laboratory preparation.

21. Singleton and Pollard. J. A. C. S., 62, 2288 (19^).

22. DlMin and Mace. Ber. JjU. U307, (I9OI).

to

Cfttoljrtle AUqrUtlea of Aaia««

Tritmrf and ••eoadaxy aleoholt will raaet with prlaary and ••ooadarj
aalaaa uadar the Influffnea of catel/«t« lo jrlold toceadarjr «nd tortiary
aalaat rospoellrol/. Tho roaetioa aajr bo oirprotsod by the followia<
•quatioaot

RCH^OH / H«I% > Tomi* / m

BC^OH / BigVH > RMR*2 / HOI

BowoTor, olaeo it has booa thowa (12) that tortiary alcohol* do not ohov
thla t/po of roaetioa, the aoehaalui of tho roaetioa aajr bo aoenaod to
bo tho doh7dre«onatioa of tho aleohol f irot to giro th« aldohydo or kotoao,
vhieh vould then reaet with an aalno to givo a product vhioh it readily
hydrosonatod to sirm aa aaiao (20).

RgCHOH ^ R2CO / %

HgCO / R'HI^ J'HgOOHiMl*

Hpcomraa* / i^ > i^ctwhr' / hoh

Nailho (13) found thht thorina oxide or xir«eaiiui oxide acted at an
efficient oatalyst at ^tOO-^OO^C. in the taper phase roaetioa botvoea anil-
ine and Bothaaol to ciTo high yields of aothyl aailino. He also foaai
that alnaiaaa oxide gaTo oo^pleto coaTorsion of orthotolnidiae iato the
soeeadary aad tertiary aaiao s with BOthanol at 350*0. by roproeeooiac (1^).

T. B. Johneon (11) aad A. J. Hi'^.l (9) asod tho hydroehloridoo of
tho aainss with tho aloohol in autoelaToe at a toaporataro of 17!i*C. with

til

]iaT)r^CaCl2«»CaCl2 catalyst and o1)tained 87-*91l' o' diethylanilln* vh«n aall-
iBehydroehlorlda and athaaol ware u*«A, and A. B. Browa (2) usad slllcagal
for tha alkylatloa.

Banay hldcal baa baan found to "ba a -tarjr affieieat catalyst la raac->
tioBS iBTolriag catalytic attqrlatlon of aalnai and catalytic alkylatioa
follewad by hydroganatioa. Adklaa aad Viaaas (21) raactad aailiae and
athaaol OTar Raaay niokal in tha praaaaca of hydregaa. Tha --iekal aetad
as a catalyst aad this fact was coafimad as ae raactioa took placa ia
tha a'bsanea of ^idtal at 200^0. Tha taaparatura also plays a rary is-
pertaat part at thay fouad that at taaparatures lowar thaa 18^<*C. pipar-
idina did aot react vith ahtaaol ia tha prasaace of aickal. Throughout
thair inrastigatioas thay astablishad the fact that tha saoa yields vara
obtained whether hydrogen or aitrogea vara used ia the siaple catalytic
alkylatioa of aaiaes.

As a result of tha work of Faden aad Adkins (18), It has been showa
that cyclic aaiaes caa be aade by catalytic hydrogenatioa froa the follov-
iag type coapouadsi

S COOXt C 0 ClOE

111 I

0. 0. 0. QL

r r r \

lis i

where "a" aay be 2, 3, or H, aad the fuactioaal radical "Z" aay be:
-C=V -COKB^ -CONHH -GIHB

till
-C-IO -C-HO9 ^=BOH -.C=B.H-

for •nM

imple :

c 1

CM^ *^W^

/ \

5 1

C -Cm^

>

e M,

Th« foraatloa of sscondary aalnea from primary amines during hjrdro*
sanation of eyanldas orar nickel may rasolt from tha following maohanlsna:

1. Tha amine may react with tha alcohol used aa a solvent to glT«

the alkylated amine and water.

2. Two mol^eoles of the primary amine may react with themselTee to

glre a secondary amine with the elimlaation of a molecule of
ammonia.

3. The alkylidene imlno compounds may react with themselres.
Klndler (12) showed that erer palladium prinairy amines underwent the type
#2 reaction given above to yield secondary amines. Ho tertiary amines
were fomed as is observed in the alkylation of amines with an alcohol.

Lakely copper ehromite catalyst has come into extensive use as a
catalyst. Generally there is a trace of potassium fluoride, or barium
ehromite or other promoters mixed with the catalyst. Baden and Adkins
(18) obtained good yields in their synthesis of pyrolidenes, piperldines,
and hexa>hydroasepines by carrying out their reaction at 2^-26o^C. under
200-UOO atmospheres of hydrogen and 700-800 cc. of dioxane per mole of
diamine and glycol over dopper ehromite. In general Baden (1?) found that
glycols reacted with amines t^en the hydrogenatioa was carried out la

<3

dloxane OT«r ooppsr ehromlte undtr 200-3OO atoospharcs of h/drogsa.

Solvents plajr an important part in the reaction. Aboro I630 alcohol
cannot be used because It would react vlth the aaine. Diexane, ether,
BMthyleycloxhezane are all good eolrents aa they are inert and hare boil-
ing points that perait easy preparation of the reaction products (1).

Sumnarjr of th« PtoUmi

The reactions of tpoxy coapounda are almost alwa/s of the addition
type. They ueually react with compounds containing a labile hydrogen
atoa, such as alcohols, phenols, aaines, etc. As illustrated tj the
following equation, the ethylene oxide ring opens up in such a way that
the labile hydrogen atom attaches itself to the oxide linkage to form a
hydroxyl group, while the rest of the radical migrates to the remaining
portion of the oxide:

_eH — CM— — CM — cp —

With this generalization in mind we decided to attempt to eynthesiie
2,3-benzopyrasine by the catalytic alkylation of amines. That is, we would
prepare in the intermediate amino alcohol and then cyclise to the pyraslne
deriTative. Cyclohexene oxide reacts with ethylene diamine to yield
SCortho-hydroxy-cyclclohexyl )-ethylenediamine :

1 \ p

-h A/»-*^C l+^CH-j^/VH, Cm^ cm -/V«ch^ r« -A/«^

^v+, e,,^ .. -c -r .^ ^-. ^

CM,

This reaction is complicated by the fact that the ethylene diamine has two
functional groups and therefore may also yield the following compound, I,
V* di(orthoohydroxyeyclohexyl} ethylene diamine t

9 \ \^- . ' '

1

-CM, ^C

r>i H -CH
1

V

1

1

1

c

c w.

Bj oAtalytleallj iatemally allgrlatlae the prlmarj aaln* of the 1^(ortho-
h]rdroz]rcjroloh«xyl)-«th7len« diaalne a deoahydrobcazopTrazlne or d«cahydro»
qfaiaoxallna would form at Is illustrated by the following reaction:

H

'^"^ ^V^ I "- ^K-^ CM <:Wi

^ I Ih, > I \ '

Th«B, by siaply dehydrogenating the decahydroquinozaline, we would hare
th« 2-'3''^*^*opyrtk*ln or quinozalina.

Xa order to farther eaploy the use of epoxy compounds as starting materials
and yet use the internal catalytic alkylation method of synthesis, we star*
tad with e->phenylene diamine and ethylene oxide. When one mole of the
oxide reacts with the amine, the following compound is obtained:

66

WHj

/V l*j^

~f- CM^- CM,

How«T«r, tvo ■&• • of the oxld* 1017 react with the diaalne to gire B-I'<
di(betahydrox7eth7l)->o<-phen7lene diaaiae:

r^^s

-»- J2 CH.-CM-^

/U /V C «_^ C M, O H

I^MU the B.('betah7drox70thyl)-o-pHenylene dlaalne is desired, a larger
molar exeees of the diaaiae is used, so that the poasibllity of the B-V*
di-(hetahydrox3rethyl)-o-phea]rlenediaoiiie being formed will be diminished.
It is understood that there will be some of the by product formed in a
reaction.

The S-(betah7droxyeth7l)o-phenylenediamine can be internally cataly-
tically alkylated as follows to yield 1-2-3-U tetrahydropyraalne:

*: M.

«7

Then "bj dehjdrogeaatlag the tatrmhydropyraslBe, th« 2*3-^«nzop]mtzia« Is
formsd:

t

The S-I' dl(betah7drox3rethyl)e<-phen7lenedlaaliie can 1}e Intemallj alkylated
to glre l-(hetah7drox3reth7l)2-3^ trlhydroqulnoxallne:

i- »-,o

The l-2-3-^ tetrahydropyrasine ha« been prepared by the follovlng
■ethodi :

1. Heating catechol with ethylene diaadne hydrate in a eealed
tube for 15 heure (I3):

en.

tu. ^

^ . 2 u^o

2. Bedoction of the 2-3 bensopyracine (10) with eoditui and alco-
hol:

->

CH,

CHi

3. Hydrolytlt of the l-U-dibensenaixilfoiiyl, 1-2-3-4 tetrahydro-
'benzopyrazin* (7):

It is soluble in ether, alcohol, cklorofora, benzene and hot Mtter. An
aqueous solution gives a blue stain with silver nitrate. It yields
2.3»benzopyrazine on oxidation with potassium ferricyanide (10). 7«rrie
chloride solution gives a violet or blue color on being aixed with an
aqueous solution irtiich on addition of HCl turns green or light yellow
and which further changes to brown or red on heating.

The 2-3 benzopyrazine or quinoxaline and its derivatives can be
prepared by the following methods:

1. Reaction of o-phenylenAdiamine and glyozal or its sodium sul-
fite addition product in an aqueous solution (6, 7)*

&9

\

-\- iLi*^0

2, RMtetioa of o*ph*a)rl«B« dlAain* aad « k«t«-i*ld«hyd«t

^^\ '~\__^

C

o''"^^

3, Ksaetioa of o-phoajrlcno diudaa Mid aa Alph*-ehloro*«tt«rt

u<H^

>l. Roaetioa of o-phoajrloao diaalaa ami mi alpha-ehlor^otoaoi

r/H^. <s(.

AfU.

)

5. Baaetion of o-phsnyleae dlanine and an alpha-ke to-acid:

10

OH

-, ^>*^^

6. Reaction of a napthaquinon* l-S^ and o-phcaylene diaain*:

t 2MtO

7. Oxidation of 1-2-3-U tttrahydrobenzopTrazina to quinozalin*:

-+ ;?!+

q^inoxalin* it a crystalline compound melting at 27"c., boils at 220>223°C.
760 am. marcury aad has a quinoline-like odor in the cold and a piperidin»-
like odor on heating. It is soluble in all proportions in «at«r, alcohol,
•thor, and bensene. It can be oxidised with potassina pemanganate to
nrracine dicarboxylic acid (I9). It forms salts with mineral acids, ox-
alic acid, and platinum chloride. A number of derivatiTes haTe been pre-
pared (8-9-16). A solution of the free base in water gives a white pre-

olpitat* with tilTer nitrate or ■•rcurle chloride (8).

SxperlBoatal

Cf4, CHOW

1 1

.< < r w

\ «

CHl '■'+L
""^•^U

>

+ M, G

Cyclozhazono tnts proparod according to the precoduro outlinod la
"Organic S/nthASos", colloctlre coluae, 1932 edition.

"In a ^ ec. aodlflod Clalson flaak war* placed UOO graae (U
molee) of technical oyclohexaaol and 12 cc. of concentrated stilfarle
aeld. The flatk was connected to a condenser and a recelrer luBersed
In lee hath. The flask vat then placed in an oil hath and the tes-
perature kept hetween I30 and lUO°C. Ice vater was clreolated through
the condenser hy aeans of a saall puap. In order to nlnlaite the loss
of cydohezene due to eiaporatlon. The distillation was continued un-
til a snail rosldao reaalned and the odor of sulfur dioxide tias appar-
ent. The distinction required 12 houre. (Beported In the original
article as taking ^S hours).

The distillate was saturated with salt and c/clohezene separated
fron the water layer. After drying orer calclua cftlorlde, the product
was fractionated In an efficient coluan and the portion boiling 80-82®C.
was collected."

When this woxk was repeated a yield of 80^ of the theoretical yield
wae obtained.

n

2-Chloro-cyelolMxmol

OrgMiio S7nth«s«a
CollcctlT* Tolum*. 1932

^fo a aolutloa of 2^ graos of nercorlc chlorido in 5OO ec. water ia
a 3 lltar flask 800 grams of cracked tea was added. A oold solution
of 190 grans of BaOH ia ^00 cc. of watar vias added 4nd a rapid streaa
of chlorine was passed into the nixture which was kept helow 3^C. Th«
addition of chlorine was continued until the jrellow precipitate of BgO
disappeared. Then 60O ce. of cold nitric acid (I.3 I) was addad with
stirring. The concentration of BOCl was determined by adding a measured
▼oluae to an excess of KZ solution, acidified with HCl, and titrating
with sodium thiosulfate. Usually the concentration runs hetweea 3.5-
U^ ¥he amount necessary to react with 123 srams (I.3 aolas) of cycle-
hexene was calculated.

In a f liter fftund bottom flask with a good mechanical stirrer ws
placed 123 grams of cyclohexene and to it was added l/k the calculated
amount of HDCl solution, the mixture was kept below I5 C. and was stir-
red rigorously until 1 cc. test portion gave no yellow color when treateA
with KI solution and dilute HCl. When the first portion of HOCl has
reacted a second portion is added and the pracess repeated. When all

73

•f the aOCl hat been added and the reaction is eoaplete, the oil/ lajer
ie on the bottom and a elight excest of S)C1 la present. If these eoiHi
ditioni are net folfilled, 100 oe. portions of HDCl add solution are
added until the reaction Is ooaplete.

The solution was saturated with salt and stean distilled. About
2 liters of distillate were required before all of the 2-ehloro~C7cle-
hexanol passed over. The acqaeous layer «as extracted with 250 ce.
of ether, and this «as added to the main portion. After drying orer
BkgSOi^ (anhjrdrous) the solution was distilled under reduced pressure,
and after rexioTing the ether by ordinary distillation. The fraction
boiling 8S-90)(, 20 am., or 10^4-106°, k^ ■■!. was collected. ••

When this work was repeated a yield of kjjk of tl» theoretical yield
was obtained.

7H

OyolohaxMi* Ozid*

Oreanie Synthss**

Coll»etlT« Tolua*, 1932

"Zb a 2 lltsr R. B. fladc fittad with a meehanleal stirrer was
plaosd a solution of 70 graos of sodixu hjrdrozids la UOO cc. wator.
To this solution was addod 230 grams of 2-chloro-oyclohexaBol. Ths
■ixture was stlrrad rigorously for 1 hour. The stirring was stopped
and the upper lajrer separated in a separator/ funnel. It was distilled
through and efficient coluim, and the following fraotion collected,
100-129: I29-I3U, 13^-175. The first fraction is cyclohexene oxide
and water which is separated with a separatory funnel before thp second
distillation. After the fraction boiling 100-129 w"^* collected, the
condenser was reaored and dried thoroughly before collecting the second
fraction. All of the fraotion were refractiooated and the portion boiling
129-13U^ was collected."

When this work was repeated 63^ of the theoretical yield was ob-
tained.

75

PraparatloB of the Oepper-Chronlta Catalyst

The nethod for the preparation of the catalyst was the same at
us«d by Connor and Adkina (3), line handrod cubic contiaotort of
(80^C. ) solution containing 26l graas of hydra tod copper nitrate, 31. 3
grans of barium nitrato was added to 900 ee. of a solution (25-30^0.),
eontaininc 151*2 graas of aaiooniua diohroaate and 22^ cc of 2S%
aaaonitui hydroxide. Tba preeipl'oate was filtered and the cake pressed.
After hariag sucked the cake as dry as possible with the suction
flask, it was dried overnight at 75-80^> It was then pulverized and
weighed 225 gn^*. It ms decomposed in three portions in a casserole
ever a free flaiM. In carrying out the decomposition, the powder
was stirred with a spatula from the beginning of the heating, and
the flaae was reaored after decoaposition was well started. After
a little acre stirring, there was a sudden evolution of gases and the
entire aass beoaae black. After stirring thoroughly, the powder was
reaoved and allowed to cool. The coabined products were leached
with 600 ec. of 10^ acetic acid solution for 30 ainutes. The product
was then filtered by suction and washed with 600 ce. of water in 6
portions. The oake was dried overnight ftt 125°C. and then pulverised.

76

STKTHKSIS 07 S-(BSmHTSBOXT]&THTL}-o-PIiaiTLSli£ DDlNIIB

AcoerdlBg to Gabel and Matzakerieh (13) ethylene oxide reacts
with a-phenylene diaaine in a sealed tal>e in the presence of ttater
to yield K-(betahydroz7eth]rl)B-phenjrlene diaaine. Howerer, work oax^
ried on at this institution utilizing this type reaction of epoxjr
coapouads indicates that the use of the sealed tube is unneoessary.
Consequently, we proceeded to carry «fat this reaction in cold aethanol,
■ittce ethylene oxide and the e-phenylene diamine are soluble in that
aediua.

Sxactly 108 gmas of o^henylene diaaine were dissolved in wara
aethanol (o. j^^C.) in a a-liter beaker, fitted with a aechanieal
stirrer and a flss inlet tube. The solution was then cooled slowly to
reoa teaperature* Thirty grams (2/3 aole) of ethylene oxide was
poured into a 2^0 oo* suction flask connected to the gas inlet tube
by aeams of a piece of rubber tubing. The flask was then closed with
a rubber stopper. The stirrer was put into action, and the ethylene
oxide allowed to distill slowly into the aethanol solution. (Wotei
ethylene oxide is poisonous, but it can be handled easily if kept la
a cylinder under pressure.) After the ethylene oxide had distilled
into the aethanol solution, %Aiich had sucked back into the suction

77

flask at the lait tracea of ethylene oxide had Tolatilised, the telu>
tion in the flask was poared back into the beaker and then the aeth-
anal evaporated on a steaa hath. As the solution becaae conoentrateA,
it was transferred Into a flask and the nethanol distilled off. The
residue was then fractionally distilled under reduced pressure and
the fbllowlng fractions obtained:

1st fraction: lU3-135^C./20 mm. mmrearj
2nd frsietion: 200*^0/8 am. of aereury
The first fraction was shown to be unreacted o-phenylene diaaine and
6$ graas were reeoTered. A mixture melting point with pore o«phenyl-
ene diaaine aelting at lOUoC. gSTO no depression. The second fraction
of 50 grass (Slj( theory) which had crystallized on cooling, was liqui-
fied by warming and then poured into 400 ec. of benzene. White mica-
eeeus crystals were separated out. After standing for sereral hours
the crystals were filtered by suction in a Buchner funnel and dried
in an oren at 65^C. The melting point of the crystals was 106. 3-107.3^0.
uncorrected. A mixture melting point with pure o-phenylene diaaine
flare a big depression, the mixture a Ited about ^3-K)'^C, The pure
compound was analyzed for nitrogen by the Kjeldahl method. Nitrogen
ealeulated 18. U^, found 18.1)(.

The compound is Tory soluble in methanol, ethaael, and dilute
hydrochloric acid. It is best reerystallized from benzene, as it
is slightly soluble in cold benzene and fairly soluble in hot. It is
stable to atmospheric distillation, but turns brown on standing. A
bottle lAich had been stoppered and stored sereral weeks g^rt off the
odor of amnaojiia when opeaeA.

78

Oth«r roas were oade in which lOS graas of th» e-phanylttn* diaaiB*
w«r« dissolved in th« w«za ■•thanol tolution and UU gxwM of ethjrlMM
exid* (1 mole) were distilled slowly into the diaaine solution. 1^
■etbanol was distilled off at ataospherio pressture and the residue
fractionated through a short coluan at atsospheric press\ire. Two
fractions were obtained:

1st fraction >p 236/ 760 am. aercurjr
2nd fraction \ip 338/ 760 an. aeroarjr
Zn this case 60 graas of the unreacted o-phenylene diaaine were reeoTered
ae the first fraction. It distilled easily and solidified on cooling.
The second fraction of 60 graas (86.3^ theory) was reerystallised froa
bensene and gave no aixture aelting point depression when taken with
fare H-(betahydrozethyl)o-phenylene diaaine. A few graas of a high
boiling red oil were obtained, which was shown to be S-I' dl(betataydro-
zyethyl)-o-phenylene diaaine by its boiling point.

The largest aole ratio of ethylene oxide to e^^^gihenylene diaaine
«m4 was 1 1/3 to 1. Under the saae conditions as used preriously,
60 grams (1 I/3 aole) of ethylene oxide was slowly distilled into 108
graas (1 aole) of o-pheoylene diaaine in 1200 ce. aethanol and after
first distilling off the aethanol, the r sidue distilled at ataospherio
pressure through a short eoluaa. Two fractions wore obtoinedj
1st fraction bp 236^C./76o aa. mercury
2nd fraction bp 338*C./760 aa. aeroury
Tifty graas of the unreacted o-phenylene diaaine (fraction #1)
were recoTored. A total of 65 graas of the K-(betahydroxyethyl)-o*

75

phebjlen* diaalae were obtained, 83*3^ theory. A total of ton differ-
ent runs vere aado.

lU(betahydrox3r«thjrl)-o-pheii3rlene diwBlne

fO

tapir loal fonala
Moleealar Weight
Malting Point
Color

Solubility
'boniono

■•thABOl

•thanol
diluto HCl
Analyflit

nitrogen

C, H^2 0 ^2
152

106.5-107.5*0.
whit*

fairly soluble In hot, slightly in
cold

rery soluble

rvrj eeluble

T«ry loluble

found calculated

18.1^ IS.ki

fl

SnrPHSSIS or the bus' -pi ( BHAHYDROXTCT HTL)-0-PHJE«LBliUi DXAMin

■f

0

'^ k

Th» saae fmeral proeedur* used for the prepaxmtloa of tbe l-(l>«-
tah7drox7ath7l)-o-phea]rl«n« dlaalne was eaployad, exc«pt that tho
■olo ratio of •thjlaao oxido to o-phenylono dlaalne vas incr«as«d.
71ft7-four grams of o-phan/lono diaalno (O.3 aole) were dleiolved in
1200 ee. of aethanel and 176 grame of eUqrlene ozlAe (U aolee) vere
•lewlj dletilled into the methanol eolution. A alight evolution of
heat vaa noticed, 10 the heaker w s iomereed In an ice hath. The
methanol was dietilled off at ataospheric preesore and the reeidxM
fractionally dietilled under reduced oreseure throtigh a short column.
Two fractions were obtained:

1st fraction 268*0. /21 mm. mercurjr
2nd fraction 2^3-256^0. /lO mm. msrearz
The firet fraction crystallized on cooling. It was recrys tall i zed
from hensene and gave a melting point of 106»7 0. ▲ mixture melting
point with authentic B-betabydroxyethyl-o^henylene diamine gare no
depression. The second fraction came oTer as a light orange oil and
solidified in 2 days. It «as recrystallized from heniene which con-
tained 2^ ethanol and yielded pinkish Tiolet crystals melting at
97**98^C* ^ mixture melting point with N-betahydroxyethyl-o^henyleae

82

diaaine melt«d at 73~^ C. It was analjc^d "by 1>oth th« boiling polKt
rlsa and by the KJeldahl methods. A bolliag point rise of 0.320<'C.
wat obtained when 2.3^6 gtaas of the coBsponnd were disselred in UO
grams of ethanel (Kb determined preTiously to be 1.0^). This gave a
molecular weight of 192. The calculated molecular wei^^t was I96.
Nitrogen by KJeldahl: ealeolated lU.35(, found lU.O)(. The compound
darkened on standing. A total of ^ runs were made.

The following eridence was used to show that th« formula of the
B-H* dl(betahydrozethyl)-o-phenylene diamine was

instead of the possible formula;

One tenth mole of the coopound (19»6 grams) was dissolved in 3OO oe.
of water and 20 ee. of concentrated hydrochloric acid «ae added. Ice
added tmtil the solution temperature was below 5^C*« *^ then 30 ee.
of eonoentrated hydrochloric acid poured in. The 10^ sodium nitrite
solution was added until the end point had been reached. Twelve and
one-tenth grams of dimethyl aniline were added and the solution stirred.
Then, caastie soda solution was added until the solution was basio. Oa
filtering the reaction mirture, only a green scum was obtained, which
led to the belief that only a nitrose compound might have been fomid.

«3

fhis indicated that there were no primary amino group* in the molecule.

».H' SI-(B]ETiLHri£OXT]!IHn.)-0-PHEHTL£IIB BUMIKB

ik

Bqplrical 7oraial*
Moloctilar Weight
Kelting Fblnt
BolllBg I^iat
Color
Stabllitz
Solubility

alcohol

'beneoao

diluto HCl
Analysis

aitrogon

■olecolar vaight

°10 ^6 '2 °2

196

97-9«®C.

2^250*0. /lO ma. aarcury

piaklBh violot

darkens on standing

T«ry soluble in cold
insoluble la cold
soluble

calculated found
lH.35t iJ+.ojt
196 192

STSTHISIS 0? l.(ORTHDHTD&OXTCTCLOIEXTL} XTHTLENX DIAMIBS

V

CH.

Cyelohexena ozld« Ithylen* dlanin*

Since the ethylene dlaalne has t«e ftuietlonal amino groups, it
It necesMiry to control the sole ratio of the eyclohezene oxide to
the ethylene diuiine so that the aone sobstituted derivatiTe will b«
foraed in preference to the di-eubatituted derivatiTe. Xa order that
there should always be an ezeeae of diaaina present, the cyclohexeme
oxides was added dropwiee to the diaaine.

Tvo Moles (120 grans) of freshly distilled ethylene diamine were
dissolved in 500 cc of cold methanol in a 1^00 ec, beaker which was
fitted with a meehanloal stirrer. Torty-niae graae (0.5 aole) of
cyclohexene oxide were plaoed in a dropping funnel and allowed to
fall dropwise into the methanol solution of the ethylene diamine, and
the stirrer was started. After the addition of the cyclokexane oxide
was ooaQ>lete, the beaker was placed on a steam bath and the methanol
evaporated. On cooling, a layer of white crystals Mttled out. These
were filtered by suction, and then triturated with hot ethanol. The
ethaael was filtered from the crystals by suction. The two filtrates
were then mixed. The filtrates lAich had been combined were fraction-
ally distilled under reduced pressure. Two fractions were obtained:

81

Ist fraction balow 7^ C./85 am. mercury
2iid fraction I88-I9O C./55 ■b. aorcurjr
Th« first fraction was tuniBod ethylene dlaalne, since It boiled at
ll6*C. under atno spheric pressure. "Fhe second fraction, a yIscous oil
vi%h a peenllar odor crystallized to glre a yellowish white mass.
The mailing point of the compound was determined In a transition
point apparatus. The point of clear solution was U6^C. The compenaA
vas a muslwllke solid at room teq^rature, and It retained that
property regardless of the somber of tines that it was refractlonatad.
▲ 70^ yield of the compotuad was obtained. The compound was rery
•oluble la ethaaol, methanol, ether, tertiary butanel, ani cold water.
It was analyzed by means of a KJeldahl determination. Nitrogen oaleor-
lated 17. 95^* found 17 ^TJ^* ^ total af four runs were made.

87

I-(ORTaOHn}ROXTCTCLOHEXTl)-STRXLXBZ OUMXll

CM.

^^S

CM
CM, CMOH

*:m.

7'

Svplrlcal Tformaln.

MolecaUr W«igh%

Melting Point

Torm

Color

Solubilit7

wKtor

othanol

other

■ethtael
AnAl/aia

nitrogon

°8 «18 ^ 0

^6^ (pt. of clear solution)
■ash solid at rooa toqperatoro
light yollov

Tory soluble
rery soluble
Tory soluble
yrj soluble
ealeolated found
17.9lt 17.7^

88

STBTHSSIS OF K-V> DZ-(ORTHDHTmOXTCTCLOHl!Xn.)-2THrLSlIE DZAMXH2

ttH

ew

MOMC z'*^ '^»

CM

Th« whit* crystals which saparated out from the reaction alxturo
dnrlng the synthesle of the S-(Orthoh]rdroxycyelohex9rl}<>eth7lene dlaalne
were shown to be the It-N* dKorthehjrdroxycyclohexylj-ethjrlene dlaaln*.
They aelted at 205«206^C. and were Insoluble In boiling •thanol. Ni-
trogen calculated 11.1^, found 11.0)(. Ihe structure was proTod by
synthesis.

Eight grams (O.O5 sole) of N-orthohydrozycyclohexyl-ethylene
diamine %rere dissolred in methanol and 5 grams of cydohexene oxide
(0.03 mole) were added. The solution mis heated on a steam bath and
the methanol driven off. Ihite erystals were obtained on cooling.
These melted at 203-6°C. , and gaTe no depression when a mixture mel-
ting point was taken with the crystals obtained in the synthesis of
the It^rthohydroxycyclohexyl-ethylene diamine. The reaction may be
expressed as follows:

K-I* DI.(OBfBOHTDB0XTCTCXX}HBXn.)-]»H{LEBX DZAMXH

29

cm^ cm — /VW C«. CW /V^— C^ <^**J

I ]

Bqtirical formula
Molecular weight
Melting Folat
Color
Solubility

>iat«r

Sthaaol
Analytic

Hitrogen

256

205-206®C.

whit*

insoluble

insoluble in boiling ethanel
found calculated

11.0^ ll.ljt

90

STHTHSSXS 01* CECA.HYSBOQ|(TIK}ZALZHB

^ 'V^ ^ <^"

r^ r ' — > V' y I '

CW, CM J-** 2^ CHj. CM CM,

V / ^Gu 1... . / \ ... / ^

\ -^ ^ /V

Thlrtj grains of l^CorthohydroxyejrelokexylKtthjrlene diamlA*, UOO
ce. of purified dloxano, and 6 grans of copper chroaite catalyst wer«
placed In the boab of an Aaerican Instrument Company "Bomb Shaker".
The bomb was closed and the pressure on the aeactlon mixture raised
to 100 pounds per square inch with hydrogen. Then the pressure mis
further increased to 800 pounds per square inch with nitrogen. The
bomb was agitated for ^ hours at 250^0. After cooling, the reaction
mixture was poured out of the bomb and the catalyst, which had not
turned a bright copper color was filtered off. The dioxane was dis-
tilled off through a short column, and then the residue was distilled
at atmospheric presstire. One fraction was obtained, and it belled
at 283-7^. There had been no reaction.

Since we know that teoiperatTire plays an Important part in the
catalytic alkylatlon of amines, we decided to raise the teiq;»erature
to see if we could obtain an internal alkylatlon. Therefore, 30
grams of K-(orthohydroxycyclohexyl)-ethylene diamine, UOO cc. of
pfurlfied dioxane, and 7 gnuns of copper-chromite catalyst were placed
in the bomb. Pressure on the reaction fixture was raised to 100 pounds
per eqinar* lash with hydrogen, and then further increased to 1000 pounds
per square inch with nitrogen. The bomb was agitated for 3 hours at

a tempemtore rang* of 27^yX>*0, After the boab had cooled oYemlghl,
it «as opened. An amnonlaeal odor «a« plainly detectable. The catalyst,
vhich had turned a copper color wag filtered off, and the diozane dis-
tilled off through a short coluon. The residue «as fractionated at
ataospheric pressure and four fractions were obtained:

-O

1st fraction bp lib C.

2nd fraction b]^ 175-80°C.

3rd fraction bp 228<^C.

Uth fraction bp 285-«T*0.
The first fraction, bviling at ll6^C. , had a strong aomoniacal
odor and was soluble in vater. Only about 1 ec. was obtained, n^ich
was ethylene diaaine foraed by theraal decoaposition of the starting
aaterial. The second fraction, boiling at IJ^'^O^C. , caae orer as a
light yellow oil. The third fraction, boiling around 228*^C., also
caae orer as a light yellow oil. The fourth fraction, boiling at 283-
T^C. , was the recorered K-(orthohydrezycyclohezyl)-cthylene diaaine
which had not reacted.

The second and third fractions ware coablned and reCractionated.
This time as the aain product, a light yellow oil, boUing 220-222^0. ,
was obtained. It was a aushy solid at rooa teaperature. The benzene
sulfonyl derivatire v.as aade according to standard procedure, and
was insoluble in sodiua hydroxide. This fact indicated that a eecondary
aaine mis present. The precipitate was filtered off and reorystallized
froa 93^ ethanol and activated charcoal. On cooling, a white precipitate
settled out aelting at 188-90C.

92

M

^CH^ ."^

\ 1 1

CJ^CP K«| <J*0 «0|M0 1"»^"«*

la ordar to verify Adaat and Winan* obteryation (7) that the cat-
alytic alkylation of amines proceeded equally as well with hydrogen
as nitrogen, we made the following runs: Forty %;nat of B-(orthohy-
droxycyclohex]rl)-ethylene diamine, 7 gnns of eoppor chromite catalyst,
and UOO cc. of purified dioxane were placed in the bomh. The bomb was
closed and the pressure on the reaction mixture raised to 1000 pounds
per square inch with nitrogen. The bomb was agitated to ^ hours
at 2S0-310°C. , and the pressure rose to 2^0 pounds per square inch.
After the bomb had cooled, it was opened. An ammonical odor was
plainly detectable. The reacted copper-chroaite catalyst was filtered
off, and the dioxane was distilled off at atmospheric pressure. The
residue was fractionated and two fractions were obtained:

1st fraction b.p. 218-220*'C.

2nd fraction b.p. 285-287°C.
The first fraction, boiling at 218-220^0., solidified to a mushy solid
at room teiq>erature. The benzene sulfonyl derivatire was prepared
and melted at 188-9^0. It did not giro a melting point depression
lAen mixed with the bensene sulfonyl dftriTatire prepared from prerious
runt, fifteen grams of the decahydroquinoxaline were obtained, 43^

93

•f the thMNtiflAl /laid. Vhm Mcead fimotloa vaa tlw vartaettd ■-(or-
thohjrdroxjrejrelelMxyD^ctlvlMM diaalaa which boilad «t 289-7*C«

Slae* «• fooad that t«9«xatar« plajra aa ii^ortaat part la th«
eatalytio allqrlatloa of this eoqwvad, «• d*eld«d to sm tho of foot
of aa iaeroaoo in tho aaouat of ootaljrot aood dariac tho rooetioa.
Ooaoofttoatly, 6o sraa« of l^Cortho-hydToz/ejelohoxjrD-othjrloao diaaiao,
UOO 00. of parifiod dioxaao, aad 20 ctmm of coppor chroaito eatal/ot
voro pl»ood la tho hoah. Iho boab woo eloaod and tfut presouro raiood
to 1000 poaadfl por oqaaro laoh vith aitrot^oa. Tho boab «aa asitatod
for fivo hoars at 300*, aad tho prooooro rooo to 2'S/OO pooada por
oqiaaro iaah« Tho boab «as opoaod aftor It had coolod aad tho rcoetod
oatal/ot MB filtorod off. tho dlozaao wa« th«a diotilled off at at->
■oophorie proosaro. rraotionatioa at atiaotphorie proasoro jioXdod two
fraotloast

1st fraetion b.p. 222-U*C./76o aa.

2ad fraotloa b.p. 288*C./76o aa.

Thirty giaas of tho first fraction, docahgrdroquiaoxaliao, woro obtaiaod,
yihieh was 7^.1^ of the thoorotioal jriold. Tho beatoao sulfoajrl dori-
mtlTO aoltod at 188.5-199.^*0. Toa sraas of tho roaetaat fraotloa,
boilia« at 288*0., woro roooTorod. Froa these ruas tro hare concluded
that the iaeroaoo in tho aamiat of oataljrst will iaoroaso the yield
of the prodaet. Six mao woro aado.

lASLE

^

Bob

araat of
Beaetant

Qrant catal/at

T«q>eratar«

Per Cent ThMr«W
leal Tl«ld

1

30

7

250*»C.

0

2

30

7

275-300<»C.

low (C. 20i)

3

Uo

7

280-310OC.

^3%

k

uo

7

290-300®C.

6l.95t

5

30

20

290-300'*C.

6511

6

60

20

3000c.

76.5Jt

95

nMOkwraBoqpnoJkLim

/^V

CH,

c H

CM

M

Bapirieal Fdnmla

KolectiUr Weight

Boiling Point

form

Color

Solubility

nator

alcohol

dilute HCl
Tiold
Analysis

Molecular weight

IHO

288*C./760 ■■. aereury

mah shlid

light yellov

inseluhle in oold water

soluble

soluble

75.5^ theory

calculated found

lltO \ki

96

STNTHESXS 0? Q^tSOIkUm

TvsIts grans of d«eah]rdroquinoxali&«, 10 grass of Baaay aidcel,
and Moo ec. of dloxaao vera plaead la the boal>. Tha bomb was closed
and the pressure raised to 1000 pounds per square Inch with nitro-
gen. The boab mis agitated for U hours at a tenperature range of 250-
300^0. (eptlHUB conditions). After cooling, the boab vaa opened and
the black nickel catalyst filtered off. The dioxane vae distilled
off through a short column at atoospheric pressure. The residue
was then fractionated through- a short coluon and the fraction, boiling
at 220-222^0. (reported Talue - 220-222 (7))was collected. It was a
light yellow oil, very fluid. It yielded no derivatiye trlth bentene-
•ulfonyl chloride, firm grams were collected, giring a yield of
^5»3i^ theory. The quino-xaline was soluble in all proportions with
water. Three runs were oade, and the abore procedure were the optiaoa
conditions deterained.

97

Bapiricftl TonwaiM
MolsouUr Weight
Boiling Point

Color

Sol«bilit7
wator

alcohol
diluto KCl
AaalysiB

nitrogon

130

220-222*0. Srporiaoatal
220-222°C. Litoratoro
light 70U0V

■itcible in cold

•olublo

•olnblo

ealeulatod found

2i.55t 21.256

9«

STHTHESIS 07 1.2-3-lt*TSTItAHT]}ROq,UXlK>XALISl

Thirty and •ight-Unths grams (0.2 aolc) of S-(l)«tabjrdroz7«thyl)
-9-ph«a7leB« diamln* wtre distolrtd Im UOO ec. of porlflod dloxano
and U grami of Baney niekal addad. Tha Hlztora wai plaead in the
boah under 30 ataoflpheroi of hydrogan and agitated for "^ hours at
200<>C. The Baney nickel was filtered off, and the dioxane was dis-
tilled off at ataoBpheric preisure. The vesidue was fractionated
under reduced pressure, and one fraction, boiling 223*^0. under 20 am.
of aereury was obtained. It solidified on cooling and was reerystal-
lized froB benzene. White aicaeeous crystals, aelting at 102-3^0.
were obtained, but they gave no melting point depression when a aix-
ture aelting point was taken out with K-(betahydroxyethyl)-o->phenylene
diamine. Ho reaction had occurred.

In order to determine whether the copper-chromite catalyst would
effect the aUcylation, the following ran was made. Thirty grams of
the N>(betahydrozyethyl)-o-phenylene diamine was disaolTed in 300 cc.
of purified dioxane, and U grams of copper-chromite catalyst added.
The pressure on the mixture was raised to 30 atmospheres with Igrdro-
gen and the bomb was agitated for k^ hours at 210 C. The same pro->
eedure was followed as before. One fraction, boiling 213-223°C undar

99

15 ■■• of pr«saar« %«8 obtained. On eoollag. It ciyotallizod and ro-
erjrstallization from benzono yleldod buff eolorod crystals Bolting
103-^^C. Thore bad boon no reaction.

BftTins •••& froa the proTious work that toapatatare played a Tory
Important part in tho catalytic alkylation of aainos, ve decided to
try Baney nickel a^ain at a higher teoperature. 7orty grams of the
>*(betahydroxyethyl)-o<-phenylene diamine vore dissolred in UOO cc.
of dloxane and 10 grams of Baney Nickel added. The mixtuxv was placed
in the bomb, and the preseore was increased on the reaction mixture
to 1000 povnde per square inch with nitrogen, ^he bomb was agitated
for k hours at a temperature of 300^0. Tlie catalyst was filtered
off and the dioxane distilled off at atmospheric pressure. When the
r«siiae was fractionated, one f raclion, boiling at 338^0. , under at-
mospheric pressure was obtained. This was the boiling point of the
l^(betahydrozyethyl)-o->pheaylene diamine. There had been no reaction.

We did, hewoTor, obtain the desired product when we substituted
the copper chremite catalyst for the Baney nickel. Twenty seren grams
of V-(betahydroxyethyl)-o->phenylene diamine were dissolred in 600
ec. of purified dioxane, and 7 grams of the copper ohromite catalyst
added. The mixture was put under a pressure of 1000 pounds per square
inch with nitrogen and agitoted at 250-70*0. for ^ hours. After the
bomb had cooled, it was opened, and the reacted catalyst Vas filtered
off. The dioxane was distilled off at atmospheric pressure and the
residue fractionally distilled at atmospheric pressure. Two main
fraetione and a smaller one of a higher boiling compound were obtained:

100

1st fraction 25U-6'C.

2nd fxAction 278-88OC.

3rd fmetion hlgh«r than 330<>C.
Th« first fraotlon tamed out to bo o-phonyleno diaaino formed
by doconposition of the starting ■atorial. It %ias identified hj
its boiling point and aelting point. Its aixture oelting point with
pure o-iiphenylene diamine gave no depression. The second fraction
was refraetionated and yielded a product boiling at 28&-g°C. The r»>
ported ralue of this product is 288-9^0. It was recrys tall i zed from
petroleum ether and yielded buff colored crystals melting at 9U-5<>C.
father recrys tall ization fromi petroleum ether gare white micaceous
flakes melting at 9&-7^C. Reported value is 96-97^0. (10). It gaT«
a melting point depressioh of twenty degrees when mixed with the
pure S-(betahydrozyethyl)-K>-phenylene diamine. The following spot
tests reported in the literature were obtained (10): An aqueous solu-
tion of the compound gare a blue stain with aqueous silrer nitrate.
On addition of ferric chloride to an aqueous solution of the compound,
a violet color was obtained which turned yellow on addition of hydro-
chloric acid, and further turned brown when heated. A few drops of
potassium ferricyanide poured into an aqueous solution of the compound
^▼e a blu»>Tiolet color which turned red on addition of base.

An increase in the tenperatures and the amount of catalyst will
increase the yllld of the desired product. A typical run is cited:
^ grams of the B-(betahydroxyethyl)-o-phenylene diamine, 20 grams of
copper chremito catalyst, UOO cc. of purified dioxsne placed in bomb.

101

The bomb was pnt uiid«r a prasiur* of 1000 pounds por square inch,
and agitated for 5 hours at 300**. Two fractions wero obtained
whoa the residue was fractionally distilled!

lat fraction 280-300*^0.

2nd fraction 230-3^0*^0.
When the first fraction was refraetionated, 9 graas of product were
obtained, boiling at 287-9*0., which was a yield of 20^. The cos-
pound Mhvk reorystallixed soToral times from petroleua ether melted
sharply at 96-91^0. It gaye the specific spot tests listed preriously.

l-2-3-'*-^''35THAHTDROQ,UIBOXiLUHI

lot

Ibpirlcal Foraola
Molecxilar Weight
Color

Crsritalline Tom
Boiling Point

Melting Point

Solubility

vattr

alcohol

potroloua other
AnAlysia

■oleoular weight

CH,

CH,

white

Bicaeeoae flakes

286-SOC. reported in literature

286-8^0. ezperiaental

96-7°C. recorded in literature

36-7°C. experiaentAl

insoluble

eoluhle

insoluble in cold, eoluble in hot

calculated found

I3U 132

103

8DMMAST "PABT #2*

1. The rMkctirlt/ of •posqr ooapouads toward diaBlaei ta»t 1>««a !&•

Tostl^tod.

2. 7iT0 now eompeunds Iiato been reported:

(a) H-(orthehjrdrox7e7clohez]rl)-eth]rlene dlaalne

(b) K»Ii-di(ortheh7drez7C]rclohex]rl)-ethyle&e diaalne

(c) l-(betah7drox7etfa]rl)-o-pheb]rleiie diaalao

(d) K>I*-dl(bet«h]rdrox]retb]rl)-o-phen]rleae dlmaia*

(e) DoeahTdroqulxiozaliao

9. The fact that eatalytic alkjrlatlon proeeeds equallj ai well vader

nitrogen at hydrogen has been rerified.
U. A nev eyntheeis of 2-3 bensopTraelne has been reported.
5. A nev eyntheeie of l-2-3~'^tetrah]rdroquiaoxaline has been reported.

104

BZBLZOaBia>Br "PABT #2*

1. Atkins and Cran*r, J. •&«. Chea. Soe. ^ 1^350 (1930)

2. A. B. Brown, J. An. Ch«m. Sqc. »|6, l«36-9 (192U)

3. Conner and Adkint, J. Aa. Cham. Soe. ^ II39 (1932)

U. 0. Bagel and R. M. MatikaTleh, Ulcrain. Cham. J. 10, U (I935)

5. A. J. Hill. J. Ind. aig. Cham. IJ, 50U-9 (I92I)

6. Hinsbarg. Ann. 237, 33^

7. Hlnsbarg, Ber. IJ, 320

8. Hlnsbarg, Ann. 222. 2U5

9. Hlnsbarg, Ber. 23., 78^

10. Hlnsbarg and Straplar, Ann. 287. 222

11. T. B. Johnson, J. Ind. Sng. Chan. 12, 636-U3 (I920)

12. Kindlar, Ann. U8^, II3 (1931)

13. Mallh«, Co^>t. rend. I66, U67.9 (I9I8)
lU. A. Mailha, Cospt. rand. I66. ^&h^ (I9IS)
13. T. Mars and C. Rls, Bar. 20, II9I

16. Sisnnd Motykawaki, Bar. kl, 8O5

17. Piadan, J. A.. Chea. Sqc, 60, IO33-5 (I938)

18. Fudan and Adkina, J. ^, Chem. Soe. ^, 2U87-99 (I936)

19. Sonn. Ber. }W, U850

20. Swoegler and Adkins, J. Aa. Chen. Sqc. 61, 3U99 (1939)

21. C. F. Wlnaae and Adkins, J. Aa. Chan. Soe. 5U, 306-I2 (1932)

105

ACaOWLEDOSMESTTS

The Author wlghec to express his sincere appreciation to Dr. C. B.
Pollard, Chaiman of the Author's tupervisory Comaittee, under whose
direction this work has been done. Dr. Pollard's friendship and his
guidance, both in the laboratory and in personal contacts, hare been
the iource of snich help and encourageaeat.

The author also wishes to extend his thanks to Professor B. J.
Otte, Curator of the Department of CheAAstrjr. for his ceoperat4n a%
all times in securing equipment and laboratory supplies.

lo6

BIOOBAPHXCi^L ITiMS

O«rabon Joseph Shofiar was lorn Juns I5, 1918* in Utrboro, Borth
Oarolla*. Hs attsndsd ths pablie schools of Tisrhero, North Carolina.
In 1935 he entered The Clt4del« Charleston, S. C. , and transferred to
the Unirerslty of North Carolina, at Chapel Hill, N. C., in 1937. ^
was graduated from the UniTorsity of North Carolina with degrees of
Bachelor of Science in I939 and Master of Arts in I9U0. He has attended
the Thiirersity of Florida continuously froa the fall of 19^ to the
present.

Vhile continuing his graduate work at the Uniyersity of Florida,
he held a graduate assiskantship in Chemistry and a graduate scholai^-
ship.

Mr. Shngar is a neaber of the Aaeriean Chemical Society, Oaanaa
Signa Sipsilon Chonical Fraternity, and Delta Phi Alpha, honarary Qemea
language fraternity.

107

Cosmlttce Report

This ditstrtation has bean prepared under the direction of the
Chairaan of the candidate** SuperTisory Coomittee, and baa been approred
b7 all the Benbere of the Cooaittee. It was subnitted to the Oradoate
Council and \m,u approred aa partial folfillaent of the requirenenta for
the Degree of Doctor of Philoaophj.

Date

<^^ir, S', Ml/ 3

Dean

Snperriaory Coaaittoet

Chairaaa

>- H. tf^iaft—

./>\

/5^

Date r>ue

■^c

Phenanlhridine derivatives pa sci
547 28S562p

3 15ba 030bl 3SS7

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