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Derivatives of benzo(f)quinoline

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m m 3XVS8 or BMf2Q{F)QUJH0LXIS
to r
S&s&ett ffaytiiQxid. Bsxntua
A
f
B
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.FreeeitbeA t© th e 9fes«3fty o f
th e Graduate C o lleg e i n th e f t i i t e r e i t y o f le b r a s k a
l a f a r t i a l S h lfiU a w te t Of R equirem ents
f o r th e D egree o f S o o te r o f ItofloiJOfily
hepiaftiaeab o f <&•«&»«*?
L in co ln , M@braak&
- M y 3 o # i*#4i
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UMI Number: DP13667
IN F O R M A T IO N TO U SER S
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Qta amfcljor w ish es fco m p m * *
M s gftttifcnte ttt Dr. €* B*
Hai-dlton, who su g g ested the
*w<S su p erv ised th®
wm k$ and fco farte#* D avis and
Qtaqtiaagr fo r a r©*«ar®h gMtett*
389722
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fabl© o f Content®
m m
X*
I n tr o d u c tio n . * «.» * * . . * *
.
XX*. §|*A|83i©aX §uiati»ry * * ,* *
* . **•*■ 4
XXI* D lseuesloa
i
XI* E x p e rim e n ta l. . * # * . , * * " , # * # * * . . . *
A* P r e p a r a tio n o f
i
IS
B & rlm tiw ii * * IS
1* S*telno**S«iiftptetnole mold
2* 3 -Oarbornethoxj«2 -naphthjlarain©
3 . 5 -Hydroxy-2 -n ap h th y lasd jae
B* P r e p a r a tio n o f 5 - S u b s t itu te d D e r iv a tiv e s
o f Ben*© I f Q u in o lin e . * . . * . . * * # • * , *
* It
4* 5 -Carboxy-ben* o (f ) q u in o lin e
. g* 5-0arbsuayl-benzo ( f )q u ln o lin a
7# §*S-D ltedr© ~fb,6?)^lo,hloro»i-*© .arbo««tia© JE jb e n z o {f ) q u in o lin e
■S# |if |- iM o r © - S - o « rb » f tii0 3 i|'-b e n * o C f )f m la o liiie '
f* Kydr&ald# o f S»oarbo3^«b®-a*o|fMuinolIn#
1 0 . A zide of S.*oarb@^'-b®nioCf|fulaollne
XX* S«*Aoefeoai^Ln©*b«a*®|f )fiila o lla #
12* S -A aln o-b eaiso|f|tiila#iin e
IS* S-l^tr© ^r-ben*o{f:) fu ln o lln o
0* P re p a r a tio n o f X -S u b s titu te d D e riv a tiv e * Of
Senz© ( f >q u in o lin e . . * * * * * * * . * * • * *
14* 1 -Carbiusyl -feeoso ( f }f ■a iaoila©
16* l-O itrb «»tli«y-b #a»o{f|fu iB @ lIne
1 6 . . l-0 ;a rb .e tl» * y -b e a io { f } fu in © lla e
17. g y tr a s id # o f 6 ,6 -b e s s o o ln e b o n in lo a d d
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
* 26
18.
19 * 1 •leetdaaiao^baii*-©(f ) fat»©M u*
, qtdnolln©
21*
{p-41@thyla»iin0- ■'
l» a » a l|4 iy 4 3 ? ® « ifi#
B.
©f a©%kyli«i»©ailsyl Broadd© Xjr4xM
»%rmi<l«s« 50
22*
fttMML# l*ydi?®©a?©aiS.<t©
23*
fepcN&d* liyiipotTOBAd©
1* §#m €#a**ttt« »#A©tl©»® o f 5*tol»0'*©«aa@Cf|t«l©#ll3a®* *
31
■24* »*.( f* -Dl@thylamlno«thylamino) -b© nzo(f) q a la o lla o
2 5 . §*{ H »a® t^ l«^ aop r@ »yl«iisl»O j ~b& nza(f) «*
q u in o lin e
26* 5 * (2 -P yridylam ino) -b e n z o (f)qulnolln©
F* A n a ly tic a l Method©* * . ♦ * * * * . » * * * # . * • *
f.
Sunmtry * . . . * * * » * * * * * * » # ♦ * * * « * *
f l* B ib lio g ra p h y * * * * * * * * *
* * * * # , * * * ♦
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
5#
•' *. . INI
■*
*
li
I*
‘Bier© i n
m
In tro d u ctio n
lu fiM tlm tft d is e a s e which i t comparable to
m alaria in i t s w idespread g eo g rap feit d i s t r i b u t i o n *
Although
l a th e l a s t two d e c a d e s much h a s b ee n accom plished t o redos®
th e m o r ta lity r a t e s , i t s prewsAenee i s . s t i l l a s e r io u s profeIHeywj,
3*
Whatever method I s ms'si i n th e treatm ent o f m a la ria ,
i t m ust fee ■based upon th e s e fu n d am en tal p r in c ip le s ;
th e
e r a d i c a t io n ■o f f e e a ® h ise a ts w tileh a r e r e sp o n s ib le f o r . th e
a t t t t e a t ta c k s , and th e d e s t r u c t i o n o f fe e gam etocytes which
tvaxuRsit th e d i s e a s e d
Quinine 3ms o n ly a s l i g h t a e t i o n upon th e garnetocytes
and to., s t e r i l i s e f e e b lo o d co m p letely o f a l l p a r a s i t e s i t h a s
t o be g iv e n i n la r g e d o s e s over- a long p erio d o f time*I n view o f th e ah ttrteo H lag e o f q u in in e many compounds
have been s y n th e s is e d i n h o p es o f d e v e lo p in g new and b e t te r
rem ed ies f o r th e tr e a tm e n t o f m a la ria *
S in ce '-m e th y le n e -b lu e h ad b een p ro v ed t o be o f value' i n
t r e a t i n g m a la ria # Schulenann, S e M o h o fe r and W ingler^ m odi­
f i e d i t s str u c tu r e l a v a r io u s ways and o b ta in e d compounds o f
S
g r e a te r ' e ffic ie n c y * .' fiiey then, u se d d ia lk y la m ln o a lk y la a in o
s id e eh afg # i n th e 8* p o s i t i o n o f q u in o lin e and it® d e r i v a ­
t i v e s and fo u n d t h a t a l l o f fees® e x h ib ite d w are o r l e s s a n t i
m a la ria l a c tiv ity *
i f t h is s e r i e s o f compounds d -m eth o ay -s*
( C(-methyl- <£-H-diethylaminobufcylamino) -q u in o lin e (plaamoq u in ), was m ost s u i t a b l e f o r p r a e t i e a l a p p lic a tio n ,
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lo w e v e r,
o lA ttle a i in v e s tig a tio n . showed th a t plaamoquin which l a a more
d e s tr u c tiv e a gen t a g a in s t th e g s a s te e y b e a th a n q u in in e , i s
le s s . e f f e c t i v e a g a i n s t the s e h lz o n t s .4
.le a se i t w as''fo u n d
a d v isa b le t o combine plaamaquln with' quiadisi*
s
In fa r th e r sea rch f o r an a n t in a ia r la l argent o f h ig h
sc h iz o n to c id a l a n t p a w it o c it a l aetiw lby*, d e r iv a tiv e # o f th e
$
a o r id ln e s e r i e s w ere I n v e s tig a te d # A te b rln o r
chl© ro«9-{ (l^ eti^ l*(l^ 4ieih |*i8g^ ln #b tt:tyijw in oI«acriti»i:# ' "
showed s p e c if i c n o tio n on th e o eh lto n to bat no a c t io n a g a in st
■ 7
f e r h a p s th e b e s t p r e s e n t d ay treatm ent i s
7
th e plasm oquln-atebrin co m b in a tio n ,
the gam etoeytes*
A ll th e e f f e c t i v e c u r r e n t i m t i j a a l a r i a l d ru g s s a y be
•Idwrod a s daatols&ag a q u in o lin e n u c le u s , i f a e r ld ln e • c a n be
re g a rd e d a s a. q u in o lin e w ith a benzene r i n g f u s e d on#
O ther
n u c l e i a r e p o s s ib le a s i n th e ca se o f n e th y le n e -b lu e hut
q u in o lin e a p p e a rs t o be th e m ost u s e f u l so f a r found#
A lthough th e r e i s
m m h
t o be le a r n e d i n th e way o f
c o r r e l a t i n g th e c h e m ic a l s b re e b u rs ' o f " 'a n tim a la r ia l,a g e n ts
and t h e i r , b h e r a p e u tis a c t i v i t y , ' i t d o es n o t see® u n re a so n *
a b le t o assume t h a t compounds, .having a n u cleu s iso m eric w ith
a c r i d i n e -and . d l a l l ^ l a » h o a l ^ l a a i n # aid # ch a in s .in th e p o s i*
t l o n an alo g o u s t o th e 8* p o s i t i o n o f q u in o lin e , sh o u ld ■
.
.m erit la v e s t l g a tlo n *
f© . f u l f i l l th o s e requirem ents b e n s o (f ) •
q u in o lin e , was s e l e c t e d a s th e n u c le u s and th e S* p o s i t i o n
c o n s id e re d analogous t o th e §* p o s i t i o n of. q u in olin e*
l a a d d itio n , th e p u rp o se o f t h i s I n v e s t i g a t i o n was to
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.*«ap«8Nr
,#f th« -win-# g«etg>
when smfestltmfeiwl
I s v a rio u s p o s it io n s i s th# b e n s o (f}q u in o lin e a a eio ss* .
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
"4 .
II*
O raphleal B w m a sj
fh@a« compounds w i l l to-# ra fa rra i, to. W .thfti# r e s p e c t ­
iv e numbers in both th * 4iaem*®4«a. « « l tto» ■«sqpt r ia a a t a l p a rt a
o f tfea th eaia* .
GOOH
CQQH
OOCH.
1
CJJH
GOOCH
(n • M and
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
»GOOCH
CGIH^
§
y \/\m
I 19
b 4
1
-
H «• GH^ tmd '0j|Kn
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
#
XXX# M so u ssio n
M c o n sid er in g t o
p o s s i b i l i t i e s o f b m so C f) q u in o lin e
d e r iv a tiv e s as a n tia a la r i& l a g en ts i f was b e lie v e d th a t d i»
ajL%|,«i^.»@al&2rii» ^,sb ©id® ©bairn*# or © t o r s u it a b le smb»
s titm e s is # l a the S» p o s i t i o n o f bens©{f }q u in o lin@ sh o u ld esc*
h i b i t g m tiam l& rlai a e tiv ib y #
f b i s b e l i e f was b a s e d
m
th e
f a s t t h a t a l l th e § <«d::f .sib y l. mat n o a ity i-ayt **© q u in o lin e s bat*
h i b i t more or l e s s antimal&ri&l a e iiw ity #
i
and t h a t th e §»
p o s it io n o f b en s© (f) q u in o lin e sh o u ld be an a lo g o u s t o th e ' 8 p o s i i i o a o f ■q u in o lin e *
q u in o lin e
bens o (f ) q u in o lin e
Bens© ( f ) q u ln o lin e i s q u in o lin e w ith a bensene r i n g f u s e d on
i s th e ' §#§ p o s itio n s *
th e § • p o s i t i o n o f b en so ( f ) q u in o lin e
i s in.- t o . same p la e # r e l a t i v e t o th e beberoeyeXf© n itr o g e n
a s th e t«* p o s i t i o n i s i n q u inoline*.
By a n a lo g y t o q u in o lin e
i t was. also oagwotod t h a t g*araino -bens© ( f }q u in o lin e shirciXd
be r e a c t i v e to a l k y l a t i o s s in c e i- a m ia o - tm in o lia e e a n be
alkylated*
ft® f i r s t s te p o f t o
in v e s t ig a t io n t o n was to prepare
i-aain© .»bess@ C ^)f^h® li»e (19)#"'
3h rev iew in g t o
llte r a tm r e
‘f©ie number (18) r e f e r s t o form ula 12 in t o g ra p h ica l summary*
t h i s n o ta tio n w i l l be used to r e f e r t o th e g r a p h ic a l summary
throughout th e d is c u s s io n and experim ental p a r ts o f th e t h e s is *
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o f b e n s o (f} q u in o lin e no d e r iv a tiv e s w ith s u b s titu e n ts i n 'the
0» p o s it io n we**® found#
M r e e t n it r a t io n o f b© »zo(f Jquin-
© line g iv e s T^aita?© and 7 , 9 -d ln itr o -b e n to ( f ) q u in o lin e ,
non© o f the ©• isomer*
1Q
Wit
fiomoe the. 'amia© group must be i n -
troduced by another method*
'
fh e most l o g i c a l procedure
»««aMid"t©.'-bc t o prepare S«earboxy*b®nao ( f )qtd.noiine (3) by
■
ft
th e Skowm^ r e a c t i o n
on 3 -amino *4 -maphth o i c a c id (a|* ■ t h i s
a c id (1 )\ them mpem. d e g r a d a tio n M M
g iv e I-aaaine-bernae*
{f}q u in o lin e (1 3 },
m a c h ie v e t h i s I t was f l r e t n ecessa ry t o p r e p a y &•
amino-3-naphthGic a c id £3}*
f h l s was a c e e o p llc h e d I n about
y i e l d s M m th e 't-h y d * * o iiy -3 * i» |h to l© mold (1 ) by ms#
13
o f sin e c h lo r id e , ammonium c h lo r id e a id dry ammonia gas* ' .
The Scrimp r e a c tio n '' w h e n /c a rrie d out on g - a a d n o - d - n a j^ l^ o lc
a c i d {3} gave 3 0 -3 5 $ y i e l d s o f th e i-«earb@jy^b«n:8@(f}'tnltt-.
o l i a e |s } #
S e v e ra l m o d ific a tio n * o f th e r e a c t i o n w ere t r i e d
in -an e f f o r t t o o b ta in th e n e a t .s u i t a b l e eom ditle& s t o -get
th e mmrIimm y ie ld #
Wm m m p lM th e m ethyl e s t e r o f i- s m ia e *
3 -naphthoic a c id was p re p a re d h u t when t h i s was su b jected to
th e 't e s w p 'r e a c t i o n .S-oarbo3^,* b e s * o (.f)q u ln o lltte w as form ed I n ,.
a b o u t th e
w
t w
y i e l d s as: from the- § * « » lm e-5 * » ap b ^ e£ e a@Mi
The m o d ific a tio n th a t §1*m^® meed f o r th e Shramp r e a c tio n m
th e v a r lo u i a ltro * t* n a |iith y ls i^ .a ® s d id n o t g iv e a s good y ie ld *
m
W
the more v ig o ro u s treatm ent d e s c r ib e d by 'tem eppel
t or
the p r e p a r a t io n o f benzo (f ) q u in o lin e *
i f t e r i* c « r ^ i^ ^ b e n a o if } f ttla ® liiie (3) h ad been prepared,
the m eth y l e s t e r Of i t
(4) was mad© by th e u s e o f m ethyl
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
a lc o h o l and d ry hydrogen ©UorKto*54
m # i^oaybosiebhoxy*
benso (£) q u in o lin e (4) was r e a d ily e©mw«rb@d t© th e hydras*
i t # of 5 -c a r b o y -b e n s o (I 1)q u in o lin e
h yd ra te,
t h is h yd ra tld e
d ilu t e h y d ro ch lo ric mold*
ft) by mean#
.
of hydrazine
ft) wa» d is s o lv e d i n an excess' o f .
Hum sodium n it r a t e was added th e
a sid e o f 5 -carboxy boim o(f)qplst«!ttlio { I t ) was formed*
Si®
a s id e (10) i s u n sta b le and decompose# even a t roe®, temper*
ature*
Wpon a d d itio n o f th e a s id e of S * o a r h o ^ -b # n « o (fl*
q u in o lin e (10) to a m ixture o f a c e t i c a o id and a o e t io an*,
hydride# rearrsn«e»*iit took p la c e r e s u lt in g i s th e form ation
u
o f l^ o # t« fls is o » M n a o ff lin in o lia # ''' CH)*
*2h® a e e b y la ie d
amine (11) was h y d ro ly sed t o 'S*iw ino*b «aso(f Iqnlnollm e by the
u se o f s u lf u r ic so ld *
A b e t t e r y i e l d Of I'*a»ino*bett.so(f)fiiiii«liii@ (18) was ©b*
ta in e d by a different* but more 'expensive method*
9 h le was
p o s s ib le by v ir tu * o f th e f a s t th a t the y ie ld * o f the h yd r a s l d e o f 5«o*rboxy•benso ( f ) q u in o lin e f t ) from w hich
$ * m
in@*
bens© (f ) q u in o lin e was made were in creased*
-Hie p ro ced u re'in *
w olves .the *•*«%&«& o f hydrasia© hydrate *
S#d*dlhydr#*d#f«
dlchlorO *S*o«b© iieth03^-ben«o (f)q u in o lin e ( ? ) ,
However'i t
1* n ece ssa r y t o u se an e x c e ss o f th e hydr a t in e h yd rate .s in c e
i t a c t# a# a reducing agen t t o remove the c h lo r in e s a# w e ll
I
a# replacin g, th e «9GK« group by a -I-lfHj* group, S i# § # t*
dihydr©*®*@-di#hl«©*i*earbom*tlic^y*b«ngo (f ) q u in o lin e (7}
was prepared by re flu sd n g the a c id c h lo r id e o f i# # * ^ h y d r o *
S*S'*ii®hl©r@ »i--carb^,*beni@'Cf;)quiaoline (e ) w ith m ethyl
a lcoh o l*
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i
5 -Amino m b ® x m o (f)q u in o lin © | l i ) ©an b® dlas© C Iged and
©oupled w ith (3 t o p h t o J * ©r & a c id t o g iv e t o
deep r e d p ro *
e lp ifc a te a c h a r a c t e r i s t i c of t n » a ro m a tic p rim a ry sa in # * *
f b l s am ine (12) v a# ©©ndanatd w ith. ^-diefehyiaain© ® thyl
bromide. t o give
ia e f
(i$ whan n » ft) isi t# » S S $ y ie ld s *
OdolooiAtlon w ith
■
^ -d ieth ylasd n op rop yl bromide lik e w is e gave 5« (|f-d ie th ylaialn o»
p*»^>yiaiftia@>-h®iaa#Cf)fml»®iia© f id when a « 3 ) , h a t in. p#@r»
on yields*
t o 5 - (^ia& ylaainopropyiajnin© ) -bens© (f ) quin*
©line (IS when
ft) wa® Isolated as the dih'|di?©©hl®rid©t
s
a wary' h ygroscop ic substance#
I t ha* an ©range ©©lor ©bar*-
a c t e r i s t l e of .to hydrochloride# described by diem*
id
to
oondotoitido ©I i« a a d » © to a i.© (.fit^ n © i4 » a w ith i-by©m®*pyri**
din® gave 5 - (2-pyridylam in o) to n s © ( f ) q u in o lin e (14) *
AootyX*
a t i i i t of 5 ~amlno~beni5© {t ) quinoline w ith acetic anhydride I n
g l a c i a l a c e t ic a c id gave good y i e l d s of i«aaetoattiao-hen$© *
(f)qulnolin®* i l l )
Comparison of 5-am in o-b en so(f )quin© llne w ith d«<toa»*
q u in o lin e showed th e two ar® analogous i n t h e ir chem ical he*
h a v io r .
Both o f t o n ©to be d la s o t is e d and ©oupled w ith 1.
acid*
A lk y la tio n w ith d la lk y la s d n o a lk y l h a l i d e s h a s been
accom plished In th e ca se o f 5 -am in o-benao(f) q u in o lin e a s
w e ll a s. fo r. t o
§«iato®*ful»©Iia®#®r ® Bach o f th e se amines
i s r e a d ily acetylafced w ith a c e t ic anhydride.*
S in ce t o
If
e n p e r ia e n ta l work v e r if ie d t o
p r e d ic a tio n
th a t S»aaiao.#beiisoC f)tiainollne should be analogous t o 8«*aa&»o~
q u in o lin e , i t was hoped t o t . o th e r a n a lo g ie s betw een
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
t o
10
amines o f qM nolin© and b en zo (f )qulnolln© cou ld be ©a t a b ll sh ­
ed .
f o r t h is purpose th e s y n th e s is o f l-©mi»o*te©nao(f} -
q u in o lin e (26) wa* @em*lder®d d e s ir a b le *
t h a t i f t h i s *■&»•
{ m
l
I t wa* be11©red
c o u ld b© s y n th e s is e d I t would
m
*
M b i t p r o p e r tie s s i m i l a r t # th o se o f 4 -a m in o -q u in o lin e.
At th e begifB tiiis o f t h is i n v e s t i g a t i o n th e on ly taow n ■
l« sttM « sa h * tit8 to 4 d e r iv a tiv e o f bens© (f }q u in o lin e was 5 ,6 b en ao elach o M M e a c i d ( 2 # * th is - had been p re p a re d by
IS
Hoblnaon and Bogert ' by th e Boetmer r e a c tio n from £*aigfe*
thylamin® {IS)*
lane© the problem of preparing l*sa&&e«
b e a s o -if)q u ia o lls e wa* reduced t o the d egrad ation o f ft, 6*
b en zocin ch on ln lc a cid to th e corresponding main©.
t,d » l® tt« o eim eb o jiittle sold (AO) was e a s i l y prepared by
th e method o f to b ln s o n an d logerb*^®
t h i s a c id {20} ;ro*
a cted a t mm- tem perature w ith tM e n y l c h lo r id e to form th e
a cid c h l o r i d e .o f 5,6-b© n»© eiaoh«M nio a@Id
(2 1 )*
fh e p r o -
d u c t {2 1 ) was n ev e r p u r i f i e d , b u t th e erne©as. th lo n y l c M e r*
id® was removed from the r e a c t i o n M a tu r e under redm eed
p resso r* and' th e ©rude a c id c h lo r id e {21} u se d i n t h i s form
f o r fu b sefm eat re a c tio n # *
5,A«b*sui«*iiMih*nitki* a c id
fty r e f lu M n g th e a c id c h lo r id e o f
{2 1 }
w ith m eth y l a lc o h o l th e m ethyl
e s te r o f .A ,A »b*ns**iB*h*niai* a c id (AS when S I s OH*) wa*
I s o l a t e d i n good y ie ld s *
the above named, compound may a l s o
be © aile d l-#arbM »eth@ ay-bea*off}'quiBO lin® {25 when 1 i s
0B*} 'ind w i l l be r e f e r r e d t o "by t h i s name,
i l m i l a r tre a tm e n t'
o f th e a e ld c h lo r id e o f § ,i-b e ji# o e ln © h e M iilt a e ld w ith e t h y l
a le e h o i gave l-carbethoxy-bem ao ( f )quinolin® {23 when 1 i s
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
11
0»He)*
d o a c c n tr a te d sutmtonium h y d ro x id e re a cted v i o le n t ly
w ith th e erode a c id .c h lo rid e ©f 5 , 6 -b © » » © * c la e li« la le (8,1)
to form th e asald® o f a #$ -h ® a« o © .lao h ^lal« a c id (ag) ( l - c a r b amyl-banco (f ) q u in o lin e ) .
f e e r e a c t i o n o f e it h e r 1 -carb © -
w efeoxy-befii© ( f ) q u in o lin e- o r X -earh«.i fe©xy-ben«© ( f ) q u in o lin e
w ith hydrazine h ydrate gave p o o r y i e l d s o f th e hydrazld© o f
cD
t>5 ,6 -h en zoeln ch on ln ic a c id (84:)*
p^one o f h y d r o ly s is , f o r
th e
f e e r e a c tio n p ro v ed t o be
most p a rt* in ste a d o f th e e x p e c t­
ed clea v a g e o f th e a lh o x y group*
ftii® was q u ite ev id e n t from
th e f a s t t h a t most o f th e r e a c t i o n p ro d u c t was ®,®-ben«©c ln c h o n in ic a c id (80) r a t h e r th a n the d e s ir e d hydrazlde o f
5 ,6 -ben soeln ch on in lo a c id (84)*
A f te r th e hydrazid© o f 5 ,6 -
b en zocin ch on ln lc a c id had been sy n th esize d th e rem aining
step® l a th e d e g r a d a tio n gave e x c e l l e n t y ie ld s *
In o r d e r t o c o n v e rt th e hydrazlde o f 5 ,6 -b en zocin ch on in 1# a c id (84) t o 1 -am ino-benzo(f ) q u in o lin a ( 8 6 ) , f e e hydrazlde
o f 5 ,6 -benao (f ) q u in o lin e was f i r s t c o n v e rte d to fe e a s id e o f
a* ® -b e n « o c ia c h fe in ic a c id ( S i) by fe e a c t i o n o f n it r o u s ac id *
A ll a tte m p ts to .get a m eltin g p o in t o f t h i s a s id e (8«) were
f u t i l e b e c a u s e . i t decomposed so ra p id ly *
.As soon a s fe e
a s id e o f ®,@ -b@ nsoeiaehoiilrf,e a c i d ( 8 f ) was i s o l a t e d I t was
d is s o lv e d i n dioxane*
t h i s im m ediately l i b e r a t e d n itr o g e n
w if e f e e e v o lu tio n o f h e a t , i n d i c a t i n g th e d e s i r e d rearrange­
ment was talcin g p la c e *
When f e e diox&ne was removed by .die-,
t i l l a t i e n and th e r e s id u e re flo a te d w if e con cen trated h y d ro ­
c h l o r i c a c i d , l-SBwino-b#nso{f)qidLa© liae (86) was o b ta in e d a s
f e e h y d ro c h lo rid e *
389722
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
m
limiiiciMii#' (3 6 ) was r e a d ily aoetyl& ted
toy the me® o f a e e t i# iuAsdrid® i n g la o ia l a c e t ic a c id t o
g iv e 1 ~ac ©t ©amino -toenzo (f ) q u in o lin e (37)*
S a le amine (86)
eondensed w ith p -dl©thylamln© -bensaldehyde to g iv e wary poor
y ie ld # o f 1 - (p -d ieth y la a ln o -to en ia la m la o } -b en io ( f ) q u in o lin e
CSS)*
numerous attem pt# to a lk y la t e 1-aialno-bensao (f} q o la o l*
in e w ith d la lk y la m ln o a lk y l h a l i t e # were u n s u c c e s s fu l.
A t­
tempted a lk y la t lo n w ider th e mum* or even more d r a s t ic ,
©ondltAen# s a t la f a o t e iy f o r th e alk y l a t i on of' §-a»iii#-toe»#e'(f)q u in o lin e were t o no a v a il*
1 -Amlno-toenao(f ) q u in o lin e
cou ld n ot be dlazofclzed a n t oeupled w ith 1 a c id or p -n a p h th o l.
d©stp&m«s» o f 1 -suaino -ben* o (f ) q u in o lin e (36) %& 4 -audne*
q u in o lin e r e v e a l# a o lo a e resem blance# . S e l l e r o f the#®
if
amine® can to# d l a s o t i a e d and co u p led w ith 1 a c i d , '
Both o f
the® can toe a o e t y la t e t w ith a a o tla an h yd rid e.20
Although
31
g-phenyl-A -ealB O '-qtdnoM 'ne ha# b een a l k y la t e d i n p o o r y i e l d s , ■■■
no example o f a l k y l a t i o n o f the 4 -amino -q u in o lin e i t s e l f w ith
d la lk y la m tn o a lk y l h a lid e # wa# found I n tide l i t e r a t u r e *
Likew ise th e d ia lk y la m ln o a lk y l h a lid e # d id n o t r e a c t w ith
l'-aiilao»toeii«o { f) q u in o lin e #
A f te r th e
1
-amino-toenmo Cf ) q u in o lin e had b een p re p a re d
and i t s ehessAeal b eh avior s tu d ie d I t was p o s s i b le to compare
th e r e a o t i v l t y o f th e amino g roup i n the t h r e e d i f f e r e n t r in g #
o f toen z© (f)q uin olin e. ' Clem10 p re p a re d th e 7 ,8 and I d - a id n e toenz o (f ) q u in o lin e s , tout r e p o r te d "-the a llc y la tio n o f none o f
them*
Be s t a t e s t h a t numerous attem p ts to a l k y l a t e th e
7 -am ino-benso (f ) q u in o lin e w ere u n s u c c e s s fu l,
A ll o f the-
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a tte m p te d a l k y l a t i o n s o f 1 -am ino-benzo (f }q u in o lin e wer®
also- f u t i l e .
I*tola©«lj@»»o.Cf
w hich was sue-cess*
f u l l y a l k y la t e d l a t h i s i n v e s t i g a t i o n , i s th e o n ly an® o f
th o se am ines t h a t h a s boon e te d e n s e d w ith 'd i a l k y l a ^ n o a l h f l
h a lid e s ,
The t h r e e is o m e ric am iao bens© if I t u l n o l i n o S ' p ro *
p a re d by G l « « ^ w ere * e # ty la t« d and i n t h i s i n v e s t i g a t i o n
th e 1* and th e i« a* iao -h ® n s© (f |fmi'ii#'liij®8 wore a l s o a c e ty l *
ated *
7 -A m ino-benzo( f ) q u in o lin e condensed w ith toensald©*
hyd® tO'giw® e x c e l l e n t y lo -ld i o f 7-benz&lamlmo-b©nzo ( f ) q u in o li n e .3,0
i'-A m iu o -h o -ia o ff)q u la o lia o gave much low®?
y i e l d s o f hh® c o rre s p o n d in g 8 -benasalaiaino-benzo {f ) q u in o lin o
-and th e 1 0«*amino -b en s o (f }q u in o lin e y lo ld o d o n ly an o i l when
t r e a t e d w ith b e n sa ld e h y d e .
A ttem pts to condense b e n s a ld e -
hydo t e d p-diethylam ino-benzal& ehyd© w ith 5 -aiain o -b ® n zo (f) q u in o lin o m m I to d o n ly 'in reco v erin g th e S-suaino-benzo {f ) q u in o lin o *
.l«laia*«beiU N »(f}q u in o lin ® was condensed .in v e ry
po o r y ie ld s ' w ith p ^ « ® y !te in o -« % tn * a ld ® % d ® t o giv® l« ( p «
d ioth fitein # -h @ n sa lteiin o |'-b ® n * o |f|'tn ln ® lln « * (88)
-search o f ®• s u b s t i t u t e d b on so( f }quinolin©a w ith o th e r
ty p e s o f te b s tltn a a s b s th a n th o s e a lr e a d y d e sc r ib e d , th e
s y n th e s is o f S-*chlor®*be»s©(f )quia© lin® was a ttem p ted *
%
th e u se o f th e ite a u p r e a c t i o n -i-«*hyii«sy*bensO'Cf| q u in o lin e
(1 8 ) was p re p a re d in- y ield ® ©f l e e s th a n I d p e r c e n t from 3 4 iy d ro iq r» i:^ a |h tl^ l« i» l» ® {17)-*
the- amount o f th e ®*hydr@asy*
bcnzo {f ) q u in o lin e (IS ) t h a t o o u ld be prepared by t h i s pro-*
cedar® was s o scare® t h a t t h e co n v ersio n o f i t to ©*ehi@r@*
benaa (f ) quinolin© was n o t even co n sid e re d *
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W m U
d i f f i c u l t y wa® encountered i n th e p rep aration o f
S-hyiroxy-ben®© ( f Jquinolin® {18) by th e Skraup r e a c t io n .
lb® condition® ns@d fo r th© p rep a ra tio n o f d^arboaywbesis®*
(f)q u in o lin © |S ) gav# o n ly d ecom position p ro d u cts, in d ic a t in g
m a t a m ild er -reaction should b# us©#* Ihen th© pfOMAnri
10
used by f l e a r f o r th© p rep a ra tio n o f 8 -n i tro -b en co {f ) quin o lin # was t r ia d non© o f th© d e sir e d product wa# obtain©#
wtiil® excess form ation o f c a rb o n was en countered, showing
t h a t a s t i l l m ild er o g l& itia g agent would be necessary*
f i n a l l y a very poor y ie ld o f the i'«byd.r@3iy*b®n*®Cf) quinolin©
was r e a lis e d by adapting, a method s im ila r t o m e on® used fo r
14
th e p rep aration o f 6 -ca r boxy -ben ao (f ) quinolin© *
»© a ’ftd a n a e has- b een p r e s e n te d th u s f a r f o r m© ©lm@id»
a t i o a o f th e itru e b u r© o f e i t h e r i-»i^diliydr®»S;###diohloro«® «
earbom © thoxy-bonao{f ) q u in o lin # (?)
m
#*©feloro«ft«oarb9'»
methoi^-»b©iis@-|f|-®ainoliae {8 ).
■men .l-*e«rboay-*ben»o{f Iq n ia o lin * (3) wa# tr e a te d with
thfonyl ohlorid© and -subaeqmeat a ic c h c ly s i# w ith m ethyl a l*
Gohol i t was ©ap#ct®d t h a t i-* o -a rb ^ eth o x y » b en so (f)q o ia o ila#
(4) would be th e r e s u lta n t p rod uct.
low®war th e m eltin g p o in t
was co n sid era b ly h t^ ie r than th a t o f S-earbom©thoxy-benzo (f ) q u in o lin e |4 ) and a fo a lita fe ly e a n a ly s is repealed., th e p r e s ©no# o f ch lo rin e*
'
A q n a a tita tiy # a n a ly s is f o r carbon* hydro­
gen and em eriti© showed th a t the compound r e fe r r e d to a s
§ , 6«dlhydtra«Sf ©-di©hl©r©*4»0 arbome thoxy -benzo ( f ) quinolin®
(7) co n ta in ed two .more © hiortn# atom# than 5 -carbornethoxytoenzo{f }quinolin© (4 )*
M a ly s i s checked th e form ula# fo r
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
it
c 1*13,301*10* (7) t a d
(4) r e s p e c t i v e l y ,
H y d ro ly sis
Of th e compound d e s ig n a te d a s Sf §-dihydr® -§,i-dl© hl@ r@ ^-» ■
earbcm tethoxy-benso { £ ) q u inolin© (? ) gave a s a c id e t h e r than.
§ -@ arb ax y -b en zo (f)q « i» o M sc { 3 ).
te a o b io a o f th e compound ■
© a ile d 5 , 6 -d ih y d ro - 5 , § - d io h lo r o - 5 - 0arbom ethoxy-benao {f ) q u in o lin e
(7 )
w ith h y d ra z in e h y d r a te im m eth y l a lc o h o l gave
th e same hydraisid# o f i-4 arh @ * 3 r* les« o |f J q u in o lla e (9 ) t h a t
was o b ta in e d by th e r e a c t i o n o f h y d ra z in e h y d r a te o s f »
© arh^ethO i5y«heaao{f)qtiln@ iine ( 4 ) ,
t o show t h i s was th e
ea se hydr&zld© a s th® one p r e p a re d from S-carbaiaefehoxyhen so (f ) q u in o lin © , m ixed m e ltin g p o in ts o f th # two sam ples
i s v a r io u s p r o p o r tio n s w ere ta k e s*
s io n ,
l i e s # shew.#d n o d e p r e s ­
e a c h o f th e sam ples o f th e hydrazld© (9)
was h y d ro ly se d w ith 'su lfu ri© a e ld and l a ea ch e a s e §*© arbexyb e n s o {f ) q u in o lin e | i ' | was o b tain ed *
S in ce th e h y d r s s id e (9)
p re p a re d by two d i f f e r e n t m ethods was th e same i n b o th c a s e s
and a ' q u a n t i t a t i v e a n a ly s is f o r c a rb o n , hydrogen and a l t n o g en was c o r r e c t f o r th e d e s ir e d hyd im sld e Of © -carboaqr- ■
b e n z o (f ) q u in o lin e (9 ) I t w as o n ly l o g i c a l t o b o ile r© t h a t
th e two c h l o r i n e atom s 'added t o th#' n u c le u s o f b -o arb o x y *
b en z o (f ) q u in o lin e fS j d u rin g th e tre a tm e n t w ith th lo n y l c h l o r ­
id e and w ere removed by th e m e th y l a lc o h o l s o l u t i o n o f h y d r­
a z in e h y d ra te * '
A r e a c tio n very sim ila r to the one J u s t m entioned h a s ■
b een found I n th e case o f th© 9,10-dibromid© o f phenanthren®.
When t h i s d ib ro n tid e was warned w ith potassium h y d ro x id e and
p o ta ssiu m a c e t a t e l a m ethyl a l c o h o l , phenanthren© i s o b b a ia m * m
' '
th e n th* d ib ro iald e was g e n t ly h e a te d l a non-aqueous
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
s o lv e n t# h y d ro g en brom ide i # l o s t and ■th® r « « a lia * it p reim iii
Q % 24
I# 9 .broaoph®n*mthr es©. * ; ■ I t wa® fo u n t th a t when t h e
@Os«>e«iid. d « i# ia b « d a»a©thossy*bess®(t )quinolin© was g e n tly teat#® w ith a w o n ia e a l
methyl aleoh ol th® resnlbaitfc i^hioro^^arbomethoiiywb®*!##**
( f }q sln olia® (s) feat
mm
molesmle o f hydrogen ehlorid® la#*,
than th# assumed 8#f*dih3dr#^#6^iehl©re^*^*rbe®*®theasybenzo{f }quinoline (?J*
fh a se r e s u lt s indio& tod that, th® d o a b le bond i n th#
5,® p o s it io n ®f b en so (f )quinolin® 1# life* th e .® ,!® bond o f
phenanthren© *
h » r> f.R ^ t )
» a i f law
j^ ® a a a th re » #
fh#3ai»thr#»# l a a b ip h en yl with' th # g*i* p o s it io n # .
HH
bridged b y -a -0*0* g ro u p Wmm tmm&am th ree ©on&ensed b®»*
«®»® idug#*/ *be ©#1# b o a t i s nor® t l i f i n i ® i n
th# e th m . bunds#
th a n
|-fmin©iln@ may b# re g a rd e d a s a '
.
X
phenanthren© w ith th# *X» gpe«p r e p la c in g the •§**' group i n
th#? 1 p o s itio n #
fim® i t $ m m lo g ie a l. t o «xpaot an. eXifimf®
ohara©ter o f the 5 ,6 doable bond i n benao{f )quin olin© *
i i a t e no r ig o r o u s p ro o f h a s b een g iv e s f o r th # p o s it io n s
o f Hi# o h lo ria® atoms i s e i t h e r Iti-d lh y d ro -S fi-d lid ilo rO '* * ® ^
©arboaethoxy-ben*o (f )q u in o lin e {7) or ®.^hXer@^«oarb®8t®the*y
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
I ?
benao{f }q u in o lin e ( 3 ) , th e se two compounds w i l l be r e f e r r e d
t o a® S
( 5, # f ) •«llehlo»»S'Mia**bi»#th®3S|,^te«ii®©(t ) *
q u in o lin e and f i t
r e s p e c t iv e ly .
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
"SP'ty
*n g n
jit m u j/kajm a**»
A* P reparation o f 8*Ia|lithyiaiiilii© D e r iv a tiv e a
,
1* d -Amino -3-n ap h th oi e a c id |S |
*
Stela ecmipound has been p r e v io u s ly prepared by F lo r a
19
and Soblor
but a m o d if ic a tio n o f t h e i r method was used*
M v f h u n d red grams o f 8*kyiroigr«i«aaj^Mateol@ s o ld was
In tim a te ly Mixed w ith 800 g . o f f u s e d l i n e c h lo r id e and
1000 g* of' m m aa& m c h lo r id e .
l a r g e m etal v e s s e l
m m
t h i s m ln tu re was p la ced in a
n e s te d t o M f - l f # * f o r 48 h o u r# w h ile
d ry u M i i g a s was p& saad, th ro u g h the m ix tu re*
'She a o lid
c o n te n ts o f th e v e s s e l was grownd gad the in o rg a n ic s a l t #
e x tr a c te d w ith 8 l i t e r s o f 10 p e r c e n t h yd roch loric gold*
th e r e s id u e was t h i n b o ile d f o r , 4 h o u r# w ith 6 l i t e r s ' o f
con cen trated h y d r o c h lo r ic s o ld and the h o t s o lu t io n f i l t e r *
ed th ro u g h a n a sb e sto s f i l t e r *
S h i# p ro cess was r e p e a te d
u n t i l no. more o f th e r e sid u e could b e e x t r a c te d w ith th e h o t
e e a e © » ira te d h y d r o c h lo r ic aeld *
W a rn
Mi# h y d ro ch lo ric acid
,
f i l t r a t e t i l e o o le d th e i* aiid so ^ * iiap b th @ ie a c id p r e c ip ita te d
a s the h y d ro c h lo rid e *
"the h y d ro o h lo rld © was d is s o lv e d in h o i
w ater* c h a rc o a le d , A l t e r e d * and th e sodium a a l t o f i* am iae»
3 -naphthoic a c id was p r e c i p i t a t e d w ith sodium a c e ta te from
th e hot s o lu tio n *
A f te r c o o lin g , the sodium s a l t wao f i l *
te re d * d is s o lv e d i n h o t w a te r w ith enough b a se t o make th e
^Ih© somber l a th e p a r e n t h e s is refers t o the fo rm u la r e *
p r e s e n te d by t h a t number i n th e g ra p h ica l summary*
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
It
s o lu tio n a lk a lin e to litm u s p aper, filte r e d again a n t f in a l *
l y p r e c ip ita te d from the h ot s o lu t io n w ith aoetl® acid*
y i e l d , 100 g*
i*
11 it*p, H i§ >
s»$«tnh*e% ho^'-a-*®i^tl^l«i^iie .
F i f t e e n grams o f i* a ^ ln © ^ « i« ^ fh th o io a c i d , 31® ©c* o f
a b s o lu te m e th y l a lc o h o l and 113 g* o f -c o n c e n tra te d sulfta?!©
s o ld
m
m
re flo a te d f o r § hours*
fh « r e a c t i o n »l& bnre m s
©OOled*. n e u tr a lis e d w ith sodium tolottfM A ftto s o l u t i o n s a d th e
y e llo w p r e o ip ita t® remowod by f i l i a t i o n *
®he p r e i u i t w as
w ashed s e v e r a l tim es w ith w a te r, th e n w ith a s o l u t i o n o f
sodium M carfeonat® ami f i n a l l y -w ith h o t w ater*
I t was .
d is s o lv e d l a d i l u t e w rttoyi alcohol,., f i l t e r e d and a llo w e d t o
c r y s t a l l i n e ! y i e l d , I I g* (8Q£)j y e llo w n e e d le s o f
hesssgonal system * m*p* 106**
■Anal.*
®al©d, fo r C mMt %mm i I, f *97*
foundt
1,
3*9®, 6 .9 0 ,
3.
i^^droiEy^*«aflithylssadtt® '( I f I
t h i s ©oapewid was prepared % the same method as d e $6
m e rite d by F r i e s * "
B. Preparation o f S*iuhatltuted. D erivative® o f
Ben20 ( f ) q u in o lin e
4*
5 -Oarboxy-benao{f ) q u in o lin e {3)
f e a '.mixture Of f ® g« o f i#aaia©»3*iMi^thol©. aeiA , ■34 g*
o f arsenic a c id and 313 g* o f glycerin® was c a r e fu lly -aided
1.06 ;g* o f concentrated aulfurl© acid*
fb* mixture was slow ly
heated t o l t f #*. While the m ix tu re was w ell stir r e d the
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
t s n p s m t w * was g r a d u a l! y in c r e a s e d to.&SS* d u rin g a p e r io d
o f 4 h o u rs ,
At th® end ©f t h i s tim e th e te m p e ra tu re was
r a is e d t o 145-150® where i t was m l n t f t i a s d f o r 4 more hours*
a ® r e a c t i o n m ix tu re was them p o u red I n t o a l i t e r o f w a te r
an d a llo w ed to s ta n d o v er n ig h t*
t o .t o i l i n g And f i l t e r e d *
I t 'w a s th e n h e a te d a lm o st
9fe* f i l t r a t e was made b a s is , w ith •■
sawo n in a h y d ro x id e* f i l t e r e d * and th e f i l t r a t e a c i d i f i e d w ith
a c e t i c a c id #
filtra tio n ,
t h i s u s u a lly gave * gust* w hich was removed b y
W m
g m
was d is s o lv e d in. ammonium bydroxfde*
tlie s o l u t i o n f i l t e r e d and th e f i l t r a t e a g a in a c i d i f i e d w ith
a c e t i c ac id *
H ils p ro cess, was r e p e a te d u n t i l a l l o f th e g a t
was i n s o lu tio n *
flie d i l a t e a c e t i c s o ld s o l u t i o n was th e n
c o n c e n tra te d u n t i l th e ©rude 5-©«fb©xy">b©ni©(f) q u in o lin e
s e p a r a te d ,
,’t t t l s proA uot was r c a y y s t n l l i M d from c e l l o -
so lv e e o l a t i o n ,
A seco n d i m r y s f c a l l l s a t i s a from e t h y l a ! »
©©hoi 'w ith th e a l t o f c h a r c o a l g av e 'W h ite n e e d le s o f th e
t e t r a g o m l ''s y s t « i # ' y ie ld * S i g* {J&jOi m*p» S®4«S#*
Axttl*
found?
$*
titled* f « '©!♦««»%I
0* ¥ § * l i f ?0*«*J
0* ?»*31|
I*. 4*00* .4*01#
1* 4«OT# f» S•£.*«
S» 4*88, 6**0v
5 '* S a rh ^ 'th ^ s y * b e n s .o { f ifu la e liii« :( 4J
A m ix tu re o f 30 g* o f S ^arh o sy « h eaa© C f |f u i,n o lin e and
300 e.O:* o f - m e th y l a lc o h o l was r e f la x e d f o r
1
h o u rs w h ile t r y
hydrogen c h lo r id e m s slo w ly b ab b led th ro u g h th e r e a c t i o n adx*
taf@»
th e m ix tu re was c o o le d said n e u t r a l i s e d w ith sodium b i ­
c a rb o n a te s o lu t io n , ' S i# resm lt& n t ©11 was w ashed w ith w a te r
and p u r i f i e d b y r e a r y s t a l l l s a t i e n from a m eth y l a lc o h o lm t s r s o lu t io n w h ich h ad b e e n d e e o io r is e d w ith c h a rc o a l*
y ie ld * 1? g* (5 4 ^ )j
w h ite «©»©-
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
2 1
f t l i a l c p la te s# m,.p*
Anal*
FOondi
6*
Oslcd*, f o r 2 w l | , i lIQ i|t
0,. 7 5 ,8 9 , 75*80#.
C#i 75*95#. I# 4.5 8 *
.
«#. 4 * a i#/'4*§2*
5 -Carbarny1 -b en so {f }q u in o lin e {$)_
On© gram o f 5-c«rb©iseth©xy-fe«»ii©(f IfmiuoHia® was d i s ­
so lv ed in 25 ©#* o f m ethyl a lc o h o l and dry ammonia g as was
p assed through the s o l u t i o n fo r 24 l w * whtl® th© r e a c tio n
m ix tu re was k e p t a t 4 § #* th e a lc o h o l was allo w e d t o e v a p o ra te
slo w ly a t room tem perate*® *
iSam re ild a © was r o o r y s t a llia e d
from m eth y l a lc o h o l s o l u t i o n w ith charcoaling-#. y ie ld # , 0 ,7 g*
(66$)# w h ite m oncolliii® p la t# .» |. »*p* 29§»6#*
A nal,
Found.!
7*
Calcd*-, fo r <U*Hi0 I aG*.
0#. 75*71#, H* 4 .5 2 .
C* 7 0 , <*#. 70 * 6 0 * Hr 4 # 6 i* 4 * 0 0 *
s#,6*Mhydr@- (0*61) tfliciilor@-5-carhOMthoay-heiag© ( f >q u in o lin e (7)
f o 13 grams o f g ^ -carh o ay -h esao ff Ifu ia o lln ® was added
75 e e . o f thiom yl eh lo rfd ® and th e n ta to r o was h e a te d on a
w a te r h ath f o r 43 adm it*•» 'f h e 'e x c e s s th lo n y l c h lo r id e was
removed under reduced p r e s s u r e and r e s id u e r e f lu x e d w ith §50 ee ©f
a b s o lu te m eth y l a lc o h o l f o r 1 h o w *
The r e a c t i o n m ixture
was th e n co o led and sodium b icarb on ate added u n t i l th e s o lu ­
t i o n was a l k a li n e *
'th e cru d e p ro d u c t was d is s o lv e d i n h o t.
m ethyl a lco h o l* c h a rc o a l added*, and th e 'm ixture f i l t e r e d *
0© oli»g o f the f ilt r a t e gave 19 g* or a 78$ y i e l d o f white
powder#. m»p* 134 - § #*
* tb * m eaning o f th e q u e s tio n mark i s e x p la in e d m page I f
o f 'the d isc u ssio n *
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
•
A n al.
01, 23*01,*
C alcd, f o r O^V^^OlcVO^t • 0 ,
Founds
O, 5 8 ,8 1 , 58,31#
MB ,43#
t , 3,66#
E, 8 ,6 2 , 3,80#.
01* 22,84* 32.87*
%
fit)
o
Cf ) q u in o lin e (8
■
Five grams o f I #i-*§U^*N»~C§*Sf}
awitfaoxy-toonKO Cf ) q u in o lin e was d is s o lv e d l a 1 80 ee* o f m ethyl
a lo o h o l w hieh had p re v i o u s ly boem s a tu ra te d , w ith ammonia ga®
a t room to i^ o a a tw o *
t h e s o l u t i o n was h e a te d a t 40-45® f o r
s i x hour®, c o o le d , th e p r e c i p i t a t e f i l t e r e d , washed wit*,
w a te r and f i n a l l y r e e r y s h a l l i z e d from m ethyl a le e h o l#
y ie ld * 8*7 g* (84$) i b r i e i i n l e rod®# sup# 1 37- f #*
Anal*
01* 18*01.
deled * f o r 0 l s I lo 0 1 I0 a |
Brandt
0*. 85*21#.:
0* 6 8 * 9 8 , 06.04#
I * 8*72#
1* 5*70, 8*77#
01 , 12*68, 1 2 .5 8 .
0*
H ydraztde o f 5-#arb@ xy»ben»© (f.Jqulnellae { 9 ),
M n eteen grams o f 5,6'»4ih^ro->-Cl,ff}»diohlcia»©«5*' • ■
cartoome th o x y -b en zo ( f }q u in o lin e was d is s o lv e d .la 800 ee* o f
m ethyl a lc o h o l*
to t o
h o t s o l u t i o n was added 40 ©e* o f
h y d ra z in e h y d r a te and th e m ix tu re refluxed on a w a te r h a th
f a r f e w h o u rs.
At th e end o f t h i s tim e a s o l i d h ad se p ­
a r a t e d from th e s o lu tio n *
A f te r o o o lin g o v e r n ig h t# t o
s o l i d was f i l t e r e d and r e e r y s t a l l l z e d from m eth y l a lc o h o l
s o lu tio n ! y i e l d 18*5 g* (32jf)#
h ex a g o n al system #
A nal.
Founds
w h ite n e e d le s Of
t o
a#p # 8 6 8 -4 * *
Oaled* f o r 0 M% # a ^
<**
0 , 7 0 .8 0 , 70*88# ■1 , 4 .7 5 , 4,68#
S* 4 ,6 8 # %
17*71*
1 , 17*40, 1 7 ,7 0 ,
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
■m
10*
to ld # o f S * e « rb e x y -t» a 80-{f Iq n la o iis ® (1 0 ) ,
T h ir te e n and one h a l f g r a s s Of th e fcydrazlde o f
5~carboxy~benzo ( f J q u ln o lin e was d is s o lv e d i n am ex e ea e Of
IS p e r o e n t fey d ro eh lo rlo a e ld and t h e s o l u t i o n e e o le d t o
1 0 °,
.Then Tf.3 g* o f sodium n i t r i t e l a IS @e* o f w a te r
was slo w ly added t o th e h y d r o c h lo r ic s o ld s o l u t i o n w ith
good s t i r r i n g *
Tk&
a s id e was p r e c i p i t a t e d w ith s o d lu s h i*
c a rb o n a te s o l u t i o n , f i l t e r e d and dried.# y i e l d , 14 g*
( a ls o s t th e o re tic a l)#
y e llo w asaerpbeus powder# s»p* «S*
§T®,
■ffels a s id e « t so u n s ta b le t h a t a # a tte m p t was mad*
to a n a ly s e ' i t*
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
2 4
3,1*.
8« A eetoasdno-toenao ( f ) q u in o lin e * (11)
When 14 g* Of tb s a s id e 'o f 5 -earboaqr-benz© {f ) q u in o l in e
was added t© & m ix tu re o f 4 0 ©o* o f a e e t l o a o ld and #® ©a* o f
a c e t ic anhydride, n itr o g e n was ev o lv ed rad boat' lib e r a te d *
A f t e r ‘t M e v o lu tio n o f a itr o g e ii to n i-c e a se d ttoe. r e a c t i o n m ix­
t u r e was h e a te d ©a a w a te r bath, f o r 1 b o w *
ffe# m ix tu re was
th e n c o o le d , 150 cc*
n o tio n m ix tu re h e a te d f o r a n o th e r h o u r t o h y d ro iy s o
m
m
a o e ti© aahydridft*
I b i s gave a r o d
g m
so lv e d by adding a w # g l a c i a l ao e ti® ao id *
O h*
m » -
w hich was d ls *
A f te r a l l o f tb s
gum was i n tb s boo s o lu tio n ,. ©hareo&l was added r a d t b s s o lu ­
tio n f ilte r e d *
g h a
f i l t r a t e was. c o o le d o v e r n ig h t*
& sm a ll
amount o f tb s ©rode 5 » a« .# to a» ia o » fe sn so (f).fiiin o lin s was r e moved toy f i l t r a t i o n
W ba
f i l t r a t e was made alb& lia® w ith
ammoniTia h v d ro x id e and th e c ru d e 5 -a c e to a m in o -b 0 n 2 o (f )~
q u in o lin e f i l t e r e d f r o * s o lu tio n *
l e o r y s t a l l l s a t l o n from a
d e c o lo r is e d .s o lu tio n o f d i l u t e m eth y l a lc o h o l gave a y i e l d
o f 1© g* (78$) o f w M te f i a t s # o f th e ©rthorhomtoi© system *
#**j>* 126-7°*
Anal*
.Found*
12*
Oalod* f o r e*******0 * «# 7t*2§* « , 5.12*
0 , 7i*.14, 7i*.0$|
i , 0 * 1 2 , $*21.
S * l« iin © -to eiw o (f)q u iao lin # (12)*
H a t t y oo* o f c o n c e n t r a t s t s m lf w io a o id was c o o le d i n
an l e e h a th , and t o i t was s lo w ly added. 10 g# o f i-a o tto # a«i»o-to#ii.so.(f I f u ia o lin e *
th e m ix tu re was a llo w e d t o s ta n d
f o r two b o a r s a t room te m p e ra tu re *
'One hundred -and f i f t y oo*
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
m
o f w a te r was .tfcm
slo w ly added and th e s o lu t io n h e a te d
w a te r 'h a th f a r t e e h ew # *
m
a
A f t e r th e m ix tu re m e e o o l e t th e
tirad e main® m e p r e c i p i t a t e d w ith n a i a l w h y d ro x id e# ■th e
g re e n p ro d u c t was d is s o lv e d l a IS jf hydroeJiA orie a c i d s a d
p r e c i p ita t e d - 'w i th
m m m & m
h y d ro x id e .
i t was f i r s t r e o r y s i a l -
I l s e d from a 'eharoo& Ied i 8 t % i a lc o h o l s o lu t io n sa d fclMMt f r e e
p e tro le m e th e r
89*1.00*} # y ie ld * 8*3 I* (76jtf) j y e llo w
n e e d le s o f t e t r a g o n a l system# »*p* 1 8 ? -§ 0#
M a s o tla e d and
s t a p l e d w ith R a c id t a d S '-n ap h th al*
-Anal*.
900*1
19*.
Caled* f o r
C, tO*Ai* 80,98#
«». i « * i S |
«f § * li.
S* 5*22, i*4S»
§ '- % d r « y •& © ««|f |: f a l a e l l a e (1 8 ).
ih e s u l f a t e o f 3 ••hydroxy**2—
n ap h th y lam in e was f i r s t
IS
p re p a re d by h e a tin g th e 34syir«^*t*i«iaphthylaffli»e'' " l a an
e x c e s s of' 2 8$ s u l f u r i c acid *
Upon co o lin g * th e s u l f a t e o f ■
3.*h.ydr®3£y*2-aa|Ai^iy3j^a* was p y e e ip i.ta ie d l a a l n o s t
th e o re tic a l y ie ld s .
A fe lx ta r* o f 13*8 g* o f t h i s s u lf a t e * 13 g* o f s u l f u r i c
acid * 28 g* o f g l y c e r i n e ' and S
g+ o f a i tr o h e a s e s e was slo w ly
©
h e a te d ' t o 110 *
©urlng. a p e r io d o f t h r e e h o a rs th e tem p er­
a tu r e was g r a d u a lly e l e w t e d t o .1 3 8 - 1 4 # w here i t was m ain­
ta in e d f o r th r e e more hours*
th e r e a c t i o n m ix tu re was th e n
poured .into- 808 ®#* o f w a te r and a llo w e d t® s ta n d
m m -
nigfet*
S ie su sp e n sio n was h e a te d a lm o s t to b o i l i n g and f i l t e r e d ho t*
Hi® a c id f i l t r a t e was e x t f a s t e d w ith e th e r*
©se aqueous ex ­
tr a c t m s th e n warmed t o 6 0 -8 0 * and made b a s ic w ith. $ II
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
m
s o d im h y d ro x id e ,
The m ix tu re was -again e x t r a c te d w ith e f e e r
and f i n a l l y w ith d i l u t e h jd re o h le rS o maid*
m ie n 'fe e f i l t r a t e
of th e h y d ro c h lo ric maid e x t r a c t i o n was n e u t r a l i s e d w ith am**
monlisa c a rb o n a te s o l u t i o n a g re e n gum warn formed#
'® ie gum was
d is s o lv e d I n d i l u t e h y d r o c h lo r ic a c id s o lu t io n mud a g a in p r e ­
c i p i t a t e d w ith
m m r n d jm
carhonat® s o lu tio n *
p e a te d u n t i l th e p ro d u c t s o l i d i f i e d *
T h is was r e ­
i t was r e c r y s t a l U s e d
fro® m eth y l a lc o h o l w ith c h a rc o a lin g * th e n from prnmrolmw*
e th e r* mad f i n a l l y from m eth y l a l c o h o l | y ie ld * 9«9 g* (8$0#
w h ite p la t# # o f t e t r a g o n a l system# sup* 104-6®.
tea l*
ta S l
Calod# fo r C ^ ^ O i
G,
79*98#
.
I* 4*66! I , 7*18*
« , 80.12, 79*941 . ■«, 4*81* 4*79# .If, 7 .Si* 7*14*
0* P r e p a r a tio n o f l- S f e s M tu le d ; Smviwfttlwmm o f
Sense (f ) q u in o lin e 14*
1 —Garbamy1 -b e n z o {t ) q u in o lin e (2 2 ).
18
f if t e e n gram® o f S*-i-he-iig#eiiieh«i®ie -meld was r e f lu x e d fo r 'iO 'iiisutes w ife 70 me* o f th len y l chloride*
the
excess t h lo n y l ch lorid e was removed under reduced pressure by
d is tilla tio n .
To the- resid u e
m »
then added 180 mm* o f
c o n c e n tra te d amacmiMi hydroxide# ■The resu lta n t product was.
reo ry stm llised -frw . eth y l a lco h o l solution# yield * ..6 .$*■-■
(40£)i w h ite n eed les, orthovtommfele system# a*p* 858*4®*
Anal#
PcnmAt
Calm*# for '4i*R&«V«0t .6*--715*71j
.6, 78*49# 76*46#
«* .4*99# 4*7S*
1* 4*69*
.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
2 7
1§*
(25, when S i s €8«) ■
'
fe n grams o f S#$«lbsiig©©inofe«iiai© aeid^® and 9 0 to*
o f th lo n y l c h lo r id e were re-fluxed fen 90 s la t t t s i*
fim m *
c e s s th lo n y l c h lo r id e wits rumored hy d l a t i l i a b l m sad the
r e sid u e r e flu x e d f o r one hour w ith #-§0 ©c, o f w ith y ! a lco h ol*
A fter th e r e * * tlo a m ixture was co o led the e s t e r was p re*
c ip it a t e d w ith •editas b icarh on ate s o lu t io n ,
The product was'
r e c r y s t a l lis e d from methanol to g i t s ' 8*3 g* (B Q 0 j mono*
© lin ie r o i s j .
Anal*
fo u n d t
15*
sup* 104*9** •
d e le d , tm
i , 76*84, 7 i* 1 8 f
i , *m*Ȥ#
1 , 4,68*
» , 4*54, 4 .7 0 ,
i^ O a rb e th o ^ r-b e a s O 'ififtiin o lin e (8 9 , when 1 i s 0*8*}
MLf .j. i«wrflrin'innitnM■...I .iiff **rrt#>i
®
a s eempimwi- was
p r e p a r eTsu'WMr®y
W
i faIM
i. iitti -—
^ ——JBi—
^
tn e same procedure
as
for- th e p r e p a r a t io n o f l;- © a r b ^ th o x y '» b # n s o C i) th in o lin e ex*
aepb a b s o lu te e t h y l a lc o h o l was meed in. p la c e o f m ethyl a l *
o e h o lf y i e l d , fl0§ te tr a g o n a l p y ram id al it*p* 5@#*
Itanl*
Fomndi
17,
fa le d *
fo r
d t# ai» 1 0 * s i* f # * 4 i| I , 6*§8*
C* 7 6 .5 0 , 7 6 ,4 4 | 1 , 6*45*. §*-58*
ly d rae id © o f 5 ,6 -b en zocin ch on in ic a c id ( 2 4 ) .
When 64 g , o f i * 0 :arb«ttetho^y-*ben»oif |-«imlaoline# 170 as#
o f m eth an o l an d 40- ee* o f h y d r a s ls e h y d r a te w ere h e a te d to *
g e th e r on a w a te r b a th f o r $0- h o w s 16 g* o f th e ©rude
h ydrasid e was o b ta in e d ,
f h e ©rode product was v e e r y e to l*
H e e d from m W m & dl w ith the- a i d o f ch a rco a l! y i e l d ,
(9 9 )0 1
w h ite -n e e d le s o f th e h ex a g o n al system s
A nal,
Fomudi
Calcd, f o r 0 j * I i s |* § i
0, 7 0 ,0 0 !
0 , 70*98, 7 0 # $ i| S , 4*77, 4,7 1 #
16 g*
ii* p , 884*5**
1 , 4#681K,
» , 1 7 ,6 0 , 17,81#
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
1 7 ,7 1 .
m
i@*
1 -Amino•bensso ( f )quinoline (36)«
Fouficeii and
m »
h a lf g# o f the hydraaide o f
6 * 6*
benzoeinchonlnlc acid wag suspended to 600 ©e* Of .loo watop
ia which 7 f* ©f sodium albflfc# M i, boom d isso lv ed ,
m int© ■
a c e t ic 'acid wag slow ly added to tho mixture w h ile i t wag
w ail stirred *
A fter the ®fmbure had been stir r e d for four
hours the aside waa removed by f ilt r a t io n and immediately ■
added to ISO «o* o f dtom ooe
The di©xa»e so lu tio n evolved
nitrogen tad lib era ted M at*
fo insure complete rearrange-
aenfc the reaction aixttir© waa Hum heated
m
a water bath
fo r flw o hours, d ecolorised w ith charcoal* and filte r e d *
6ho dioatooo wag d is t ille d and a 00 tc» o f concentrated
hydrochloric acid added to the wtm
m ®
resid u e,
so lu tio n waa then neiluxed fo r 5 hours*
the acid
%©» eo o ila g in an
ic e bath the hydrochloride o f the a n ise separated*
This was
filt e r e d , d issolved i s water asd p recip ita ted w ith masonic®
hydroxide#
The m dse was r e c r y s ta llis e d frost aqueous ethas»
o il y ie ld 1© g* (85<£); tetragon al n eed lesi ®*p. 149®*
A n al,
Found*
li«
M e d * f o r ■Q x &
x & *
* % 80*68* H, 5*1% » , 14*68*
% @0.21, 80*101 « , 5 .2 1 , 5,30*
» , 1 4 ,1 5 , 14*18*
l^eetoam lno~benzo (f) quinoline (87)*
So & so lu tion o f 1 g* o f l^SBffldm@*to@sso(f)'fuinollae i s
4 e e , o f g la cia l, a c e tic acid was added 0«6 ee* o f a c e tic
anhydride,
the Mixture was heated under r e flu x fo r be»
Minutes and then, poured in to 40 et* o f water and w ell stirred *
then the so lu tio n was n eu tra lised w ith csM tlia i hydroxide a
white c r y s ta llin e product was precl.pltated*
Shi® was f ilt e r e d
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
89
and r e c r y s t a l lis e d D m al@o!i@i*iWater miatiir® t o giir® w h itl
n e e d le s , mono c l i n i c system#, y ie ld 1 g* (86$)# »*p* 1 9 9 ' *
Anal*
G&led* f o r S-jtaSjta^a®^
®#' 11*86*
Founds ■ I , 11*66, 11#86*.
90*
1 - {p -D ie tl^l«8iln©»fe@ii«aaa»lnd ) -hens© (f ) q u in o lin e {28 ) *
One g n « o f I-iM .» o » t# n i® (f )quln© lln# and 1 g* o f p»
dl«%Myliwlii@©®»«ald®toyde wet® r«#lnas®d to g e th e r l a 16 oe* o f
o e llo s o lv e f o r 4 hour®.
ffee »i«tur® was poured in t o §0' co*
o f w ater and t t » r e s u lta n t #11 r e o n y a ta llls e d from d ilu t e
a lc o h o l w it h ch arcoalin g# y i e l d , 0*4 g# (gijft# .amorjdioua
yellow'powder# ®*p* 138-8®.
Anal*
Pounds
Caled* f o r 0M8 a « la t
% 11*99*
1 , 11*86, 11*86#
SI* C(-{5,6 -B onaoeinchoninyl) ,
{p -d le th y la m in o -b en m l) -
h y ir a ila e {99}*
Oae and e .l^ t'* t® a tl# grama o f th e hydrsaM # o f 6 ,8 *
h en so o ia ch o u in le a c id , 1*4 g* o f p#dietliyli«la#*h® asald#hya®
e a t 99 oc* o f i i f f e t h y l a lc o h o l were r e ila g a d f o r 8 hours*
A y ello w product a sp ira ted when the s o lu tio n was cooled*"
IWLa was d is s o lv e d l a h o t ®thi*»©i, d e c o lo r is e d w ith char­
c o a l, and y e llo w n e e d le s o f th e ortho*h,«»hle system sop#'
arated 'on . co o lin g # y ie ld 9* 9 g* ( 7 8 jf tf m .p. 218*8®*
A nal,
dalod* f o r a»4B**Xt0«
Pounds' 0 , 7 0 * 4 0 , 7 9 * 0 9 |
% 76*74#
1 , 6*10.
I , 6 .2 1 , i* lt *
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
»* P r e p a r a tio n ©f Blettoylaiafm oaltoyi Bromide
2 2 ,
£?
brom ide toydretoromid®*.
S ix ty gram s o f ^ -d ie th y la a & iio e th a n o l was c a r e f u l l y
a id e d t© St'S g« o f
m %
fcydrotorooio a e ld with. c o o lin g *
fo llo w in g am ounts ©f d i s t i l l a t e war# coXXeeted w ith a
fto©
m m
■
toour p e r io d o f alow r e f l u r i n g between, each d i s t i l l s t i o r n
SS ©©*#. 1.8 ©.©** IS *©»* f ©•#* S ©o*> 4 ■*©*# 3 to#* I o c .
I eo* f r a c t i o n toad b ee n c o l l e c t e d , th o m ix tu re
was allo w ed t o r e f l u x slo w ly f o r tfavoo h o u rs and a f i n a l
f r a c t i o n o f 7© to * d i s t i l l e d .*
B is s o l u t i o n was ©@©l®d t o
7 0° and I t cc* ©f a c e to n e added*
When th e o o o ttn o s o lu t io n
was co o led f o r s e v e r a l d ay s i n th e r e f r i g e r a t o r * a y i e l d o f
110 g , (89$) o f th e d o s t r e d p ro d u c t was o b tain ed # m.p* 111#
M te ra tu re
13*
2 6 ,2 7
sup* !©§«*#*#
^ «M © thylam lnopropyl b ro sild o toydr@tor«iid®*
a ® sam e' p ro c e d u re was u se d f o r ^t h i s p r e p a r a t io n a s t©
p re p a re ^ • d le th y la m in o e th y l torotatde liydrobroaido#
and © ae-tentto gram s ©f
%
T h ir te e n
^ e th y lam in o p r ©panel was r e a c te d
w ith 48' c c . @f ■4 8 $ toyteeteroaic acid *
t h e fOiXowliig amounts
o f d i s t i l l a t e w ere c o l l e c t e d w ith on* h o u r i n t e r m i t t e n t r e *
f lu x in g t ’ 11 ®c** 4 oo«# 8*8 oo*# I c c * * '1*8 ©©-## 1 cc##
0 .6 so## 0*8 so*
a f t e r r e f ltu tiiig f o r th r e e a d d i t i o n a l tooura*
18 oo* more o f d i s t i l l a t e was c o lle c te d *
Th© r e s id u e was
©©©ltd t o ro ta i te m p e ra tu re and 1 8 cc* ©f d ry a c e to n e .added*
t t o a c e to n e was removed under' re d u c e d p r e s s u r e and th e
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
3 1
r e s id u e p la ced l a a m tuum d e s i c c a t o r where 1%. slo w ly
s o lid if ie d * y ie ld i i g*
($ $ 0 )
o f crude p ro d u ct# »#p* i i * '
She p ro d u c t was used In the ©rude form f o r subsequent
28
re a ctio n s* fh e p u r ifie d product ' / has a rep o rted a* p .
70%
of 91*®®%
A sm all' m m m t o f th e ©rude preduet was r e »
c r y s t a llis e d from dry as®tone ta d eth er*
th e w h ite c r y s t a ls
had a m,p# e f it#94% .
1 * Condensation Ee&etions o f 6«Anlno»benso { f ) q u in o lin e
S -{ g «M©thylafflino©thylamlno) -b e n z o (f Jq u ln olln e
24.
(13 When n i s 2)
■One gram o f 5-s«d m e'*'b eaie(f|fu la@ ili»f 2 .7 g« of-Ai»
©bhylaminoethyl b r e a d s bydrobrom td® , 1 .8 g* o f sodium a c e ta te
and 30 ee* o f a b s o lu te e th y l a lc o h o l w ere r e f lu x e d f o r tw en ty *
f o u r hours*
fh© a le o h o l w as resto red by d i s t i l l a t i o n and 100
so* o f w ater was added t o 't h e re sid u e *
The aqueous s o lu tio n
was then made b a s ic w ith an e x c e ss o f ammonium hydroxide*
T h e
y ello w o i l s o l i d i f i e d upon s ta n d in g l a th® l e e boat*
th e
p ro d u c t was f i r s t r e t r y a t u i i l a e d , fre s i a w ater-m ethanol so lu *
t l e a and then from an aeet«® e--w ai«f M ixture# y ie ld * 1*2 g»
#
(800) 3 y ello w n e e d le s o f th e t r i o l l a t o system# 'is.p* 65 *
Anal*
fo u n d ;
IS#
C alcd. f o r % # * # » *
0, 7 7 .8 8 , 77*78#
% 77.77* 1* 7*90.
% 7.91* 7*58*
5 - (^ -D1 e thy laadnopr opy la a ln o ) -bensso { f ) q u in o lin e
d ih y d r o c h lo r id e (15 when ». I s $|.»
A m ixture o f 2.® g* o f sodium a c e t a t e , 7*8 g* o f
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
m
& 1 sth y la n in o p ro p y l brcMsld® hpdrotoroiidd®* 8-#® g* o f
b e n a o ( f ) q u in o lin e t a t 1©# 00*, o f a b s o lu te a lc o h o l was r e *
flaw ed f o r tw e n ty -fo u r hours*
th e a lc o h o l was d i s t i l l e d a p t
12# ©®# o f w a te r added t o th e re a ld u e and tb® s o l u t i o n mat*
b a s ic w ith ammonium hydr@Kid«#
so lv e d i n and re c o v e re d
f r m
hopes i t would s o li d if y #
$
f h e o i l produeod was d ig *
a lc o h o l, a c e to n e and e t h e r i n ■
f i n a l l y th e o i l was d is s o lv e d i n
d ry acetone. and p re© 4 p lb * t« d by h ydrogen ch lo rid e# -
fh e r e d
s o l i d was- f i r s t r e e r y s t a i n sod f r o a -a*bmiyl a lo o h o l and
e t h e r and. th a n
tw m
n - b u ty l a lc o h o l> y i e l d 2*1 g# {50^),*
o ran g e iaygreasopie n e e d le s | »*p* 815-24#®*
I n a l*
Founds
25#
CftloA* f o r
0 1 , lS«6tt*.
C l, li-*-SC, 18*89*
S .* { 2 * ^ rS ,d y l^ l» o )* b o a a o (f J q o ia o lin e {M l*
'Us® and
p* m
®
o f d««Aso»to#n»oCf |'^m inoll.ne#-
1 .5 g* o f 8-*bre® opyridiae* 1 g*- o f sodinst. a c e t a t e , a. t r a c e
o f co p p er torsos** sa d 25 so* o f a*totttyl a lc o h o l w ere r e *
f l a r e d t o g e th e r f o r bwe»ty*f@ur h o u rs*
A f te r th e r e a c t i o n
m ix tu re had been w e H cooled*- 60 .**« o f e t h e r was added and '
th® © en ten te o f th e f l a s h e x t r a c te d w ith, d i l u t e h y d r o c h lo r ic
add*-
When th e a c id e x t r a c t was nad® aHsa.Hn® w ith awwieaeiup
h y d r o x id e 'a .brown sb ic tiy s o l i d was f o ile d *
l.® © ry « ta lllta b l© a
from e th a n o l gave 0*8 g* (40$) o f y e llo w o rth o rh o m b ic
c r y s t a l s | a* !* 142*4 '\
AnH*
Pounds
Caicd* f o r C2.#l t *»*i
C*' 78.50* 7i*41#
«* 78#«8|
H, 4*85*
H, 4*S1* 4«9l»
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
•3
F* t a a l y t i o a l Method®
Carbcn-hyirogen a n a ly s e s w ere p e rfo ra ted by th e m 1* :
a l e r e com bustion method o f a n a ly s is f o r carbon and hyd ro g en
l a ' th e .p re se n c e o f n itro g e n *
fftr o g e n a n a ly ses worn p erfo rm ed by th e #etd»® d#r#
Dumaa .method*
Carbon -hydrogen a n a ly s e * a s w e ll a s th e n itr o g e n
a n a ly s e s w ere made by Mr. H eb ert Coles*
A nalyses f o r c h lo r id e ism # w ere c a r r i e d o u t by t he
u su a l g r a t i s # t r i e m ethod f o r s o lu b le e b lo rid e S f i*«* d is *
s o lv in g th e sam ple i n t a t o r w ith th e a d d itio n . o f a sm all
amount o f a ife rio n e ld # p r e c i p i t a t i n g w ith s i l v e r n i t r a t e
and w eighing th e s i l v e r o h le r id e ..a fte r © o lle o tin g i n a
dooeh c r u c ib le ,
l « » l o n i e afe& wiae a n a ly s e s were c a r r i e d ■
o u t in the u su a l fa sh io n by th e Carius m ethod,
f h t c r y s t a l system s w ere d e t e m i a e d as. d e f i n i t e l y Os
p o s s ib le w ith a s a u se h and X
m
lbjM Clorising a d er@»c@pe from
a ttn d j o f th e ty p e s o f oxteLnotlao# c r y s t a l l i n e shape -and
d iffra c tio n p a tte rn s * ^
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
m
V.
l a s e a rc h o f confounds i M l k r l a s t r u c t u r e and a n t i m a la r ia l a c t i v i t y t o th® derivative* o f 8««aino*fU lnellm o*
'd e r iv a tiv e s o f §*«a3»@ »t)#a8o{f)fwl»@ libe have been sy n ­
th e s iz e d .
S-#**AjainO'-b#a*off)ialaolla# was prepared froa ©*earto03sybenso ( f }q u in o lin e by mesas of thug Ourfeius degimytafelea*
amine was condensed with
@
^lobfeyliM liieethyi bromide,
Shis
%
-d l-
@th y land nopropy 1 torpid® and l:*tore»e«^yrldla® to give .
8*(£>- d ie th y la a in o e th y la a ln o ) -b e n z o (f) q u in o lin e , ©• ( #-di®thyl<*
w slnopr opy l a s i n o }♦toeaz© {f )q u in o lin eb e a a o tf ) q u in o lin e r e s p e c t i v e l y .
m &
8 * (8*pyvidyXiuriUM>} *
i-* a ia o » b @ a t© |f Jq m ia o lla e
e x h ib ite d r e a c t i o n s ' and p r o p e r t i e s s i m i l a r t o th o s e o f
8 -fiuaino-quinolin© .
5 -C ar boxy-benso (f }quinoline w as o b ta in e d .in 80*88' p e r
c e n t yields fro® 8'-»®asiao-i*naphtholo a s i d fey Means o f th e
Seraup reaction.
l*%dr#Xf«toe»8©Cf 1q u in o lin e was a l s o p ro *
p a re d u s in g th e aor&up re a # tl@ s.fe u t i n wash p o o re r y ie ld s *
By vmm o f the Curtins d e g ra sfta tim l*aadta6«tNmvo{fj~
q u in o lin e w as s y n th e s is e d
fr o m .
5 ,6 -b e n z o c ln c h o n ln ic so ld ,. ■
th e i#seBiao»feens©Cf;)'quinoliii® -was found t o be an a lo g o u s t o
4 -a m in o -q u ln o lin e l a i t s ch em ical b eh a v io r#
d O sp sa ise a o f th e r e a c t i v i t y o f th e is o m e ric amino
to e aso -ffjq u in o litte a showed t h a t a l l o f Huns c a n b e a e e t y l a t e d
'tout o n ly th e i'-asd ao ^ b en so C fM b im o lln e h a s b een a l k y l a t e d .
V»4idnO'»ben®®CfI'fui.iiOliae co n d en sed r e a d i l y w ith benzaldehyd®
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
and i t a d e riv a tiv e ® tout
showed
l e s s tendency tft eOfidas®®*^
would condense i s v e ry p o o r y ield ® w h ile the § » and th e
1 Q-aaiin©-toenz g (f ) q uin oline s would s o t undergo t h i s o « »
d e n sa tlo n .
ffiie author w i« t# » t o a o te o w le % # th® h e lp fu l «ug~
geatlss# gives 'fey Hr*
W alter ?»
leleiw h *
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
m
tX* Bibliography*'
1*
B u rg er, *Sen* Problems o f Chemotherapy", J , Ghem* SA*,
M , 68 (1940)*
8*
M»H£y> * T h ® Chemotherapy o f M alaria** I* So©* Chest*'
Ihd*, i § , 111*(1936)
1*
Sehuleaaiwi, Schoenhoefer and W ingler, "Synthes© d es
Haamoahin*# I le in is e h © W ocbenacbrift,
381 (1938)*
4*
P illa b u r y , "P iagjaoquin#*, J* Am*. l e d . A sso c, JM|, 991 (1930)
6*
Altman* "C ontribution a 1* etude dee Medicanta d© Synthes©
Centre l a Malaria®, He©* Trav* Chlm## §2* "941 (1938)
i»
1* 0 , Parbenimduatri© Akt#, "O aratelluag 1 - auba t l t u i e r te r
2-A lk osy-6 -halogen•S-aaM noacrldin* , B,Jt*P* So# 563,072#
7*
F in d la y , "fieaent Advances In Chemotherapy®, 2nd Id*
p, 106, P h ila d e lp h ia (1 9 3 9 ).
8*
Oettlngem, * f h e Therapeutic A gent* o f th e Q uinoline
Group*, She Am* Chem* See* h M « So* 84, 10® (1933)
9*
Schulemam, Schoenhoefer and W inkler, 1* S* P aten t So-*
1 ,7 4 7 ,5 3 1 (1930)
•10* Clem, Bo©tor*a f h e t l e . U n iv e r s ity
O f
leb ra sk a (1939)
11# 8 k v ii9 | "M a e S y n th ase d e e S h ln o lin a * , SAfeaber* Akad#
Wiae* W ien, Math-natur* H a a se# Abt, 11b*, 1 1 , §93
( l l t i ) .'
ZM* m e n and f o b l e r , " f b e r d e r 2 ,3 ,2 * ,3* -»aphthindig© «,
Belv* CM a. A c ta ., f , §51 (1922)#
13* Rnueppel, "Saber ein e Verheaserung d es Skr&upsehen
. ferfa h ren a aur P a r s te llu a g von O hlnolln m A G h tn olin d erivaten® , B e r .,
703 (1896)
14* Jaco b s and' C ould, " S y n th e s is o f ' S u b sta n c e s B e la te d t o
l y s e r g i c A c id " , J* M o l* Chen*,' 110# 141 (1937)
15# C o ld ste la and S tern , "Sur 1»Acid© §,®«dibreia®»2«.
naphtol^m® #b l a 5 , 8 -d lb r ora©~2-rmphthylaaln©*, le lv *
Chim* Acta* 1§# 809 (1940)*
li*
H o w its, Fraenkel and Sohroeder, "Ueber o«* p - , uai.
ana- J o d eh in o lin und deren D eriv a te" , Ann*# 396# §4
(1913)
17* Claus and S e tse r , "Zur K enntnlss des a n a -n itr o - und
des o - n it r o « , d es ana-am ido- und d es o -a m id -ch ln o lin s" ,
f* Pr. C h e a le., 5&# 404 (1896)
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
IT
IS* Robinson and B ogert, ®Sy»tlteai.# e f S u b s titu t e d 5 ,6 BenEoeinohonlnl® Aoida by the Doebner and by th e ■
P fita in g e r R eactions® , J* Org* Chest., Jm* 65 (1956)
19. Claus and H ow its, *,Ueber d-brom ehinolin la d 2f-brcrate M n e lla * , J* Pr* •Cb©»i©; t | 237 (1894)
SO* Olaus and Frobenlus, *2w
1* I * . Ohemie, fig#
W rn m b M m
dea X-Amidochinolins”,
(lifT )
Si* Basu and Das-Qupta, S. Indian Chem. See* i t * 101 (1 9 1 9 ) «
O.A*
1021 (1940)*
SS* H e a e r , Jaeobaen and P r ic e , •She A ctio n o f Bromine i n
Methyl A lcoh ol S o lu tio n o f Efcenantfarenej a low Route
to 9-phenantbrol and S -p bon an th sylaain os*, J . Am* Ghem*
So®,, I t , 2163 (1936)
S3* Hayduck, ®Hetoer das PbeiMttaMtt** Ann* 1ST* 181 (1878)*
24* P r ic e , * Study
tion® , J* A®.
of
Phenanthrene Srotsln® A d d ition R eacSo®, 58 , 1834 (1 9 3 6 ),
2 5 . P r i e s , "Konstitufclon des N aphthalins und s e n le r Be*
r i r a t e ® , B e r ,, M b ^346 (1926)
2 6 . Meyer and H opff, ”Bber &lMet!wl«vlayl"MMi2j|9f Ber*,
M8» 2274 (1921)
27. Amundsen and K ra sts, * p ~D ialkylantinoethyl Bromide
Hydrobromides and 0~D lalkylam ino©thylam inss*, J . Am*
Chem. S a c ., M b 305 (1941)
28 . M arrel, ZeLPtm&n and Blubhiirdt, MH alogenated f e r t i a r y
Amines®, <7. Am, Chea. to®*,, 4 9 , 2299 (1927)
2 9 . Chaaot, * Ileste»tary Chemical M icroscopy”, .2nd M .,
John W iley and Sons, Ike* (1921)
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
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