THE SYNTHESIS AND REDUCTION OF SOME

N-PHENACYLPYRIDXNSS,

APPROVED?

Major Profassor

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BiBL IQGRAPHY • • * » • * • • » • • « » » * * « * *

HI

CHAPTER I

INTRODUCTION

4

In 1930* Blicke and Biake r epor t ed t h a t the hydro*

eht®rid#e of N- (2*phenyl *&4iydro&ye thy l )p i per I d ine ( I ) and

the corresponding beneoate have a n e s t h e t i c p r o p e r t i e s * , These

workers a l so ind ica ted t h a t N~phenacylpiper i d i n i u a hydro-

c h l o r i d e possesses s im i l a r a c t i v i t y * KrRhnke* observed t h a t

c e r t a i n N-eubf11tuted«*pyrIdinium compound* posse t# both

preasor and e rgo t s l i ke a c t i v i t i e s # .

An investigation of various derivatives of N*phenaeyl*-$

pyr id ines was undertaken a t t h i s l a b o r a t o r y because of the

s t r u c t u r a l s i m i l a r i t i e s of these compounds to c e r t a i n wel l*

known pressor amines, such as Epinephrine ( I I ) and

Ephedrlne {I I I}# y

sx CHOH - CHA — ^

M<*{2-phenyl*£*hydroxyethylJpiper id ine ( I}

I D F» F* Bticke and E# S* Blake* ,?«a*C«.3»* 52. 235-240 (1930)» : - ***""*

U) F* KrShnke and K# Faso ld , Ber*, 67 . 656 (1934)*

(3) W* E« Goode^ Unpublished M# S* t h e s i s * Dept« of Chemistry | North Texas S ta t e College* 1947*

OH NH-CH 3

H O ^ ^ Y C H O H - C H ^ N H C H 3 < \ _ Y C H Q H - ^ - C H 3

Epinephrine (11) Eph*4rln« {III) 1

Kr Slink* ,and Fasold aubjeeted H-ph©naeyipyrMinim

bromide. to toi^ife$m,atur« $ l©w»pr#atw« catalytic hydrogen-

%tton In an attempt, to prepare the corresponding «iri>ln«lw

Contrary to their expectations, they found that tinder these

condition*, the pyridine ring was preferentially reduced, and

their final product <wns !<J-phenacyl piperidinltim hydrochloride* . $

Riegel and Wittcoff , however, were able to effect prefer-

ential reduction of this ear bony! group by temperatu?e|

high-pressure (dO atmospheres) catalytic hydrogenation#

The results of these investigators indicated that either

tho.feirbonyl. group or the pyridine ring could J» pr#ftraa«

tially hydrogenated* Blicke and Blake1 were able to prepare

lM^^iiyl*M^**^thyI)piperidiitt by the condensation of

phenacyl bromide with piperidine followed by low-temperature,

low-pressure (4 atmospheres) catalytic hydrogenation* There-

fore # further investigation of these hydrogenation reactions

seemed warranted*

The following procedure seemed feasible for preparing

$ L J ^ m R i @ g e l ai,d Harold Wittcoff, M * I0O5 (II46)#

the f u l l y reduced expounds, namely, 2-(4*alkyl»l-pip@ridyl}-

t-phefiyl«thtnolt•

Q - £ - C K , C L + , Q . R Q - l -

CHOH - R • HCL

,, M %lttrnat* method of pp#iwlfi§ these compounds

.therm® of ttyrene broaohydriri, and pr oceeds accord lag;

;fo|idwi*tg r««*tioittt

& : : .

n"™* i jp.CHOH-CHaBv + l ^ y > | ^ ^ C H 0 H " C K a - ^ ~ ^ R

Ka r^j l- CHOH - CHj l - i /~ \R . HB, H5. > \ /

t f t i i i reactions m m used in Mfefifming tti* structure of th@

i?«poufidt obtained by catalyt ic hydrogenation of th# I-phd|M* •>,

j&eylpy? id ines* ' •*— • "

Because of their structural s imi lar i t ies to t i» pressor

aaia&Sf,. th«f« piper idino eth&nols are expected to i» phy&i®*

logically active* Since the rtat## of the alkyl group

attached to the piperidine rlftg ha® fee«i» varied, differences

la the physiologieal ac t iv i t i es pt the cexpounds are expected*

T h e compounds of this series are being tested for m i l *

%nkmtcn%mpt sympathocsimeticr and aniihlytaaiiii2^--nativity

%* Davie tad Company.

CHAPTER I I

EXPERIMENTAL PROCEDURE

The phenacyl chloride m m in th i s Invest igat ion was

f i n i s h e d % Parke, DavU and Company. The pyridines were

purchased from Re i l ly Tar and Chemical Corporation and were

a*ed without fu r the r ptirif ication*

All melting points m m taken on a Fischer-Johns

netting- point block and are uncorrected# lfe« nitrogen

analyses mt* fey the micro wmm method# T h e palladium^charcoal and platinum oxide ca t a ly s t s

m m also famished by Parke, Davis and Company*

©

K»Phe n i c y 1«4« |5*n ony! )pyr i d i n i u a Oil or Id©

0 Cl CH^CCHa)ACH3

c — C/V+2 — /)"" CM v _ / ,

CH^CCHO^CHa

On* hundred and f I f t e a n s , (0»S6 mole) of 4 » | S * u o « y i } -

pyrldlne and: 75 §# (<M65-*rc&«) of phanacyl ch iorIde « r « •••

mixed and heated u n t i l t o l u t i o n w e f f e c t e d # The s o l u t i o n

wm u n t i l s y r u p y and 150 ml* of benzene were ®d#d#

The mixture wai heated t o bo i l ing# M add i t iona l 150 mi*

of benzene m m added and the mixture m% heated while the •

p a r t i c l e s of s o l i d mater ia l were broken with a s t i r r i n g rod .

the mixtura wm allowed t o stand w a r n i g h t * • the pre* ••

c l p i t a t e d s o l i d was f i l t e r e d , and bo i l ed with f r e s h port ions

«T benzene three times# A y i e l d of 142 g# (81®/® t h e o r e t i c a l )

*f crmde product was obtained# A small port ion m r # « r y i i a l # * *

llESd from bentene and found to mel t a t 166-168° {dec#} . s

Good* reported that N~phenacyi~4-.<5-nonyl)pyr idinitoa ' 4 i

c h l o r i d e melted at 162-167® (dec#)#

lM*hft!iaeyt*4»< 1-octyl }pyr ldtntua Chi op ld«

O Cl C - CNa - N ^ y ~ CH* CCI+̂ X c h 3

Tw«nty*ona §* 10,41 mole} of 4<*{1«*oetyi)pyrWine and

15*5 9# (0»i mole) of phersacyl chloride were dissolved in

75 mU of benzene. The solution was Heated to holllng*

thin allowed,to stand m% room ttnperftture ovpfnlght# • Th*

ery t ta l s wer® f i l t e r ed and washed with ether , then f*»

crystal l ised fro® an acstone~ether aixttife-* A yield of *• ' t * 1 " •

£1*4 §« (6£*2®/o theoretical) was obtained# The cry*tills

ia@lt@d at 180*100* (doc«)« » « . « *

Anal; Calcd, for CttHs^ClNO» ti, 4«04>« Pounds £»$9#

s

N» [l*{Z**ph®ny I*&»hydr©xyethyi)] -4*»{l-»octyi }pyridini«m BtrnM®

B -

j / ^ C H O H - C»4X _ f/~~y(CHa)7CH3

Styrene WmtMy&fim was prepared by the method tf Re«d

and R«i4**< Six g# (0*0$ mole) «f this materialf dl t tUUng

mt l®#«40®* mndtf presume® of 8 asm#, and T*G §. (0*04' »»$#)

of 4-(l^oetylpyridine were dissolved In 50 ml# of absolute

•tfefcfttl and re f ined for three hettr»*.

The alcohol ww evaporated until the wltstf of the

setatlea was approximately 20 at* Ttx© addition of dry ether *

caused lamed!ate preeI p i t at 1 on of whit# pl*telet«» Upon

filtration and exposure to air , the material changed to .*

reddish gum* Attempts to obtain well-formed crystals were

unsuccessful» The material was rtdttttd. without furtht#

pur ifleftion*

(5) J* Read «b* W» Q* Reld# JUgg* iSS*i

9

!l#Phenaeyt«4*{I-nonyl)pyridinium Chlorid#

v j - c h , . 0 Cl

~ >CCH^,CHa

Ti»enty~six 0* <0#169 raole) of phenacyl chloride and

M+%- q» (0.158 aol« | of m m mixed and

heated unti l solution was effected* F i f ty ml* of beneen© <• #

and 100 »if. of n*hexane i»ere added to the hot ©olution*

th* solid which ..pre&lpifcated upon cooling ttts f i l t e r e d and

recrystall ized twice trm an acetone-ether mixture * * * 4 ' ' *'

A yield of 37*5 §# {6®#2®/* theoretical) of product#.' 4

iselting mi abfc&in*4U * 1 * * * i ,

. #ialf Caied# f«r CtaH*0ClNOt Nr 3#69, Found! $.•?£*

to

thyl )pytI4lnlm Chloride

C-Ha - CH - CCH^ _ CH

Fifteen and five-tenths g« (0#1 mole) of phenacyl

<8hlwl4© Slid 22*6 gt {0*i 1 mole) of

din* wira heated Owe httxtf**4 «I# ftf * t t y |

W « «M«< atti the mixture heated to boiling, then allowed

t* H«nd overnight at rote tftaptrfttajw* The eryst&ls mm

ffI&®r#-4 and the solution was concentrated fey boilin$« upon

cooling, a t*cond erop of «ry«t*l« pr«cipitated fj»o» the

t o l u t l a u

Twenty-one g. {5B«40/© theoretical) of er$m«»colored

e*y*t«|*f w i t i n g i t 145-147° (4**# }*«**« obtained,

M i l l C«M4* f@r C-mU^IMOi Nf 3*Utf Found*

i i

M* [t»(£~phenyl*2*hydponyethy!}]i~oetyl )pyrWiltIm Bromide

Sy

/ V CH OH - O.H, _ < ^ - y _ C c H ^ C H j

A solution of € g» (0*03 stale) cat styrene hromohydrin ! * t ' \ ;i

and 8*t 0* <0«Q4 tmU} of 4-fC^oclyl»thyi^yrM$»e In SO' sit*

of absolute t-thapftJl was refluxed im twelve hftttftu

th« solution was «m»ati<&t6d toy evaporation i© «ppr«cl*<

mately 10 ml* The addition ©f dry ether promoted efyjttftlH*

The crystals w r t fltt-ered and watfmrd with ether*

These crystals mm dim®lm4 In ethanoi and

by the addition of dry ether. After <t#yt»s In v<cw<>.« ft

a»U!ng point mm taken. The crystals began ftt ' • f

iifcS* and Mf* ftll « i lU4 ftt 149% - " 1

The material m% reduced without further purification*

12

}*l*p iper Idyl ] *&*phefiy|« thm&%

- CH OH - CHa - N ^>- (CH a ) 7 CH = v_n w n - v^rta, - (\ V

i * f ) : p y r 1 4 I n t m . - C M . « r g «

(0 .029 mole) of M * ^ e n « e y | 4 ^ ( l » 0 e t ^ } p 3 ^ i d l n t a K '

w m d i s s o l v e d in 10 ml, of 95®/« and 1 g* of 5°/&

pali«ilw»M3httf ,@0al c a t a l y s t w t % added* . 'the s o l u t i o n -imsm ' ••

shaken a t $®m mtot hydrogen a t 4 a t a s # .<*»*•'•• *

t e n t h a d | « of hydrogen was absorbed In f o u r t e e n h o u r s . The

s o l u t i o n « « • f i l t e r e d I n t o ftqueottt sMl t ra - b i c a r b o n a t e . ' Hit

p r e c i p i t a t e d s o l i d was r e e f y * t a l I i & e d . f t m m

m i x t u r e . Seven and t h r e e - t e n t h s g . of wh i t e n e e d l e s ,

©I p . 7 £ . 5 % were o b t a i n e d . * , - t * ji, j,

Aftiill €«lod*- f o r c»*f%#IIOi Kf 4*42* Foundl 4*5?#

F ran H» fX- (2 -ph8ny | . a .hy<l roxv« thy t ) ] « 4 . ( i - o c t y l i -

p y r l d l n l m a Q* of ermd® N*] l*(£*pftff«iyakS»

hydroxys t h y ! ) [«4«( l * o c t y l )pyr Id ln lum bromide ( p . 11) were

d i s s o l v e d in 50 m l . of a b s o l u t e e t h a n o l # and p l a t i n u m oxide

c a t a l y s t was added* The s o l u t i o n was shaken a t room te japera -

t u r e w i th hydrogen a t 4 a tins. A f t e r two hours# 0 . 0 2 mole

of hydrogen had been a b s o r b e d .

The solution mm f i l t e r e d <ua about h a l f t h e a l c o h o l

was e v a p o r a t e d . The s o l u t i o n was poured i n t o aqueous sodium

b i c a r b o n a t e . The p r e c i p i t a t e d f r e e base was d i s s o l v e d in

13

alcohol atid treated wiih JforHe* then rec?3f$isiil^#d twice

t t m eth*nol« Or® g# of m W M p W * was obtained*

TI10 free Jbmse obtained from the reduction N-phenacyK

4*Ci^aiyl}pyf iI4iisiai ehlerld® a»U«4 *t 7**5*« A siEtttr®

«f the two material® sieited *t 73®•

14

Z*[4* (5»nony i )* l*p i p e r I d y l ] • l - p h e n y l e t h a n o l

CU3

j ^ V c H O H - CHa, _ /v/ y CH

^ C H a £ C B * ) * C H 3

Tew 0# (G«G£8 mole) of M*phenacyl«4«( 5* ' f ionyi)pyridiniuia

c h l o r i d e were d i s s o l v e d In 50 m l . of a b s o l u t e e t h a n o l , and

& 9* of 5°/© p a l l a d i u m c h a r c o a l c a t a l y s t were added . The

s o l u t i o n was shaken o v e r n i g h t under hydrogen a t 4 a tms .

Hydrogen a b s o r p t i o n amounted t o 0 . 1 1 mo le . The s o l u t i o n

wa® f i l t e r e d i n t o aqueous sodium b i c a r b o n a t e , and the p r e *

c i p f t t t e d free b a t e was r e c r y s t a l l i e d f rom an a l c o h o l ^ w a t e r

m i x t u r e .

Seven and s i x ~ t e n t h s g . { 8 2 . 2 % t h e o r e t i c a l ) of wh i t e

n e e d l e * , a* p . 66* f were o b t a i n e d . Goode** r e p o r t e d t h a t t h i s

r e d u c t i o n gave a f r e e base which m e l t e d a t 66-68®, bu t had

the s t r u c t u r e o f I " * f t i e i a e y l « 4 * | $ * « o n y l ) p i p # r i d I n « #

15

2*[4-{ I-nonyl )*l~piper i dyl] • l»|>henyie thanot

P Y CH OH- CHa - 1/ (.CHx), -CH3

f t m Hyphen acyl *4* (l»n6nyi)gyrtdiolum Chi ort4i

and o«#*hal£ g» (0.028 mole) of K~phenacyi~4^ l~nonyl)»

pyridinium tiblorld* w r e 4is*olv*4 In t S « i * of 95°/© ethanol,

and 2 g» of $a/e pal4adiuza*chare©al catalyst were MdM# Tfri

solution was shaken with hydrogen at 4 atms. Hydrogan absorp«*

tion totaled #.#0f m®l«#

The solution was f i l t e red into aqueous sodium bicarbonate,

and the precipitated free base was recryslail iaed from m

acetone*.water mixture. Five g, {7a.3°/© thMfatl***) «f.

uhltti needles, a* p» 76, f 6 , ware ̂ obtained.

Gfctat'*- fdf •% 4«$l% Fowdt

• ' M* [lH£*Phenyl«%*hydro*yethyl]«4Mtmmyt.)pyridlftiutB

l»«*ldf g» (®#0S mole) «f styren© br«ohydrIri and 6*2 g*

(0#04 »ol«) of 4"Ml-*»orsyi}pyridin® «•** dt*tolvodi in SO a l f

of absolute ethanol. The solution was refluxed for five

hours, then transferred to a container for hydrogenation.

Platinum oxide catalyst was added, and the solution was

shaken at room temperature with hydrogenation at 4 atms#

unti l 0.08 mole had been absorbed. The solution was evap-

orated to * volume of approximately 10 ml* ant poured into *

an mqvtmm solution of sodium bicarbonate*

16 '

Hi® precipitated free base was filtered, dissolved in

95®/® eth&nol •and treated with Nori te • The product which

prteipittt®d fro® th# chilled solution wm ftetfyttallim4

twice ft on 95*/* «thftnolf then dried Jjnt tMno*. Appr*Kiafct#|y

on# §• erysitlt, su p* 75% lifc# obtained* tti« fr«« bi»*

of reduced l'i»phenteyi*4*( 1-nonyl}pypidiniuai chloride wit*

at 76#5®# A mixture of the two materials melted at 76®#

ti

Z^[4*{'2»oetyl«*thy} )*4«f ijfer idyl] •Kphvnylathanol

-CHOH-CH-*- N/ V (LHi- CH3 \ / t

CLH;

From tcyl^.4* ( i d i ® l w Chi or

Ten g#< (0«O9& mole) of i«p^enacyt*4»{2»octytai«thyi}«*j»yrMinium

fhiorld# were dissolved in 100 ml, of ethanol* m& Z g» of

«atat;yai .ware added# The «lmtio»;.;

^••'jihtkin a t rota iea®wpatmre.-"#llli hydrogen at 4 aiat* -until

0#t oole was absorbed. The solution was f i l t e r e d Into afttidtta

sodium bicarbonate, and the precipitated f ree hmt was f l l *

teradk Purification of tMa 'atiu^ouiid «@uJd not be «<w<M^liihc4

sa t i s f ac to r i l y , «© i t was eonvtrtad to tit® ftyttrechlortdi* by

treating I t , in ethereal solution, with dry hyirogan ehtorld*

gas. . The hydrochlorid® was readi ly purified by r a c f y t t a l l l *

nation from ethanol. The free base was then recovered by

f i l t e r i n g an alcoholic solution of the hydrochloride into

di lute ammonium hydroxide* • Six and one-half g . of whit*

needles, ra. p . 64®» were obtained*

Analt Calcd* for C t t%?ff0t M, Found» 4«43.

•-ggflSl i«» telate thy! )*

ftyyi^iitltaa ,gp#sl.<f»**<&ie g* of li*[i#-Ct»i>henyl#2*hydroxyithyl)]'»

4-(2-octylmethylJpyridinium Bromide was dissolved in 75 ml. of

ethanol and platinum oxide catalyst was added. The solution

was shaken at room temperature with hydrogen at 4 atma. unt i l

%$

0*04 mole had been absorbed• The solution was f i l t e r e d and

evaporated to a volume of approximately 15 mU th i s concen-

trated solution was poured into aqueous sodium bicarbonate am#

the precipi ta ted f ree base was f i l t e r e d , then r ec rys ta l l ited

twice from alcohol-water# Approximately one-half g, of white

ery«t«l*a a# p . 66% mm obtained# A mixture Of th i s

pound and the f r ee base obtained by reduction of N~phenacyl»

4- (£«*octytae thyl) pyr id in i urn chloride melted at 66-6?® ,

IS

' 2»[4*(i*0etyl)*l*pipe«> idyl]*l~phefiyi®thyt Acetate

Hyirochlor14®

H O " \ u / \ 1 "

H3c N - CLHX - c. - O - o - CHj • HCL

'Two 9» of 2#[4»( 1-oetyl )*l«pip$r Idyl] »»l»phenyletiianoi

were refluxed with ZS ml* of acetic anhydride for seven .. - • t -

hours» The solution was evaporated to approximately 5 ml*,

then cooled and treated with aqueous sodium bicarbonate,

The mixture was extracted with e ther , and the extract was

evaporated to yield a f*d41s2i»or*fi0* o i l . All e f f o r t s to

c rys t a l l i t e th i s .o i l failed*.

1M» ©jU ym* dissolved: in dry e t h e r a n d hytfregtn

chloride gas was jmbfetod into the solution# precipitated *

material was f i l t e r ed and dissolved in absolute ethanol. The

addition of dry ether caused re Precipitation of the crystals» 4

Approximately one $» of-white c rys ta l s , ®# p* was

obtained* * * * - *

Anali Calcd* for W, foundi 5*®»

A sample of the hydrochloride of £~[4*(1-oetyl)~1*

piper idyl]f^phenylethsaol. was prepared and found to s la ter

at 167° and raelt over the range 194-198°• A mixed melt of *

the two hydrochloride# was taken and found to be 152*155% This indicated that the two materials were not identical*

m

The ftm base this acetate ,**» prepared by m u r i n g

m alcoholic solution of tht hydrochloride into aqueous

eodium bicarbonate• Wilt® crystals precipitated after the

solution stood in the ice box overnight# The crystals were

filtered* but found to be m oil at roan temperature*

zx

&»[<M 5»nonyl M ~ p i p e r Idyl] *|»pha«ylethyl M e t ate

Hydrochlor ide

H3C-(CHA) - CJ+A I $

I H - C <f N — C-A/j, - c - o - c> " CH3 • He/

B j C - C C H ^ - CH*

Two g* ©f 2» [4*< 5»n©nyl }«4»pip#r 14y^<4<*phenyl6 thanoi

were ref luxed with Z5 ml. of ace t ic anhydrtde f o r twelve

hours# F i f t y ml* of water were added, and the mixture was

allowed to stand fo r three 4«ys»-

The solut ion was concentrated on a hot p l a t e tinder a

stream of a i r* Beit gene was added and the solut ion boiled

to remove water• The res idua l o i l was taken up in dry

• t h « r , and hydrogen chloride gas was bubbled through the

t o lu t l o ru th* so lu t ion was allowed t# stand in th* i<st bm

overnight*

The separated so l id was f i l t e r e d , d fas t tved In athanol

<antf t rea ted with decoloris ing charcoal# The a lcohol ic to lu*

t ion was c h i l l e d , and the p rec ip i t a t ed c r y s t a l s were f i t -

tared* Two g, of f l u f f y , white powder, which s in te red a t

130° and melted over the range 150-157°, were obtained* * * r «

M a l i Calcd* fo r C t*l%#£%Cti H# 3 # « * Foundi 3*44*

22

Z*[4#{ l-nonyi )**l<*ptper Idyl] -1-phenylethyl Acetate

Kydrochio? 14®

H H3C - (CHa.)̂ \t _ CHa. - C - O - C - CH3 • HCl

I

Two 0* of Z~ |4*{ l*nonyl )«l»p Iptt idyl] »i»ph*ayl«th&no|

m m r«fluxed l» 25 al* of acetic atthyttrMi for sixteen hours.

Th« solution was evaporated to 5 ml* and treated with

tqtttoua tod Itm bicarbonate* The mixture was «xtr«ctt#4 with

ether , and the ether solution treated with dry hydrogen

chloride gas. The precipitated material was f i l t e r e d and •

recrystalliEed from an absolute efchanol«dry ether mixture*

Appftt*Ia*Uly 1 g* of product, melting «t IS0*158% wit® obtained.

* * * # * M i l l Calcd. for i Hf 3*42. Feuntt 5,32*

CHAPTER H I

DISCUSSIOK

When till# investigation wat begun, i t was desired to

th# N-phenacylpiper idines a# well a® the m t f m * •

ponding carbinol$» AtUnpt* to $top the oatalyt ic rttfwir*

tion before the w b o n y l group w*a «it«£lc«4 * r e tmsuewiftt*

:fmif Two ettatlyvt** platimsn oxide and

were used# No la j&« f ina l f»rodm#it was noty4#'

although |li@ platinum ox id* eititiyvt* reductions proceeded

a»** tupldly*'

Reductions wire carried out in both absolute #tha»oi

tBdt 50°/«> ethanol# Th* hydrogenstions proceeded more rapidly

In tti# absolute ethanol solvent, sad th# product wis more

firadlJy iiolnted*

While proving the structure of the reduced compounds,

i t urns found that the carMnols r t ae t rather slowly. Ho

acetyl derivative could be isolated af te r refluxing the

^*[4«C2*o@tyiffitlitylJ*|#piperIdyi]-*l#|*li«iiyl@th«ioi in i&fctlit

anhydride for two hours• When the reflux t in t was extended

to seven hours, however, the acetyl derivative was isolated

iU f a i r yie ld . The acetyl derivatives can also fee prepared

by .ftaatifiQ the carbinols with acetyl ehiorlde in dry ether«•

Car© must be exercised to exclude a l l moisture from the

m m i i m mixture, or ItytoolyM* - *f the acetyl chloride wilt

%$

34

lead to formation of the ether insoluble hydrochloride? of

the piperidino ethanol.

While preparing the N«phenacyl~4*»alkylpyr idinitaa

chlorides, It was found thai yields could he improved by

f i r s t heating the phenaeyl chloride with the pyridine in

mmnm of a solvent, Although the yields mm better when

this siethod was used, this advantage was offset by increased

dlf ficulty of jollification* The cr utf® lf*ji^ena©yil,»^#aiJtyl* •

pyridinius chlorides shots®d great tendency to form oi ls in ,

the presence of tfacas. of urate? »• thin tendency waa so'gftai

that f i l trat ion of the crude products in an ©pan f l l t t r was

often a problem. After purification, however, the compounds

coaii fee l e f t exposed to th@ atmosphere with no oil fwb£tt*n»

although they are quite soluble in water*

Purif icat ion of the reduction product of JWphenacyl**

4-<2~octylmethylXpyridiniua chloride and i t t acetyl deriva-

tive was very diff icult# The reduction product was contam«*

inated by a light-yellow material whose solubil i ty was the

aaoe aa that of the white compound» Repeated treatments with 4

decolorizing charcoal failed to remove the traces of oold#*

f t was* found that a fa ir ly pure" product ©ould he ©btaiitt&' fey

.^•precipi ta t ing this material as the hydrochloride and

treating th i s hydrochloride with fforite* The f ree base *$*•

that| Isolated fey f i l t e r i n g an alcoholic solution of the •

hydrochloride into d i lute amontai hy&roirf da *

25

Pfettattni^y report® from Parite, Davis and Company t a i l *

6at* that two of tlw pip«sr1d1no - #thanols have &f»p«j<sia'hit'.

ait t l * tubercular act ivi ty# The i^oetyl }*l«pij>er idyl^ *

1-phenyiethanoi was found to be amebicIda! at d i lu t ions of

Us5QDG* It# an1i-tubercu i ar < reactioyi thawed that i t wtf •

active a t p. m$* */<* * I» plassta meditim, no growth of the

« » " O f " ! « » •«»>/ • • . « • : .

l*$lper idyl] *3>ph2ny!«tb«f!Oi showed a c t i v i t y a t 1*15

Thara 'was no growth lu plasma at- 10 ng* .,*/•*•;:, f twta r e su l t s

may be $0qp«r«4 with the standard* 4f4"t*4i«Ifio*'«l|phanyt

ttilfcmsji which ah©1!® ac t iv i ty a t S m©«.;-.*/• # with no growth.'

its,piai®a isedium a t 10 ag» VW;; Reports on othar eeapmutd*

have not l#«m received at the tin# of th la uniting*

BlSUOpAPHY

Ai*iiei@s * i » * * „

JMcte, r* Fif awl Blake, £ » & « , : J j » 2$5*&4® (1930). Kfttutk*,/*, *it* Fasoid, K»# ̂ fltr**, j g f «$g (1934)* Read, 4#f and fluid* £* SB*,i£B*f J2SSU l w *

tad Wlticoff, Htf t ld , J.»A.»€fc§»« 68, leOfi

Uiipttbli*h«d Material

Good®# UnptiM I shed M» S* thesis, Dept. of chemistry, North T « w SUtt College, 1047* .• f

26