IULOGEMATION OP PtfBKOL SOLPONIC

IDS

IK MVSm BEKZEKE

A T h e sis

S u b m itted t o th e F a c u lty o f t h e
M ich igan S t a t e C o lla g e o f A g r ic u ltu r e and A p p lie d S c ie n c e
in p a r t i a l f u l f i l l m e n t o f t h e req u irem en ts fo r
th e Degree o f

D octor o f p h ilo so p h y

by
Arthur Ifruse N e ele y

1955

ProQuest Number: 10008395

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ACJOiOlLEDGMSST

th e author w ishes to express h is
a p p recia tio n to Dr* £U C• Button for h is ad­
v ic e and su p erv isio n in the accomplishment
o f t h is in v e stig a tio n *

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I S ! l 0 0 i e

u

u

f o r t h e n e s t p a rt* t h e methods re c o rd e d In t h e l i t e r a t u r e
f o r t h e p r e p a r a tio n o f th e s e h& logenated phenol* l a which th e
h alo g en s o ccu r a d ja c e n t t o th e hydroxyl group a r e u n s a tis f a c to r y •
\ B it h e r t h e p re p a r a tio n r e q u ir e s t h e u se o f e x p en siv e chem icals
o r t h e method l a to o in v o lv e d o r la b o rio u s and q u i t e o f te n t h e
y i e l d s a r e e x trem ely le v *
t h i s i n v e s tig a tio n e s s u n d ertak en w ith t h e view o f d e v sl*
o p in g a a e r o co n v en ien t e f f i c i e n t p ro ced u re f o r t h e p ro d u c tio n o f
t h e s e compounds* to g e th e r w ith a stu d y o f th e p r o p e r tie s an d
s t r u c t u r e o f t h e l e s s w e ll known ones *

£ 1 $ $ 0 U U I .

A rev iew o f t h e l i t e r a t u r e re v e a ls a g r e a t many methods
f o r th e p r e p a ra tio n o f erthe*s»ene^ and d ih a lo g o n a ie d phenols*

a

b r i e f resume o f t h i s m a te r ia l fe llo w s &
o

1* B is e c t b re m in a tio n o f phenol in v a rio u s s o lv e n ts *
Hftbner, Brenken* Her** 0 , 171.
Oerdon* fre e * * (1 8 0 1 ), 6 4 .
&>Usman* ainkes* Chen# z e n tr # , 181G I I
U eldola# s t r e a t f i e l d , d* Chen# See#*

661 (1 6 0 5 ).

** Z m

D inw iddio, f e s t l o C . A* £* 48% (181%}*
Bainoa* <1. Ch*m« $oo»* 181* 8818 (1828)*
5fc**typ* 8«1IU |8, Bill* Soo* 5 him*, j £ f 808 (1887)*
8 * M t l i i g # 8 3-broi»o-2-hydro*y fconsolo a o id In th o prsaonoo
o f w ato r a t 180® f o r s o v o ra l hours *
Sollraim , Orottoman* Boy** 17 . 8788*
3* Haplaeomont o f th o amino group i n e-bromo a n i l i n e w ith
fcy moans o f a diasonnium in te m o d ia to *
Kt}rn«r# #a**« ehim . i ts ! * * 4 , 388*
P o ttig * Msgsr* Bor* 3 , 362«
B ailsm an* Bathos* Boo* tr a v * ehim* 30* 51*
4« Bsplacem ent o f th e amino group l a 2-araino phono! w ith
bromine by th o Sandmsyer re a c tio n *
Moldola* S tr o a i f i e l d , d« Cheau S ee* , 7g* 885*
3* P assin g o f brom ine v ap o r th ro u g h phonal a t a te m p e ra tu re
o f leo-ioo*.
ttw ek B .R .F . 766871 B or. 8 7 , 8 867.
BOlloma^ Bfthksa* Boo* tr a v * chlm *, Jg* 77*
8 * B rem inaiion o f phono 1 s u lf o n ic a c id and e a r b o s y llie
mold w ith a m ix tu re sodium bromide and sodium hypobroralte.
O b o rm illo r, fior ♦ft 4^r* 4881*
7 # Slow b ro m in a tto n o f a w ator s o lu tio n o f th o sodium s a l t
o f p h o n o ld is u lfe n io s o ld a t room te m p e ra tu re and su b seq u en t
s o l d hydrolysis a t h ig h tem p era tu re *
fah a g l« K u ta n i, J* Pham * S o c .J a p a n , §l*?a 247 (1925)*
Tafcagl, K u ta n i, 0* A* 2£» 2669*
B a llard * O rganio s y n th e s e s , Vol* 217* pago 14*

m3 m

8 * a re m in o tio n o f p h en o l w ith a m ix tu re o f p etaaeiu m b ro ­
m ide an d d le h le re u re a #
U k h e e h e re b e v , 4 * Ifeie* Fhye# Chem* s e e * , j* l, 1019#

(1999)* C« A« 24# 886*
2#

1* iipliieeneAt o f the amino group in 2,6-dibrcmQaniHne
w ith fcydreayl through a diaaennium intermediate#
Sienlehen, Ann** 2 § |, 281*
Orton* C oatee# B u rd e ft, <1# Cheat# See* J | * 51#
t * HepXacement o f th e amine group o f 2,6*dibrasu»«4«*mlne~
p h en o l w i t h ' hydrogen th ro u g h a dlasonnlum in te rm e d ia te *
Bahian* Ber*# J£ * 2494*
3* O l a t t l l a t i e n o f t e t r a brem ephenelphtha 11 en w ith o eneen t r a t e d o u l f u r ie aoid*
Baeyer* Ann** 202* 136#

4* Heating o f tetra bremooyoleheaane to 120-130®*
wallaeh# Chem* 3*ntr*.

878*

8 * B sa tin g o f 3,S-dlbro8«>-<4-hydre;ay b e n so ie a c id t o 165® i n
th e p re te n c e o f HaOH*

Pope, Wood# d# Chem* See## 101* 1827*
O-CHLOaOFHEaOL.

1« D irect ehlorinatien of phenol in various solvent® *
pauat* l& lle r, Ann## 178* 308#
V a rn h o lt, J» p ra k i* Chem* (2} 3fi* 88*

Loosen, B*R*P* 198431* Chem# 2entr »* 1904 I I . 1486*

—4 *»

8* treatment o f phenol with aedium hypochlorite solution*
Chandelen* Ber*, 16, 1749#
S* Beating o f 8~ehlere-phenel sulfonic meid-4 in an autoclave*
Haaerd, Flamand 9.IUP* 141781, Chem* gent*#, 1908 I. 1884*
4* Replacement #f the amine group In o~©hloroaniline by an
h ydroxyl group#

BeiXatein, Kulatow, dan*# 174* 39#
3# Beplaeemeni e f the amine group In o-amlnephenel with
chlorine*
Sandmeyer, Bor*, J £ , -2661 #

6# Paso ing e f ehlerine through molten phenol at 160-160° *
B»*ek»

76897#

7» Chlorination e f m 2,4-phenol disulfoni© acid with euhsequent hydrolysis of the sulfonic groups a t 200°*
fakagi, Kutani, J# Pham# See# Japan, §17*- 847#
cu a# i s , m m *
2,6«DICHU)R0PHM0L.

1# d r eat chlorination of melted phenol#
i

r

Holloman, Bee# trav* ehlsu, jgf, 97*
Fischer, ami* (apl*), 2# 181*
2* Beplaeesxent of the amino group In 2,6-di©hlere-4~aminephenol with hydrogen by means of a diasonnitam intermediate#
S e ife rt, Ann* (apl*), 7, 208•
9# treatment of phenol with a odium hypochlorite#
ChandaIon, Bar**

1762*

* $ *

. 4* Seating i f

b en seie s e l d w ith

c alc iu m o xide * '
g lu ck a , Ann *, 8841* 251#
5* C h lo r in a tio n in a lk a li n e s o lu tio n e f th e sodium s a l t e f
p -p h en o l s u lf o n ic a c id and th e rem oval e f t h e s u lf o n ic group
by h y d ro ly s is a t a h ig h tem p eratu re*

Tanaki, gutani, J* pharra* See# Japan, 641* 194 (1987)*
C* A# | 3U 2265*
6 * l i i S 4 4 I M <«
,

1* Seatin g 6-broiw-4-1^ droay-3-m ethyl b en seie a e ld w ith
lime*
R obertson, J* Chem* See** 9&, 749*

6-CELOfiO-O-CHESOL*
... 1*. Seating, th e potassium s a l t o f 3-chiGro-2~hydro*y to lu en e
s u lfo n ic a c id ( 5 ) w ith d ilu t e su lfu r io a c id to about 130°*
Pahlbefg:#. L ist a Co ** B*R*P* 254345, Chem* Z e n tr«

aau>
K aschig, B*R*P* 160904* Chem* geatr** 1905 I , 1444*
%-8hOSO-li^R£SOh*
1* R eduction e f 2 - n itr o - m - e r e c e l t o th e co rre sp o n d in g amino
and rep lacem ent o f th e amino group w ith bromine*

asdgsen, Board* J* Chem* See** 187, 494 (1925)*
2* D ire c t b rw a ln a tle n e f m*sreeeX In fo u r volumes e f fuming
s u l f u r i c a e l d and removing th e s u lf o n ic groups by h y d ro ly s is

with ateam «* 180*800* .
B urton, P e te rs o n , J* Am. Chew* Soo*, 5 5 , S880 (1933)*

1 * D ire c t b ro m in a tio n o f mH&reeol In carbon t e t r a c h l o r i d e
a t - 6° tft *40°*

Tho coispound m elted a t 68®* Be p ro o f o f

s t r u c t u r e woo g iv e n .

Whither, fclpper, J . p r. Chem* 91* 364-414*
8 . Replacement o f t h e amino group e f 4-am lno-m ~«re»ol w ith '
brom ine by d ia » e ii* a b ie n .

a w e ltin g p o in t o f 38* was ob­

ta in e d *
aedgeen, itoore, J* Chem. so©*, (1906) 8036.
8 * D ir e c t b ro m in a tie n o f m -e re e o l in ch lo ro fo rm a t * 1 8 °.
Hueton end B ito h in e o n , J . Am* Chem. 306# J&» 1804* (1932)*
4« B rem lnatien a e e i-m -to lu id in e in a c e ti c a e l d t o form
£~brom a-5-am inete lu e n e , fo llo w ed by t h e rep lacem ent o f t h e
amino group w ith fcydrexyl by th e diasonnium r e a c t Io n ,
Hueton, BU tehinson, 4* Aft# Chem. 3#e«* 54, 1804 (1 9 3 8 ).
8* D irect hromination o f m -eresol in g l a c i a l a c e t ic a c id
in th e co ld *

A m eltin g p o in t o f 68* le reported*

Baronse and Levey* Cempt * rend*, 198, 292 (1 9 3 1 ).
^BK5k0-MXHE30L*
1 . Along w ith 4-hrom o-nM sresol by brom irm tion o f m -c re so l
i n c h lo ro fo rm a t - 1 0 ° .

The p ro d u ct d id n o t s o l i d i f y •

Boat o n . B abehinson, J . Am* Chem* S ec* , 5 4 , 1504 (1 9 3 8 ).

«ft 7 ft*

1*

replacem ent e f th e amine group In th e hydrochloride

o f 6<*amtae*m»eresol irith bromine by th e Sandmeyer reactio n *
Huston, P e te /so n , d . Am* Chem* Soe*, ££» 5880 ( i m ) .
C^e^BIBaoHK-ii-CliBSOJ- was re p o r te d from t h i s la b o ra to ry by Boston
end P e tersen *

f t m e o b ta in e d a s an e l f *

Boston* P e te rs e n , J* Am* Cham, sea*# 88, 5880 (1958)*
B^HLOm^M^HKSOb.
! • Along w ith 4 « e h le re * and 8*ehiere**m -areeol by th e
c h lo r i n a t i o n o f *B*eyesel i n carb o n t l t r a c h lo r id e w ith a
s a t u r a t e d e o la ti o n o f c h lo r in e i n carb o n t a t r a c h lo rid e *
BtfeCiA*

Chem# S e a * , l i f t (1988)#

8 # Beplaoement o f t h e amino group i n 2#*33djie-B w sresol w ith
c h lo r in e by t h e diasennlum re a c tio n #
Huet o n , Chen, d* Am* Chem# Boo*# f£ # 4810 (1958)#
8 # S t r e e t c h lo r in a tio n o f t h e sodium s a l t o f 4*©~phenel
d le u lib n to a c i d w ith subsequent h y d ro ly s is o f th o su lp o n i*
g r oups a t 800°#
Beaton* Chen* J# Am* Chem* Boo*# 8 5 , 4814 (1985)*
4 - chloho- m- chbsol .
1# Direct chlorination o f m-cresol in the vapor state#

Bredermann* Bar#., j6, 585 (1875)#
8 # C h lo rin a tio n o f m -c re e e l i n a o d d s o lu tio n o f g l a c i a l
a c e ti c a c id *

M#$« 55®#

JSSlle and Co*# D*2*P. 90847* 95594*

- 8 *

5 . A ction o f a u lf u r y l c h lo r id e oh m - e r # s e l•

M»p* 8 8-03°•

JW ratcner and Condors 111,* das*# shim# i t a l . ,** fM
88MOM
1*
pW
,

818 (1898) *
4* C h lo rin a tio n o f a te c h n ic a l m ix tu re o f m» and p -e re s e l s
w ith a u ifu # y l c h lo rid e *

Only th o m -e ra s e l m o found t o ho

a tta c k e d #

JMWfctg* D*lUP#t 838071*
3* C h lo rin a tio n o f mixed e r a s e I s fo llo w ed by eu lf© n atio n *
Only th o 4-ehloro-m -*ere»ol Is e u lfo n a to d and own ho r e a d i ly
s e p a r a te d .
S ie b r e e h t, &•&*?*» 833118*
f* Along w ith 8- c h lo r o - an d 8*^hi©r o-m-e re a o 1 by c h lo r i n a t ­
in g ft o a r bon te b r a c h lo r id e s o lu tio n o f m -e re so l w ith a
s a t u r a t e d s o lu tio n o f c h lo rin e in o a r bon t e t r a c h lo r i d e .

Gibson, J* Chem# See* 1484 (1830}*
7# T reatm ent o f »«*ereeel w ith a m ix tu re o f © u lfu ry l c h lo ­
r i d e and c h lo rin e *
h a se h in g e r, m» 8 # 1847380#
3« h i t r a t io n o f e -o h le r e te lu e n e t o f e r n s - e h l c r e - 5 - n i t r o t o l uene#

H eduetlon o f t h i s compound and replacem ent o f th e

amino group by hy d ro ay l by means o f a diaserm ium in te rm e d ia te #
H uston, Chen, J* Am* Chem# S e e * 5 £ , 4314 (1933)*
£,4*DJCHU)fi0^M-CESS0L*
1# P a ssin g a e a le u l a t e d amount e f c h lo r in e i n to a warm
s o l u t io n e f 4-ehler© *® *er© sel i n aqueous sodium hydrogen
c a rb o n a te #

M*p« 48-48°*

#* 9 *

W ith e r * S lp p e r, J* prakfc* chem*, igi, 574 (1 6 6 4 ).
$« C h lo rin a tio n o f a e r o s o l in carbon t e t r a c h lo r id e in th e
cold*
T an a k i, iforafeaea, Sakam oto, J* Chem* se c # Ja p a n ,
H * 873 (1§S0) * €# A* 8 6 , 703#
3» D ire c t c h lo r in a tio n o f 2 -e h lo re -m -e re s e l w ith a c a l c u la te d
amount e f c h lo r in e i n c h lo ro fo rm i n th e © old.

M* p« 33°#

B atten* Chon, J . AW# Chem# Boa*, g g , 4217 (1955)*
4# D ire c t c h lo r in a tio n o f d -ch le re-m -ere * © ! w ith a c a lo u l a t e d amount o f c h lo r in e in chlo ro fo rm i n th e cold*

M#p# 36®*

H uston, Chen# J . Am* Chem* Soc#, Jgg, 4217 (1953)*
BEOigJ^CHJjQBO-M^EHSGLS*
1# Replacem ent o f amine group i n 2 -e hloro-4-hrom o-6-am inom -c re so l w ith c h lo r in e y ie ld e d 2 »6-dichXere~4~brojao*i&*ereeo X*
m e ltin g a t 33®*
H a lfo rd , le a v e 11, J* Am* Chem* B ee*, 5 6 , 1509*
3# D ire s t h ro m in a tio n o f 4 -c h lo re -m -c re s e l in g l a c i a l .a c e tic
a c i d gave Z , 6-dlhr<aao^4-chlcre-*m -cr«aol m e ltin g a t 70-75*5®*
W alther# a ip p e r , j* pr# Chem*(2 )

375#

sm w A xioh of v w m w .
U n re stIg a tlo o s i n t o t h e u se o f e u lfo n ic a c id groups a s p r o t o o ti n g a g e n ts in h a lo g e n a tio n and n i t r a t i o n o f phenols has been
c a r r i e d o u t by a number o f workero*

i t is w e ll known t h a t r e p la c e ­

m ents o f s u lf o n ic a c i d groups by h alogen ta k e p la c e w ith mere o r
l e s s e a s e in t h e p resen c e o f aqueous a c id *
DatAa (4# Am* Chem# See## 4 3 , 303 (1 9 3 1 )) re p o r te d q u a n ti-

<* 10 -

t a i i v e y i e l d e f 2 ,4 ,4 -trib re m e p h e a e l when a n aqueous s o l u t io n e f
p h e n o l mono# end d i- * u lf e n ic a c id s a r e t r e a t e d w ith bromine*
2 , 4 , 6~ trio h lo ro p h « m o l when th e y a r e c h lo rin a te d #

m found t h a t

t h e r in g wee a c t iv a t e d In th e p o s i t io n o ccu p ied by th e s u lf o n ic
g ro u p , a llo w in g th e brom ine t o e n te r w ith g r e a t e r e a s e th a n In th e
unoeew pied pee I t io n s#

The c h lo r in a tio n o f 2 ,6-m ~ cre#ol d e e u lfe n le

a e i d i n aqueous s o lu tio n (D a tta , B i t t e r , 4* Am. Chem* See * , 4j.,
2033 (1 9 1 8 )) y ie ld e d a compound w e ltin g a t 43* w hich was assumed
t o b e 2 , 6-d ie h le ro -m -o r e s o l *
On t h e o th e r hand i t has been found t h a t i f th e s u lfo n ic
groups a re i n th e form e f t h e i r sodium s a l t s , th e y a re n e t r e a d i ly
r e p la c e d by halogen and se rv e a s e f f i e le n t b lo ck in g a g en ts*

T anaki

a n d KUtani (4* P h a m * S o c * Ja p a n , 34ft* 180 (1 3 2 7 ); 0* A* 2 1 , 2255)
o b ta in e d good y i e l d s o f 2 , 6- d ie h le r o phenol by c h lo r in a tin g th e
sodium s a l t e f p -p h en e l s u lf o n ic a e id in a l k a l i n e s o lu tio n and r e ­
moving t h e s u lf o n ic group by h y d ro ly s is a t h ig h te m p e ra tu re i n th e
p re s e n c e e f a e id *

t y a m o d ific a tio n e f t h i s method, T akagi and

KUtani (4* Fharm* goo* Ja p a n , 511, 280 (1 9 2 5 ); c* A*

8349)

have p re p a re d 2 -eh lo P e phenol In good y i e l d and 2-brmao phenol In
somewhat low er y ie ld *
B a lla rd (O rganic S y n th e se s, V e l* 817, p» 14) has developed
a te e h n lq u e f o r t h e e f f i c i e n t p ro d u c tio n o f 2-brsm ophenol*
M odifying a method developed by Kauf&aann and Depay (B e r* ,
g,7 , 785 (1 9 0 4 )) f b r th e p re p a ra tio n o f 2 - n i t r o re s e re i n o l , Gibson
(J « Chem* S ee*, t f f *. 1839, (1983)) and l a t e r HOdgson and Beard (4*

* 11 *

Cherny See* I g f,* 490 (1 9 8 0 )) u se d fam ing s u l f u r i c a c i d t o p r o t e c t
tfe# fo u r and s i x p o s itio n s o f m~©re*ol d u rin g n i t r a t i o n *
n e e d y i e l d s o f 2-hromo~m-erooo 1 (H uston, P e te r s e n , j * m »
Chem* S ee* , f £ , $900 (1 9 0 3 )) and 2 -ch lo ro -m ~ e re« e l (B o sto n , Chen,
0§> 4814 (1 9 9 8 )) s o re O btained I n t h i s la b o ra to ry by b ro m in a tin g
o r c h lo r in a tin g m -e re e s l d i r e c t l y w ith one mol o f halogen in fo u r volum es o f fum ing s u l f u r i c s o ld an d th e n removing th o e u lf o n ie a e id
groups by h y d ro ly s is w ith su p e rh e a te d ste am a t 180-200®*

I 1 H

ft 1 MB B f A h

Humorous a tte m p ts t o a d a p t t h i s method t o th e p re p a r a tio n
e f ft , 6-dibrom ophenol and 2 -brem ephenel f a i l e d t o g iv e s a t i s fa c to r y
re s u lts *

I t was found t h a t i f enough s u l f u r i c a e id was u sed t o

keep t h e p h en o ls in s o l u t io n d u rin g th e b ro m in a tio n , t h a t s u lfe n a *
t l o n to o k p la c e to to e g r e a t an e x te n t and th e phenols would r e a c t
w ith o n ly a e m a il p o r tio n o f th e e a le u la te d bromine#

I f on ly enough

s u l f u r i e a e id was used t o e u lfb n a te one p o s i t i o n , th e phenols would
s o l i d i f y a f t e r a s m a ll amount o f brom ine had been added and f u r t h e r
a d d itio n e f brom ine would r e s u l t i n th e fo rm atio n o f trlb rsm e p h en o l*
F i n a l l y , how ever, a e m a il amount e f Z, 6-dibrom ophenol was o b ta in e d
by th e fo llo w in g procedure*
$1 grams o f phenol was t r e a t e d w ith 68 grams e f c o n c e n tra te d
s u l f u r i c a e id a t 1 0 # f o r 9 h o u rs, se ele d * and a m ix tu re e f 48 grams

x$ <*►

o f fuming s u l f u r i c a e i d (4 8 $ ) and 25 grams a f eon©* s u l f u r i c a e i d
added#

$9 grama o fb ro m in e was added b e fo r e th e mass s o l i d i f i e d *

B rom ination was d is c o n tin u e d and th e mass e n b je e te d t o steam d i e t i l ­
l a t i o n a t 800®* 20 grams e f 2 , 6-dibrosaoph«nol was o b ta in e d , b o i li n g
a t 8 0 - 9 # (4 swu)*
T hia r e a c tio n in d ic a te d t h a t th e s u lf o n ic a e id group® were
e f f e c t i v e l y b lo o k in g th e p a ra p o s i t io n o f t h e phenol and t h a t th e
h a lo g e n a tie n m ight t a k e p la n e a s d e s ir e d i f c a r r i e d o a t in an i n e r t
anhydrous so lv e n t*

A c co rd in g ly , a number o f runs w ere made in

v a r io u s s o l v e n ts , in© lading p e tro le u m , e th e r* g a so lin e * kerosene
a n d n itro b e n se n e *

I t was found t h a t f r e s h ly d i s t i l l e d n itro b e n se n e

was v e ry w e ll s u i t e d to th e purpose and th e fo llo w in g p ro ced u re
was developed w hleh gave e x c e lle n t y i e l d s e f Z , 6-dibrom ophenol *
S l i g h t m o d ific a tio n s gave s a t i s f a c t o r y y i e l d s o f 2-brom epheiioI,
2 , 8-d ieh lo rep h ® n e i , fc-e h lero p h c n el, 6-b ro m e -o -c re s o l, and 6- e h lo r o -

o-cresol*
a

adw ture o f sx * s

great* ( 1 /8 m % ) e f phenol and 80 grams e f c o n c e n tra te d s u l f u r i c
a e id id * 1*84) was h o o ted w ith s t i r r i n g a t lOO-llO® f o r two hours
on an o i l b a th *

I t was c o o le d and 100 g ran s e f f r e s h ly d i s t i l l e d

n itro b e n s e n e added*

C ooling was c o n tin u ed w h ile 15 grams o f fuming

s u l f u r i c a c id (49$) was added a t su ch a r a t e t h a t th e te m p e ra tu re
d id n e t r i s e above 10°*

107 grams {%/$ mol) e f brom ine d is s o lv e d

in 30 grams o f n itro b e n se n e was added d ro p s ie s over a p e rio d o f
Z h o u rs , and s t i r r i n g was c o n tin u e d f o r an hour t o com plete brom inetio n .

one l i t e r o f w a ter in w hleh 5 -10 grams e f sodium b i s u l f i t e

*

h ad been d is s o lv e d we* added#

u

*

The w a te r and r e a c t i o n m ix tu re wee

ita ere u g h ly s t i r r e d f o r 15 m inute* t e f a c i l i t a t e e x tr a c tio n e f th e
b re m in a te d p h en o l s u lf o n ic a c id s#

jw r t h e meet p a r t th e tr ib r e m e -

p h en o l rem ained In t h e n lire b e a s e n e *

This wee drawn o f f by means

o f a s e p a r a tin g fu n n e l and t h e s o l u t io n o f s u lf o n ic a c id s was evapo­
r a t e d from a 2- l i t e r f l a s k , s u i t a b l y equipped f o r steam d i s t i l l a t i o n ,
on a n e l l b a th m a in ta in e d a t 20Q®#

The d i s t i l l a t e o b ta in e d d u rin g

th e e v a p o ra tio n c o n ta in e d a sm a ll amount e f n ltre b e a e e n e and was
d isc a rd e d *

Chen th e te m p e ra tu re o f t h e s u lf o n ic a c i d s o lu tio n

re a c h e d 119®, ste am , su p e rh e a te d in a copper c e i l , was p a sse d th ro u g h
i t * The te m p e ra tu re o f th e o i l b a th was m a in ta in e d a t 200®, w h ile
th e te m p e ra tu re o f th e c o n te n ts e f th e f l a s k c o n tin u e d t e r i c e t o
176-180® d u rin g t h e h y d ro ly s is * The b rem in ated phenols were e x ­
t r a c t e d twm . th e d i s t i l l a t e w ith e th e r and th e phenol r e s id u e , a f t e r
e v a p o ra tio n o f th e e t h e r , was d i s t i l l e d under red u ced p re s s u re (4 mm*)
from a m o d ified C la is e n f l a s k having a S6 cm. column*

Under th e s e

c o n d itio n s a 10*4$ y i e l d e f 2-brom ophenol b o ilin g a t 55-60® (4 mm*)190-191 (740 nan*)- and a 72*7$ y i e l d o f 2,6-dlbrom opheneI (M.p* 65§6®) b o ilin g a t 0 0 - 9 # (4 mm. )-2 55-256® (740 am *)- were obtain ed *
A n a ly sis.

C a lc . f o r C6 %0Br2 9 5 r , 63*4*

founds

B r, 62*9*

v^a o r d e r t e determ in e th e e f f e c t o f t h e amount e f s u l f u r i c
a e i d on th e y i e l d s o f 2, 6-dibrsm e* a n d 2-brom ophenol, a number o f
ru n s w are made u sin g th e above pro ced u re w ith th e e x c e p tio n t h a t
in c r e a s in g amounts e f s u l f u r i c a c id were u se d i n su cceed in g ru n e ,
s t a r t i n g w ith 46 grams*

as

would be e x p e c te d , th e amount o f brom ine

can 'b e g ra d u a lly red u c ed , w ith o u t re d u c in g th e y i e l d , as th e amount
Of s u l f u r i c a e id i s In creased *

- 14 -

BiOi-DfiiEWOhS

X.
Order
o f runs

Grams o f
u se d

Y ie ld o f
2 a6-p ibrom oph en ol
W

Y ie ld o f
2 -Br omopheno1

m

1

45

60*0

10*0

Z

50

7 2 .7

1 0 .4

3

55

6 9 .5

1 4 .0

4

60

6 4 .8

1 8 .2

5

65

5 4 .9

25*4

6

70

5 1 .4

2 9 .3

7

75

40* 0

3 2 .6

8

80

35*0

3 4 .8

9

85

32 «8

36*0

10

SO

29*6

4 5 .0

11

95

9 .5

46 • 5

12

100

8 *5

4 6 .0

2 ,6 - -0icH.U)fiOpamoL

,

g^BLDKOPinstlOL;

B eset a n ts were u se d

in th e same q u a n t it ie s and under th e sa n e c o n d it io n s as in th e
p r e p a r a tio n o f th e brom ophenols

t h a t 200 g ra m o f n it r o g e n

a an.® a n d t h e n itr o b e n z e n e s o l u t i o n o f s u l f o n i c a c i d s m s m a i n t a i n e d
a t 55° w h ile c h l o r i n e was p a s s e d u n t i l no f u r t h e r r e a c t i o n t o o k p l a c e
The f o l l o w i n g t a b l e g i v e s t h e y i e l d s r e s u l t i n g fro m t h e u se
o f i n c r e a s i n g amounts o f s u l f u r i c a c i d :

* 15 *
ii.

Order
o f run*

trama of
^ s O | uaod

e jM w iw o i#

H old of

H o ld Of

2,ft*& iehlo?opHeziel

W
I

■ftft ■

ft

0ft

ft

ft~ehioro]
m

63

1ft

09.«4

20

62

04

18

♦4

ftft

70*9

17

ft

n

6 6 .6

10

ft

to

60

Sft

f

85

ftft

52.8

ft

ftft

ftft

50*1

ft

95

SI

ftft

10

100

24

72'

11

105

27*4

6 6 .8

1ft

lift

ftft

64

19

lift

ftft

ftft

.

A maximum f i e l d o f 7Q.8# o f 2,6-dichX oroph«nol (M«p* 6ft«*
67*) b o i l i n g a t 80*85* (4 mm. )*2X9~ftE0® (740 nm«) and 72*0$ o f
2 ^chlorophonol b o ilin g a t 50~86* (4 mm.>*177^178* (740 am*) nor*
obtain® d .
A ^ y a i* .

8*3** f o r 0 ^

6-B8Q1&.^CHBBGI.i

001^1

C l, 45*5*

Foundj

0 1 , 45*4*

d o m in a tio n o f 54 grama o f o ~ c re e o l a t

5- 10° , u aln g 6ft grama o f e o n o o n tra to d a u lf u r io a d d , 100 grama o f
n ltre b a n a o n # and 0 0 grama o f brom ine In 60 grama o f n ltre b e n a o n o
gaoe a 0001 y i o ld o f o f ado 6*.b*om«.*e~ereaoX b o ilin g a t 05*05* (4 mm*)
v h io h c o n ta in e d a b o u t 8# e ~ e r e * e l.

When r o d l a t i U o d th ro u g h a

* 16 *

00 on* eeXuan (su rro u n d e d by an e v ac u ated ja& feai) a p a ra p re d u e t
was o b ta in e d .

B. p . 206*207 (740 an*)*

Analysis*!

C a le d , f a r e 7% o ir« BP* 42*77.

Founds

Br* 42*6*

A e m a il amount o f 4,6<*dlbreiae~©*©r«s0l m s o b ta in e d b o ilin g
a . 108* ( « a m .) .

6*OSi60M l*e2BOl.s

60 grams a t e**ereeel c h lo r in a te d a t

06®* u s in g 60 g ra m o f c o n c e n tra te d s u l f u r i c n i l and 200 g ran s o f
n iire b c n s e n e * y io ld o d 6<# 6*ohloro*o*ero»oi b o i li n g a t 45*00® (4 mu*)*
188*189° (7 4 0 «m*)*and 18# 4 ,6 ~ d ic h lo ro -o -o re a o l b o ilin g a t 75*78®
(4 mm*)*
4#0^O *ll*O W O i«* 0*aKM fe»*A2M L and
2*6 ~BIBB0MD-m-CBB8QI*s

S e v e ra l runs m m e a r f i e d o u t using' 66 grams

o f m ~ e re se ll 66 g ra m o f © o n eentrated s u l f u r i c s o ld . (Ber»* 2.0*
6089 (1 6 8 7 )) and o th e r re a g e n ts in th o amounts gluon In th o pro ced u re
f o r hrom ophonols»

I t was found n ece ssa ry t o broiain&te a t 86*60®

t o p re v e n t p r e c i p i t a t i o n o f th e s u lf o n ic a c id s b e fo re th e r e a c tio n
was com pleted*

Two f r a c tio n s

mm

obtained#

The f i r s t * b o ilin g

at 80*88* (4 » » *) «. 014*216® (745 am*) * w m i d e n t i f i e d a s g~bromo*»
m -cre so l*

It mm o b ta in e d i n an average o f 7$ and s o l i d i f i e d on

e te iia ih g i n th e re c e iv e r*

nfhen c r y s t a l l i s e d r a p id ly from a em a il

amount o f p etro leu m e th e r* i t form ed a s h e a f o f t e t r a g o n a l c r y s t a l s .
Slow er c r y s t a l l i s a t i o n from a g r e a t e r amount o f s o lv e n t gave la rg e
s o l i d prism s* m« p . 81*88®#
ftnalygis*

C a lo d . f o r C y& ftM i Br# 4 2 .7 7 .

founds

Br* 48,4*

The seeen d f r a c t i o n , b o i li n g a t 108**1G5G (4 mm«) a ls o

# 17 -

s o l i d i f i e d i n t h e re c e iv e r*

a m e e r * t e e e r d th e end e f th e d i s ­

t i l l a t i o n a e m a il amount o f m a te r ie l name e v e r a t about th e same
te m p e ra tu re w hich d id n e t s o l i d i t y #

(T h is was aeeumed t e be due

t o t h e p re s e n c e e f a e m a il amount e f 4 ~ brene-m ~ eresel and 2 ,4 - d l brom e^m -creeol* which have ap p ro x im ately th e came b a i l i n g p a i n t , )
T h is s o l i d f r a c t i o n was a l m a by a n a ly s ts and t h e fa llo w in g s e r i e s
o f r e a c t to n s t e b e 8 , 6-dibromo»m-c r e s o l * f i e l d 8 3 # ,

f t c ry s ta l*

H e e d from p e tro leu m e th e r in c l u s t e r s e f n e e d le s which m elted a t
36,6*97,0® an d form ed a p*tolu«n« s u lf o n y l e s t e r (Biaheum and
H olland* Aim,* 501. 06 (1 6 6 6 )) m eltin g a t 151*162®*
. A n aly sis * C a lc d . f o r CylfeOSr*! Br* 60*16*
m m

of u tm tm m m z ^ u z o m ^ u s m Q u

Foundi B r, 59 *7*
p u re 4 * n itr e *

nv*eresel, p re p a re d by th e method o f S t cede 1 and Kolb (Ann** 0 6 6 ,
210 (1660)} was b rom inated w ith two mala o f brom ine In g l a c i a l
a c e t i c a c id (C la u s , J* p ra k t* Chsm *(i) 5 9 , 61 (1 8 8 8 )) a t 16*20®
and t h e r e s u l ti n g 2 ,6*dibrom o*4*nit ro~m~c re s o 1 was reduced by means
o f stan n o u s c h lo r id e and h y d ro c h lo ric a d id (B aefo rd , Am* Chem, j * ,
4 6 , 416 (1 6 1 1 ) ),
The h y d ro c h lo rid e o f 2,6*dibromo*4*SJBiino*m*oresol was
d la e c t ls e d by th e p ro ce d u re o f Bigelow, debason and Sandborn
(Organic s y n th e s e s , Vol* V I, p* 16) and an u n s u c c e s s fu l a tte m p t
was made t o p re p a re Z, e-dibromo-nwc r e s o l by red u c in g th e diasonnium
group w ith a lc o h o l In t h e p resen ce o f f i n e l y d iv id e d c o p p e r,
an d P e te rs e n , J * Am* Chem, See *,

5061 (i9 6 0 ))*

(H uston

The f i r s t ty ao *

t i o n o b ta in e d by th e ste am d i s t i l l a t i o n e f t h e r e a c tio n m ix tu re re *

18 *

m ained a n o i l , w h ile subsequent f r a c tio n s s o l i d i f i e d in th e r e ­
c e iv e r and w ere shown by a n a ly s is t o be 2 ,6 -d ib ro m o -4 -c h lo ro -m -c re so l.
R e c r y s t a ll i s a ti o n from petro leu m e th e r gave n e e d le c l u s t e r s m eltin g
a t 68§ - 68j ° * A n aly sis o f th e liq u i d f r a c t i o n coming over In th e
f i r s t s ta g e s o f t h e steam d i s t i l l a t i o n fo r halogen in d ic a te d a mix­
t u r e o f £ , 6~dibreme<*m«eresol and 2 ,6 -d ib ro m o -4 -c h lo ro -m -cre so l*
D ire c t c h lo r in a tio n o f t h i s f r a c t io n in ch lo ro fo rm , a f t e r re p e a te d
a tte m p ts t o p u r if y i t had f a i l e d , gave 2,6-dibrom o-4-chloro*m *
e r e s o l m e ltin g a t 68’|*69<J0 # The p -to lu e n e e u lfo n y l e s t e r (E inhom
and H o llan d , Ann*, SOI. 9 6 , (1898)) r e c r y s t a l l i s e d from a lc o h o l
m elted a t 108-109°.
C onclusive p ro o f o f th e s t r u c t u r e o f th e 2,6-dibrom o-m c r e s o l was o b ta in e d by c h lo r in a tin g i t d i r e c t l y in chlo ro fo rm t o
th e 2 , 6- d i b r orao-4-chloro-m -c re so 1 w hich was a ls o p re p a re d by t h e
b ro m in atio n o f 4 -e h le ro ~ m -e re so l w ith two mo Is o f brom ine *

In a l l

c a s e s t h e i d e n t i ty o f th e p ro d u cts was checked by e s t e r fo rm atio n
and a n a ly s is *
An a tte m p t t o p re p a re 2-brom o- and 6-brom o-m -cresol was
made by b rem in atin g 36 grams o f m -ere so l (1 /5 m ol) and 36 grains
o f c o n c e n tra te d s u l f u r i c a c id in n itro b en zen e a t 5-10°*

However,

t h e r e a c tio n was found t o y i e l d a m ix tu re o f 23 grams (40#) o f
2-b ro m e-m -eresol b e llin g a t 67*70® (4 mm*) and 6 grams ( 8# ) o f
4 -brom o-m -cr eso 1 b o ilin g a t 1G5-10S® (4 mm*)*

The l a t t e r form ed a

mass o f v e ry f in e n eed les when r © c r y s ta llis e d from p etro leu m e th e r
w hich m elted a t 58$-$9&®*
112-113°*

I t s p -to lu e n e s u lfo n y l e s t e r m elted a t

R e c ry sta l l i e a t ion o f 4-brom o-m -cresol, p re p a re d by Huston

* 1ft #

and Hfctehinsen (J* Am# Chon# S ee#, 5 4 , 1608 (1 9 6 8 )) gave t h e e a se
m e ltin g p o in t from t h e same s o l v e n t, and i t s p * to lu en e s u if e n y l
e s t e r a l s o m o lted a t 112-1X3° * To f u r t h e r prove th e s t r u c t u r e o f
t h e 106*106® f r a c t i o n , 4 - n iir e - w - e r e s e l ess reduced by t i n end
hydrebrem ie a e i d i s a lc o h o lic s o l u t i o n , th e method used b e in g
a d a p te d from t h a t o f R a ife rd , (Am* Chem# <?«, 4 6 , 419 (1911))*

The

hydrebromld© o f d-am ino-in-eye*e 1 was d ia s o tle e d In hydrebrom ic a e id
s o lu tio n *

Replacement e f th e dlasonnium group w ith bromine by th e

Sandneyer r e a c tio n (O rganic S y n th e se s, C e ll# Vol* 1, p* 161*} y ie ld e d
4-bro»e*«s*ereseX , which was I d e n t i f i e d by th e s m itin g p a in t and t h a t
o f i t s p -to lu e n e s u lf o n y l e s te r *
In o rd e r t o prove th e s t r u c t u r e o f 2 v4 -d ie h le ro ~ m -e re * e l
o b ta in e d in t h e c h lo r in a tio n o f m -c re so l s u lf o n ic a e id - 6 , 6-brom em -e ? e se l was p re p a re d by th e fo llo w in g sequence o f r e a c t i o n s s
e - n itr o - m - c r e s o l, th e v o l a t i l e f r a c t i o n o b ta in e d in t h e
n i t r a t i o n o f m -e re so l by t h e method o f St& edel and Xblb (Ann#*
660* 610 (1 8 9 0 )) was reduced to th e co rre sp o n d in g amino compounds
w ith sodium b y d r e s u lf ite (Anwer®, Borsch# and W e lle r, B a r. 64*
1616 (1 9 2 1 )); (Huston and P e te rs e n , J* Am* Chem* S ee# ,
(1935))*

6660

The 6-am ino-m -oresol th u s o b ta in e d sms d i a s o tl s e d In

s u l f u r i e a e id s o l u t io n and th e dlasonnium group re p la c e d by bromine
i n th e p resen c e o f cuprous bromide and hydrebrom ic a e id a cc o rd in g
t o th e method r e p o r te d by Bigelow (O rganic S y h th e se s, c e l l * T el* X»
p . 151)*

The p ro d u ct was o b ta in e d as an o i l by e x tr a c t i o n w ith

e t h e r and was p u r i f i e d by d i s t i l l a t i o n under reduced p re s s u re (4 mm,)
B* p* 70*75° (4 mm*) - 210-216° (745 nm ,)«

Upon s ta n d in g i n th e

- 20

r e c e iv e r t h e S -b rom e-ja-cresoI s o l i d i f i e d .

I t form ed in s o l i d

a n g u la r prism a when r e c r y s t a l l i z e d from p etro leu m e t h e r .
&• p . 3 8 ||- 3 9%°.
I t s p - to lu e n e s u lf o n y l e s t e r m a lted a t 8 9 * 5 -9 0 .5 when
c r y s t a l l i z e d from a l c o h o l .
A n a ly s is *

C alcd* fo r CyB^OBr: Br 4 2 .7 7 .

Founds Br* 4 2 . 8 .

SCHMK OF REACTION

0
tr

%
&tt

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E-CiUDBO-H-CBESOL, 2,4-DICHORO-M-CHESOX,, 2,6-PXCHlOflOM-CKB801 AMS 4-CH10fiD-tt-CLi

a

miafrer o f ehlsrinatlons of m~

ofesol sulfonic aeid were carried out by a procedure sim ilar to
th a t w ed for the bromo^Bweresole • 86 grams of m^eresol, 86 grams
o f concentrated su lfu ric sold and 200 grams of n ltro benzene were
used# Chlorination was carried on to saturation a t room tempera*
ture#
I n t h i s e a se th r e e f r a e t lone c e r e o b ta in e d from c a r e f u l l
d i s t i l l a t i o n under reduced p re s s u re In a m o d ified c l a i s a n f l a s k
h a rin g a 66 cm. column (2 cm* bo re)# th e f i r s t f r a c t io n b o ilin g a t
88-57* (4 m * ) - 186-186° (740 nm*) - s o l i d i f i e d In «h« r e c e iv e r
and upon r a p id c r y s t a l l i s a t i o n from a sm a ll amount o f p etroleum
e th e r gave a s h e a f o f f i n e t e tr a g o n a l c r y s t a l s m e ltin g a t 49-60° •
Prom a g r e a t e r amount o f so lv e n t la r g e s o l i d prism s were o b ta in e d .
A n a ly sis and p r o p e r tie s o f t h i s compound i d e n t i f i e s i t a s 2 -c h lo ro m -o re a o l.

f i e l d - Id##

An»ly»i« . C l o d . fo r C1^8^ OCX* 0 X, 2d*-0 1 .

Pound.$

0 1* 2d#8 #

th e second fr a c tio n * coming over a t 75-00° (4 mm.) - 235*
236° (746 mm«) * a ls o s o l i d i f i e d in th e r e c e iv e r and c r y s t a l l i s e d
from p e tro leu m e th e r in c lu s te r s o f n e ed les m altin g a t 5 8 -5 9 °.

its

p -to lu e n e s u lf o n y l e s t e r form ed in Sm all p l a t e l e t s from a lc o h o l
w hich m elted a t 101-108°.

These c o n s ta n ts and t h e sequences o f

r e a c tio n s below show i t t o be 2 ,4 -d ic h lo ro - m - c re s o l.
A nalysis# C a lc d . f o r C y^O C lg: C l, 4 0 .1 1 .

f i e l d - 25##

Pound: C l, 3 0 .3 5 .

The t h i r d f r a c t i o n b o ilin g a t 80*85° (4 mm.) * 239.5*240.5

- 22 -

(746 ram#) * rem ained an a i l a t room te w p e r a tu r e * A nalysis and th e
r e a c tio n s given below show i t t o be 2 ,6 -d ie h lo ro -m -e re s o l*
PROOF OF SfRSOYOBB C0 Z ,4~DlCHI0B9-.lM3fiEBQI,;

Y ie ld * 6£#

2 ,4 - d ic h lo r o -

m -e re s e l o b ta in e d in th e c h lo r in a tio n o f m -e re se l s u lf o n ic a c id -6
i n n i t r o bensone was b rom lnated w ith one raol o f brom ine i n c h lo ro ­
form a t tf** C lu s te r s o f f e a th e r y c r y s t a l s c r y s t a l l i s e d from p e tr o ­
leum e th e r which m elted a t 5 8 -6 9 °, th e p -to lu e n e s u lf o n y l e s t e r o f
which m olted a t 9 5 -9 6 °.

A n aly sis o f th e compound showed i t t o be'

a num obroran-diehlero-ra-eresol #
A n a ly sis * Calcd* fo r O ^ O B rC lg *

h a lo g e n , 58*98.

Founds halogen, 59#6*
6-bromo-ra-e r e s o l p re p a re d from 6 -n itro -m -e re e o l by th e
r e a c tio n s d isc u sse d above, was d i r e c tl y c h lo r in a te d in chlo ro fo rm a t
0 ° w ith an amount o f c h lo r in e c a lc u la te d to occupy two p o s itio n s *
(Houben Dio Met ho den der o rg an isch en Chem rte, V o l. XXX, p . 799;
B e r* , 5 5 , 45u, 6754 (1006))#

The compound o b ta in e d was

shown by

m e ltin g p o i n t , a n a ly s is and e s t e r fo rm atio n t o be th e same as th e
one o b ta in e d by b ro m in atin g Z ,4 -d ic h lo ro -m -e re s o l *
pjiqof o f m m m m m o f 2 , 5- 010mjoso-iM3R5sohj

2 , 6-d ie h io r o -

m—e r e s o l was i s o l a t e d alo n g w ith 2 ,4 - d le h le r o —ra -e re s e l in t h e r e ­
a c tio n s d e s c rib e d above*

I t was brom lnated d i r e c t l y w ith one mol

o f brom ine in ch lo ro fo rm a t 0° t o 4-brom o-2, 6 -d ie h lo re-m -c reso 1
w hich c r y s t a l l i s e d i n n eed le c l u s t e r s from petro leu m e th e r m e ltin g
a t 64-65**

The p -to lu e n e s u lf o n y l e s t e r o f 4-brem o-2, 6 - d ie h lo r o -

m -e re so l formed in n e e d le s from a lc o h o l which m elted a t 10& J-106|°.
A nalysis* Calcd* fo r C»fi-0BrCXs>s
Found;

h a lo g e n , 59*6#

h a lo g e n , 58*98*

- 25 *

i - n it r o - m - e r e a o l ( S te e d e i, K olb, Ann*, Sggg, 210 (1 8 9 0 ))
wa* c h lo r in a te d w ith two mol* o f c h lo r in e in g l a c i a l a e e ti e a e ld
( a w t e n , Chen, d« Am, ©hem* S ee*, 6 6 , 4817 (1988)}*

The 4 - n i t r e -

8 ,8 * d ie h le re * ia -e re a e l th u s o b ta in e d wee red u ced w ith t i n an d h y drobrom ic a e id «

(188 gram* o f 4 - n itr e - 8 ,6 - d ic h lo r e - m -c r e s o l was d i s ­

s o lv e d in 800 ee« o f a le e h e l and 108 gram* e f messy t i n added#
480 ee* o f 40# hydrobrom ic a e ld wee added t o th e h e ll i n g m ixture
d rep w iee, w ith c o n tin u e d r© fluxing*

A fte r re d u c tio n was com plete

th e h o t s o l u t io n was poured in an eq u al volume o f 48# by d r ebromle
a e ld «

The c r y s t a l s o f th e hydrebrezaide form ed in f in e n e e d le s upon

c o o lin g o v e rn ig h t in a r e f r i g e r a t o r , and were removed by f i l t r a t i o n * )
Beplaeem ent o f t h e amine w ith bromine was accom plished by th e p ro ced u re
Wf Bigelow (O rganic S y n th e s e s , C o ll* Vol* 1 , p« 131) and th e o i l
o b ta in e d was f r a c t io n a te d a t 4 am* t o remove t h e u n d e rc h lo rin a te d
p o rtio n *

The d e s ir e d 4 -b ro ia o -8 ,6 -d io h lo r e-m-eres© 1 come over a t

110-120° (4 mm*)*

I t c r y s t a l l i s e d from p etroleum e th e r in n e e d le

c l u s t e r s m e ltin g a t 64-68° and I t s p -to lu e n e s u lf o n y l e s t e r m elted a t
1 O 8 |-1 0 8 |°*

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IS -e reso l was c h lo r in a te d by t h e p ro ced u re u se d f o r th o p re ­
p a r a tio n o f 2 f4*diehXerO"*m*eresol, 2 , 6 -d lc h lo r o -m -ereso l and 2 - e h lo r e sM * resel w ith th o esc opt io n t h a t 46 grams o f s u l f u r i c a c id was used
f o r 66 grams o f m *eresol and c h lo r in a tio n was c a r r i e d cu t a t 8 0 ° .

At

t h i s te m p e ra tu re about &% o f th e m -e re so l was c h lo r in a te d in th o 4
p o s i t i o n ,t h e g r e a t e r p a r t b ein g re c o v e re d u n c h lo rin a te d *

The 4 - e h lo r o -

m -e re e o l b o ile d a t 86-86® (4 mm*) and formed a maes o f f in e needle#
from p e tro leu m e th e r which m olted a t 58-66° *
Dur in g th e c h lo r in a tio n o f m -e re so l a t 86®, a mass o f y e llo w
l e a f l e t s p r e c i p i t a t e d from th e n itro b e n se n e which w ere removed by
filtra tio n *

th e y were s l i g h t l y s o lu b le in a lc o h o l and e t h e r , b u t

I n s o lu b le in p etro leu m e t h e r , h o t w a te r, and c o ld c o n c e n tra te d s u l­
f u r i c a c id *

They d is s o lv e d in h o t c o n c e n tra te d sodium h y d ro x id e , th e

s o l u t i o n d arkening t o g ree n -b lac k *
Q u a lita tiv e a n a ly s is fo r elem ents showed c a rb o n , hydrogen and
c h lo r in e to be p r e s e n t; s u l f u r t o be ab sen t*
in d ic a te d c h lo r in a tio n o f th e s id e chain*
a t X9«* when c r y s t a l l i s e d from a lc o h o l*
may be m-hy dr oay -b e n » o -t r ie h lo r Id s *

s a p o n if ic a tio n t e s t e

Decom position o c c u rre d
I t i s p o s s ib le th e compound

26 *

D I S C U S S I O N
I t la re p o rte d by C laus and Krause (B er*, 2 0 , 3089 (1887))
t h a t e u lf o n a tio n o f m -c re e o l w ith an e q u a l amount o f s u l f u r i c a c id
a t 110-120® fo r 2 t o 3 hours produces a 5 /6 y i e l d o f m -c re so l s u l ­
fo n ic a c id -4 *

S in ce s im ila r c o n d itio n s y i e l d p-phenol s u lfo n ic

a c i d , b ro m in a tlo n and c h lo r in a tio n o f m -c re so l s u lf o n ic a c id in an­
hydrous n i t r e hen sens was ex p ected t o y i e l d m ainly 2 ,6 -d ib ro m o - and
2 ,6 - d le h lo ro -r a -e re 8 o ls * T h is was t r u e in th e b ro m in atlo n r e a c tio n s
a lth o u g h a sm a ll amount o f o i l was o b ta in e d along w ith th e 2 ,6 d ibrom o-m -cresol f r a c t io n w hich would n o t s o lid if y *

In th e c h lo r ­

i n a tio n r e a c tio n s 2 ,4 -d le h lo ro -m -e re s o I was o b ta in e d in g r e a te s t
y i e l d alo n g w ith an o i l which was shown t o be 2 ,6 -d ie h lo re -p h e n o l*
Under m o d ified c o n d itio n s b o th 4-brom o- and i- c h lo r e - m - e r e s o l were
o b tain ed *

I t would seem in th e l i g h t o f th e s e r e s u l t s t h a t m -c re so l

s u lf o n ic a c id i s n o t form ed In th e amounts re p o r te d by C laus and
Krause b u t t h a t a m ix tu re o f th e 4 and 6 s u lfo n ic a c id s I s formed*
This co n clu sion Is supported by th e work o f Haworth and Lapworth (J*
Chem* S e e . , 1 2 5 , 1 2 9 9 ( 1 9 2 4 ) ) , who s t u d i e d t h e a c t i o n o f c o n c e n t r a t e d
s u l f u r i c a c id on m -c r e s o l a t v a r io u s te m p e r a tu r e s*

T r e a tm e n t f o r o n e

h o u r a t 3 0 -3 8 ® g a v e t h e 4 a n d 6 s u l f o n i c a c i d s i n a r a t i o o f 1 t o 2 * 7 |
1 to

2 a t 1 0 0 ® , w h i l e a t 1 2 0 ° t h e p r o d u c t was m a in ly m - e r e s o l s u l f o n i c

a c id -6 *

T h a t 2 , 6 - d i b r o m o - , 4 - b r o m o - a n d 2 , 4 - d lb r o m o - m - c r e s o l c o u l d com e

o v e r i n t h e sam e f r a c t i o n , a n d 2 , 6 - d l c h l o r o - , 2 , 4 - d l e h l o r o - a n d 4 - e h l o r o m - c r e s o l c o u l d com e o v e r a t a p p r o x im a t e ly t h e sam e t e m p e r a t u r e i s
by t h e

fo llo w in g b o ilin g p o in ts fo r th e s e s u b s ta n c e s t

sh ow n

—27 m

d-breme-awsreeel

158-140* (16 mm*)

2 #4-dibr ome-m-cre* ol

130-140° (16 mm*)

2v6-dibrome-m-oresol

140-146® (16 mm,)

4-ehler o-m-cresol

231-233* (746 *nu)

2 ,4 -d ie h lo r© *©«*©re s o 1

266-286® (748 aw*)

2 #6 * & ie h lefe -m -e rese l

239*8-240*5® (748 mnu)

I

2 8 M A I 1

2 - B rom inatlon and c h lo r in a tio n o f p -p h en o l s u lf o n ic a c id in an­
hydrous n i t r e bensene gave e x c e lle n t y ie ld s o f 2 #6~ditorome-#
2 96 - d l e h l e r o - , 2-brom o- and 2 -c h le re p h e n e l* *
XX - B rom inatlon and c h lo r in a tio n o f th e p a ra s u lf o n ic a c id o f o o r e s o l in anhydrous n i t r o bensene gave d -b ro m o -e -c re se l and
6 -c h lo r o -e -c re s o l*
I XI - B rom inatlon and c h lo r in a tio n o f a mixture o f m -e re so l s u lf o n ic

acid-4 and m-cresol s u lf o n ic acid-6 in anhydrous n itre bensene
under v a rio u s conditions gave fc-brorao-m-cresol, 4-bremo-iaeresol, 2*6-difcfomo-m-er eso 1, 2-chloro-m-cresol, 4-ehlero-moresol, 2,4-dlchIoro-m-eresel and 2 ,6~dlehloro-m-c r esol *
I f - 6-brom o-m -eresol was p re p a re d in c r y s t a l l i n e form from 6 - n i t r e m -o reso l*
f - S u lfo n ic a c id groups on th e bensene r in g o f phenol and phenol
d e riv a tiv e s were shewn t o be s t a b le tow ard h a le g e n a tlo n i f
c a r r i e d out i n an i n e r t anhydrous so lv e n t#