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“in \,,C;1\'CEZ\'SATEC1\' CFTERUARY

M! Ara; TERTEAR‘.’ BL'L‘YL

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‘j\ THE. PRESENCE. OF

ALVMI.‘ 'QM CHL'JRELE

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$73523 01mm GE‘SCL g m. 3"““3’313 .93 Am @931; cxmsz

A Th 6-3:? 3
submitted to the faculty of L'ichigen State College of Agiculture
and Apglied Science in partial mlfinment of the requirments for

the Lbs-rte:- 01’ 530 5.3an deem

Ross Iii 41‘ 3.701323;

Auglmt 19:5?

f0£KHWE
I tabs this opportunity to admouledga my infie‘btodness

and to 9213033 my mtitzfie to Dr. R. C. Ensign for tho
assistance and enema-mt he has given during this work.

331-680

C 011131738

 

 

 

 

 

 

 

 

 

Page
I .. mzouuumon I? w M .r 1
II - HISTORIGM. r: ~ _ w : 2
III - Immmlcm. :4 W I w 8
Iv - DISCUSSION I I I; A _ I 11
V . EIE’J‘ELH‘IL , _ A _ w :
VI - momma Immmmu T I v I w 25
VII - mm or ImTIIL‘S I I 25
A - m :frmaY B‘U'I‘YL comm-3:310:15“
B - T4.I?1‘I:‘IIY 1m Guzmmmozzs
VIII - summit! :s 27
IX «- BIBLIOQ-ZAHIY T W A , I _ I 23
I -. norms on nmmmum Rum --(1n back binding mar)

11m ZODU (YI‘ ION

The condensation type of chemical react ion, wherein benzene
or substituted benzene rings are reacted with aliphatic or mastic
alcohols or 91153;]. halides in the mesence of a catalytic agent have
constituted a large portion of the synthetic studies of tandem or-
ganic chmistry. Sons of the materials that have been used to cute-
lgze these reactions have been eulplmric acid, phosphoric acid,
phosphorous pentoxide, magnesium chloride, zinc chloride, phosphor-
ous pentachloride, altnnimm chloride, ferric chloride ( both unlu-
drone am Ian‘s; 5 ago ) and bleaching earths (tor m1. teasu.
filtrol. and other acid activated earths).

Thieleborctowyheebeenveryprolificinthcetudyofthn
reactions using almnimnn chloride as the condensing agent for arom-
atic caupounds with various aliphatic and aromatic 616011018.

The mteriol that follows is a contribution to this can
field or work, and although it hours every oer-ml: or! the work of
a hoginner in the field a: scientific research, I sincerely hope it
may add something of value to our rapidly mowing collection of
knowledge.

(1)

ELSE-()EICAL

"Tr '.|"1',‘1 'r . 1r 1-
I'm». 4.1-1) Iflflul‘OLS

v.1 w --~

 

in 15581 3:10an (1) prepared butz-rl, may]. and propyl phenol
by condensing phcmol and isobutyl cloahol, using molten zinc chlor-
ide as a catalyst.

"in 1:32:72 Lisszaro (2) condensed prowl alcohol and m—crosol us-
ing mgnosim chloride as a catalyst and a year later (3) he used
the some catalyst to propere mthyl-hutylephonoli butyl-m-croool; .

In 1884 urn-oats .(4) moored is.:butyl-o-creeol by diozotiz-
ation and hydrolysis of o-«t‘oluidine. he obtained a reddi‘ on yellow
oil boiling at ass-237°. This was described as a very thick ero-
mstic oil which would not crystallize. he considered the butyl
group to be in the pore position and attempted to prove its atm-
ture by oxidation of the iso—butyl-o-methyl 3111301 to form a math-
cry phthelic acid. he reported that the mthylation ifomtion of

the methyl other) was extremely difficult. and although the pro-

duct he obtained was not noticeably different hem the expected pro-

duct, it one or such a small qmntity that he was forced to give up
the study.

In 1889 Unttexmunn, Ehrhnrdt mid inisch (5) treated onisol and

phenotol with soy]. chlorides in the prosonce of alumimm chloride and

obtained condensation pro-ducts in which they proved the acyl group on-

tered the ring in a position porn to the Odie-3 group.

(2)

In 1891 Wells) aw the theory of Gettemn (5).
by Wing aniline and other aromatic compounds. He stated that
the entering substituent om mm to: pox-o position on the ring, .
and that this lo also tron or the higherhmnloguee of the. phenols.
whichere preparedbytreetingemixtureotpimmlwiththe appro-
piato alcohol in the presence of zinc chloride.

In 189]. Door (7) mt} o—amino—teI't-btrtyl—tolnem by the ‘
reduction or mono-nitro—butyl-otohm with zinc and hydrochloric acid.
miemoduct meayellmoilvithahoiflngpointetadso.which
game the some acetyl and homey]. derivatives as the amine need
abon m Emu (4). Be Woo-o considered to. tertiary butyl
group to be in the para position, although I could no: nothim in
thisarticlo aboutehengingthomninetoemenol. Threeyeere later
he carried on a related study (8) and mpered WWho-oreeol
no: o-croaol am ieo-butyl alcohol with aloe ehlorido as a catelyet.
He obtained a yellow oily product with a boiling point or zoo-237°. 1/
which he considered to be p-tert-bntyl-ortho-oroeol, the sons pm-
duct eeEm'onte (4) hadpreporedn'unthomine. Kenya-comm
strong mbability that the ieo-bntyl was arranged to the tart-
‘butyl gong. A tri—nitre derivative was prepared which mltod at
85-860.

In 1899 Gurwitch (9) reported tort—min and tort-m3»
phenols prepared by the action at the tort-m1 chlorides with
phenol in the presence of ferric chloride.

Won (10) prepared 811W]. phenols by the reduction of
ketonee with zinc melgem and hydrochloric acid.

(3)

In 1907, three years later, Hex-313 an! Wane). (11) Minted
phanois by treating the phenol with cum iodide in an alkalin-
solution.

In 1909 motinsky and Paczemtch (12) caned attention to
thc fact that emu. carnal-y cal-13111018 my be condensed with
manysubetanoos mmmmemlabythoaiddmtuacmw
which 13 added a 11th staphuric acid or zinc chloridn.

In 1911 Banana and Host. (1:5) prepared Mert—butyl-ortho—
meolbyrepeatmgthomkutlim (t). This Wm
halogenated to prepare a wthyla-butylahenlwdrophnnol.

mmmmmm (111 Monaco-ammuth
mobutylclcohmmthomsemctmcmphuru acm atsooc. [/
They reported p-tert-butyl-o—crcsol with a boiling point at 255-
2570, which gm 3 mm derivative with a wilting point at 835-89".

In 1934 W (15} used hydrated ferric chloridn as a cata-
lyst for the condensation of tertlm'y elk-3'1 helm. with phenol.
by refluxing at 80-900 tor twenty-d‘mn' hours.

In 19:54 D1ctz1er,'hm1quist and Perkins (16) obtained a pat-
ent on a process m preparation or amylated phonon by tho action
of the anal halide with the phenol 1n pmsoncc of almimm chloride
and other «mamas at tmperaturcc tram 50-2009. Thu: upon-ted a
63.9 5% view at tic-tert-b'trtyl-G mthyl phenol with a boiling point
“cm-1590125 cm a 20 93 yield a: 2,4 11493-me 6 mtby]. "
phem1.bouingatw5.5°/25m. andanastimtealtoszor
z-tert-butyl-G methyl-phenol with a boiling point or 1%.6-157.5°/25
and with a melting point of 50.99.- ‘

(4)

In 193.3 Tehitchibabim (17) prepared oral and benzyl deriv-
et ives of phenols and meals by heating the phenol with secondary
and tertiary alcohols in the presence of phosphoric acid. He
showed that the product or the condensation 0: W801 and tertiary
butyl alcohol could be nitrated to produce misc mbrstte (lanthoxy
2-tert-buty1-5 mthy1-4,6-dinitm benzene). This was to prove that
in the case or the butyl-m-cresol the butyl pomp is ortho to the by-
dmzyl mug). He also condensed tertiary butyl alcohol with c-crc.
so]. and obtained about a 78 2‘» yield at a product boiling at 122.5/14
mm. which fumed colorleas crystals neltim at 27°. E demo.
that the tertiary butyl is ortho to the hydroml group in this
compound beczmse it was in the case of the mpound obtained frat
m-cresolc

ms for I have given some history of the prepsrdt ion of buty].
and any}. cresols and related commends by various methods. The
previous articles from this laboratory hm covered them quite
'thozouMbnt Idowishtoyresont efewofthe steps inthe dev-
element of the condenset ions of phenols with decimals in the pre-
sence of elumimm chloride. Prior to 1915 there were several ret-
erences (18) to the use or altmimm chloride as n dem'drsting
agent od- catalyst but not by the present procedure.

the literature contains mny articles recording the Preidel
and Croft’s synthesis. In these an alkyl halide reacts with an
aromatic substance by formation 01’ on intomdiate addition product
which then rearranges and regenerates the elimimm chloride for
continued reaction. Here we can consider aluminmn chloride as a

true catalyst. However, in most of our syntheses the slmnimzm

(5)

chloride met be in a relatively large and quite definite quantity
to have the reaction yield satisfactorily. This fact would indicate
no regeneration and it is questionable whether we can call it a
true catalyst.

In the present Elston method the alcohol is used rather than
an anal halide and definite quantities of almimm chloride are
needed. Thisnethodnas bogimbyhstonandl'riedmm (19) in
1916. hey fmmd that primary and secondary aromatic alcohols con-
dense with benzene. When triphenyl carbine]. ms reacted with A
benzene the expected tetrephewl methane was not received but tri-
phenyl mthane resulted.

In1924itstcm (so) condensed benzylelcoholwith pheneieni
obtained p-benzyl phenol in a as $ yield.

“years laterhstonandsagor (21) mmbletceondenee
phemL-ethy1-. WWI-ml. and other ml- and ice-alcohols.
maid condense ally]; alcohol with benzene. Iranthie theyeon-
chdedtbatonlythoee alcohols condense innhiohtheelphncarbon
1s a umber of a benzene ring or is double bonded.

Tamwonandawartout (22) condeusedbmylelooholwith
Wool and later work in this laboratory included the condom-
ation a: mi alcohol with p—cresol (23) ml n-creeol (241. In
each at these cases they obtained a di-encyi- mbstitirted and tan
mom-sliml— substituted products.

hmotthaacam-hathe resultehavc agreedwiththetheory
ernetterm £5) management (a) that thencet ettmeihatnntion

it)

1n the ring is pure. to the Imam]. mop, so we could ennect this
to be the probable stmetm'e or the m1 ereools of the present

study.

(7)

MOEEI‘ KL" "-1.

MM inthehistorieolreviewthenseotoltminumohloride
as a catalyst is not of recent derelomnt. althoua the improved
and cheaper methods of production of recent years have mobshly in-
creased greatly its industrial uses.

The mechanism that the reaction follows is not definitely
established but the most accepted idea is one or e dehydration pro-
0953. As in the general fonmla :

R50011+ECZD—9330C::> H+Hz°
This procedure hmzever does not give any idea of an intormdiste
Mtion, which we would strong]: expect as indicated by the
color produGed during react ion.

Tmbemnm (25} reported the ammtion of benzene and tol-
uene by the use or: secondary and tertiary alcohols in the presence
of alminnm chloride. He eonsidered the formation of en elmimm
elmholste, which demnses to on slkene. The elm then takes
up hydrochloric acid to form the alkyl halide which reacts with
the hydrocarbon.

Although the evidence of other formt ion by the use of alim-
inum chloride is not plentiful it is possible that we might @-
ploin the reaction by the tenant ion of an intermediate ether
followed by rearrangement to the phenol. It was reported by Kern
and Weith (18) that alumimm chloride reacted with phenol to give
a diphem‘l ether, although the first step in the process was

(s)

considered to b. whyiretion. .

mice (.25) has offered a mechenim which sew quite
possible although like each of the others does not have enough
evidence to he conclxzaive. He considers firm the romtion of
e hydro-elm pbeholic acid (I) which then reacts with the
alcohol (II) to mm on intermediate addition product mien re-
arranges to give the substituted phenol and alumimm phenolste (III) .
.The water formed in step 11 then reacts with the elmzimm phenolate
to produce the phenol and elmimm hydroxide {N}.
I“ sfirmcgz-é emf} (A1 (OCqH9)5f+ 3 H01
11.... 35A; (OC7H7}5+5 Rscmelm. (0075;)6.(-035)3+m2°
III- Al (0073)}5. (fish??- Al (0075723‘0'5 Iwoc'InfioCI‘Zfi
NW 11 (00937 )g‘l'fi 1130-) “(Mb‘fs Om3

The hi story of the react ions of this type has shown that
there is a general tendency to condense with the allcyl group
entering: the ring pore to the hydroxyl group. If we notice the
forces acting: this is Idiot we should expect. The directive in-
fluence of the following groups- is considered to be to the ortho
or 1mm position, usually pore yrodminctineg. The order or the
relative directive powers of the groups is 0H>Nf12)1>3r> Cl) G35.
Titus in o-crewl we can consider the directive power of hydrozyl
as greatly predominate over the metiml group. We could expect
then frm the hydroxyl group alone to receive min” a para
substitution. However the mall amount of ortho influence would
be dissipated because to have a mug: enter ortho to Mm]. it
would be mte to methyl and this would not be very pmbahle.

\9)

If‘we consider the electrical effects preeent 1n phenol (I,
below) the meet in field (general effect) or the phenolic omb-
gen will tend to repel the negative field of an alkyl group and
we should expect to find the group entering the pure position
most easily. In the case of o-crerzol ”I helm?) where 813531 and
hydroxyl groups are alreafly present their negative fields will
repel each other and increase the stenric hindrance effect on
the 2-poei’cion and decrearze the mount of expected OI'tho sub-

31: itut ion.

[O ’ \
m3

 

 

 

 

(10)

D 135186 ION

The resulting percentage yields \ 132138626 and26a } ere eel-
cvlated on cmda products, basing calculation on the theoretical
amount to be expected from a given quantity of alcohol used.
Although individual rune gave large vex-int ions I consider the
average yield of pure prom for tort-butyl—o-orenol is 55 S and
for tort-mimooi 50$ .

me preportion of reactants seems to be on Optima at about
one mole of the alcohol to two moles of erase]. and one-half mole
of aluminum chloride. In the bitty]. run the better method is to
add the alcohol-cresnl-petrolm other solution to the suspension
of aluminmn chloride in petroleum other. I tried several runs
by adding dry olmninm chloride to the slammed-patrolman
other mixture but there seemed to be a tendency for the Motion
of a solid complex where there was excess of reactants and a de-
ficiency of elumimm chloride present. his red Jelly-like
solid would tom after the reaction was midst-way and by increas-
ing elumimnn chloride and solvent 1 ton-I it oouid be stopped on
some occasions. In other cases the solid toned so rapidly that
the mess me too heavy to stir and the additional almimm chloral
ids and petroleum other only remained on top. a. time or this
Jelly formtion was apparently the and of condensation W,
in those cases which had eolii’ied early in the reaction the yield

was practically 1111; Wu t1: solvent and excess creool are '

(11)

removed from these rims which had solidified practically nothing
was left but a dork gammy mass which deeomyosed and left a dry
char in the flask.

In the ease of the ml alcohol the oondenset ion react ion
sound to proceed more slowly, and by adding; almizmm chloride to
the alcohol-creed loss Jelly formtion was noted and the yield
was better then by the same procedure for WY]. condensationao

In the Duty]. runs the reaction mixture usually developed a
hright‘bloodto a very red color. and this coloration .96de to
indicate owning of the atrium: of condensation. However. in
the em]. reaction the color formation ms meh slower am in
some cases only a straw color resulted after too days stirring,
but in spite of this the yield me quite good. In the first two
runs or the butyl condensation the almimm chloride wee added to
the creeol and than the alcohol dropped into this mixture but the
yield one Very poor. This W hen been‘eeoeed because the all-
001101 one added to the are 9-01 and elmimnn chloride but more
probably because the rot 5.0 of elminmn chloride need was very
ml]. in morison to the ratio need in later condensation

which gave better yields.

(12)

$332133me

A 500 042‘. round bottom three necked flask was fitted with
a Want stirrer with a mercury seal, dropping funnel, and
a reflux: condenser closed with a calcium chloride tube and ham.
1:33 a themmtar extending through the air sonaenser into the
solution. Dry ah- ms forced throng: the Empty apparatus for
some time to mm 11; as dry as possibh. Thu solvent used in
an mnswas petrolmmother dried madcimehlowide.1'ho
alcohols were dried over anhydi'mm potassim ar sodium sulfate.
The o-m-esol ms redistillod at atmpheria pressure. The size
ofmnasmiedmmmst part%m10 (18.53) uttera-
1:317 butyl alcohol and from a} to 1:23 moles of ortho msol were
diwlved 111100 me. dry petroleum cther and placed in the
Mapping; fume}... Van-yin: prOpatrtions at 91mm chloride were
usedbutnsuauyL/S mole (16.7 g) ofantuflrous almixmfilort-
firms added to .100 e.c. patrolman other in tha reaction flask.
Thu stirrer Ias started and the aluminm chloride formed a white
to yellw suspension in the solvent. The alcoholmol-petmo-
1m ether solution was dropped into the flask over a period of
about two hours at such a rate that tho tanporatuire remained
from 25—300. regulating the addition and cooling the flaw with
water and 100 bath 1f mam-y. Hydrogen chloride rims es-
capedfrmnthomrhhofthe refluxcondmmeramlmrelodtotho
Wearababarofwateroranmdtoascapa thrtmghahood.

(13)

As the reaction msscd a coloration. usually dark blood red
appeared in the flask. The stirring was continued about two to
three hours after all of the material had been added and then
allowed to stand at room temperature overnight. The next day
the contents or the flask was poured into 500 0.3. of a 50 if:
100 Won-lo acid mixture in a liter beaker. After stirr-
ing and standing cum-ha]: hour or longer, the beaker contents
was transferod to a liter separator-y renal m the water Layer
drawn of! the bottan. 21:. rod 011 (upper War) was collected
mammdbottmflaak. Thnmtcmsagammtotm
mtoryfmlandutmctedflthdi-otlwlothortwnthno
times. This extract was added to the min 01.1 in the flask and
anhydrous sodium sulphate added. Thu flask was left stoppared
with occasional shaking over h period of twenty-four hours or
longer and the extract than filtered or decanted m the sod-
lun sulphate. Th:- solvent was removed by distillation on a
steam bath and the product distilled in a claim flask and the
distillate collected mamter cooledwurtz flaskundarraduood
pregame (about 15 and. Three min fractions were obtained.
(1) a low boiling fraction consisting of patrolmn Other. alcohol,
its cum-id. and unsaturated derivatives, (2} that mess meal.
am (5'5) tho minted cresol. The crude fractions were then
fractionatedln. mono mamdifiod claiaenflaskhmringam
and one-half foot calm.

(14)

mommm P-rln-Jiwmohmsoh

I placed 27.4 grams of the p-tort- butyl-o-cresol, boiling
at lz’A-lefioflfxm. m a 200 me. three necked round bottm flask
equipped with a mrcury seal stirrer, reflux condenser, and
dropping tunnel, and dissolved it in 100 me. or chlorofom
The flaskoas placed inanice bath, and 26.6 msorbranine
in 50 c.c. of chloroform was added slowly over a period or two
hours with eonstant stirring. much hydrogen bromide was given
off and the flask was kept cold until the evolution stopped and
was allowed to warn slowly to room tanperature. The chloroform
was then driven off and the product tract innatod, giving the
following fractions:

 

 

 

 

2 grams v T A lad-3.260%
24 m — —-— 126-129°/]Jm. mg.) 1 1.5436
7 grams :w A 129—i54°/um. ago: 1.54.37
‘4 grams 7 WJS4-JE8°/Dm.

The fwrth traction decomposed quite easily. I expected the 126-
129 fraction to be l-hydronw-z mthyld tort-butyl-G hm benzene
but analysis indicated a dibrom command. Thinking that there
was a possibility that two moles of bromine had been added, the
work was repeated as above except for 301m, using carbon
. tetrachloride in this run.
The original dietillot ion gave 42 grams or product 130-138°/15

and redist-illat ion gave \

20 mama-- iss-m°/nm. 1153 .~ 1. 5440

16 grams-- 126-129°/11m.

IRho index of retract ion showed that I again had the some compound
(15)

but still the analysis intimated a dihromo conmfimnd. Aryl 0313-
acetic acid (:27) was made and melted a}; 74.45%
137301 EPIC E) I’m-$31 Era-@3301.

This material was prepared by the same momma as above.
I used :30 moo of p-tertéowl-o—crosol with. a boiling, point of
WVO/Véc m. in 100 0.9. of carbon tetrachloride and cooled
to zero. Iowa! 153 grams of bromine and ot- rrod until no mm
hyfirogen Maids was given off. The tollcmLm tract ions were

 

 

obtained 3 .
10 gm: -_ w 135-33560/1m . '

4 owns w Loo-1.500%. Residue

 

file‘s. the above or o primed I Wye-Lined the follocfing from: ions :

 

 

 

4grtnzzsw: worn- ECO/nun.
5 mm *— 133-140°/11m. H22; 1.5433
”3 mm 3.... a m 140-14~°°/nm. mfg: 1.54.35
3 m w 2 Rosina:

 

A diatom“). urethane was pmmrcad (39} from the 140-142 froct ion
of the above. promot. The fine mute gran-ales now very hart to
dissolve but Wanted to the melting point of 178.5—1‘79.5°.
Analysis of 635 BEG 03 N Br

Colmzlotod B]: 17.70 $3

Pom-.6 2.8.69 53
@WmL

This mm was prepared by the method of Nealefi 28}. O—eI-esol
was smlfonofioa to block the 4—pooit ion and braminoted, followed
(16)

by distillation with super heated atom. Rodiotillation gave
the following fractions 3
33 grm M 197—3030
65 mam ............... 2205-210"
10 grams 210-220"
The high boiling mtsrm crystallized and was mobobly «ii-branc-
o—oreool. The main fraction used In the following condensations

 

boiled , at zoo-206°.

flowmmmx.

' MGWmofimpomdabmmsmdmeduthtu-t-
1arybutylaloohoxbytmaammthodasmmremhaabm.
mmmmmmoymmmmd at 129-151°/1.1m. Itahawed
the index or mfmction equal to 1.5241. Aryl mimetic acid
derivative (27) a: this W melted at 92-93% Amen-s or
this mound indicated only ambminu to ho present.

Since this product agreed inbuiling 1:011:5(1299/11mdwith
WWW-hawlmmlltmt thaymrotho sam-
but the mm: of refraction and the derivati'u mum; points
on not agree.

iquM-HIYI—i BROI.tO-O-CRE£:,'»OL
The 6 homo-unease]. pupal-ed above was condensed with tert-
arvl alcohol and the ramming tract 10118 We collected 3
9 m -------— 131-136°/J.1m.
20 grams W 136-143°/11-.
5 m .................. los°111m

(r2)

These mre hid-tho:- purified and the min 3x111: of the product
boiled at 140-le
Th3 diphmwl urethane of this compound was pregnred by the
method of Km (29) and melted at 177-173.s°.
Analysis at 835 326 02 N Br.
' Calculated Br 17.70 93
Found ._...... 17.53 a;
This checked very closely with tho 6.1le urethane of the bra-
ninoted p-tort-mnyla-o—erosol 178.5—179.5°. These diphonyl ur-
ethones were quite insolubln in alcohol and the available 1m
boiling ligroin and therefore recrystallization was difficult.
Hmmor, the melting points egg-ea so closely that the possibility
of their being different compounds is very slight.

mowers 03‘ mayo: m M? 01:01. CQLLIL‘II

 

The products of this condensation. theoretically, should
consist; of three ollvlatod creools (1) W methyl-4 tert-
butyl benzene. (a) lW—é—mthyl—G—tm-butyl benzeno and
(3) ¢,6-di-ter't- butyl-z mtlwl-vlhhydrm benzene. The work or
Dietzlar (16) recorded each of these products.

I distilled the main portion or m product mm tires at
various pressures and fund the boiling point to be 124-1360/13111...
wo-mW/o'm and zoo-oovo/vom‘ ‘

This product was a colorl as 011,, very viscous and
one at glycerin“ After standing in an ice-salt both for several
hours it formed crystals. Those were transfers-d to a filter
paper and dried in the ice box. 11121101131 they were thus found by

freezing the oil it was impossible to find a solvent from which
(18)

they would recrystallize. Even in the ice box they melted uhen
touched with a spatula to transfer them to a tube. Eherei‘ore some
of the oil was put in :2 mil glass tube and nineed in an ice bath
and a seed dromed in. The next mining all use frozen. The tube
was plucod in a beaker of ice outer and allowed to come to room
temperature. In this my I found a melting point of 22—23%

Although the product is one of the what ituted phenols, the
characteristic phenolic odor was not not ic‘eoble; it had only a
faint rubber like 3:911 which probably was due to materials
taken up during dist illet ion but could not be removed.

There being: a slight pose bility of other formtion during
the react ion, the product was treated with Cluisen alcoholic
potassim hydroxide (130) but no indication of an other rm given.

then the oil was crowned. to the sunlight for a length of
time it took on a light yellow cost. than it was distilled at
atomsphorie pressure it boiled at 255-3370 but soon took on a
reddish yellow: color. This probably one due to oxidation and
decompos it ion.

Usually we find ortho, and (ii-substituted phenolic compmnda
are insoluble in a fire percent potassium Imdroride solution.

The lower boiling mteriols'ESS-I‘ES" which should have contained
the Mort-butyl—o—ere 301 were poured into this solution but all
seemed to be empletely dissolved. This mixture was extracted
with other and a small portion of oil was found on driving off the
ether. This material hmvevor boiled at the com point as the
materiel which bod not been extracted from the solution with

(19)

ether and which ma reclaimed an a substituted cresol by aciai-
tying the solution. Thus if any 6~t art-butyl—o—cresol was pre-
sent it was in a. m 33:21.1 quant 113;.

I ma unable to get a mno-brmfi ated aerivut ive of the
mat erial which I could check: with the 6-brmo—4-tert-butyl—0a
crass}. prepared by the oondcnsat ion of 6-bmm—o—creml with
my my butyl alcohol. The boning point,124~L’36°/15IM. ,and
glercm mmmwz" agree Wat closely with the boiling
point andm‘lting 1301111: of the Enterin which Tchitchibabbm (1'?)
prepared by phosplmri" acid condensations having a boiling
point of 122.50/1411'3. and a melting point of 27° and much he
called o-terta-bu‘byl-c-crencl. Hammer, in Spite of the above
facts I consider that. my product is p—terb-butyI-o-m'esol since
(a) 11: wiser: such a high percentage of the total yield and
since all e: the past works on substituted phenols have shorm
the urgent (mom of substitution to be para to the 313ml.
(1)) 117 product checks in boiling point. appearance. and mlting
point or the nitm derimtimmth that a: EWe (4) . Bam-
(7),(8) and Mayer and Bemhauar (14) and with the boiling point
of the p-tert-bntyl—o-cresol of Dimmer, Iamdeuist am: Perms
(16). (c) The bmirmtion__ of the tertcemyl condensation product
proved the alky]. gé‘oup to be in the para position. I

Analysis for, Cu Eu; 0
Calculatofi G: ($.42 3715 311: 9.83 55
Fm «- c= 79.84% ; 3:9.94 $3

(20}

A171 omeetie acid derivative was prepared by the mthod
or Kaelaeh (so) and units fleecy erystele were obtained with a
melting point or 94.95%
511813318 103: C13 11133 05

calculated 0 = 70.2? $3; H= 8.105 '35

Found-«-—--— c = 70.45 3%; H: 8.094 3'3
I prepared umi urethane by the method or Kenn (27). I
obtained white nosey noodles true alcohol with a melting point
at 115.5414" and then magma fer nitrogen by the mere K391-
dehl method.

Analysis for 02.7 335 02 N
Calculated H: 3.900 55
Found -——- H; 5.801 %
Attempts to nitrate the prodmt at roan tame-attire resulted

in demoeition and 02113 a black tarry use was obtained. I
then tried 'eooling‘hitric acid in an ice bath and dissolving the
erase]. in glacial neetiei‘vacid. This solution we also cooled
and the cold acid added drop by 6:01). If no action resulted a
little malphm'ic acid was added and the solution Inmd cere-
mm. A etreng reaction than am set in. The mmtre ms pour-
ed into water and the yellow needles-were metallizea from
alcohol, they had a melting point of 85-96".

m DI—TM-BfimpO-CPJSOL
The canbinod black terry residues hm all the distillation
of each condensation were collected and retract ionated. From
these resumes I obtained about 33 grams or clear thick (even
not-e viscous than the min product number (2) pogo 13) 013. boil-
1138 at 155‘1510/25nn. which probably was the product number (3)

m)

on page 18. This product was cooled in on ice be th for ubout
two hours and then it did not crystallize it was placed in the
ice box and seeded with one of the above most ioned crystals,
but could not be made to cwmmizc.

This product use poured into a five percent potassium hy-
(II-oxide solution and oltho or}: its density xms about the some
as that of the solution ,prevezrt ing a layer format immndissolv—
ed droylets of oil were visible. IThis solution was extracted
with petrolom other and after driving off the petroleum other
from the erbroctBS warm 2.3 of product boiling ot 156—151°/2&m.
was recovered. This quite definitely indicated t a product

was the di substituted crosol, as given by 31613216? (16).

Pf OTEU'TXFi 01* 003‘" 2.1.11. .=" -‘I -I 03‘ “ ‘I’ ”rt-“:31 .t"- 300‘ . Ll‘l’fi O-C 'Lifirill.
This reaction seemed to progress samvmnt slower and did
not produce such a deep red colorst 1011‘ although it gave good
yields.
'i‘he original product was froctionoted other the hydrolysis
of each condensation. These products were then combined and re-

frectionnted at different pressures to give the following, results:
12 g ' = 110-12°°/10m.

 

 

24- g 34- 2-239 00/740m.-——--- 12341500/103121.
s7. 3 ---- sofa-redP/vm.

45 g ...... ZFA-fl’fi'ZO/VGMW L'SO-lsco/lann.

 

 

7 g -a--- 255- 256 0/74011111. 1so-mz9/1m
10 g ----- :35: 4600/7 1012121. mo—moo/icrn.

(22)

The main fraction above was redistilled and the pure product boil-
ed at moo/mm. or 2550/?o0m.

L is gradual: was a viscous colorless oil which soon too}: on
a reddish ember color when exposed to smalls-ht. This could not
be moo to arm 93.1 5.30 in an iee~selt both, but when seeded with
the p—tortm utyl crystals and left in the ice be: several days
did sending but united as soon as it was placed in the room.-

This product was bronimted and the product obtained boiled
at 140-1420/11m, the some as the product obtained by the con--
dens-at ion of thrmo-o-crecol with tertiary m1 alcohol. These
boiling, points and the melting points of their diphenyl urethanes
showed quite conclusively that the products were 01' the same
structure and that the tort—aw]. mop was pure to the hydranrl
of the 0173301.

The black tarry residues from all the condensations were

combined and refmctionated. The follmwing results were obtained:

 

 

4 ms .; w m 132-154°/10m.
8 {rams v w 154-1580/10m.
e gmms —: s: ~138-2oo°/mm.

 

The mdawaollm my have contained a di-el‘quated eresol but
I wold not be sure that it ms not mm of th. Men-anvil.»-
cresol. The mo-sooOAm. fraction was very thiek and had a
flight yellow coloration.

The low boiling fractions were distilled and a fraction of
oil boiling at mum/13m. was obtained mien I thought might
be the o—tert-qml—o-cresol. Hanover this dissouroo in 2; {17:6

(23)

percent potassim hydroxide solution and crystallized. when seeded
with p—tert-butyl-o-cresol metals, so it probably was more of
the p-‘tort-ozvl-o-cresol.
The 25 256° fraction was eoelyzed for carbon and hydrogen.
Analysis of 012 318 0
Calculated C - 9.0.90 55; H 210.11 $3
Rom c = 80.51 %3 B 40.18 5‘3
m1 amoebic acid (27) ms prepared and gore a melting
point of sea—100°. I
Anahsie of 014 H20 03
Odculated c = 71.19 is; a: 8.475 75
Found a = 71.22 93; H= 8.392 ‘23
Diphemrl urethane (29) was prepared and gave a melting point of
121.5—122.s°.
| Analysis 01' 325 1127 0:3 H
caooloted N=3.49 53
Emmi 13:15.95 5’»

(24)

LEOL‘ZCUL—“Ji ELLEIL’ICI‘IOH

'3

--'I'UDY OF P-WZLWT-UU'IYIFO-CPEROL
N22,: 1.5228
D = $973.95
11 ' 164.125
M: H x

D N"+ 2

w 'x AWL: 51.57 (Observed reading )
.9719?» 4.31.89

{

c = 26501 x 11: 27.51].
H 7- 1.051 I 16 3 15.815
0 = 1.521

Double
bond .- 1.70725 gm

50.969 (Calculated reading )

STUDY OF PJI'JTTW.‘ LSOL

 

ago = 1.5239
D 7' . .9691
m = 178.144

mgzfinirz

.9691 x hszzzg ,_ 56.23 ( Observed reading)
78.144 4.3222

G = 2.501 I 12 = 30.012
H 5 1.051 I 18 518.918

0:1.52111 '- 1.521
Double

bond: 1.70m ; $243;
55.572 (Calculated reading )

(25)

I3

W14 Field : % yield =
85 100 z 120 :
to to z
oo : '70
l
I»
:

MRTIOI

fine
i

4.. 00:"? '

JETEUZ

lLHTIf

booed on
o-cresol

O
O
O
O

0.0

based on
to 8 alcohol

90‘

0.000.059...

 

 

 

8
fi
7+:
lgfi-QO:
A

O. a.

:....::z:..00

 

 

 

 

2

00900000....

0. 06:. O. .0

57

30.3.3.0:

 

O.

 

O.

O.

 

 

 

 

 

.‘

 

O.

 

Q.

o. — co
m o

m u

0. '6 .0
.0 a. o.
6

90 Q. 9.
no

no on no

:33

 

33

.L

TEST LEI'IY [£131. 001101113310

:3'5 yield

:% yield

Ob a nod

Use;
Alcohol : O-ere- :75
2

0-01-0801

0...

:besed on =besod on
:elcohol

O
O

00:00

105
to

CO 00.:

:to
z 05

sol

O. 00

 

3

Trlal

: A1613

0.

o.

 

O.

.0

O.

 

O.

2

.0

.0

O.

 

a.

a

5

no

0.. :0. C. O.

 

O.

O

O.
5 mi
00 n

no a;

mo 2*

 

 

 

 

 

(26)

gummy

Tort butyl and tort any]. alcohols were condensed with o-

cresol 1n the presence of elminum chloride.

The moduets mete practically all p-mlbstituted o-cresol.

Arylmcetic acid end dlphenyl urethanes were prepcmed.

The yields varied in the neighborhood of fifty percent.

The use of large excess of arose]. increases the yield.

Addition of the Mabel-creed mixture to the elm

chloride-patrolman other memnsion produces better results.

(27)

BELIOCEL’ETN

(1) m Ber. 14, 1342, (1331)
(2) W Gaza. K . 505
(5) «- Bar. 3;, .242. (1883)
13(4) ---~- 386.11 g 25:34, (1834)
(5) ..... Boo. g ._, 1129. (1889): a . 1199. (mo)
(5) --—- 13». 25 , 2974, (12391)
(7) «- Bar. 3 .. 2838... (1891)
, (e) «- Bcr.£z_ . 1615. (1894)
(9) - Bea‘.§g . 2424. (1999)
(lo) - Bar. 3 .7 54. (1904.)
(11) ~— zhmtooh 32 . 781. (1907)
(3.2) ~— Bocr. g . 3104. (3.909)
(13) - cm. Bend. 1g; . 609. (1911)
x,- (14) «— n‘bootooh g . 7:31. (1929)
(15) ...... U. 3. Bloom; 1,972,956 (1934)
x » (1(3) - U. 5. Patent 1,972,599 (1934)
“(17) - Bull. Soc. Chum. 3 . 497. (1035)
(18) ~— Ehn em town-— Ber. 34, 1:39, (1831)

 

Shell and Soar-— mm . 119.. (1912)
Um: -- Bar. 1% .. My (1882)
Net: w :Am..m.255.(1897)

 

Creche -- Chem. along . 268, (1901); (Berg , 1773,(1901)
Jaubert M WW.1§§ .841. (1901)

(28)

Mural-tel- and Kritchevolq - 3'. An). Chem. Sm&lfin.(1914)
£1529J1914)
21, sos.(1915)
(19) - J’. Am. Chem. Soc. 515; , 2527 . (1916)
$9 , 735 . (19m)
(20) ~— J. Am. Chem. Soc. 5;. 2775. (1924)
(21) ~— J. Am. Chan. Soc. 32 . 1955, (1925)
(22) «- J‘. Am. Chem. Soc. a ., 2579. (1931)
(:2) - J. Am. Chm. Soc. 27, . 4484. (1935)
(24) - J. Am. 012m. Soc. 3 . 1506. (19:52)
25) «— J'. Gen. Chem.(U.s.s.R.), 2 .117, (19:55)
26) ~— Rodrick, Ph. D. thesis, 1937
~ (27) ”KoolocthAn. Chm. Sommgem. (1931)
28) - Boeloy «~— J‘. Am. Chm. Soc. 2?. . 2176. (19235)
(29) ~— kom .- Qualitative We Analyslofloho l'iiley and Sons
page 125, (1935)
(30) ~— Cleisen .— 111m. % , 210-45, (1925)

_ u
_ o I I
#- F I 'I U I I u . u I .
I .I I I I I .O|.II I I In C J I u I I
r & u C O . . u 5 a I. .. o u u a u - u . N. O a.” I... n .r .

u. .1.— Iu.lu..d.u.. w

 

 

 

 

 

10': 0:: 3:?

E I) 4171273552"??? 031-" Téili.i‘l‘...1 1.1." ill-".2- IL COKBJf-Kl-C' COT-T

Trial 3. ..... The 21112111an chloride was added to the or sol and pet»

role w- ether 111M“?- , sold then the “loo“: 25::s dropped

22::
in over 2-: yer-led of two 1-1: ore: o, and 2213. ed three hours
more. It 122;: let 2:531:16) 02's: mono and those. hydrolyzed.
The "ll-lull loo-1.. deride use:- 2222': in very 102': psoportion
and the yield was the lozt'root of any lull.
I added the also) ml to the crosolavollmillm «bier-ide-
troll-sum eth mixtu: :2. dl Wizlj.’ elle~helf 73:3. It me
53:13“- rreu tlioc "lad ensued? hours and then stood over-
Eli-31:40.11: fez med 2-: red jellyulilze r2133.
"" {—2 alcohol and cross-“L 2113282132;- was added to " e 81:12::-
lomzl ehloride in pet roleum other and was stirred for
£011.? 3:1: ~- £3 11-}- le’c- “'17::le for tbs. “co day-r3. There seem-
ed to be 5111 (3:: one of aluminum chloride lelt in t”: e
bottom of the flea-:11.
I added the 22:12:: ' whydrous 6‘ win-1.3m chloride to toe
petrol-em.- on e‘her and it turned to :2 light yellow solu-
tion or melon-1101:. I fll’O’Dg‘md in the alcohol-crew].
mixture slowly colds tire-'20 “ed for four hours SEW-tel: ““- .3.

me cresol~sloohol mixture was dded to the elm-em

, 07.1.0 :2. owpetrolemo other mixture over one hour period.

Trio-l 6 -1-

It 22:22:: tir red two and one-half hours and then left
over night. A deep red solution resulted.

I. added the alcohol-acre sol pet rolesm other mixture to

the 2122;131:102: chloride suspension over a period of one

 

 

Trial 7 -

*3
13.
B
to
I
I

Trial 10 -

hour and allowed it to stand ten days before hydrolysis.
Allard-1m chloride was mopended in 100 (3.8. petroleum
ether and I added the eloohol-creeol in 50 o.c. petrol~
eum.other Lizture to this suspension.

I added the dry aluminum.ehloride to tle alcohol and
erosol mixture in petroleum.ether. The result one the
formation of o. my :5: and e 102': 2' yield.

I mmpeoded the slum-tout: oblosride in 100 0.0. petrol-
um.ethex and added the alcohol~creeol~petroleum.other,
0v :2 a two he: :3 period. It oer-3 stilwed four hours and
left eve: night. The product was bright red.

I added dry aluminum chloride to the alcohol oroool
mixture end the :':1':.ole moss: boom-lo almost ool id at once.
It 2:23 too solid to stir ma when hydrolyzed and distill-
ed only on: acted cresol woo reclaimed as on oil. Over
sixty percent of the interiel mar: left as: a solid
cherred Ill-“.1533.

In all the eondenoet loo-e the tor-lyemtdre was: kept

between twenty and thirty degrees ,end condit ions were

kept as mmydrouo or: ooooible.

~

 

 

11".“. .TISS

011' 11111311331111; .2 22:: 011‘ 2 51L '1' 5.2 .11., 0:23-...1. " 53:2. :12

-. no

‘l‘risl l .. I added dryr 0.13 mm c1110 rid 0 150 13110 01001201 ~eree01

1,125.31

(‘1 .9
iriel

Trial 5

 

0:

91

mixture over 0. period 01" 151120 11:)" we The mixture
was 015 irred 15-50 0.2 yrs 1112.00 101: stand 0110210132: ’6 011d
hydrolfmed. 110 0r 12:11: red col 0.”: 1:00 1710 11910,
slowly 0. f0 :11 15 1513:0010? appermed.
1‘ sided dry aluminum 011.105.15.110 150 13110 alcohol-0:102:01
mixture. The mixture 1:00 stirred three days, let

.. 0170:. weekend and then hydrolyzed.
The aluminum eizleride 1111:: added 150 1515.0 pe'trelezm
ether in 13110 flesh- and I dropped in the alcohol-ere-

sel-petrelem ether mixture .

I added the alcohol-02:0 r101 1011:1311:

E!»

11150 myidly 130

the aluminum chloride 012013000100. 3.11110 . 'W‘ stirred.

four 11012.1er and "it-110:1 01.101706: "50 six 1.11 over 213151215. 115
1:0 0 hydrolyze : 15110 1105115 (10:; but I left 15110 product

in 15.112 hydrolysis solution for 15021 days before 02:-

_- 1 adds 2. 15110 03.115.137.111: .2 chloride 150 13110 alcohol-verses].

1113:1501 -.. r 1111 e. 01 151:0 (10.1370 :31; 1.211103 only 0. faint
15:10}: color 121.0 present. 3'. 1513.021 added 01500.1: 131- 0 grams
of {‘3 111120110 23-110 chloride and the color deemsed,

nid 00151119 2:10:10 rer. etien 1... . 1815:1121; 131000. This 011015-
062 131.10 11.27.511.001: yield 01‘ say of 15110 amyl condense 10:10

and m‘ 0 11 indicate 15110.1; weri: 17:11:11 aluminum chloride-

zine chloride mixture migdii; be 0. method to improve

yields 01; ill farther.