80MB EBUMU DERIVATIVES 0F BBNZYLPHENBLS

THESIS FOR THE DEGREE OF M.S.

HAROLD MELWN D’ARCY

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San. Bruno Dorivativu
of

the Bonsylphonoll

Some Bromo Derivatives of Benzylphenole

By

Harold Kelvin D'Arcy

Theeie

submitted to the Faculty of Michigan State
College of Agriculture and Applied Science as
Partial Fulfillment of the Requirements of the

Degree of Master of Science.

1930

Acknowledgment

The writer wishes to express his sincere
and cordial appreciation to Dr. R. C. Huston
for his kind assistance and courteous advice
given in this work. without which this work

would not have been possible.

331625

Contents

Historical Page
(1) The work of E. Peterno (1872) ---------------- 1--2

' (2) The work of Zincke and Walter (19o4) ------ -—-e--5
(3) The work of Claisen and his followersvf ------ 6--13
(4) The work or Friedel and Crafts-----~~-------l4--17

(5) The theory of Action of Aluminum Chloride-~-18-~20

(6) The work of Dr. R. C. Huston--f---~-~---s-~~21~~2§,
The probium_der1ned-.~L--~- -------- ¥ ------------- --24
Experimental- ~~~~~~~ ~----~------e ------------------- 25-~38
Summary----f~~-----;--- ------- ---l,n --------------- 59

Scheme of Condensation-~---- ------ ¢~--~ ------------ -4O

1.

Some Bromo Derivatives of the Bensylphenols

l. The work of 13. Paterno (1872).

A rewiew oi the literature has shown that E. Paterno
(Gaza. Chin. Ital. g. l--6 (1872)) was apparently the first to
. prepare benzyl phenol. lie heated gently a mixture of henzyl
.chloride and phenol in the presence of zinc dust. It was noted
that a reaction started and hydrochloric acid was given off,
and the liquid entered into ebullition. Later. a brown liquid
or oil was separated from the unchanged zinc. and distilled.

The uncombined benzyl chloride and phenol were distilled
of! below 260° . The remaining mass was distilled at 6 m. The
main fraction distilling at 180—: 190° solidified to amass of
small needles. which retained some of the original oil. The
crystals were pressed between filter paper and the oily part
discarded. while the needles were recrystallized from alcohol.
This bensylated phenol crystallized in white silky needles M.P.

84 which were soluble in alcohol. other. benzene. and chloro-

form. The pure phenol boiled at 175--loo°(4-5 mm).

It was soluble in alkaline solutions. but was repreci-
pitated by acids. It was not soluble in ammonia. When it was
treated with nitric acid it would form substitution products.

_ When treated with sulphuric acid it produced a sulphonic acid
with the phenol. the bariuni salt of which was soluble in water.

2.

They also found that benzylated anisole treated with
hydriodic acid. and boiled for eight hours at 170’ gave methyl
iodide. and the same benzyl phenol as Just described.

Two years later in 1874. E. Paterno and.ht Fileti
(Gazz. Chime Ital. §, 121-129. 251-254) gave a further descrip-
tion of possible derivatives of the same benzyl phenol. The
action of bromine on benzylated phenol in acetic acid solution
gave rise to an unstable oily compound. But they also describ-
ed a compound prepared by adding excess bromine to a solution
of benzyl phenol in carbon disulphide which.melts at 175°. This.
remained an amorphorous substance. soluble in chloroform.and
carbon disulphide. but insoluble in alcohol and ether. They
say it. “appears' to be a 'di-bromide'. However later workers

have questioned this compound.

3.

2. The work of Zincke and Walter (1904).

In 1904 Zincke and Vialter (Ann. egg. 357-385)
published some work on bromine substitution in phenols. espec-
ially in the case of para- benzyl phenol. They prepared the
benzyl phenol by condensing benzyl chloride and phenol with
zinc dust. as E. Paterno had done before. (Gazs. Chhm. Ital.
g, 1-6 (1872)). This 4-hydroxydiphenylmethane formed silky
needles and melted at 84°. Its benzoyl derivative formed

needles and melted at 87°.

The 3 z 5 -dibromo~4-hydroxydiphenylmethane was pre-
pared by the gradual addition of the calculated amount of bromdne
to a cold solution of 4-hydroxydiphenylmethane in chloroform.
which existed in two crystalline modifications; one formed color-
less needles and melted at 44°. the other formed rhombio
crystals and melted at 57°. The former variety is unstable and
passed readily into the latter on being left at the ordinary
temperature. The acetyl derivative formed monoclinie prisms
and melted at 53°.

H Br
H 3,

3 : 5-dibromo~4-hydroxydiphenylmethane

It may be noted here that Zincke's didbrom- deriv-

4.

ative did not have the same properties as Paterno's di-brom-

compound.

The acetyl derivative of 3 : 5-dibromo-4-hydroxydi-
phenylmethane formed mono-clinic prisms. melted at 53°. They
base the proof of the structure upon the following facts; when
the di-bromo benzyl phenol was treated with sodium nitrite. a
bromine atom was readily replaced with a NO; as is the case

when ordinary brom-phenols are treated with sodium nitrite.

Zineke and Walter in the some paper described a tri-
brom compound. This 3 x 5 z. 4' ~tribromo-4-hydroaq'diphenyl-
methane was prepared by agitating 4-hydroxydiphenylmethane with
a calculated excess of bromine until all had dissolved. After
the removal of the bromine from the petroleum other. they cry-
stallised the product. which formed slender needles melting
at 88'. When its solution in glacial acetic acid was treated
with sodium nitrite. one atom of bromine was replaced by one

nitro- group. Its acetyl derivative melted at 105°.
They assigned the following formula;
H :50"
H .Br-
3 s 5 x 4' ~tribromo~4~hydroxydiphenylmetheme

In the same paper they describe a penta- brom deriv-

ative but give no absolute proof of its formula.

5.

They also found that by the reduction of benzylide-
nedibromquinone by the use of hydriodic acid a di-brome4-
hydroxydiphenylmethane was formed.

It may be noted here that this tri—brom compound
of Zineke and Walter's will be further discussed in the dos-

cription of the exPerimental work.

6.
3. The work of Claisen and his followers.

In 1923 L. Claisen published work on the carbon
alkylation of phenols in the ring. (Z. Angew. Chem. pg. 478-479)
He found that both oxygen and carbon alkylation of phenols took
place. when the reaction between alkyl halides and the sodium
derivatives of monohydric phenols of the benzene and naptha-
lens series took place. This was due to the medium in which
the reaction was carried out which is the important factor.

When a dissociating medium was used such as methyl or ethyl
alcohol or acetone as a rule we hawe‘more oxygen alkylation;

while in a non-dissociating.medium.such.as benzene and toluene

more of the carbon alkylation is produced.

He further noted that the unsaturated alkyls. (e.g;
allyl. homoallyl. etc.) effect the carbon alkylation to a
greater extent than do saturated alkyls. The use of the halide
of the unsaturated alkyl permits the carbon alkylation of phenols
that could not otherwise be than alkylated. The tendency toward
carbon alkylation is still further increased if alkyl phenols
be used. The substituent enters in the ortho- position to the
hydroxyl. provided this is unsubstituted. in

In 1925 L. Claisen. F. Kremers. F. Roth. and E. Tietz:
(Ann. 33g. 210-245) studied the Claison's reaction further and
gave a number of interesting points. Claisen in his early
work most generally used an alkali metal in a suitable medium
(e.g; toluene) which was allowed to react with the phenol making
a phenolate. ‘When in turn this mixture was treated with alkyl

7.
or bensyl halide it reacted to give a mixture as shown in the

{ensuing diagram (Z. Angsw. Chen. §_6_.); the oxygen elkylation
or the ether and the carbon alkylation of the banal phenol.

 

‘1’
9 ‘5'”
H 0
OH DIVA 61’6"” :Be/szlEn‘er
or

NALLflifi— 4' /NA

I’CIH
q». : :

O 1.4

ma
0 /
ll H OH H

 

If we should examine the above equations closely we
could see why Claieen said. the other is the product one would
expect to be formed. and that the benzyl phenol is the result
of ring allquation. Claisen's theory of the mechanism of the
reaction in which the substituting group takes the position ortho
to the hydronrl is based on Michael’s theory of the reaction
between silver cyanide and methyl iodide. (J. Pr. 12. 486: fig.

189) . A
% u
c’ c

C’Ac , ‘1
II -———> I! +A I
w +CH31 .—+ ”‘C/{Ig ”‘0 3

' also know by Olaisen's reaction there is the elimination of
e

8.
sodium chloride. therefore the only possible chance is for the
substituent to enter in the ertho- position to the hydroxyl. pro-
wided this is unsubstituted. para- substitution to the hydroxyl
where the ortho- position is occupied has not yet been demon.
strated with certainty.

We can see how a shift of the bonds produce the ortho-
prcduct. but in other condensation methods thei; is nothing
assured that we will have the para compound. but are likely to
produce mixtures of para and ortho compounds as shown by Huston

end Houk (1928) .

Claisen in this report enumerated the factors which

effect the reaction. and listed them as follows: '

l. The kind of phenol.

2. The kind of halide.- whether saturated or unsaturated,

aliphatic or aromatic.

3. The kind of halogen.

4. The kind of metal in the metal phenolate.

6. The temperature.

6. The medium in which the reaction occurs.
In discussing these factors Cleisen stated that the more com-
plex phenols introduced more trouble than a simple phenol. As
was shown in his early report (Z. Angew. Chem; so, 478-9 (1923))
the unsaturated halides are more easily introduced into the
nucleus than the saturated. He stated that the looser the bond
between. the halogen and the alkyl radicle the more smoothly the

reaction progressed. The metal used in these reactions was

9.
generally sodium thus forming sodium phenolate. The temperature
apparently had little effect so long as the mixture was refluxed
gently. The effect of the medium in which the reaction scoured
can be shown by the following example taken from Ann. 253.; allyl
bromide with sodium phenolate in alcohol gave 90 % of the ether.
while in a now-dissociating medium like benzene or toluene it
gave only 30 % ether. the remaining 70 53 being mostly monoallyl-
phenol with s. slight trace of diallylphenol. The carbon derivab-
iwss predominated in non-dissociating media. whereas oxygen-
compounds are produced in dissociating solvents. Further more.
the tendency towards the production of carbon- derivatives in-

creased with increasing mobility of the halogen atom of the halide.

ll. Busch in 1925 working on the alkylation of phenols
published a very interesting item in Z. Angew. Chem; §§_. 1145-
1146. He stated. that the tendency of bensyl radicals toward
carbon-alkylation of phenols increased with the increasing sub-
stitution of the methane carbon. It was possible to obtain others
with benzyl chloride in non-dissociating media, but diphenylmethyl
chloride yielded only the carbon-derivatives.

Busch had found that diphenylbrom methane with phenol.
with or without a solvent. in the presence of heat gave para
hydroxy triphsnylmethane and with sodium phenolate itigave the
ortho- hydroxy triphenylmethane isomer.

n. Busch and R. Knoll (Ber; 60 p. 2243-2257 (1927))
have been able actually to isolate some of these long sought for
addition products: claiming the reaction between C H OH and RX

10.
(Io-chloride) is seemed to proceed according to the schemes
wagon +— RX f a p- RCLHflH + 11x
with.cgflgofla according to the scheme;
Ceflrwa + RX -—————+ 0- Ramos + NaX

 

in dissociating solvents partly according to the last scheme and
partly according to the scheme; I

CLmONa + RX —v-——->C‘I{50R + flax.
They also reported that the accumulation of alkyl groups. especi-
ally those of high.molscular weight. on the phenol nucleus mater-

ially diminished the ether formation.

1K.‘won.Auwers. G.‘Wegener. and Th. Bohr explained the
formation of carbon substituents from.salts of kete- enols and
alkyl halides by three hypothesis which.had‘been previously ad-
wanes Chem. Zentr. 3;. 2347-2548 (1926).
(l) "The initial formation of addition products with subseque-
nt splitting. (hishael).
(2) "The initial formation of normal oxygen derivatives. with
rearrangement of these into carbon derivatives.
(3) "The separating of the metal as a metallic halide. forms

ation of free alkyl and anal radicals.

 

'0... o

and with the slight reactivity of the alkyl group partial
or complete rearrangement of the cool to keto radical.

and finally union of the radicals." (Wislicenus)

Some recent investigations have shown that the course of the

ll.
alkylisation or a.keto-cnol depends upon its character and upon
the alkylization agent. .Experinents by L. Claisen (z. Anger. Chem;
‘QQ. 473~479 (1923)) showed that saturated alkyl halides promote
the formation of oxygen derivatives and allyl and'bonsyl halides
promote the formation of carbon derivatives. Allyl. benzyl. and
similiar radicals furnish preponderantly carbon derivatives and
saturated alkyl radicals forn.oxygen derivatives. At the same
time. inactive media were shown to favor the formation or carbon
derivatives and dissociating media that of oxygcn_dorivativcs.
These taste came under the first hypothesis on which Claisen'based
his theortical consideration.

The second hypothesis is inadequate. for it is not
comprehensible why an oxygen other should be transformed into a

carbon derivative in benzene more easily than in ethyl alcohol.

The third hypothesis stated. that the oxygen derivative
ehould'be formed with allyl and with.bensyl radicals because of
their great reactivity. but this is not the case. However. the
formation of radicals and the isomerization of enol to keto rad-
icals is necessary to explain the reactions. we can assume that
the greater reactivity indicates a large requirement for valence.
and vice versa. since allyl and benzyl radicals are distinguished
by their slight valence requirements and therefore hold oxygen
only loosely. they show a preference for combining with carbon to
form.a stabile combination. Claieen in.Anna $2§,alse confirmed
these views. when he stated. that unsaturation in the allyl and
henzyl radicals result in a comparatively loosely held halogen.

and furthermore thatvreaotion medium such as toluene. and
benzene exert a loosening effect on the valenee bonds between
the alkyl or benzyl radical and the halogen.

J. Van Alphen in 192? published a article on the
emigration of the diphanylmethyl and benzyl groups in phenol.
(Rev. trav. Chin; so, 799-812). He found that by heating phenyl
benzyl other. 2.1. P. 39° (Ann. La. 81 (1867)) with zinc chloride
to 160° for one hour; it is converted into 4-hydroxydiphenyl
methane. M. P. 84°. and a dyestuff. He'aleo reported the same
' compound when phenol and benzyl chloride and a small piece of
sine chloride are heated together at 100°.

e. F. Short reported in the J. Chem. Soc. ,3, 528 (1928)
that‘nhen'benzyl phenyl ether in heated to 225' in the presence
of zinc chloride. or to 180’ if a stream of hydrogen chloride was
passed through the mieture, a vigorous reaction occured. The
product. on distillation under reduced pressure. yielded phenol.
o~ hydroxydiphenylmethane H. P. 54°; phenylurethane h. P. 118‘;
else p- hydroxydiphewlmetmne H. P. ao‘ems". Tile para. eon.-
pound was identified by conversion into p-methoxyhenzophenol
1-1. P. 01° ~62”. and "products of high boiling point. Since phenol
'eae produced. it was prObable that the reaction followed a course
similiar to the Hermann rearrangement of alkyl~anilinee. benzyl

chloride being formed as an intermediate.

o. Vevon and H. Zaharia. oompt. rend. m 346~548 (1928(9
stated. in the purification of phenols. it was recommended that
petroleun.ether‘be used for the extracting of the oxygen derivative
and that an excess of alkali be employed. Phenols may be partially

13.
extracted from their alkali solutions by means of ethyl ether.
The proportion extracted depends on the structure of the phenol.
With the introduction of radicals into phenol. the proportion
extracted increases. and is greater for ortho- substituted

phenols than for the meta- or para- isomers.

l4.
4. The work of Friedel and Crafts.

Friedel and Crafts (Compt. rend. lagggz. 1392-1395) in
1876 discovered a new synthetical method of producing hydro-
carbons. They noted when amyl chloride was treated with small
quantities of anhydrous aluminum chloride there scoured a brisk
disengagement of hydrochloric acid gas. accompanied by hydro-
carbons which are not absorbed.by bromine. When this reaction
was made to take place in the presence of a hydrocarbon. it was
easy to obtain a combination of the radicle of the organic
chloride with the hydrocarbon. less the hydrogen replaced. Thus.
they were able to condense amyl chloride with an excess of ben-
zene. and having added aluminum chloride by small quantities at
a time. they obtained. by fractional distillation of the products.
.a liquid boiling at 185- 190°. and having the composition and
properties of amyl-benzene. O‘H5Q5H”. The other halogen salts
of aluminum.gave reactions analogous to those of the chloride.

rrledel and Crafts. (J. Chem. Soc; 5;. 115-116. (1382)).
stated. 'we found in general that compounds containing the
group OH or OR. i.e: alcohols. phenols. acids. and their others
undergo decomposition with chloride of aluminum. and the reactions
which we have decided are usually impossible in the presence

of such bodies.‘

The mechanism.of Friedcl and Crafts' reaction has been
studied very thorough by J. Boeseken in the following articles:
(Rec. Trev. Child; (1) _1_g, 19-26 (1900). (2) pp. 102-106 (1901).
(:5) pg. 501-304 (190:5). (4) pg. 515-317 (1903). (5) gg, as (1904).

15.

(6) Q9. 148-150 (1911)). these views have also been confirmed
by G. Perrier (Ber; pp, 815-816 (1900)). Boeseken stated.
(Rec. Trav. Chim; 1g, 19-26 (1900)) that in the synthesis of
aromatic ketones and sulphones by means of Friedel and Crafts'
reaction. the condensation takes place in three stages:

(1) 11-0061 4- AlCl, -—-—»R-0001.A101.

(2) 11-0001,.»11013 + HR' -—-———+R-COR'.A1013 + H01

(:5) 11401251111013 4- :1 H20 -——»R-c0R' + A1613.nII._0
The HR' represented an aromatic hydrocarbon or one of its

derivatives.

Analogous additive compounds can be isolated‘ihen
ferric chloride is used instead of aluminum chloride which has
been shown by H. henekl. (Ber; .10., 1766-1768 (1897)) and (Ber;
;_2_. 2414-2419 (1899)). J’. Boeeeken (Rev. Trav. Chim; 52g, 315-
1317 (1903) stated that the reaction of ferric chloride was pre-
cisely similiar to that of aluminum.chloride in the Fricdel

and Crafts' reaction.

J. Boeseken. (Rev. Trav. Chim; 19. 148-150 (1911)).
stated that in the case of a typical Friedel and Crafts' reaction.
in every case the initial reaction is the simple addition of

the two molecules.

The preceding explains the nature of the Fricdel and
Crafts’ reaction. Three molecules must be present: (a) an un-
saturated molecule. (b) a.molecule which can‘be so activated that
it can combine with the unsaturated molecule. (c) a catalyst

which activates the molecules in (a) and.(b). The possibility

. 16.
of the reaction is determined by the loss of free energy.
The initial action is due to the encounter of the two molecules
with the catalyst; in the case of benzene and other unsaturated
cyclic systems the initial additive product. a derivative of
dihydrobenzene. etc; cannot be isolated. because by elimination
of hydrogen chloride or the like it is converted into a system

containing less free energy.

Schaarschmidt (z. Angew. Chem; g1, 286-288 (1924))
based his theory of the mechanism of Friedel and Crafts' re-
action on the fact that the aromatic hydrocarbon was activated
by the aluminum.chloride or ferric chloride which he claimed
appeared possible in producing a simultaneous "loosening“ of
the bonds of the organic halogen compound. A primary complex
was formed. consisting of metallic chloride. hydrocarbon. and
addend. in which the metallic chloride was held by auxillary
valences and the addend by ordinary valences. thus
((113 {ll :1":::.:*::::: c‘ / R

6\RZ

The stability of this complex depended upon the division of the
inner valenoes; and according to the author.may persue one of
two courses. a “molecule course“ and the 'catalytic course“ of
the synthesis. The synthesis may be hindered.by'substituents

in the benzene ring which decompose the metallic chloride.

Other authors which confirmed the theory of additive
compounds of aluminum chloride. are; Gustavson. (Ber: 11, 2151

(1878)). (Comp. rend; 136. 1065 (1903). 140. 940 (1905)),

17.
Sohleichen. (J. Pr. Chem; II. 05. 556 (1922)), Kronberg.
(J. Pr. Chem; II. 51;. 494-496 (1900)). and henschutkin.
(3'. Russ. Pnys. Chem. Soc; 31. 1053-1089 (1909)).

18.
(5) The theory of the action of aluminum.chlcride.
Friedel and Crafts‘ reaction is connected more part-
icularly with the union of aromatic hydrocarbons and their
derivatives with a variety of other organic compounds. such as
alkyl halides. acid chlorides. etc. (Org. Chem.- Cohen ;, 224).
Cohen. stated. (Org. Chem.- Cohen 1, 347) that the results are
best explained by assuming the formation of a compound between
one or both of the reacting substances and the aluminum.chloride.
and‘by the removal of the latter from.the system in combination

with the ketone formed.

It1may be observed that the union'between molecules or
parts of a molecule is nearly always determined by unsaturation
and by a consequent tendency for the unsaturated atoms to satur-
ate themselves. Thus Cohen. (Org. Chem.- Cohen. ;, 196) divided
the condensation processes roughly into two groups:

(1) Those in which the combining molecules are induced
to unite by being rendered. as it were. artifically
unsaturated as the result of withdrawing certain elements.
(2) Those which. being already unsaturated. combine
either spontaneously or with the help of a reagent
or catalyst.

‘We can see the general theory of the anhydrous aluminum
chloride by a number or different authors:

The formation of temporary addition products was showed
by: J. Boeseken. (Rec. Trev. Chin; 13, 19-26 (1900); pg, 102-106
(1901); gag. 301-304 (1903); gs. 315-317. (1903); g. 93- (1904);

19.
pp. 148-150 (1911)). c. Perrier. (Ber; §_3_. 815-816 (1900)). .
Gustavson. (Ber: 11. 2151 (1878)). (Comp. rend: 1.9.9: 1065 (1903).
159, 940 (1905)). Schleichen. (J. Pr. Chem; 11. 19p, 355 (1922)).
Kronberg. (J. Pr. Chem; 11. 5;. 494-496 (1900)). and uenschutktn.
(J. Russ. Pnys. Chem. Soc; 5;. 1053-1089 (1909)).

Sabatier stated (Catalysis in Organic Chemistry. 173).
the catalytic activity of anhydrous aluminum chloride in the
Friedel and Crafts' reaction can be explained by the production
of a temporary combination between the chloride and the organic

material. Thus with aromatic hydrocarbons. we would have:

(31,,
C‘E—H + can ———-—-ch + At/(c‘
5

The latter compound would react imediately on the halogen der-

ivative present and we would have:

C. '
Al<clfl+R'Cl~—-9A(CI3+ R‘CGPJ
‘

The regenerated aluminum chloride would react again
with the hydrocarbon and the same reactions would be repeated.

We can see three important uses of anhydoue aluminum
chloride. namely:
(1) Catalytic action (J. Boeseken. (Rec. Trav. Chim: _39_.
148-150 (1911)). Norris (Ind. Eng. Chem: L6, 184 (1924)).
(2) Dehydrating agent (hers and Yieith (Ber; 15. 187 (1881)).

(3) Intermediate compounds (Gustavson.Perrier. Boeseken. etc.).

Sabatier stated. (Catalysis in Organic Chem: 174) the
reality of the formation of addition products of the aluminum

20.
chloride with the organic compounds has been established by
Gustavscn (Ber; 2.1..- 2151 (1878)) who has been able to 1361ate
an addition product with benzene. an orange colored oil.
AlCla-S C‘H‘. decomposable by water. and in the case of the mix-
ture of benzene and ethyl chloride. 1!).1C13--(C..,~F£,,«)/z «45 C‘H‘. which
heat dissociates into benzene and /Cl . which 'is

1841\(02H701)

1.
stable and serves as catalyst for the transformation of the
mixture. (Compt. rend; 156. 1065 (1505); 140. 940 (1905)).

By these quotations we can see the general theory for
the anhydrous aluminum chloride in the Friedel and Crafts'
reaction is to form addition products with the organic material
and this in turn reacting imediately on the halogen derivative

Drumt o

21.
(6) The work of Dr. R. c. Huston.
Huston and Friedmann in 1916 directed their attention

to the action of aromatic alcohols on aromatic compounds in
the presence of aluminum chloride. (J. Am. Chem. Soc; §§, 2527-
2533 (1916)). ‘When benzyl alcohol in benzene was constantly
stirred and slowly treated with anhydrous aluminum chloride their
was obtained five products; the chief product being diphenyl-
mwthane. They further stated. that the yields are greatly influ-

encsd by the amounts of reagents used and by the temperature.

In 1918 Huston and Friedmann (J. Am. Chem. Soc; 39,
785-793 (1918)). further studied the action of aromatic alcohols
on aromatic compounds this time including secondary alcohols.
They concluded that methyl and ethyl groups interfere to some
extent. while the presence of the second phenyl group stimulates

the condensation.

Huston (Sci; 52. 206-207 (1920)) applied the theory
of the above condensations to the condensing of benzyl alcohol
and phenol in the presence of aluminum.chloride. He stated a
good yield (40-50 %) of p-‘hensyl phenol was obtained. This
po'benzyl phenol had previously been prepared by Paterno (Gaza.
Chin. Ital; g, 1-6 (1872)). (Ber; p, 288 (1872)) by using zinc
dust as a catalyst; Paterno and unzzuru (Ibid; 8, 505 (1887)).
Paterno and Fileti (Ibid; Q, 381 (1884)). by the use of a mixture
of sulphuric and acetic acid; and Liebman (her. ;§, 152. ($882))

'with the use of zinc chloride.

22.
Huston (J. Am. Chem. Soc; 5.9. 2775-2779 (1924)) noted
when phenol in petroleum ether was acted upon by aluminum chloride
it gave a viscous mass probably aluminum phenolate. from which
the phenol is quantitatively recovered on decomposing with hydro-
chloric acid. This aluminum phenolate formed may be considered
as 9. intermediate product described earlier. When phenol reacted
with benzyl alcohol in petroleum ether the yield was greater than
when the petroleum ether was omitted. Ie further stated. that

the yield was not increased by a larger amount of the aluminum
chloride.

In 1926 Huston and Sager. (J. Am. Chem. Soc; it}... 1955-
1959 (1926)). studied the effect of unsaturation on the activity
of alcoholic hydroxyls on benzene in the presence of aluminum
chloride. They concluded three points were essential in this
study.
(1) Alcohol derivatives of aromatic hydrocarbons. only those
in which the hydrcxyl is on the carbon atom adjacent to
the ring condenses with benzene.
(2) The saturated alcohols up to and including amyl alcohol
do not react with benzene.
(:5) The unsaturated aliphatic alcohols. as allyl do react
with benzene.
Huston. Lewis. and Grotemut (J. Am. Chm. Soc; $2. 1365-
1568 (1927)) studied the action of aromatic alcohols on armatic

compounds in the presence of aluminum chloride. They condensed

secondary alcohols with phenol. in the presence of aluminum
chloride. These experiments gave additional evidence oi’ the
effect of unsaturation of the DC- carbon atom onthe reactivity
of the alcohol hydroxyl group which tended to increase the
yield of the product.

24.

The Problem defined.

The work to be studied in this problem.are;
(1) To see if ortho~ substitution is found
in the aluminum chloride condensation of
p- brom benzyl chloride and phenol.
(2) To establish the position of the bromine
when introduced directly into the

compounds;‘

’1
H

and

’!
-9--Br

H

OH

Experimental

‘36 made 13- brom toluene by the method described in the
Org. Syn. g. 21 (Bigelow. liarvel. and Broderick). This was then
chlorinated by the method used by Jackson and. Field (Ber. LL. 9‘04
(1878)). According to the Central-Blatt ;, 1136 (1904) it was
found to have a n. P. of 41" and 13. P. 236°. Errera. (G. .13, 239)
in Beilstein E. 62 described p- brom benzyl chloride as glossy
white crystals with a 2i. ‘9. of 38-390.

The first condensation was with p- brom benzyl chloride
and phenol in the presence of anhydrous aluminum chloride. (Huston.
J. Am. Chem. Soc; fig. 2775 (1924)). The procedure was similiar to t
that described in the Journal. We took (1 mole) 205.5 gms; of
p- brom benzyl chloride (p- Browns/2m). (3 moles) 292 gms: phenol
(0535010. and added slowly while being stirred (4} mole) 63.8 gms;
of aluminum chloride (A1013). The temperature was kept well below
.25". but it was not necessary to cool as the reaction was very
vigorous and the petroleum ether evaporates rapidly so the temp-
erature remained at 12°. Two layers are formed as the anhydrous
aluminum chloride was added the tap one being mostly all petroleum
other while the lower one was rather viscous and ranged in cplor
from a dark red to a white. A precipitate was formed. The

mixture was allowed to stand about twenty-four hours.

The decomposition of this mixture was accomplished by
ice and hydrochloric acid (l-l). We should add the acid first so
that the. oil is well acidified (about 20 cc.) and then pour this
into cracked ice. A heavy pink oil settled out. The petroleum

ether was then separated and distilled off. the residue was dis-

26.
solved in ether and was poured back with the original solution.
This was sometimes dried over anhydrous potassium.carbonate but
in two different dondensations. we found it advisable to omit

the potassium carbonate.

The first condensation was carried out as described
using quarter quantities:
52 gm. p- BrcbhyCI‘IZCI
72 gm. C‘H50H
15.95 gm. AlClg

400 cc. Petroleum ether

After the reacted substance had stood for twenty- four

hours and decomposed. It was then extracted with ether.

The ether was distilled off and the remaining residue
fractionally distilled. The following was obtained;

0

-85 14 mm. 35.5 gm.
85--125° 10 mm. 31.5 gm.
loo-«175‘ 2 m. 9.0 gm.
175--205" 2 mm. 12.5 gm.
205-.260° 2 mm. 8.0 gm.

'The fraction boiling between 175-2050 at 2 mm. was the

fraction in which we expected the phenol condensation product.

It was first thought we had two different compounds.
upon recrystallization from gasoline a number of times we obtained
a white compound which.melted at 59-60’. also e.yellcw compound
which retained its color after several crystallizations from
gasoline which.melted at 85-86 . The benzoyl ester of these two

_27.
were made and they melted at the same temperature (118.5~120°),
and had the same physical properties. In order to arrive at a
more definite conclusion we fractionally distilled both compounds.
he obtained from the white crystals (SS-60°) a white crystalline
solid which was left in the distilling flask which resembled a
metal. and also white crystals in the distillate; while their was
a heavy yellow oil separated from.the yellow compound (SS-86°).

Both of these compounds distilled over at 164-165°(2 mm.) and

when recrystallized had the same melting point 82-83’.

When recrystallized from high test gasoline the crystals
were white. small and took a needle-like shape. The yield of
this condensation and other similiar ones was 19 5 or the theor- -.

tical. However in the last condensation it was increased a little.

The Parr bomb determination for bromine indicated the

formula; cuH,,OBr

Next we condensed by Claisen's method p- brom benzyl
chloride and phenol. Using the following quantities; (1 mole)
phenol 94 ans; (1 mole) p- brom.benzy1 chloride 205.5 gms; (1 mole)
sodium 23 gms; and 500 cc. toluene.

The sodium.was first put into the toluene and this
was then heated. The sodium and toluene was shaken after the
sodium was put into a molten-mass. This was to break the sodium

up into small particles.

The sodium.toluene solution was then allowed to cool to
room temperature and the phenol then added. The cooling was

necessary as the reaction would be too vigorous if allowed to go

28.
at some high.tempereture. A cheesy white mass was formed being

sodium phenolate. We allowed this mixture to stand overnight.

At the end of the twelve hour period the p- brom
benzyl chloride was arded and allowed to reflux at 150° for
eight hours in an oil bath. The product was then shaken out with
water to dissolve the sodium chloride. The toluene was distilled
off. and the mixture treated with 100 cc. of Claisen's alcoholic
potash (Ann. 53g, 224} solution which dissolves any of the
free phenolic hydroxel derivatives leaving a little ether behind.
This in turn.wes separated out.with three. fifty cc. portions
of petroleum.ether. It is not necessary to dry this over anhy-
drous potassium carbonate as previously stated. This ether por-
tion is saved also for further use and identified as Claisen's
ether. This confirms Claieen's early work in which he said

their were both oxygen and carbon- derivatives formed.

The alcoholic potash'was acidified with 6 h hydro-
chloric acid and their was formed a heavy red oil. (If this was .
allowed to stand it solidified). The oil was extracted with ether
and the ether distilled off. The remainder was fractionally
distilled in a vecum.

In the oondensations we used the following portions:

19 gm. . CbHfiII
41 gm. p- BeriiqCHzCl

4.6 gm. sodium

100 cc. toluene

From.this we obtained the following;
ass-400° 18 m. 4.5 gm.

125--210° 2 mm. 14.9 gm.

Fesidue 8.0 gm.

The fraction boiling between 125-210” (2mm. ) was the
portion in which the phenol desired exists. When the fraction
was shown to have a boiling point of 159—160” (2 mm.); and when
recrystallised from.high test gasoline has a melting point of
72-73°. The phenol was white and separated out of the gasoline

in rather large rosette needle crystals.

The yield for this condensation and other similiar ones

was 38.1 % of the theortical.

The Parr bomb determination of bromine showed a formula

We dissolved a known amount of this 2 hydroxy 4' brom-
diphsnyl'methane in chloroform.and added a ten per-cent excess of
the theortical amount of bromine required to form a tri- brom
phenol. The reaction preceded very smoothly with a small heat of
reaction. The chloroform.was allowed to evaporate off and a solid
formed in the beaker. This was recrystallized from.gasoline and
formed a very fine white crystal. When recrystallized again it
was found to have a melting point of 80-81‘.

The Parr bomb determination of bromine showed the
formula CBH703r3.

In order to prove more definitely the structure of the
brominated compound we condensed 2-4 diébrom.phenol and p-‘brom

benzyl chloride by Claisen's method. The procedure was similiar

30.
to the preparation of 2-hydroxy-4'4brom diphenyl methane.

We used tne following in this condensation:
41.0 gm. 2-4 di-brom phenol
26.5 gm. p- brom.benzyl chloride
2.3 gm. sodiwm

50.0 cc. toluene

The reaction yielded ether and phenol as described before.
Promethis condensation their was obtained a 29.71 5 yield of the

theortical.

This compound had the same physical preperties as the
brominated compound. The boiling point being 255-256"(2 mm.)

and the melting point 80-81o.

A Parr bomb determination shosed it to contain the three
utmms of bromine as was calculated. Thus we could assigns the
same structural formula as that for the bromineted 2-hydroxy-4'-

brom diphenyl methane.

1n-
2 hydroxy 5-5-4' tri brom.diphenyl methane

This is further evidence that the compound resulting from.Cleisen's
reaction of phenol and p- brcm.benzyl chloride is 2 hydroxy 4'
brom.diphenyl methane.

The possible ether formation as mentioned earlier in
the work will now be described. The oxygen- derivatives were

extracted with petroleum other which was then distilled off. and

. 51.

then the oxygen- derivatives were distilled in a vacum.

The portion coming from the mono brom- condensation has
the following properties. It has a boiling point of 158.3-159°
(2 mm.) and melts at 90-91°. The ether formed white flaky crystals '

when recrystallized from alcohol and water.

The Parr bomb determination showed it to have one atom

of bromine as calculated from;

H

4 brom~ benzyl phenyl ether

The other possible ether formation is that produced from~z
2-4 d1 brom.phenol and p- brom.benzyl chloride. This tri brom ether
has a boiling point or 187-188° (2 mm.) and melts at so-ecm'.
It formed small glossy white needles when crystallized from

alcohol and water.

The Psrr'bomb determination showed it to have three atoms

of bromine as calculated from:

H
” 3r

4 brom benzyl 2'-4’ dibrom.phenyl other

In order to prove more definitely the position the benzyl
‘yroup took in the aluminum chloride condensation we carried out

the following reactions.

be dissolved the 4 hydroxy 4' brom.diphenyl.methane in
chloroform and brominated with.two equivalents of bromine. This

tri brom para phenol when seeded with 4 hydroxy 2-6-4' tri brom

32.
diphenyl methane. solidified. It formed small white crystals
‘when crystallized from gasoline, It boiled at 205-:03"(2 mm.)

and melted at 81—82°.

The Parr bomb determination showed it to contain three

atoms of bromine as calculated from

H 3r
H 3r-

4 hydroxy 2-6-4' tri brom diphenyl methane

In order to prove more definitely the position the brom-
ine took in substitution in respect to the hydroxyl; we condensed
2-6 di brom phenol and p- brom.benzy1 chloride with the use of
anhydrous aluminwm chloride. (1 wish to make note here of the
scaperation and kind help of nr. F.H. maxfield in the preparation
of the 2-6 di brom.phenol also this condensation of 2~6 di brom
phenol with p- brom.benzyl chloride in the presence of aluminum

chloride as a catalyst.)

The 2-6 d1 brom.phenol was prepared by adopting the
method of preparation of 2-6 di chlor phenol (K. Tanaka and K.
Kutani. J. Pharm. Soc; Japan. 54;, 196-199 (1927)).

Twentyotour grams of phenol were added to twenty- six
grams of sulphuric acid and heated gently s--1o minutes to change
all of the 0* sulfonic acid to p- sulfonic acid. This mixture was
then made alkaline with 30-40‘% sodium.hydroxide on standing some
crystals of sodium phenol-p-lulfonate may separate out. -ighty-
one grams of bromine was added and the contents in the flask was
mixed.with rotary action. Bromination takes place rapidly but

smoothly and in five minutes the mass will resemble a mass of un-

worked butter. Their was no vigorous evolution of h droren bromide
a

‘

probably because of the sodium hydroxi-e present.

The three neck flask was set for steam distillation. also
in a oil bath kept at loo-135°. The tri brom phenol is all distill-
ed out. coming over as flakey material which is apt to clog the
condenser. After the tri brom phenol mixture has cooled it is
ncidified.with concentrated sulphuric acid and steam distilled
again with the aid of a 011 bath at 150-170“. in oil distilled off
as the SQ,H is hydrolyzed off the para position. This oil cry-
stallized in needles and may be separated from the water by the use
of other. When purified it boils at 248-253. atmospheric pressure.

This eXperiment yields 62.74 % of the theortical.

The 2‘6 di brom phenol Just described was condensed in
the usual manner with the p- brom.benzyl chloride with the use of
anhydrous aluminum chloride. The condensed product was decomposed
with ice and hydrochloric acid (1--1) and extracted with ether.
When the other evaporates off it leaves a solid which was crystal-
lised.from high test gasoline. It was found to have identical
preperties as the brominated compound with a boiling point of

zoo-206‘ (2 mm.) and melted at si-es.5’.

The method of preparation of this compound allows only

one possible formula:
3r

4
H r
4 hydroxy [-1.4' tri brom diphenyl methane
J—5
The Parr bomb detemmination verifies the above state-

‘ncnt as it shows thred.bromine atoms are present.

34.
The benzogl .oriveoivcs of the ph: nole were prepared
by dissolving two areas of the phezol i.n WV- .klino and adding e

.Lv

ten per cent excess of the calculated {mount of benzoyl chloride.

) H '0 w lln r
' its 0 Obs)"-
H
(2) I 1:9. 50-51
‘1’

OW
' O
(3) 9 1:. P. 1154.16

Br ‘Q’ 3?

These benzoyl esters were crystallized from alcohol
and water. The ortho compounds gave much.more trouble in
crystallizing than do the corresponding para isomer. The ortho
benzoyl esters are oils and take a great deal of caution to sep-

arate them out in the alcoholdwster solution.

4All of the above compounds found in this thesis were

analysed for bromine content. by the Parr bomb method. (J. F.

or
u'do

Lemp and H. J. Erodorson, J. in. Chem. Soc; 39. 2653 (1917)).

\ .

I!
I

Dr. “g-Oofi/ 4 tawny-:3? 4' brom :‘Liphenyl methane
f]

Sample Wt. bromine in ocmple f Deter. f Cele.
I 0.2230 0.06759 30.31
II 0.2065 0.06114 29.60
Average 29.955 30.01
all!”
—¢-<:>»
II 2 hydroxy 4' brom diphenyl methane
Sample rt. bromine in sample % Deter. % Cole.
I 0.2079 0.06229 29.96
II 0.2120 0.06356 29.98
Average 29.97 30.01

oH' H
.Br -é1<<::::>>3r (By brominstion)
H 2 hydroxy 3~5-4' tri brom.dipheny1
ir methane
Sample Wt. bromine in sample % Deter. fi Cale.
I 0.2101 0.11925 se.§5*,
II 0.2063 0.11731 30 56.86

Average .2 56.955.‘ 56.97

. 56.
all

H
3:- 1.3-0.3)“ (By phenol and 2-4 d1 brom phenol)
2 hydroxy 5-5-4' tri brom diphenylfi
r methane
Sample Wt. bromine in sample % Deter. fl Cale.
I 0.1939 0.11521 56.92
II 0.2021 0.11509 56.95
Average 56.955 56.97
c’ x . . .
BrO'S*O‘© 4‘oron bonayl phcnyl other
Sample Wt. bromine in sample % Deter. % Cale.
I 0.2104 0.06506 29.97
II 0.2056 0.06168 50.00
Average 29.985 50.01
6’
31‘0- g - 0-03,. 4 brom ’benzyl 2'49 (11 brom
fl /41,/€E?

phony). {5.1.1.6}:
Sample

Wt. bromine in sample % Deter. % Cale.
I 0.2031 0.11524 56.74
II 0. 2025 0.11439 56.49

Average 56.615 56.97

4 as»
.B r O _ C _. OOH (By brominetion)
” JFr

I
II

I

II

4 hydroxy 5-543 tri brom di-

phenyl me thane

Samp1e Wt. bromine in sample 5'5 Deter. 573 Cale.
0.2122 0.11949 55.31
0.2541 0.14415 56.73
Average 56.52 56.97

:4 3!“ (By phenol and 2-6 (11 brom
Bro _ C! __ OOH phenol.)
1"! 3r 4 hydroxy 5J-4* tribrom diphenyl
methane
Sample Wt. bromine in sample 5’3 Eeter. :51 calc.
0.1834 0.10546 57.50
Average 57.50 56.97
{I '9 Benzoyl ester of 4 lrwlrox;r 4'
q-O-O-C-O brom diphenyl methane
H
Sample Wt. bromine in sample 53 Deter. $3 Cale.
0.2014 0.04418 21.93
0.2445 0.15064 21.61

Average 21.77 :'1 {1.2006

O
I

‘H Benzoyl ester of 2 hydroxy

-¢-O.Br 4' brom diphenyl methane
H

Sample Wt. bromine in sample f3 Deter. i? Cale.
I 0.2291 0.05134 22.40
II 0.2143 0.04710 21.98
Average 22.19 22.2006
0
9
f’ Benzoyl ester of 2 hydroxy ,
H 5-5-4' trl brom diphonyl methane
19r
Sample Wt. bromine in sample 22’; Deter. 75 Cale.
I 0.2133 0.09891 45.31
II 0.2016 0.09508 46.17
Average 45.74 45.85

a Benzoyl ester of 4 hydroxy
3VO-S-C>::‘o 5-02-6-4' tribrom diphenyl methane

Sample Wt. bromine in sample $3 Deter. $3 Cale.
I 0.2250 0.10397 46.21
II 0.2125 0.09663 45.47

Average 45.84 45.85

59.

Summary
(1) Did not show the presence of a ortho eUbetitution
in the aluminum chloride condensations of p- brom

benzyl chloride with phenol.

(2) Prepared and identified the following compounds:
e. 4 hydroxy 4' brom.diphenyl.methene
b. 2 hydroxy'4' brom diphenyl methane
e. 2 hydroxy 3-5-4' tri brom.diphenyl methane
d. 4 brom benzyl phenyl ether
0. 4 brom benzyl 2'-$' di brom phenyl ether
f. 4 hydroxy 2-6-4' tri brom diphenyl methane

A review of literatu°e shows the preparation of 4 hydroxy
2-6-4' tri brom.diphenyl methane (Zineke and Welter. Ann. 534,
567-585 (1904)). but they did not give any proof of the structure.

For the above formulae consult ”Scheme of Condensation.“

(5) Bromine entered into the following compounds.

H OH ."

I 9; ~C- Br
WOO V ,9

H

in the unoccupied ortho and para positions of the

phenolic ring.

Scheme 0/ Condensation

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