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5mm. .17} I.’ 0? 3-02.3301,

BE‘ITJZYLATION OF M-CR E3801.

Thesis

Submitted to the Faculty
of the Hichigzm State College .
in partial fulfillment of the requirements
for the degree of Master of Science

by

Alva Lehoy Houk

June 4, 1928

Acknowledgment

The writer wishes to eXpreee
his sincere appreciation to
Dr. R. C. Huston,
whose guidance and helpful suggestions
have made possible the completion of this work

3316341.

C 031"? ‘INTS

Historical.

1. Organic Condensetions

2. Aluminum Chloride as Catalyst
3. Work of Huston

4. Work of Claisen

5. Benzylation of Cresols

Experimental.

1. Sondensation by the Huston‘fiethod
2. Condensation by the Claisen Method
3. The Cleisen Ethers

4. Bromine Derivatives

5. Esterificetion

6. Ritro Derivatives

'7 . Summary

Page

12

14
18

BFHTZYLATION 3F lI-CE-‘a 523-31.

1. Organic Condensationg.

Condensations of organic compounds have been
effected since about 1870. The variety of compounds
used is very wide but those in which we are most inter-
ested are the aromatic compounds. and especially the
phenols. Likewise. a great many different catalysts
have been used. some of the earlier ones being sulfuric
and acetic acids, zinc chloride, hydrochloric acid.
phosphoric anhydride. and aluminum.chloride. In most
condensations either a halogen acid or water is split
off, so in some cases the catalyzer acts also in the
role of dehydrating agent.

A mixture of sulfuric and acetic acids was used in
187:5 by Meyer and Wurster (Ber. 5, 963) in condensing
benzyl alcohol with benzene to form.diphenylmethane. Two
years later the same catalytic mixture was used by Patuno
and Fileti (Gazz. Chim. ital. 5,381) in condensing benzyl
alcohol with phenol to form a benzyl phenol. Still another
use of this catalyst was in 1899 when "Ohlan and K10pfer
(Ber. 32,2147) condensed benzhydrols with paraquinone and

its derivatives.

as"

In 1881 Liebnann (Ber. 14. 1842) prepared
p-benzylphenol from benzyl alcohol and phenol by
using zinc chloride as catalyst. He also prepared
butyl phenol, condensing isobutyl alcohol and phenol
with molten zinc chloride. Prepyl and amyl phenols
were similarly prepared.

The action of Zinc chloride on Phenol alone to
form.diphenylether was investigated in the same year by
Her: and Weith (Ber. 14.187 seq.). Auer (Ber. 17.669; 1884)
prepared ethylphenol from absolute alcohol and phenol in
the presence of zinc chloride.‘ This was also prepared by
Dennstedt in 1890 using zinc dust (Ber. 23,2569). Baur,
four years later. (Ber. 27,1614) condensed isobutyl alcohol
with o-cresol in the presence of zinc chloride.

Phosphoric anhydride was used in 1886 by Hemilian
(Ber. 16,2360) in forming diphenyl-p-xylylmethone from
benzhydrol and p-xylene.

Hydrochloric acid was used, in condensing phenols
with cemphorquinone. by Day and Son-Grysta (Proc. chem.
Soc. 29,155). It was also used by Dionin (J; Russ. Chem.
Soc. 46,1310; 1914) in condensing phenols with unsaturated

ketones, such as mesityl oxide.

-5-

Stannic chloride was used by Bistrzycki
(Ber. 37,659; 1904) in condensing benzhydrol with
toluene to form diphenyl-p-tolylmethane.
Small quantities of iodine were used as
catalyst by Knoll and Co. (Ger. 250,236,Apr. 23, 1911)
in condensing organic compounds with alcohols or—
ketones. It was found to set also as dehydrating agent.
?hosphorus pentachloride was used by'Hahn (J. Am.
Chem. Soc. 43,175;l921) in condensing 4-methylbenz0phenone
chloride with phenol.
hagnesiun.chloride was shown by Hozzara (Gazz.‘12,505;
1882) to have catalytic effect in condensing mpcresol with

prOpylalcohol.

2. Aluminum Chloride as Catalyst.
One of the most important catalysts in present-day
chemistry is aluminum.chloride. One of its earliest
uses was by Friedel and Crgfts in 1876 (Compt. rend.
84,1392) when.they condensed amyl alcohol with.hydrocarbons
forming anyl-hydrocarbons. They confined their work to
aliphatic compounds and even stated that alumdnum.chloride

would not dondense aromatic compounds.

-4-

custaxson (ser. 13.157;1eso and Bull. Soc. chem.
42,325;1884) believed an unstable aluminumporganic compound
to be formed, which breaks down again giving aluminum
chloride. This theory was recently confirmed by Schiechen,
and by Buttgenbach (J. prokt. chem. 105,355;1923) although
it has been denied by others.

In 1881 Herz and Weith (Ber.14,18? seq) prepared a
diphenyl ether from phenol; using aluminum chloride. In
1914, Frankfurter and.hclpers (J. Am. Chem. Soc. 36,1511,
1529; 37,585) condensed chloral, chloral hydrate. bromal,
and trioxymethylene with various organic compounds. with
the elimination of water. He believed that aluminum
chloride, while a catalyst, acts at the same time as a
dehydrating agent. a theory Which is now generally accepted.

Jaubert (conpt. rend. 132,841; 1901) prepared aniline
and p-toluidine from hydroxylamine hydrochloride and the
hydrocarbon in the presence of aluminum.chloride or zinc

chloride. This was definitely a dehydration reaction.

3. 311.2 3221‘. 9; Huston
Aluminum chloride had not been used to condense
aromatic alcohols with aromatic compounds until Huston
began a series of investigations in 1816. Huston and
Friedemnnn (J. Am. Chem. Soc. 38,2527) condensed benzene

and benzyl alcohol. forming diphenylmethane and a little

. - 5 -
p-dibenzyl benzene with a trace of the ortho.
Anthracene was formed as a by-product. The proportion

of the reagents used and the temperature of the reaction
influenced the relative yields of the different products.

Two years later (J. Am. Chem. Soc. 40,285) they re-
peated the experiments using secondary alcohols on benzene
in the presence of a1uminum.chloride. The alcohols used
were methyl phenyl carbinol. ethyl phenyl carbinol, and
diphenyl carbinol. the first two containing alkyl groups
and the latter being entirely aromatic. This gives an
idea of the effects of the various groups on the reaction.
It was found that aliphatic groups have a retarding action
on condensation by aluminum.ch1oride. ethyl more than
methyl. but that phenyl groups do not retard at all.

In 1920 (Science 52,206) Huston reported the pre-
paration of p-benzyl phenol from.benzyl alcohol and
phenol in the presence of aluminum.chloride. The same
compound had been prepared using zinc Chloride as catalyst,
and also with a mixture of sulfuric and acetic acids. as
stated earlier in this paper. Her: and Weith (Ber. 14.189)
reported a 10 - 12% yield of diphenyl ether from.bsnzyl
alcohol and phenol when heated with aluminum chloride under
a reflux condenser, but Huston (J. Am. Chem. Soc. 46,2775;
1924) found scarcely any ether formed if the phenol is sus-

pended in petroleum ether and the temperature kept below

- 6 -
30°. He also condensed benzyl alcohol with anisol and
phenetole, obtaining the methyl and ethyl ethers, respectively
of p—benzyl phenol.

Huston and Bartlett, in 1926, condensed phenol and
phenyl butyl carbinol in the presence of aluminum chloride
to produce p—hydroxy diphenyl butyl methane, and Huston and
Strickler, the next year, condensed phenol and phenyl
prepyl carbinol to form.p-hydroxy diphenyl butane, with a'
little of the ortho product, which was identified by con-
densing by the Claisen method, in which the ortho is the
sole product.

Huston, with Lewis and Grotemut, in 1927 condensed
secondary alcohols with phenol. Ecthyl phenyl carbincl
gave a larger yield than ethyl phenyl carbinol and benz-
hydrol gave a larger yield than either. which corresponds
with the results obtained in condensing the same alcohols
with benzene. showing that unsaturation on the alpha carbon
atom.tends to increase the yield of condensation product.

Huston and Sager (J. Am. Chem. Soc. 48,1955; 1926)
investigated the effect of unsaturation on the activity
of alcoholic hydroxyl and found that only these compounds
in.which the alpha carbon atom.is a member of the benzene

ring. or is double bonded, show any appreciable activity.

Normal aliphatic alcohols showeo no reaction, however allyl

- 7 -
alcohol condensed with benzene in the presence of

aluminum chloride.

4. 33s 59.22% 2; Claigen.

In 1924 L. Claisen published an article (Ann.
442.212) describing a different method for both the
alkylation and benzylation of phenols. In this method
the alkali metal salt, usually the sodium salt, if the
phenol is first prepared and dissolved or suspended in a
suitable medium, such as toluene. and then treated with
an alkyl or benzyl halide. The resulting product is a
mixture of the possible mono- and di-alkyl or benzyl phenols.
and a little either which may be removed by shaking the
methyl alcoholic potassiumfihydroxide solution of the phenols
with petroleum ether. This other is the product which we
would expect to be formed, by the simple splitting out of
metal halide. but a transformation occurs whereby "anomalous
metal substitution”, or ring alkylation, takes place.

Claisen believes that only ortho substitution products
are formed by his method. He bases his view on Michael's
theory (J; pr. 57,486;2l6,189) of the reaction between
silver cyanide and methyl iodide. According to this Claisen's

reaction would take place as follows:

-8-

OH ‘H H0 81 H R

-—C « C~ e PLClta'n (1 -~- c~ pHCl
o n a on R
C M... C“ -. -- -. c :.-.-.:. c ........

This is brought about in a "non-dissociating" medium
which seems to promote the splitting apart of the alkyl
and halogen radicals. In a dissociating medium, as
Methyl alcohol, the ether is the main product.

Claisen and Tietze (Ber. 583,275; 1925) showed that
when alkali phenolates were treated in non-dissociating
media with halides of unsaturated alkyls, such as allyl,
there is obtained a greet deal of, and often almost entirely,
ortho alkylphenols instead of the others. The same year
Claisen, with Kramer’s, Kath and Tietze (Ann. 442,210) reports
the formation, fron.sodium.p-cresylate and allyl bromide. of
90% other with methyl alcohol as solvent, and of 30% other
and 60% carbon alkylation with benzene as solvent. showing
the effect of a non-dissociating medium in lowering the
amount of ether formed.

K. von Auwers, with ’{s’egener and Bohr (Chem. Zentr.

1926, I, 2347) performed experiments to explain the formation
of carbon substituents from salts of keto-enols and alkyl
halides. They sum up the three possibilities as:

l. ”The initial formation of addition products with

subsequent splitting" ffiidhael)

-9-

2. ”The initial formation of normal Coderivatives

with rearrangement into C-derivatives'

3. "Separation of metal as metallic halide, formation

of free alkyl and enol radicals,
-C'I=IC< ~C—C<
A- ““9 3 '
and with the slight reactivity of the alkyl group.
partial or complete rearrangement of tho enol to
keto radical, and finally untion of the radicals“.
(aislicenus)

The course of alkylization depends on the nature of the
enol-keto and on the alkylization agent, as well as on the
type of medium used. Saturated alkyl halides promote the
formation of 3-derivatives while unsaturated halides, as
allyl or benzyl, promote the formation of C-derivatives.
These facts are best explained by the first hypothesis, which
also agrees with the theories of Cleisen. According to the
second hypothesis it is not comprehensible why an ether
should be transformed into a carbon derivative more easily
in benzene than in alcohol. and according to the third
hypothesis ethers should be formed from allyl and benzyl
radicals because of their greater reactivity, which is not
the case. Allyl and benzyl radicals are characterised by
their slight valence requirements, so they hold oxygen only

loosely and form armors stable combination with carbon.

- 10 -

Shorigin (her. 588, 2028; 1928) found that benzyl
ethcrs reanange to form carbinols under the influence
of sodium, according to the equation:

cesbcngoa acasscsmsm
This is true when U is p-tolyl, cyclohexyl, or benzyl,
but with o-cresyl benzyl ether the phenol. instead of
carbinol, was formed. The phenyl and ethyl ethers of
o-cresol also gave no rearrangement but formed toluene
and the alcohol, showing that the ability to rearrange
depends upon the presence of a benzyl group. Shorigin
also found (her. 59B,2502;1926) that when condensing
carbinols with o-cresol, the migrating group enters the
side chain to form. in the case of triphenyl carbinol,
(06H5)3ccs2ccn4os instead of {0635): cccssmsmra as

assigned to it by the experiments of Baeyer, Claisen and
Busch.

H. Busch (Z. Angew. Chen. 38.1145;1925) showed that
the tendency of benzyl radicals toward carbon alkylation
increrses with the increasing substitution of the methane
carbon. It is possible. in non-dissociating media, to
obtain others from benzyl chloride, but diphenylchlormcthane

will give only carbon derivatives.

- ll -

Fushh and Knoll (Ber.60s,2s43;1927) found that
diphenylbrommethane with phenol, with or without a
solvent, gives the p-hydroxy product, and with sodium
phenolate gives the o-hydroxy product. Shcrigin obtained
mostly ethers but he used the phenclates in a large excess
of phenol, which is a dissociating solvent and, according
to Claisen, promotes ether production. Busch and Knoll also
found that the introduction of electro-negative groups causes
3 pronounced loosening of the nuclear hydrogen stone.. Phenols
and cresols show a slight tendency toward formation of
disubstitution products, while with p-nitrophenol, hydro-
quinone, and p—hydroxybensaldehyde the disubstitution product
is formed almost exclusively.

r. Vbn Alphen (Rec. tray. chin. 46,799;l927) heated
phenyl benzyl ether with zinc chloride for one hour at 160°
and obtained 4-hydroxy diphenylmethane. showing a migration
of the benzyl group. He prepared the same compound by
heating phenol with diphenyl chlormethane. He also prepared
(Rec. Ivor. chin. 46,287;1927), from.potassium.phenolate and
triphenylmethyl chloride, a triphenylmethyl phenyl ether,
which on heating with zinc chlarids or hydrochloric acid was
converted into p-hydroxytetrOphenylmethane.

Shorigin (Ber. 60B,2573;1927), in the reaction between
sodiumpo-cresylate and triphenylmethyl chloride and also
between o-cresol and triphenylcarbinol, found the triphepyl-

methyl group to enter the side chain. H—cresol, under the

- 12 -
same conditions, yields a cryptOphenol which is believed
to be a tetrgphenylmethane derivative. P-cresol gave
triphenylmethane almost quantitatively in the presence of
sulfuric acid. A little amorphous crimson powder which is
probably a highly polymerized quinomethane was also obtained-

5. Benzzlation.g£,8resol§.

As early as 1888 Paterno and Hazzara (Gazz.5,38l)
condensed benzyl chloride and cresol in the presence of zinc.
Aluminum chloride was not used as condensing agent until
recently, when Huston and Lewis condensed p-cresol with
benzyl alcohol. One monobenzyl and one dibenzyl derivative
were all that could be formed. These ortho derivatives were
also formed by the Claisen method.

Huston and Swartout condensed o-cresol and benzyl
alcohol, both by usxing-aluminum chloride and by the Claisen
method. In this case the para position is open, so a larger
number of derivatives would be possible.

The position taken by any entering group depends upon
the nature of the group or groups already present in the
ring. The relative directive strengths of the saturated
groups have been investigated by Hollsmsnn (Chem.‘hev.
July,1924.187 seq.). He found that the hydroxyl group has
the greatest, and the methyl group the least influence

toward the ortho and pars positions. Therefore in cresol

- 13 -

the hydroxyl would so greatly predominate that the effect
of the methyl would be practically nil and the entering
groups would go ortho and para to the hydroxyl.

The benzylation of mpcresol should proceed similarly
to that of o-cresol and p-cresol except that in mpcresol
all of the ortho and para positions are Open, so a greater
number of derivatives would be possible. Benzylation by
the Huston method should give a mixture of para and ortho
compounds, with the para somewhat.in predominance. The
Claisen method should give only ortho compounds. The com-
pounds which are theoretically possible are two ortho and
one para monobenzyl cresols and three dibenzyl cresols.
The properties of the compound, ease of esterification. etc..
are considered in determining with which of these possibili-

ties each product conforms.

Rxperimental

1. Condensation by the Huston Method.
a. In the first trial the following amounts were used:
K;Cresol .. ........... .. 60 go.
Benzyl Alcohol ......... 50 gm.
Petroleum Ether . . . . . . . . 75 33:1.
Aluminum.Chloride ...... 30 gm.
The mixture of m-cresol and benzyl alcohol in.
petroleum.ether was stirred constantly and the
aluminum chloride added in small amounts over a
period of about two hours. The temperature was
kept at about 35°. Additional petroleum ether
was added occasionally- HCl was given off cOpiously
and the substance became a light brown viscous mix-
ture. The layers first formed disappeared. It was
stirred an hour after final additionkof aluminum
chloride, and then let stand over night. The next
day it was decomposed with ice, extracted with ether,
and distilled.
It was divided into the following fractions. dis-
tilling under 4 mm. pressure:
125° - 140°
140° 165°
165° - 185°

185° - 250°
b. In the second trial the amounts were doubled:

‘{“Cr8801 00.00.000.0000000130 gr“.
Penzyl Alcohol .......... 100 gm.
Petroleum Ether ......... 150 gm.
Aluminun Chloride ....... 60 gm.

O.

- 15 -
Aluminum.chloride was added over a period of
one hour. The resulting brown, thick mixture was

treated as in the first trial. The following

fractions were obtained, using 4mm. pressure:
To 225° (at. press.) 54.0 gm.
100° - 165° 58.0 gm.
155° - 155° 41.0 gm.
185° - 250° 48.5 gm.
Residue 15.0 am.

After éive distillations the fractions were as

follows:
140° - 160° 40 gm.
150° - 185: as gm.
185° - 250 44 gm.

In the third trial the smaller amounts were used
as in #1. This was stirred in a closed container
fitted with reflux condenser, addition!“ tube. and
thermometer. It was allowed to stand 48 hours
before decomposing. The following fractions were

obtained, all at'4 mm. pressure:

To 125° 15.0 gm.
125° " 1400 400 {Sine
140° - 155° 21.0 gm.
155° - 185° 18.0 gm.
185° - 250° 24.0 gm.

In the fourth condensation the double amounts
were again used. Treatment was the same as in the

third trial. The fractions obtained were:

- 16 -

1403 - 1553 58.0 gm.
155 - 185 55.0 gm.
185° - 250° 45.5 gm.

The fraction 140° - 155° in each case
boiled mostly at 155° . 157° (4 mm). It was a
thick yellow oil and solidified after standing for
sons time in the refrigerator. Crystallization was
carried out in petroleum ether out-of-doors in
freezing weather. The substance c.ne out in a mass
of soft, shite, felted, needle-like crystals. melting
after several crystallizations at 480 - 47° and 5511-
153 at 155° - 155° (4 mm). This compound will be
discussed more fully under the Claisen reaction.

The fraction 155° - 185° solidified in the
receiver and was crystallized from petroleum ether
in colorlessprisms, melting at 93° - 94° and boiling
at 168° - 170° (5 mm). The factors causing a relative-
ly higher melting point are compactness of structure
and symmetry. A para derivative is, in general, more
'symmetrical than an ortho derivative, so would tend
to melt higher. Hence, since we would expect one
para derivative by this method of condensation and
since this compound melts much higher than the first

one mentioned, we assign to this the para structure:

-17-

I. on m. pt. 95°-94°
b. pt. 158°.170°
(5 mm.)
CH3
cqzcb H5

3 methyl 4 benzyl phenol
Analysis: 014H14°
_.2154 an. gave .6680 am. 002 and .1381 3mm 820

Cele. C 84.80 R 7.12
Found C 84.57 H 7.17

The fraction 185° - 250° nearly all came over
at 220° - 230° and solidified to form an oily mass which,
after several crystallizations, ceme down as a very soft,
felted, white mass, melting at 105° - 107° and boiling
at 260° - 232° (5 mm). This compound we assumed to be a
dibenzyl derivative, which assumption was verified by
analysis. The two benzyl groups would be in the same
positions as those in the two mono-benzyl derivatives.

It is apparently very difficult. by this method of con- b/'
densation, to introduce a group between the hydroayl and
methyl groups. This compound we will designate es II,

and assign the fonmule:

II. 0 m. pt. 1050-107°
C H CH H b. pt. 230°-252°
° 5 L (5 mm.)

CH

QHICQHS

- 18 -
Analysis: 021H200
.1902 gm. gave .6074 gm. 002 and .1184 gm. H20.
.1908 gm. gave .6059 gm. 30. and .1194 gm. H20.
.1874 gm. gave .5964 gm. GOP and .1147 gm. H20.
Gale. 0 87.45 H 7.00
Found C 87.09; 86.60; 86.79. H 6.96; 7.00; 6.85.
2. Condensation by the Cloisen Hethod. _’,l
In the first trial the amounts used were:
Sodium .................... 11.4 gm.
hearesol .................. 54.0 gm.
Toluene ...................l25.0 go.
Benzyl chloride 64.0 gm.
The sodium'wss added to a solution of the cresol in toluene,
forming the sodium cresylste, a white, cheesy mass. The
action was rapid, the temperature being controlled by im-
mersing the flash in cold water. After the mass had stood
over night the freshly distilled benzyl chloride was added
and the mixture heated. under reflux condenser, to 1100 on
an oil both, when the reoction started. when the cresylate
was all dissolved the beth.sas raised to 150° and the mixture
boiled for five hours. It wee then cooled, washed twice with
water to remove the sodium.chloride, and the toluene distilled
off. The residue was dissolved in 250 cc Claisen’s methyl
alcoholic potash (Ann. 442,224). Any derivatives with a free
phenolic hydroxyl group would dissolve, leaving the small

amount of the ether free to be taken up in petroleum.ether.

using 200 cc in 50 cc portions.

 

- 19 -

The potash solution was then acidified with 6 N. H01,
again freeing thephenolic derivatives. A dark, heavy oil
separated out, which was taken up in ether. The ether was
distilled off and the residue fractionated. After the
second distillation, at 4 mm.:

To 140° - - 8.5 gm.
140° - 150° 54.5 gm.
150° - 250° 12.5 gm.

Six other trials were made, with results and amounts of
various fractions very similar to the above data. pmflmfl
The fraction 140° - 150° partially solidified in the

receiver. As this fraction contained two isomers. one
solidifying and the other remaining an oil, the two were
separated by pressing the mass between filter papers, which
absorbed the oily compound and then could be extracted with
ether. The ether, after being distilled off, yielded_a
heavy. yellow 511 boiling at 155° - 155° (4 mm.). This 011
solidified after standing in the refrigerator some time. It
crystallized from petroleum ethen,in the cold. in fluffy.
felted needles, melting at 46° - 47°. That this compound was
identical with that melting at the same temperature from.the
Huston reaction wee proven by mixing the two and taking the
melting point of the mixture. This was the same as that of
the separate compounds. This being made by the Claisen
reaction, we expect it to be an ortho isomer, and since it

has a low melting point we give it the ortho structure which

has has the least compactness and symmetry:

- 20 -

CH 0 0
III. . m.pt. 46 - 47
CtHs° “7 b. pt. 155° 3 155°
,4mm.

\/Q“3

3 methyl 6 bensyl phenol

.279? gm. gave .8658 gm. €02 and.1792 gm. H20
.3157 gm. gave .9719 gm. 002 and.2004 gm. H20

Gale. 0 84.80 H 7.12'
Found C 84.23; 83.96 H 7.17; 7.10

The crystals from.the fraction 140° - 160°, after
being pressed between filter papers, were crystallized
from petroleum ether. They come out as long, regular
needles. melting at 71° - 72° and boiling at 157° 7 159°
( 5 mm.). This also must be an ortho isomer. according
to Claisen, and since it melts considerably above com.
pound 111 Just described, we assign to it the structure
which, on account of its compactness of grouping, and
symmetry. tend to cause a.higher melting point than that

assigned to III. Compound 1V; then, we designate as:

IV. 'H H c a m. pt. 710 ~ 72°
{/ C 1 L 5 b. pt. 157° - 159° (5 mm)
\/C‘:\3
2 benzyl 3 methyl phenol
Analysis: 0143140

01769 3121. {5870 .5483 gm. CO. and .1127 #2.)“. H20

Cale. C 84.80 H.7.12
Found C 84.53: 84.53 H 7.13: 7.08

“‘ “‘“fi’nib m! .1131“ .171:

- 21 - L
The high boiling fraction. which we assumed to
contain a dibenzyl derivative in which a benzyl group
occupies each ortho position, was very difficult to
narrow to a definite boiling point. After many distilla-
tions a fraction boiling at 203° - 212° (4 mm.) was
collected. This was a very heavy yellow oil. After
some weeks in the refrigerator it began to solidify and
a very small amount of fhffy crystalline substance was
obtained. melting at 105° - 107°. This proved to be
identical with compound II in which one of the benzyl
groups is in the para position. The amount is small \/
but it is interesting in that it apparently contradicts
the theory advanced by Claisen that only ortho deriva-
tives can be formed by this method.
The remaining oil was in such small quantity that
it was decided to make more from compound IV, by the

Claisen neaction:

CNa OH
\CH CL,“ 5 ( RICbHS CLAS‘CR2(\QH,CL “5-
“ .
)m“ MO > 3 M7 VCH3

The quantities used were:

Benzyl cresol ........... 8.0 gm.
SO<11MIIOOOOOOOOOOOIOIOI 1.0 gm.
Toluene ................. 50 cc

Benzyl chloride ......... 5.7 gm.

- 22 -
The sodium.reacted to give a brownish yellow

solution of the phenolate. This was heated to 150°

to complete the reaction, the benzyl chloride added.

and the mixture treated as in the former Claisen con-
densations. After four distillations two grams of heavy
yellow oil boiling at 215° - 215° (5 mm.) were obtained.
This checks very well with that obtained from the other
condensations so we are safe in calling this the 0-0-

dibenzyl derivative:
on

v. chase“; calcbug b.pt. 315° - 215° (5 mm.)
on '

3
5.methyl 2,6 dibenzyl phenol

Analysis: CalHZOO
.2145 gm. gave 16869 gm. 002 and .1355 gm. H20
.1969 gm. gave .6368 gm. 002 and .1239 gm. H20
.2157 gm. gave .6852 gm. 002 and .1560 gm. H20

Gale. 0 87.45 H 7.00
Found C 87.53;86.61; 86.63 H 6.96; 7.04:1.05

3. The Claisen Ethers
The petroleum ether extracts containing the
Claisen ethers were distilled. That from the first

condensations should give an ether of the structure

OcHzcbug
.CH33 methyl phenyl benxyl ether

which has been made by Steedal (Ann. 217,4631882). The
ether was described by him as crystallizing from alcohol

in lustrous platelets. melting at 43° and boiling without

decomposition at 300° - 505°. The product obtained from

- e3 -
our condensetions distilled nostiy at 280° - 290° and
underwent vigorous decomposition above 200°. Distille-
tion was repeated several times with the same result so
the work of Staedel was repeated. The reaction proceeded
as he described, but the product distilled at 280° - 290°
and decohposed above that temperature. Finally it was
distilled under reduced pressure, at which it boiled at
142° - 145° at 5mm. pressure and solidified into white
platelets which, when purified, melted at 45° - 46°.
This is somewhat at variance with Staedel's results but
the Claisen ether gave identical results so we conclude
that it has the composition of the ether described by
Staedel, end has the formula given above.

The petroleum.ether extract from.the last condensa-
tion. that of cOMpound IV’with benzyl chloride. solidi-
fied as soon as the petroleum.ether had evaporated off.
Recrystallized from alcohol in fine yellowish needles.

it melted at 71° - 73°. This would be the structure:

OCH

nchg o o
CH ch Hf m. pt. 71 O 73
0.83

2 benzyl 5 methyl phenyl benzyl ether

' ' ' I |
Analysis. 021L200

.0804 gm. gave .2568 gm. 002 and .0505 gm. H20

Cale. C 87.45 K 7.00
Found C 87.10 H 7.03

- 24 -
4. groming Derivativgg

Bromine, when added to a phenol, easily substi-
tutes in the ortho and para positions, filling as many
of those as are open. The calculated molecular quantities
of bromine were added to the chloroform solutions of our
benzylated cresols, with vigorous reaction and capious
evolution of hydrobromic acid. In most cases thc_bromine
derivative crystallized out on evaporation of the chloro-
form. Petroleum ether and alcohol were both used as
recrystallizing solvents, but the better results were
obtained with alcohol.

Compound 1. formed from the Huston reaction and
melting at 95° - 04°. when treated with bromine crystal-
lized in shiny tan flakes from alcohol. ?rom.petroleum
ether it had less definite form, creeping up the sides
of the beaker and turning green on standing in the air.
The melting point was found to be 88° - 87° when crystal-
lized from alcohol. This is a dibrom derivative of the

OH
structure: 73W ggAJ

0H3 m. pt. 86° - 87
aulcbtig
2,6 dibrom—S-hethyl-d-benzyl phenol

0

Analysis: 314h1203r2

0.1289 gm. gave 0.0570 go. Era °“7a~ °”’337
0.1609 gm. gave 0.0712 gm. “r2 .. c.1573

Cale. 44.913 %; found 44.217, 44.281 %.

-25..
The bromine derivative of compound II, a
dibenzyl cresol, melting at 106° - 107°, crystallized
from.both petroleum ether and alcohol in white platelets.
The melting point was 65° - 67°. Analysis showed this

to be a monobrom derivative. as expected, the formula
0H

b61113 019]}.5'6/{1 (BR

m. pt. 65° - 67°
c H3
H5105 H5
2'Bron-3amethyl-4,6 dibenzyl phenol

Analysis: 021H190Br
0.1643 8111. gave 0.0351 8111. bromine. enveno. 0313'
Cale. 21.76%; found 21.38%.
Compound 111, formed from both the Huston and
Claisen condensations and melting at 46° - 47°. gave
a dibrom derivative which crystallized from.both
petroleum ether and alcohol in fine. felted form. The
melting point was over a range of 99° - 103°. The
structure would Be:

an m. pt.'99° - 103°

I
CC [75.ch- 3
h 2"“ r I e 3 a

 

2,4 dibrompsemethyl-G-benzyl phenol
Analysis: 014HlBOBr2
0.l267 gm. gave 0.0568 cm. bromine.

Calc. 44.913fl; found 44.8150. e‘Eifiwajt.

- 26 .-

Compound IV, formed from the Claisen reaction
and melting at 71° - 72°. gave a dibrom derivative
crystallizing from petroleum ether in light , feathery
' crystals and from alcohol in white felted crystals.
melting at 106°H- 107°. The structure is
m. pt. 106° - 107°

 

2 benzyl S’methyl 4,6 dibrom phenol
Analysis: 014H1203r2

0.1574 gm. gave .0721 gm. bromine 018m WHY.

Cale. 44.9lss; found 44.7sefi.

Compound V, a dibenzyl cresol from the Claisen
method which did not crystallize. gave a bromine de-
rivative which also did not crystallize. A reddish
oil formed, the quantity of which was insufficient for
distillation, and since the amount of V on hand was small
more could not be made up. However. a vigorous reaction
having occurred with evolution of HBr, we would not hesi-
tate to say that the monobrom derivative, in the form

of an oil, had gormed. having the structure of
Ct, HgC“1 QHZCBHS

(1H3

I‘U

2,6 dibenzyl 3 methyl 4 brom phenol.

- ¢7 -
5. Esterigiggtion

The benzoyl esters of the five phenols were
formed by the Schotten-Baumann reaction. The ease of
solubility in the alkali and formation of the esters
further substantiates the structures which.we have
plassigned. When the phenolic hydroxyl is “crowded“ betweew
two groups we would expect extreme difficulty in effect-
ing this reaction.

Compound I dissolved very easily in a slight excess
_of 5% potassium hydroxide. 0n addition of benzoyl
Chloride and shaking a gummy mass separated out. ‘When
a dissolved in petroleum ether and crystallized in the
cold. rosette-like crystalls formed. From alcohol the
crystals were thin, flaky plates, melting at 70° - 71°.
The structure woulg,be

‘-CeLH
S m. pt. 70° - 71°

H} H a
3 methyl 4 henfyi'phenyl benzoate
Analysis: CZlHlaoz
.2230 8m. gave .6789 8m. 00;; and .1194 {gnu H20

Gale. 0 83.40 R 6.00
Found C 85.03 H 5.99

Compound 11 dissolved in an excess of 405
potassiumfihydroxide. the less ease of dissolving pro-
bably being due to the poximity of the rather large
benzyl group. With.benzoyl chloride it formed a gummy

- 28 -
mass which hardened in the refrigerator and
crystallized from.both petroleum ether and alcohol
in very fine, fluffy needles. melting at 88° - 89°.
The compound wouldohave the structure:
('4 f/gcl/z O-é'cbil; m. 1315- 880 " 890
l aua

C/chéilb.
3 methyl 4,6 dibenzyl phenyl bensoate

.1431 gm. gave .446? gm. 002 and .0753 gm.IH20

Calc. C 85.67 H 6.17
Found C 85.13 H 5.89

Compound III dissolved in a slight excess of 5%
potassium.hydroxide. The mass formed with.benzoyl
chloride hardened and was crystallized from.alcchol.
forming fine. slender needles. mmlting at 58° - 59°.
A second quantity was made up but did not crystallize.
so a larger quantity was prepared. taking up in other.
.shaken with sodium.carbonate. and distilled. The pro-
duct was a pale yellow oil distilling at 215° - 220°
(5 mm.}. The strgcture of this ester would be:

.O-CCé [If

m. pt. 58° - 59°

c4 #50,; b. pt. 215°~220° (sum)

(ff/J

3 methyl 6 benzyl phenyl benzoate

- 29 -
O
.2135 gm. gave .6508 gm. 002 and .1173 am. H20

Calc. C 83.40 H 6.00
Found c 83.13 H 6.14

Compound IV dissolved in excess of 5% potassium
hydroxide. The gummy mass formed with benzyl chloride
was crystallized from.a1cdhol in shiny platelets, melting
at 71° - 73°. very nearly the same as the original phenol
whien melted at 71° - 72°. The structure of ths.ester
would be: 0-50% H5.

Mace/21,. m. pt..7l° - 73°
CH3 - '

2 benzyl 3 methyl phenyl bensoate

Analysis: °21H18°2 '

.2207 gm. gave .6733 gm. co, and .1142 gm. s20 ’

2.
.2475 gm. gave .7512 gm. 002 and .131? gm. H20
Cale. C 83.40 H 6.00
Found C 83.20; 82.77 H 5.78; 5.95

Compound 7; having the hydroxyl group between two
benzyl groups. we would expect to be very difficult to
esterify. The oil was put in an excess of 50% potassium
hydroxide and the mixture heated to boiling. The phenol
did not dissolve but became very dark colored. The
alkali was poured off and the remaining hard mass washed
with water. Benzoyl chloride was added and stirred up
with the dark mass, causing great evolution of heat. An

orange-yellow oil resulted. which was washed with water,

taken up in ether. and distilled. Some benzoic adid

- so -
came over first, then a yellow oil which finally became
constant at 235° - 240° (5mm.). A drOp would not crys-
talize from alcohol. Since the original phenol boils
at 216° - 213° (5 mm.) this product is sufficiently
different to Justify us in calling it the ester, of the

0

structure: cn—écéyg.
C4 ’3 C"’2 cfigc‘ 6(5— b. pt. 235°-940°
GHS (5 mm.)

3 methyl 2,6 dibenzyl phenyl benzoate
Analysis: 02832402 .

.1914 gm. gave .6004 gm. CO2 and .1089 gm. H20

Cale. C 85.67 H 6.17

Found C 85.55 H 6.36

6. m Derivatives

Several of the phenols were treated.with concen-
trated nitric acid. .In each case a vigorous reaction was
obtained with formation of a reddish yellow gummy mass.
The only one, however. which could be obtained in crys-
talline form was the derivative from compound IV, the
Claisen monobenzyl cresol melting at 71° - 72°. This
solidified and was crystallized from.a1cohol several
times, finally giving thin yellow plates, melting at
111° - 113°. This compound was not analyzed but we

assume it to be a dinitro derivative of the structure
0H

0 O
C H3

”v;

2 benzyl 3 methyl 4,6 dinitro phenol

-31..
The other nitro derivatives remained as heavy reddiSh
oils and time would not permit their purification.

7- §2£E§£1
l. Hpcresol was condensed with benzyl alcohol by the

Huston.method, forming a para and an ortho mono-substi-
tution product and a para-ortho disubstitution product.
2. Hacresol was condensed with benzyl chloride by the
Claisen method, forming two ortho monosubstitution
products and an ortho-ortho disubstitution product, also
a trace of the para—ortho disubstitution product. A
small quantity of the corresponding ”Claisen ether' was
formed.

3. 8 benzyl 3 methyl phenol was condensed with benzyl
chloride to form.the same ortho-ortho disubstitution
product mentioned above. A little of the ether, 2 bensyl
3 methyl phenyl benzyl ether, was formed in this reaction.
4. Bromine and benzoyl derivatives and one nitro deri-

vative were prepared.

Scherrie 9;; Conggnsation

 

 

 

\‘ /
\. ./'
v
0H
.‘J "I
Claisen Eesction Cal/s Q“ (m.4e°-47j
_ c
0N0. "J R 3
,QH
./ 3 CH
CH... Cb ”5"
(M110 41")
us
; 0H
caugcuz‘ ('ch5 ”3”

CH3 ((6 flag-Alto
5m

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