Feb.

, 1939 CONDENSATIONS WITH PHENOLS

OF KETONES 345

tained from the mother liquor. One recrystallization Summary

yielded pure calcium ~-altronate.3.5H&,which was iden-
tified by analyses, and by its mutarotation in N hydro-
chloric acid (Table I).
Anal.'E Calcd. for ( C B H ~ I O , ) ~ C ~ . ~ . Ca,
~ H ~8.13;
O:
HzO, 12.78. Found: Ca, 8.13; H20, 12.63.
One of the authors (N. K. R.) desires to thank
the Chemical Foundation of New York for a Re-
search Associateship.
(16) Through the kindness of Dr. W.T. Haskins of this Laboratory.
1. Sedoheptulose, the ketoheptose occurring
in Sedum spectabile, Bor., has been degraded to
D-altronic acid; this reaction confirms its for-
mulation by Ettel as D-altroheptulose.
2 . Sedoheptulose is suggested as a valuable
starting point for the preparation of the rare su-
gars D-altrose and D-ribose, and their derivatives.
D. C.
WASHINGTON, 8, 1938
RECEIVEDDECEMBER

[CONTRIBUTION
FROM THE CHEMICAL
LABORATORIES
OF ST.JOHN'S UNIVERSITY
AND OF NEW YORKUNIVERSITYJ

Condensations of Ketones with Phenols'

BY MARTINE. MCGREAL,VICTORNIEDERLAND JOSEPH B. NIEDERL
The systematic investigation as to the conden-
sations of carbonyl compounds with phenols by
J. B. Niederl and co-workers2 has been extended
to the field of saturated ketones.
The purpose of this investigation was to es-
tablish whether the behavior of phenol and that
of the ortho alkylated phenols with ketones are
similar, regardless of the type of saturated ketone
and of the reaction conditions employed (mole
ratio, type of catalyzer, concentration, tempera-
ture and solvent). Representative ketones of the
three main types, i. e., saturated aliphatic, alicy-
clic and aromatic ketones were selected. Thus,
of the saturated aliphatic ketones, methyl ethyl
(I, 11), methyl n-propyl (111) and methyl isobutyl
ketone (IV, V) ; of the alicyclic types, cyclohexa-
none (VI, VII) , 3- and 4-methylcyclohexanone
(VIII, IX) and cyclopentanone (X), and of the
aromatic series, acetophenone (XI, XII) and
methyl $-tolyl ketone (XIII) were chosen for
this investigation.
It was found that the condensation products
were invariably the crystalline diphenylmethane
type of compounds, regardless of the reaction
a l l ~ x a n ,and
~ d-fructose. This would indicate
that the first step in the condensation is an ad-
dition of the phenol to the carbonyl group, com-
parable t o the addition of hydrocyanic acid, with
the subsequent formation of a phenol-hydrin type
of compound.6 I n the next step one molecule of
water is lost intermolecularly, i. e., between one
molecule of phenol-hydrin and one molecule of
phenol with the subsequent formation of the crys-
talline diphenylmethane type of compounds.
Thus, in this latter step, the ketones differ from
the aldehydes, which lost water intramolecularly.
All the diphenolic condensation products ob-
tained in the condensation of the alicyclic ketones
(VI-X incl.) were subjected to pyrolysis and
through disproportionation yielded in all cases
the respective crystalline, alicyclic monophenol
(VIA, VIIA, VIIIA, IXA and XA).
Schematically the reaction in both the con-
densation and the disproportionation may be
presented as
Condensation: (I - XIII)
RzC+=O- +
HCaHaOH ---f

conditions or of the mole ratios of reactants.

RzC-O--H+ _C R2C-OH +
I I
Such findings, a t first glance, would suggest a CaHiOH CsH40H
direct elimination of one molecule of water from Phenolhydrin
one molecule of the ketone and two molecules of
the phenol. However, mole for mole addition Diphenylmethane compound
has been observed in the case of acetophenone,3
(1) Several parts are taken from the theses of Thomas Murphy and
Disproportionation : (VI - X)
of Daniel Marino presented to the Graduate School of St. John's A
University in partial fulfillment of the requirements for the degree of
Master of Science, June, 1938.
CsHtoC(CsHa0H)z+csH11CeH40H + C E H ~ O H+ resin
(2) J. B. Niederl, THIS JOURNAL, 50, 2230 (1928); 51, 2426 (41 Boehringer. German Patent 107,720 (1900); 1111, 817 (1901).
(1929): Z. angew. Chem., 44, 467 (1931); Monatsh., 60, 150 (1932): ( 5 ) E. Fischer, Bey., 27, 1355 (1894); C. Councler, ibid.. 28, 24
J. B . Niederl and co-workers, i b i d . , 51, 1038 (1929); THIS
JOURNAL, (1895).
58,657 (1936); 59,1113 (1937). (6) J. B. Niederl and R. Maurmeyer, Rochester Meeting, Am,
(3) Zincke, A n n . , 363, 275 (1908). Chem. SOC.,Sept., 1937.
346 MARTINE. MCGREAL, VICTORNIEDERLAND JOSEPH B. NIEDERL Vol. 61
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Feb., 1939 CONDENSATIOXS WITH PHENOLS
OF KETONES 347

Experimental acetic acid and making a mixed melting point with a stand-
Condensation Method ard sample, which showed no depression. The new phenol
was fractionally redistilled and in all cases crystallized in
A. Aliphatic and Aromatic Ketones (I-V, XI-XIII).-
the receiver (VIA, VIIA, VIIIA, IXA, XA).
One-half mole of the ketone and one mole of the phenol
Diacetates.-The diacetates were formed by the method
were placed in a one-liter round-bottomed flask which con-
of Shriner and Fuson.‘ Three grams of the crystalline
tained 50 cc. of glacial acetic acid. Dry hydrogen chlo-
condensation product (11, VI, VII, XI-XIII) was mixed
ride gas was passed through the contents of the flask
with 1.5 g. of powdered fused sodium acetate and 15 cc. of
vigorously for three hours. The solution changed in color
acetic anhydride. The mixture was heated on the steam-
from yellow to a deep red. The flask was disconnected
bath, with occasional shaking, for two hours. At the end
from the generator and tightly stoppered so as to keep the
of this time the warm solution was poured, with vigorous
reactants in a n atmosphere of hydrogen chloride. On
stirring, into 100 cc. of ice water. The mixture was al-
standing, the contents of the flask became extremely vis-
lowed to stand, with occasional stirring, until the excess
cous and finally crystallized. The period of standing
of acetic anhydride had been hydrolyzedr The crystals
ranged from one to four weeks; the yields from 10-250/,.
were removed by filtration, washed thoroughly with water,
The product formed was purified by being washed first
and purified by recrystallization from alcohol (IIa, VIa,
with diisobutylene, and then rewashed with toluene.
VIIa, XIa, XIIa, XIIIa).
Petroleum ether was used in some cases in place of diiso-
Aryloxyacetic Acids.-These compounds were prepared
butylene. Recrystallization was carried out from a mix-
according to Shriner and Fuson’ (p. 148). One gram of the
ture of ether and toluene in the case of the mixed alkyl
phenol (VIA-XA) was dissolved in 5 cc. of a 33% sodium
aryl ketone-phenol condensates. The alkyl ketone-phenol
hydroxide solution and 3 g. of chloroacetic acid added.
condensates were recrystallized from water.
The mixture was shaken thoroughly and heated on a water-
B. Cyclic Ketones (VI-X).-One mol of the phenol, and
bath a t 100’ for one hour. The solution was then diluted
one-half mol of the cyclic ketone were placed in a 2-liter
with 15 cc. of water, acidified with dilute hydrochloric acid
2-necked round-bottomed flask and 200 cc. of glacial acetic
to congo red and extracted with 50 cc. of ether. The
acid added. The reaction flask was provided with a re-
ether was washed with a n equal volume of water and then
flux condenser and a gas inlet tube extending to the bottom
shaken out with 25 cc. of a 5y0sodium carbonate solution.
of the vessel. A vigorous stream of dry hydrogen chlo-
The solution was acidified with dilute hydrochloric acid
ride gas was passed through the system for four hours,
and the product which precipitated out was filtered and
during which time the reaction mixture was heated to re-
dried on porous tile. It was recrystallized from diiso-
fluxing. After this the flask was removed, tightly stop-
pered and left standing a t room temperature. The phenol- butylene (VIAa, VIIa, VIIAa, VIIIAa, IXAa, XAa).
Nitro Derivatives.-These derivatives were prepared by
cyclohexanone (VI) and o-cresol-cyclohexanone (VII)
treating the diphenols (I, IV) with concd. nitric acid with
condensation products were left standing for twenty-
the application of heat until complete solution was effected.
four hours and the phenol-cyclopentanone (X) condensa-
The reaction mixture was allowed to stand until crystalli-
tion product for a week. During this time the reaction
mixture crystallized in all cases. One liter of water was zation of the nitro derivative was complete. The com-
pounds were recrystallized from alcohol (Ia, IVa).
added to the reaction flask, and the crystals were collected
Dipheny1urethan.-This compound was prepared by
on a Biichner funnel and washed with distilled water.
The compounds were recrystallized from benzene or, in treating the diphenol (VII) with an excess of phenyl iso-
cyanate in a sealed test-tube on a steam-bath until the
smaller quantities, from water. They were soluble in
contents became crystalline. The diphenylurethan was
Claisen solution and in dilute alkalies. The yield of the
recrystallized from diisobutylene (VIb).
above products ranged from 60% in case of the phenol-
cyclopentanone (X) to 80 yo for the phenolcyclohexanone Summary
(VI) and o-cresol-cyclohexanone (VII). The phenol 3-
and 4-methylcyclohexanone condensation products (VIII, 1. The condensation of aliphatic, alicyclic
IX) were prepared as above, except that they were re- and aromatic ketones with phenol and with o-
fluxed for eight hours and left standing for three days. cresol yielded crystalline products of the diphenyl-
They also crystallized in the reaction vessel and were
purified as stated above. The yield was approximately
methane type of compounds.
70% in the case of the 4-methylcyclohexanone (IX) and 2. Alicyclic diphenols upon pyrolysis under-
50% in the case of the 3-methylcyclohexanone (VIII). went disproportionation to the respective alicy-
Pyrolysis.-Thirty grams of any one of the above com- clic monophenols.
pounds (VI-X) was placed in a 125-cc. distilling flask, and, 3. The reactions, both the condensation and
after heating for about thirty minutes below the boiling
point of the substance, was subjected to slow distillation
the disproportionation, were presented sche-
a t atmospheric pressure. In each instance about 10 g. of matically and show an intermolecular effect with
the phenol or o-cresol, respectively, was obtained, and the resulting loss of a molecule of water between
about 10 g. of the new monophenolic compound. The two molecules of the phenol and one molecule of
rest remained as a charred residue in the distilling flask. the ketone.
The phenol was identified by melting point and mixed
(7) Shriner and Fuson, “The Systematic Identification of Organic
melting point with a pure sample. The o-cresol was iden- Compounds,” John Wiley and Sons, Inc., New York, N. Y., 1935,
tified by its boiling point and by preparing the o-cresoxy- p. 142.
343 JOSEPH B. NIEDERLAND VICTOR NIEDERL Vol. 61

4.This type of condensation is being extended influence of the substituent group of the benzene
to meta and para alkylated phenols and polyhy- ring in its different positions.
N. Y.
BROOKLYN, RECEIVED 8, 1938
NOVEMBER
droxyphenols with ketones in order to check the NEWyORI(,N. y .

O F NEWYORK UNIVERSITY ]
[CONTRIBUTION FROM THE CHEMICAL LABORATORIES

Simultaneous Multiple Alkylation of Phenols. The Synthesis of a Phenolic

Coumarane Involving the Condensation of Diethyl Ketone with Resorcinol
BY JOSEPH B. NIEDERLAND VICTORNIEDERL

Theoretical ortho, meta or para to the hydroxyl group. The

In continuation of the studies of the conden- nature of the catalyst used in these condensations
sations of carbonyl compounds with phenols, the appears only to influence the yield but not the
condensation of diethyl ketone with resorcinol was course of the reaction nor the type of condensa-
investigated. In this condensation a new phe- tion product ~ b t a i n e d . ~
nomenon was encountered, namely, the simul- Elucidation of the Structural Formula
taneous di-alkylation of a phenol, regardless of Although the empirical formula of the crystal-
the mole ratio of the reactants employed. line condensation product suggests immediately a
The empirical formula of the crystalline and dipentenylresorcinol, structure proof work, how-
non-polymeric condensation product obtained ever, revealed that there is only one free phenolic
in quantitative yields by condensing diethyl ke- hydroxyl group present in the compound (forma-
tone with resorcinol in glacial acetic acid solution tion of a monoacetate (IV) and a monophenyl
in the presence of dry hydrogen chloride, corre- urethan (V)) and that there is only one double
sponds to an addition of two molecules of diethyl bond in the compound, as evidenced by the for-
ketone to the resorcinol followed by the elimi- mation of a tribromide (VI) from the free phe-
nation of two molecules of water as follows nolic coumarane (111) (treatment of an aqueous
solution of the phenol with excess bromine water)
+
HCI
2(CH3CHzW0 C6H4(OHh-(1,3)+ C16H2202
HAC
+ 2H10 and a dibromide (VII) from the acetate (IV)
(addition of an excess of bromine in carbon tetra-
This fact then adds to the already reported
chloride to a solution of the acetate in the same
condensation systems of the mole ratios 1 : 1 (one
solvent). All this then suggests ring formation
mole phenol and one mole carbonyl compound),'
between one of the phenolic hydroxyl groups and
2 : 1 (two moles of phenol and one mole of car-
one of the pentenyl radicals leading to the forrna-
bonyl compound),2 2:3 (two moles of phenol and
tion of a coumarane type of compound as has
three moles of carbonyl c o m p o ~ n d )and
, ~ now a
been observed in related condensation systems5
condensation system involving a mole ratio of
Summarily, the reaction mechanism then would
1 : 2 (one mole of phenol and two moles of car-
involve first the addition of the two molecules of
bonyl compound). Thus i t becomes apparent
diethyl ketone to resorcinol with the formation
that the nature of the end-product is influenced
of an intermediate and under the given reaction
not only by the type of carbonyl compound em-
conditions unstable phenol-dihydrin (I), which
ployed, but also by the type of phenol used in the
upon the loss of two molecules of water would
condensations. This influence exerts itself par-
give the dipentenylresorcinol (11). Then under
ticularly through the position of the second sub-
the influence of dry hydrogen chloride, ring closure
stituent in the benzene ring, i. e., whether it is
between one of the pentenyl groups and one of the
(1) E. Fischer, Be?,, 27, 1355 (1894); Niederl and co-workers,
Tins J O U R N A L , 58, 657 (1036); 69, 1113 (1037).
phenolic hydroxyl groups appears to ensue with
( 2 ) McCreal, Niedrrl and Niederl, ibid., 61, 345 (1!130); Lunjak, the formation of a phenolic coumarane (TIT), as
J . K ~ s s .Phys.-Chern. Soc., 36, 3113 il9f14); Dianin, ibid., 23, 492
11S!ll); C l a w and Trainer, H u i . , 19, 3009 (1886); Zinckc and follows
(:rueters, A n n . , 343, 8 3 (1905); Xiricke, i b i d . , 363, 255 (190R). (4) J. B . Nicderl, I n d . Eric. Chens., 30, 1269 (1938).
( 3 ) J . E , Nirdcrl, Titis J O I I K N A I . , 50, 222;)O (1Y28): Moiro/sli., 60, Iordull,
( 5 ) Niederl and Storcb, T H I S JDUKNAT., 66, 4540 (l!l:<:<);
1.-,0 (1!1:<2); Nirtlrrl auil C a s t y , '1'111s ~ < I I I K Y A l . 51,
, Ill.'<R (l!l2'l). ('eruiuo Paleiit. ,501,723 (1926).