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STERICALLY HINDERED ALIPHATIC KETONES

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The Pennsylvania State College
The Graduate School
Department of Chemistry
ALIPHATIC STERICALLY HINDERED KETONES
A Thesis
By
David Irwin Randall
Submitted in partial fulfillment of
the requirements for the degree of
Doctor of Philosoph
ACKNOWLEDGMENT
Sincere gratitude and appreciation are
hereby expressed to Dean F. C. Whitmore who has
patiently and faithfully directed this entire research.
To Dr. C. S. Miner, Jr., many thanks are
due also for supply of materials.
iii
Table or Contents
Page
INTRODUCTION AND HIS TO RI CA L............................. 1
D I S C U S S I O N " .............................................. 10
E X P E R I M E N T A L ............................................ 24
Description of fractionating columns
Preparation of beta-Butlerow's acid*
.............. 24
• • • • • • •
.25
Preparation of beta-Butlerow *s acid chloride • . . .26
Preparation of methylmagnesium chloride.
. . . . .
.28
Reaction of beta-Butlerow's acid chloride on
methylmagnesium chloride
.......................... 28
Reactions relating to the structure of methyl betaButleryl ketone {5,5,5-trimethyl-3-t-butyl-2......... • • • • • • • 5 2
h e x a n o n e )• • • • • • • • • •
Attempted ozonolysi3« ....................... • .32
Attempted bromoform reactions .............. . .33
Attempted preparation of the oxime. . . . . .
.34
O x i d a t i o n ......................................... 35
Determination of molecular w e i g h t .............. 35
Attempted reductions of methyl beta-Butleryl ket o ne .36
W ith a luminum isopropylate....................... 36
With "hydrogen and Raney nickel................... 36
With sodium and moist b e n z e n e ................... 37
With sodium and ethyl alcohol
.................37
With hydrogen and Adams' c a t a l y s t .............. 38
With hydrogen and a calcium copper chromite
catalyst............................................ 38
Preparation of 2-beta-Butleryl-2-ethanol (3,5,5triiiiethyl-3-t-butyl-2-hexanol) • • • • • • • • . • • 3 9
A ddition of methyl beta-Butleryl ketone to methyl
G-rignard reagent
..................................... 40
Table of Contents (continued)
Page
EXPERIMENTAL (continued)
Treatment of methyl beta-Butleryl ketone (3,5,5trimethyl-3-t-butyl-2-hexanone) with dehydrating
agents.
.............................................. 41
Attempted oxidation of methyl beta-Butleryl ketone
with potassium p e r s u l f a t e .............................. 41
Preparation of acetyl-beta-Butlerowyl-methane (5,7,7........... .42
trimethyl-5-t-butyl-2,4-octandione)
Preparation of beta-Butlerowylacetic acid (4,6,6trimethyl- 4- t-butyl- 3- keto-heptanoi c a c i d ) ............ 45
Attempted synthesis of acetyl-beta-Butlerowyl-methane46
Preparation of 1-beta-Butlerowyl-2-phenyl-2-ethanol
(4, 6, 6 - triifa.ethyl-4-t-butyl-1-phenyl-l-heptanol-3-one )47
Preparation of be ta-Butlerowyl-benzoyl-met ha ne (4,6,
6-trimethyl-4-t-butyl-1-pheny1-1,3 - h e p t a n d i o n e ) • • .48
Attempted preparation of the pinacol of methyl betaButleryl k e t o n e . ......................
48
Preparation of di-beta-Butlerowyl-methane (2,2,4,8,10,
10-hexamethyl-4,8~di-t-butyl-5,7-undecandione)• • . .49
Preparation of beta-Butlerowyl-triethylacetyl-methane
(3, 3-di ethyl-7,9,9-trimethyl-7«-t-butyl-4, 6-decandione).
.............................................. 50
Preparation of beta-Butlerowyl-alpha-Butlerowylmethane (2,2, 8, 10,10-pentamethyl-4-neopentyl-8-1butyl-5,7- un d e c a n d i o n e ) ................................. 51
Attempted preparation o f alpha-Butlerowyl-beta-Butlerowylacetyl-methane (2,2,8,10,10-pentamethyl-4-neopentyl8-t-butyl-6-acetyl-5, 7-undecandione )............. . . . 5 1
Attempted preparation of 1,5-di-beta-Butlerowyl-2, 4pentandione (2,2,4,12,14,14-hexamethyl-4,12-di-tbutyl-5,7,9,11-penta de ca n et et ra o n e) ................... 52
V
Table of Contents (continued)
Page
EXPERIMENTAL
(continued)
Attempted preparation of the peroxide of methyl betaButleryl ketone • • .
53
Synthesis of ethyl be*ta-Butleryl ketone (4,6,6t r iflieth yl-4-t-butyl-3- hep ta none ).......................54
Preparation of alpha, beba-Butlerowylpropionic acid
(2,4, 6, 6-tetramethyl-4-t-hutyl-3-keto-heptanoic acid)55
Preparation o f beta-Bu.tlerowyl-benzoyl-me thylmethane (1-phenyl-2,4, 6,6-tetramethyl-4-t-butyl-1,
3-heptandione). . . ............. . . . . .
. ... .56
Treatment of betasButlero wyl- benzoyl-me thy 1me thane with alkali. « . . . ....................... . . 5 7
Preparation o f 1— beta-Butlerowyl-1-methyl-2-phenyl2-ethanol (1-phenyl-2, 4,6,6-tetramethyl-4-t-butyll-heptanol-3-one • . . • • ............................. 58
Oxidation of l-beta-Butlerowyl-l-methyl-2-phenyl-2ethanol • • •
. • . .
..59
Bromination o f ethyl beta-Butleryl k e t o n e ........... 60
Treatment o f alpha-bromo-ethyl beta-Butleryl ketone
(4, 6, 6-trimetbyl-4- t-butyl-2-bromo-3-heptanone ) with
alkali....................................................61
Attempted preparation of the acetate of 1-beta-Butler­
owyl- 1- ethanol (4,6 ,6- trimethyl-4 - t-butyl-2-heptanol3 - o n e )........................
61
Preparation of isopropyl beta-Butleryl ketone (2,4,6,
6-tetramethyl— 4- t-butyl-3— heptanone ).................. 62
Preparation of alpha-methyl-alpha-beta-Butlerowyl­
propionic acid (2,2,4, 6,6— pentamethyl-4-t-butyl-3keto-heptanoic a c i d ) ...............................
*63
Attempted preparation of 1,1-dimethyl-1-beta-Butlerowyl-2-phenyl— 2-ethanol (l-phenyl-8,2,4,6,6-pentamethyl4-t-butyl-l-heptano 1-3-one)
64
T a b l e o f Coirfcen-fcs ( o o n t i n u e d )
Page
K X P E R I M E M 1A X (continued)
Preparation of the enol benzoate
Butleryl ketone • . • » . . .
of
isopaopyl beta...
. . . ....65
Saponification of the encl benzoate
Butleryl ketone • . . . . . .
...
of isopropyl beta...
... ...66
Preparation of the peroxide of isopxropyl t>etaButleryl ketone (2,4, 6,6-tetramefchyl-4— t-tjutyl3-heptanone ). • ................. .
...
. . . . . .67
Preparation of metbyldie thylca rbi n o l . - . . . .
..
.68
Preparation of mettyldiethylca rbi nyl chloride
..•
.68
Preparation of mettyldiethylca rblmyl Grignar*!
reagent . . . . .
. . . . . ...
. . . . . .
..
.69
Attempted, preparation of be ta- Tut lerrowo in (2, 2,4s,7, 9,
9-*hexamethyl-4, 7-di-t-butyl— 5- decane 1-6-one).
... .*70
Action o f sodium o n beta— Butie row fs aldehyde.
Preparation of methyl iodide.
. . . . . .
...
.. .
.*71
...72
S U M M A R Y ..................
74
BIBLIOGRAPHY
76
I
INTRODUCTION A3® HISTORICAL
This research was begun in connection with the
preparation of hydrocarbons related to beta-Butlerow’s
acid.
C-C.-CL
C
//
O
The synthesis which was followed is that involving the
treatment of beta-Butlerow*s acid chloride with a
Grignard reagent,
dehydration of the tertiary carbinol
so obtained, and hydrogenation of the resulting olefin.
Only the first step could be effected.
c
(R is methyl ethyl or isopropyl.)
These ketones were found to be so sterically hindered
that their carbonyl groups would not undergo further
addition of the Grignard reagent.
To investigate the
properties of these unusual ketones, became then the
main problem of this research.
It is known that in general many reactions of
organic compounds are affected to a remarkable degree
by the extent to which the reacting system is surrounded
by other groups.
Opinion is divided with respect to the
manner in which these surrounding groups exercise their
influence, but whether the effect be regarded as spatial
2
or chemical,
it is generally designated as steric
hindrance.
Acetomesitylene (I) has been known and studied by
several workers.
Its oxime cannot be obtained by any of the ordinary
methods.’*’*2 *
4
With o-phenylenediamine substituted glyoxals
react to give quinoxalines.
Steric hindrance inhibits the reaction with mesityl
glyoxal (II) and only the anil (III) is obtained.^
n
f3 o o
c - c ^
m
In contrast with this behavior which indicates a pro­
nounced hindrance to reactions involving the carbonyl
group, acetomesitylene is easily reduced to the cor­
responding carbinol.6
It is of special interest that
the sterically hindered ketones of the present study
apparently cannot be hydrogenated.
The haloform test when applied to acetomesitylene
fails.
It has been suggested that this is general for
sterically hindered methyl ketones.
alpha, alpha,
Fuson
7
found that
alpha— tribromoaoetomesitylene does not
cleftve in a n alkaline med iu m and he offers this as
final proof that acetomesitylene will not undergo the
haloform reaction.
To base the failure of the halo form
reaction upon the resistance o f the trihro mo ketone to
splitting i n alkali seems to be unjustified since
J. G. Aston and co-workers8 have found that trichloroacetophenone,
employing the conditions of the haloform
reaction, splits very slowly while acetophenone under
the same conditions cleaves easily.
According to Klsges,^ acetomesitylene adds Grignard
reagents.
However,
it does not actually add these
reagents; instead the reaction involves enolization.
2
S ^ 9 =cH^ h
"c i H i i <n ~ C H > ' t
°
TST
This reaction is not dependent upon the nature of the
R residue of RMgX.
Acetomesitylene
alone of all ketones
that have
been examined forms no addition product at all and
gives a quantitative yield of hydrocarbon with a Grig­
nard reagent.
It has appeared possible that the differ­
ence in behavior of acetomesitylene and other ketones
might be due to the greater ease or rapidity of enoliza2
tion.
Kohler has shown that the mesityl group neither
hinders nor promotes enolization.
The question as to whether the h a lo ma gn es iu m ketone
derivative has structure
(V) o r (VI) has be e n definitely-
decided in favor of the enolate
(VI) acc or di ng to Kohler.
_ _
R - C -C
It } R
o
'
o/v\yX
-/v^/c
3 T
3 Z T
For the purpose of establishing the structure,
Kohler
ii
employed the reaction between ph en yl magnesium bromide
and alpha-brom-alpha-bet a-triphenyl propiophenone
m - G H - C-~ C ~ CD -h
®
/v[f
cH “
g
9 ~9
(VII).
~ ^
00
~snr
On decomposition with iced acid in the presence of ether
the m a g n e s i u m compound gave a solution which absorbed
oxygen from the air,
f o r m in g a peroxide of known structure
(VIII).
^ <2>
0
0 —
0
m u
Only enolic forms are known to give this type o f perox12
ide.
Umnowa
treated alpha-bromo-pentamethylacetone
with m e t h y l m ag ne si um iodide and represented the process
as follows:
e
C
c
1 1
^
- ■- «
5
She based her conclusions upon the fact that the mag­
nesium derivative when treated w ith COs gave a salt of
a carboxylic acid.
It is well known now that sodium
enolates readily combine with COg and that the products
are salts of carboxylic acids1 3 ,
Carbonation is therefore
not a reliable method for establishing the structure of
metallic derivatives.
The place of attachment of the sodium a t o m in
sodium aoetoacetic ester offers a similar problem.
The
ti
fact that C//<C'C-C - o c '
is obtained when sodium
3O
l! fK o
11
acetoacetic ester reacts with R X has been used as an
argument that the sodium compound has the structure
C
C'- C. - CL - o-E7
!> /Vu, it
O
o
formulation
.
c H ~ ^ "" ^
J o/Vcu,
This conception and the enolate
<7' ' ^ rare both at fault since
£
they are based upon the assumption that the reaction
between sodium acetoacetic ester and an alkyl halide is
a simple metathesis like the action of aqueous barium
chloride on a solution of sodium sulfate.
The negative
acetoacetate ion may be represented as a resonance hybrid.
Whether A o r B reacts with R
energy relationships involved.
of R X
depends upon the
In the case of aceto­
acetic ester, resomer B is favored.
6
Magnesium enolates of ketones are also ionic in
nature and may be represented in two electronic tautomers
(IX) and (X).
(R is tertiary)
Consideration of* this resonance hybrid aids in explain­
ing the reactions of balomagnesium enolates of sterically
hindered ketones.
ferent
These reactions occur with three dir*-
types of reagents:
and ketones,
carbon dioxide, aldehydes
and acid chlorides.
Carbon dioxide o n reaction with the halomagnesium
enolates of acetomesitylene, propiomesitylene and isobutyromesitylene yields the corresponding beta-keto-acids
CXI), (XII), and (XIII)1 4 .
o
r z i
These acids w h e n heated regenerate the original ketone
and liberate CO .
2
Aldehydes and ketones give derivatives of alcohols 15 •
For example,
the product of the reaction of the mag­
nesium enolate of isobutyromesitylene (XIV) with benzaldehyde is 2— mesitoyl-2, 2-di-methyl- 1-phenyl- 1-ethanol (XV).
7
CM
C?H„ - C - C.^
1
{
\
fU
OM^
b -- >
CH
H
c H - e - <L - C - d>
7
I*
vi
a O - C.-CD
o
i
1
C H 3 oh
H
XIV
X E
Acid chlorides give either enol esters or 1,3di-ketones depending upon the enolate employed.
In
general sterioally hindered ketones with two or more
alpha hydrogens yield 1,3-di-ketones while those with
only one alpha hydrogen give enol esters1 5 .
Thus with
benzoyl chloride the enolates of* acetomesitylene and
propiomesitylene give the corresponding 1,3-di-ketones
(XVI) and (XVII).
_u
C n^
-C-c - c- ®
o
°
o
h
o
X V T
TTVTf
However, the enol benzoate (XVIII) Is formed when the
enolate of isobutyromesitylene Is treated with benzoyl
chloride.
Co*,, -C. = c X CHi
1 "
I
\ C H ,
O-C-di
j
m
o
The problem of deciding whether the product of the re­
action of a hindered magnesium enolate with an acid
chloride was a 1,3-di-ketone or an enol ester was first
1 fi
attempted by Kohler and Johnstin • By benzoylating the
magnesium enolate of (XIX) they obtained a product
8
which w q s
formulated as an enolbenzoate*
CD
- C H - C. H - C -
^
CD
i
on<jX
T E r
It was shown later by Kohler^ by synthetic methods to
be a 1, 3-di-ketone#
The benzoate formula was chosen
because o f ease of hydrolysis and also because the
compound gave no ferric chloride test nor copper deri­
vative.
This evidence is no longer valid since it is
2
now known that alkylated di-ketones are very easily
cleaved b y alkali and also that the alkylation de­
presses the enolization to such an extent that the di­
ketone no longer gives a ferric chloride test or reacts
with cuprio acetate*
Several aromatic ketones similar in properties to
17
acetomesitylene have been reported by Smith and Guss
•
They found that only those ketones having at least three
methyl groups,
and two of these ortho to the aceto group,
showed 100$ enolization and 0$ addition*
TR
Kohler and oo-workers
have reported that the
addition of 2,4,6-trimethylhexahydrobenzoylchloride to
excess metbylmagnesium chloride gave a mixture contain­
ing 70# hexahydroacetomesitylene,
15# hexabydromesityl-
difiiethylcarhino 1 and 5# of the hydrocarbon obtained by
dehydration of this carbinol.
These results indicate
that the hindrance offered by the hexahydromesityl group
9
is not as great as that offered by the mesityl group*
r
10
DISCUSSION
It has already been mentioned in the intro­
duction that this investigation began with attempts to
synthesize a tertiary aloohol through the action of a
methyl Grignard reagent upon beta-Butlerowrs acid
chloride*
With few exceptions the action of CHgMgX
upon acid chlorides produces some tertiary aloohol;
however, in this instance only methyl beta-Butleryl
ketone (I) (3,5,5-trimethyl-3-t-butyl-2-hexanone) was
isolated.
C
The yields were 70-90$.
C
C-C.-C- C —
»
^
'
C-CI
U
C-C-'C
O
+-CH
R-c - C H 3
■
o
e
The purification of beta-Butlerowfs acid and the prepa­
‘
ration of its acid chloride are fully described by
Dr. C. S. Miner1 9 .
Proof of structure of methyl beta-Butleryl ketone
(5.5.5-
trimethyl- 5-t-butyl-2-hexanone).
The proof of the structure of (I) (methyl beta-But­
leryl ketone) was completed with
some difficulty and will
be discussed in detail in order to demonstrate the abnorm­
al properties of the substance.
That the product of the action of beta-Butlerowfs
acid chloride on methyl Grignard reagent was not a terti­
ary alcohol was indicated by its inactivity with dehydrat­
ing agents.
Dehydration was not observed on heating it
11
with CuSO^. at 150°C.
At 150°C. chloronaphthelene-
sulfonic acid had no effect; this reagent at 200°0.
split hut did not dehydrate the molecule.
was stable in boiling 30$ HgS04.
Finally it
Determination of the
molecular weight using the freezing point lowering of
benzene gave an average value of 193 which agreed
fairly closely with 198, the molecular weight of methyl
beta-Butleryl ketone (I), but was far removed from 213,
the value for the tertiary alcohol (II).
c
c
c- c- c- iC
C-c-C
c.
c.' O H
C*
TT
hypothetical
The possibility of (I) having an olefin structure
resulting from dehydration of (II) was next considered.
C
C-
C - C - O C
*
C = C
'
c. c-c-c
I
I
'
(__
c
(hypothetical)
The absence of an olefinic double bond was shown hy the
failure of action with bromine, potassium permanganate
and ozone on (I).
When (I) was heated with a 2$ solu­
tion of bromine in carbon tetrachloride, no color change
was observed.
However, on heating the ketone and bromine
alone, a rapid reaction took place with the evolution of
HBr.
Ozone failed completely to react with (I).
Neutral
and basic potassium permanganate had no effect upon (I).
12
The structure of a secondary alcohol (III) seemed
improbable
since CHgMgX is not known as a reducing agent.
C.
C'C
ur
C
-C -C.
c
c. — c.
c-i-c
oh
E v e n this possibility was eliminated by the following
facts:
acetyl chloride and phenyl isocyanate did not
react with
(I)j
chromic acid in glacial acetic did not
attack it at 20-6O°C*; finally,
the suggested alcohol
(III) was synthesized by the action of methylmagnesium
chloride on beta-Butlerow’s aldehyde, and was found to
be different in properties from (I).
c
e
cl c. c d —
i
c
f
,
c-c-c
c
C ^ O f C H s
H
3
H c A
a
-EEEE
The yield of alcohol was very small (5%); a sufficient
quantity to oxidize to methyl beta-Butleryl ketone was
not obtained.
Phenylisocyanate with the alcohol gave a
urethan melting at 103-105°C.
Before (I) could be shown to have the structure
o f methyl beta-Butleryl ketone certain contradictory
facts were considered.
Xt was found impossible to make
ketone derivatives such as the oxime,
2,4— dinitrophenylhydrazone.
semicarbazone, and
This same difficulty is
encountered with acetomesitylene^” ^ and may be explained
by steric hindrance.
The haloform reaction although
attempted repeatedly on (X) was uniformly unsuccessful*
13
Acetomesitylene also fails to give a haloform test.
Every effort to reduce (I) failed including sodiummoist benzene,
sodium-ethyl alcohol, Hg at 3000 lbs.,
and 357°C. with Raney nickel, aluminum isopropylateisopropyl alcohol, Hg at 3400 lbs. and 330°C. with copper
calcium chromite.
In the hydrogenation attempts where
high pressures and temperatures were used,
ting occurred.
some split­
Water and unreacted ketone were the
only products identified.
If any alcohol formed it
was immediately dehydrated at the high temperature used.
Ketones which cannot be reduced by at least one method
were not to be found in the literature.
Even aceto­
mesitylene is reduced smoothly by ethyl alcohol and
sodium.
Thus methyl beta-Butleryl ketone is unique in
its resistance to reduction.
Oxidation of (I) at 90°C. with a chromic acid,
glacial acetic acid mixture gave beta-Butlerow1s acid
thus showing the skeleton of 12 of the 13 carbons.
C
I
c
I
C -C_-c -c
>
U
o
c_ c- a - c
The structure of the
—
C
1
u o 3
R.C.-OH
11
o
' fli. group was proved by
11
o
indirect methods.
Enolization of the ketone was found by
Dr. L. P. Block20 to occur to the extent of 94% with 0%
addition.
14
C_
C
c-c.-c.-d.— c- c.h3
C- c-c-c o
^
H
The enolate is given that structure although Gilman21
has reoently suggested that the enolate formula is
incorrect#
He has found that acetomesitylene gives a
color test with Michler’s ketone and reasoning from
this postulates the true Grignard formula
"CH
a
A proper explanation, as already noted in the introduc­
tion, lies in the two resonance forms of the enolate ion#
With acetyl chloride the bromomagnesium enolate of
(I) reacted as a true Grignard reagent giving beta-Butlerowyl-acetyl-metbane (5,7,7-trimethy1-5-1-butyl-2,4octandione).
V
c
C- C*- C -IC
d C-c-c
c
This liquid
CI- ^ C H *+ C I - C (|CH 3— ^
II
-L »/
oHcBa
°
o
°
*
di-ketone was characterized by a positive
ferric chloride test, by its 2,4-dinitrophenylhydrazone
and by its copper derivative.
X R-C - CH - C - C H
u
0
^
II
O
5
+ Co. CAd), ■
---
~F\ - C ~ CH =■ C - CH
ii
1
i”
°
'' C w
/
o
T\-
/
\
o
c-cn = c - c H
^
15
When the bromomagnesium enolate of (I) (methyl betaButleryl ketone) was caused to react with CO 2 a betaketo-acid was obtained.
.c
c
c -c'-c.-c. —
e =,
c- c-c-c.
c
c h
, —
>
C C
-
T'-
R- C - C H
COOH
o
°
The foregoing tests and reactions constitute proof
that compound (I) is methyl beta-Butleryl ketone.
Reactions of methyl beta-Butleryl ketone
(5.5. 5- triiiiethyl-
5-t-butyl-2-hexanone).
The action of carbon dioxide and acetyl chloride with
the enolate of (I) has been discussed above.
Other acid
4
chlorides used were benzoyl, triethylacetyl, beta-Butlerow's and alpha-Butlerow's, which gave respectively, betaButlerowyl-benzoyl-methane(X V ) (4,6,6-trimethyl-4-t-butyl1-phenyl-1,3-heptandione), beta-Butlerowyl-triethylacetylmethane (V) (3,3-die thy 1-7, 9,9-trimethyl-7-t-butyl-4, 6decandione),
di-beta-Butlerowyl- me thane (VI) (2,2,4,8,10,
10-hexamethyl-4,8-di-t-butyl-5,7-undecandione), and betaButlerowyl-alpha-Butlerowyl-me thane (VII)
(2,2,8,10,10-
pentamethyl-4-neopentyl-8-t-butyl-5,7-undecandione ),
c
c
c
C ^
C-C-C-C — C - C U ^ - C - C D
c.- c -C - C — Q - C H r C - C - C
•
'
II
M
r
I
U
C
c C'c-e
o
c
0
c-
c-C.-Co
c
JQT
:3z:
o
xC
16
c
/
c
c
CrGC-C.-C.-CVA
1
I
c-c
C
c.
I
/
-c-c-c- c - e
a
1
o C-C-C
(
c - c - c-c - C - C H
I
I
c
C -CL-c M
■i.
C)
1
c
c
Ml
- C - H
c
c-c
\
VII
All of these di-ketones are white solids; they give a
positive ferric chloride test and a copper derivative.
Of particular interest is beta-Butlerowyl-alpha-Butlerowyl-methane.
It was prepared by two methods.
The first
involved the action of alpha-Butlerowfs acid chloride on
the enolate of (I) and the second which was run by Mr. C.
Lester, involved the action of beta-ButlerowTs acid
chloride on the enolate of methyl alpha-Butleryl ketone.
c_
c_
H e
C.-C-C-C.- C ■=- C.-C - C - C - C
I
I I
<II I
I
C C-c-C
o C
C
I
c-c-c
c_
H
I
c - c - c - c - C,
v
I 1
c
f a n S aC'-c-c
3
i
c.
-V- c_l
c
?
I
C - C - C - C - CL
u
I
V ^
oC'cj <
c_
c
a
o
The compound obtained in the first reaction was identical
with that obtained in the second.
In preparing similar di-ketones using acetomesiiylene
14Fuson
found that if the amount of acid chloride was
not carefully controlled some tri-ketone was formed.
was thought, therefore,
It
that the enolate of beta-Butler-
owy1-alpha-Butlerowyl-methane would react with acetyl
17
chloride to yield a tri-ketone*
However,
this step was not realized since only unreacted
di-ketone could he recovered*
Although the carbonyl group of methyl beta-Butleryl
ketone is exceedingly unreactive, it was supposed that a
reducing couple such as B a c h m a n n s ^ might react success­
fully.
This reaction failed to give any trace of pinacol.
Reactions of ethyl beta-Butleryl ketone (4.6.6-trimethvl4-t-butyl-5-heptanone).
Before the properties of ethyl beta-Butleryl ketone
could be examined it was necessary to prepare the com­
pound itself.
A yield of 79% of the ketone was obtained
from the action of 5 moles of ethylmagnesium bromide
upon 1 mole of beta-Butlerow's acid chloride*
c
c,
CL -C_-C-C - C_- O \ I- 11 TA a, C3a.
^
— C. - fc.tr
c
ru
^
^ C-C,Co
o
c.
Ho product other than the ketone was isolated from the
reaction mixture.
By analogy with its methyl homolog
(I), ethyl beta-Butleryl ketone would be expected to
show st er i c .hindrance.
This was well borne out by the
fact that derivatives of the ethyl ketone other than
the bromomagnesium enolate cauld not be made*
18
Dr* L* P* B l o c k 2 ® determined the enolization value o f this
ketone at 57$ with 0*0$ a d d it io n taking place.
Treatment
o f the enolate of eth3^1 beta-Butleryl ketone with
carbon
dioxide yielded the corresp on d in g beta-keto-acid,
alpha­
bets- Butlerowylpropionic acid
(2,4,6, G-tetrainethyl-d— t-
butyl-S-keto-heptanoio acid).
^
c
c-C-C-C
— C| ^ CH - CH ^ CO x
i
j
ft-c-cII t
c-c.c
COoH
°
This acid was characterized by its instability at lOO0C.
At this temperature carbon dioxide was evolved a n d the
original ketone was obtained.
15
Fuson's w o r k
has shown that the enolate of
propiomesitylene gives a 1,3-di-ketone w h e n t r e a t e d with
benzoyl chloride,
therefore it was expected, t h at ethyl
beta-Butleryl ketone would react in a similar manner.
Such proved to be the case as the a ct i o n o f ben zo yl
chloride o n the enolate of ethyl beta-Butleryl ke to n e
gave a compound which was f i n a l l y identified as beta—
B u tlerowyl-benzoyl-methyl-methane
(1-phenyl-2 ,4, 6, 6-
tetramethyl-4-t-butyl-l,3 - h e p t a n d i o n e )•
c
c
c-c-c-c. - <z.-=L c H — ^ H ,----> T V C-CH' C.—
c
C' V C
i
c
6
(DCOCl
n
o
cd
it
o
F ormulation of the above di-ketone as an enol ester was
believed to be incorrect f o r it did not sapo ni fy w i t h a
a strong base.
Nevertheless,
it was deemed d e s i r a b l e to
19
syn thesize b e t a - B u t l e r o w y l - b e n z o y l - m e t h y l - m e t h a n e u s in g
s dif fe re n t method.
(1 )
Th e s y n th es is contained two
steps:
Benza 1 d eh y de w h e n added to a n enolate s o l u t i o n of*
ethyl b e t a - B u t l e r y l ketone gave a 1,3-ketol,
B u tl e r o w y l - 1 — m e t h y l - 2-p h e n y l - 2 - ethanol
1-beta-
(1-p h e n y l - 2 ,4,6,
6 -t etramethyl-4=-t-butyl-l-heptanol-3-one).
(2)
Oxida­
tion of this ketol w i t h potassium, diohromate a n d sulfuric
acid p r o d u c e d a
c ompound identical with b e t a - B u t le r ow yl -
henzoyl— methyl- me thane.
Thus the p o s s i b i l i t y o f a n enol
e ster having been obt a in ed was eliminated.
O
It
HI
Hi
» "R - C - C - <!:-<£
’ C:cd
CD
t
U
it
v
i
was n ot s u r p r i s i n g that this di-ketone did not enter
into
since
r e a o t i o n w i t h f e rr i c
chloride and c o p pe r ace ta te
it is w e l l lcnown that a l k y l a t i o n o f di - ketones
reduces
To
t h e i r e n o l i z a t i o n values greatly.
test
the p o s s i b i l i t y of the b e t a - B u t l e r o w y l
g r ou p extending its b l o c k i n g influence to an ad ja c e n t
r e a c t i v e center* a l p h a - b r o m o - e t h y l b e t a - B u t l e r y l ketone
w a s syn th es iz e d a c c o r d i n g to the directions o f Bavorsky^®.
c
c - c - c - c — c_
-nj
C H a
' , 1 ‘i
i
c.
20
That steric hindrance influenced the reactivity of the
hromine atom was shown by the failure of the bromoketone to hydrolyze to the corresponding alpha-hydroxy
ketone and also by the failure of fused potassium acetate
to react with the bromo-ketone in boiling glacial acetic
acid*
Long boiling of the bromo-ketone in aleoholic
silver nitrate gave only a faint precipitate of silver
bromide*
Reactions of isopropyl beta-Butleryl ketone (2,4,6,6tetramethyl-4-t-butyl-5-heT3tanone)»
This ketone was prepared in 60$ yield by the action
of 3 moles of isopropylmagnesium bromide on 1 mole of
beta-Butlerow*s acid chloride*
Beta-Butlerow’s aldehyde, which is obtained2^ by treating beta-Butlerow’3 acid chloride with t-butyl Grignard
reagent, was not isolated probably due to the comparatively
weak reducing action of isopropylmagnesium bromide.
Iso­
propyl beta-Butleryl ketone as might be predicted, under­
goes none of the normal ketone reactions.
Dr. L. P*
Block20 found it to be 25$ enolized with 0.0$ addition.
The enolate of this ketone did not add to benzaldehyde to
give the expected 1,3-ketol; it did however, react wit|j
carbon dioxide and benzoyl chloride yielding respectively
a beta-keto-acid and an enol ester*
21
c-
o
6 a
o
Saponifi oa-bio n of the eiiol ester in (2) above took place
•readily.
Since it is known that some alkylated di2
ketones
also split umder similar conditions saponification
oannot b e u.se<3 as evidence i n favor of an enol ester
structure.
I f the compound in
its melting point would
(2 ) above had the structure
be expected,
for reasons of sym­
metry a n d increased m ol ecular w e i g h t , to be at least as
high as the melting point of beta-Butlerowyl-benzoylmethyl— methane (l-phemyl-2 ,4, 6, 6-tetramethyl-4-t-butyl1,3-heptandion.e) • 1
?u ■C-CCNy
a H
-C —
n
o
CP
(melts at 115°C. )
The enol ester In (2) above fciowever, melted at 52°C* thus
eliminating a di— ketone
structure.*
M e n t i o n of K o h l e r ’s w o r k o n peroxides of ketones
has already
thesis.
been made
in the historical section o f this
.A perusal of the l i s t ^ ® o f ketones which give
the peroxide test shows
ratber complex B groups to be
o n both sides of the carbonyl group.
It is therefore
somewhat surprising that isopropyl beta— Butleryl ketone
should
give
this
test-
In this
reaction a rapid stream
22
of oxygen was ‘bubbled through an ether-ligroln solution
of the freshly decomposed enolate for several hours*
The resulting oily impure peroxide when treated with
KI dissolved in glacial acetic acid liberated a copious
amount of iodine.
Cc.
-
^ = c ( c H 5\
c.
4
-0 ^
O C < o H
O H
CAccording to Kohler2 ^ the action of HI on the peroxide
of a ketone results in the formation o f an alpha-hydroxy
ketone.
,,
lOy-..
OH
' >
- —
^
-
9 - 9
° "
With the peroxide of isopropyl beta-Butleryl ketone this
reaction must have prooeeded differently since beta-Butle row’s acid was isolated and a positive iodoform test
obtained.
One equation which explains these facts is as
follows:
C
—
K - C - o h + c H j- c ~c
OH
After the completion of this work, the related
problem of finding the smallest tertiary alkyl group
which promoted the steric hindrance effect was to have
been investigated in compounds of the type
R.
. O-CH
u
O
.
23
Because of work on National Defense, the problem was
interrupted at an early stage*
laboratory,
Mr. 0. Lewis2 6 , of this
has found that ketones derived from tri-
ethylaoetyl ohloride, suoh as 3,3-diethyl-2-pentanone
-C - C H ^
, were sterically hindered*
Henoe
o
it was of interest to synthesize 3-methyl-3-ethyl-2pentanone C C t ) - C - C~ CfiL The Grignard reagent of
GC °
methyldiethyloarbinylchloride was prepared by the follow­
ing series of reactions:
CL-d-c_-e
+-
£ t r \ a 6 n .
C
—
MCI
n
1
.>
*
cHi
~
Q
\-\
^
(Et) - c — ci —
^
C.
M
> (Et), c
*
ch
3
^
Using this Grignard reagent as an intermediate, Mr. Lewis
prepared 3-methyl-3-ethyl-2-pentanone.
In preliihinary
experiments he has found that this ketone does not add the
Grignard reagent and hence is probably the smallest
sterically hindered ketone, since Nasarov’s2 ^ work has
shown that ketones of the type
add the Grignard reagent.
R-CCCH^C-CH.
o
do
EXPERIMENTAL
Description of Fractionating Columns,
During this work two fractionating columns of the adia­
batic variable take off type were used.
Column I
Inside diameter— -------- —
------------—
Length-
-—
1.2 cm
75
Theoretical plates--------------------------15
cm
cm
Packed with 3/16 inch glass helices.
Column II
Inside diameter—
Length-
---
- - - -
—
-—
Theoretical plates
Packed with 3/16 inch glass helices.
—
0.8 cm
-45
cm
--11
cm
25
Preparation of beta-B u t l e r o w Ts Acid.
Duri n g the progress
of this work three different hatches of crude beta-Butlerow's aoid were purified.
The following is a typical run*
The crude beta acid was that prepared by Johnson and
28
Moersch in a n oxidation of triisobutylene.
The triiso­
butylene used was fractionated b y Ton g b e r g and included
14.2 liters from can #2 distillation 1, fractions 143 to
185 (n20/D 1.4303-1.4305), and 15 liters frotfi can #3
distillation 2, fractions 46-125 (n20/D 1.4305-1.4312),
and 6 liters from can #13 distillation 3, fractions 108145 (n20/D 1.4307-1.4314).
The experimental procedure
followed closely that developed by C. S. Min e r 1 9 and will
be given in full.
The starting material consisted of
mixed crude alpha and b e t a - B u t l e r o w ’s acids.
All of the
acid (8200 grams) was divided into 8 equal portions,
and
each dissolved in 2 liters of 1 0 $ sodium hydroxide solu­
tion and heated to 70°G.
in a 3 liter beaker.
The solu­
tion was cooled overnight and the sodium salt filtered
and sucked dry the following day.
The filtrate was then
chilled at ice temperature for 1 2 hours;
the sodium salt
which separated out was filtered by suction and combined
with the first crop.
The mother liquor after acidifying
with concentrated H C L was filtered,
washed and suoked dry.
the precipitate
This procedure gave 4000 grams of
partially dried crude acid whose melting point was
55-60°C.
(m.p. of pure alpha 8 8 - 8 9 ° C . )
The sod i u m salts
26
were divided into 800 gram. portions and each portion "was
dissolved in 3 liters of water heated -to 70°0.
After
cooling overnight the so dium salts crystallized out; they
were filtered and sucked as dry as possible.
The fil­
trate was plaoed in an ice hath overnight and the second
crop filtered and dryed.
A small sample from, each crop
was dissolved and acidified and the melting points of the
beta aoid taken.
The beta acid from the first crop
melted at 115-120°G* ; that from, the second at 113-118°0.
(m.p. of pure beta acid 12S-129°C. )
The two crops were
combined, dissolved in hot water and the beta acid thrown
out by acidifying the solution.
The weight of the beta
acid after drying by suction was 3300 grams.
was further dried
liquors were
by spreading on paper.
The acid
The mother
concentrated to half their original volume
and the sodium salts were recrystallized following the
previously mentioned procedure.
of beta acid
The resulting 480 grams
(m.p. 114-118°C. ) were combined with the
previously obtained 3000 grams.
Preparation o f beta— Butlerow* s acid chloride.
In a 5
liter flask were placed 1500 grams of thionyl chloride
and 1500 grams of beta acid.
(m.p. 115-120°C.)
The
reaction proceeded smoothly in the cold and was allowed
to stand overnight.
To free the reaction mixture of
thionyl chloride a n d K C L the
crude acid chloride was re­
fluxed for 7 hours on a steam b ath and fractionated
27
through Column I.
Cut
1 .
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
4%.
45.
46.
47.
48.
49.
Weight
297
111
7.1
6.2
13.4
16.7
32.2
9.2
13.7
14.5
13.4
15.1
9.2
11.5
8.2
15.4
16.2
20.3
16.3
17.4
19.6
15.8
19.3
16.8
19.8
11.2
16.6
15.1
15.2
15.7
15.4
16.0
15.2
15.0
15.7
15.9
15.3
15.8
15.6
41.9
21
15.4
127.5
124
124
120
114
82
13
P.T.
C.T.
160
84
160
84
180
110
184
139-143
185
143
191
148
191
148
191
148
(air hath)
148
rr
143
it
142
tt
142
tt
153
tt
154
it
155
tt
143
tt
143
tt
142
tt
141
tt
141
tt
145
tt
147
it
142
tt
144
tt
147
tt
147
tt
150
tt
151
tt
150
tt
150
tt
151
tt
151
tt
140
tt
142
tt
141
tt
140
tt
139
tt
140
tt
140
tt
140
tt
140
tt
139
tt
138
tt
140
tt
140
tt
138
tt
138
tt
132
tt
132
H.T.
75
75
65-105
105-115
115-118
118-120
118-131
129
129
129
128
130
129
127
122
121
122
123
123
123
124
123
123
123
126
127
133
133
136
135
135
135
111
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
111
n20/D
1.4682
1.4520
1.4472
1.4453
1.4454
1.4443
1.4431
1.4432
1.4437
1.4562
1.4600
1.4600
1.4660
1.4618
1.4624
1.4628
1.4628
1.4629
1.4625
ft.4628
1.4628
1.4628
1.4631
1.4631
1.4631
1.4633
1.4634
1.4635
1.4635
1.4635
1.4636
1.4638
1.4641
1.4641
1.4639
1.4639
1.4639
1.4639
1.4639
1.4639
1.4640
1.4641
1.4642
1.4643
1.4649
1.4649
Pressure
738mm.
738
60
55
55
55
55
55
54
52
53
53
35
28
27
27
27
27
27
27
27
27
27
27
34
34
38
38
39
39
40
41
18
17
17
17
17
17
17
17
17
17
17
16
15
15
15
14
14
28
The fractions were combined as follows:
6-9 weight
72 grams, 10-11 consisting of pore alpha acid chloride
weight 28 grams,
12-22
weight 165 grams, 23-33 weight
178 grams, 34-47 pure beta acid chloride weight 640 grams,
48-49 weight 95 grams.
72$.
The total yield was 1178 grams or
Three grams of beta acid chloride were dissolved in
20 cc. of ether and dry ammonia passed in for 5 hours.
A small amount of ammonium chloride precipitated but no
amide could be isolated.
Preparation of methylmagnesium chloride.
Into a three
liter round bottom flask fitted with a trident was placed
97 grams of magnesium and 1320 cc. of ether.
held a condenser,
stirrer.
The trident
separatory funnel, and mercury seal
An inlet tube fitted with a wire for unplug­
ging was inserted in the stopper of the flask.
The
methyl chloride was passed through a mercury and a Gilman
trap into the flask.
The reaction was considered complete
when methyl chloride escaped through an outlet Gilman trap.
The addition took place over a period of 16 hours.
Reaction between b e t a - B u t l e r o w ^ acid chloride and methyl
Grignard.
Two moles of beta acid chloride and 250 cc. of
ether were added to the methyl Grignard accompanied by
vigorous stirring.
The addition was complete in 2£ hours.
The Grignard complex was decomposed by pouring it over a
liter of cracked ice placed in a 5 liter flask.
The
29
water layer was extracted with ether and the water
layer then steam distilled.
Both the distillate and the
residue were extracted with ether and the ether extracts
oombined.
After stripping off the ether the residue was
purified by fractionation through column I.
Cut
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
Weight
C.T.
3.5
3.2
3.7
7.5
7.4
7.1
Ill
115
116
119
118
118
10.6
122
122
122
120
120
122
10.4
15.1
15.0
13.6
14.4
13.0
15.0
14.7
15.0
14.7
14.4
15.2
14.0
12.5
123
120
120
119
119
123
126
121
123
H.T.
n2 0 /D
Pressure
80-99
99-101
1.4370
1.4521
1.4525
1.4528
1.4530
1.4531
1.4532
1.4532
1.4533
1.4533
1.4533
1.4533
1.4533
1.4533
1.4533
1.4533
1.4533
1.4535
1.4535
1.4537
1.4542
15mm.
15
14
14
101
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
Cuts 5-19 were! combined giving 195 grams of pure product
Yield 60$ of theoretical.
The compound proved, as will be shown later,
methyl beta-Butleryl ketone.
to be
The ketone was prepared on
two other occasions and because of differences in experi­
mental conditions these preparations will be listed.
(a). Four moles of magnesium and 1600 cc. of ethyl ether
were placed in a 5 liter flask equipped with trident.
Methyl chloride was passed in until no magnesium remained*
30
The Grignard was filtered through glass wool.
To the
filtered Grignard reagent 310 grams of beta chloride
was added accompanied by vigorous stirring.
The addi­
tion complex was poured over cracked ice and steam dis­
tilled.
The distillate was extracted with ether and
refluxed with alcoholic silver nitrate.
The silver chlo­
ride was filtered off and the filtrate fractionated
through column A.
Cut
1.
2.
3.
4.
5.
6.
7.
a.
9.
10.
11.
12.
13.
14.
15.
16.
17.
Weight
foreshot
2 grams
1
2
3
4. 4
5
4
2
1
2
9
10
20
20
20
12
C.T.
120
120
122
122
122
122
122
122
130
130
130
130
130
130
130
130
H.T.
100-106
108
109
109
109
109
1«9
109
118
118
118
118
118
118
118
118
n20/D
Press
1.4475
1.4508
1.4510
1.4510
1.4515
1.4521
1.4521
1.4521
1.4520
1.4522
1.4522
1.4523
1.4523
1.4523
1.4523
1.4523
14mm.
14
14
14
14
14
14
14
20
20
20
20
20
20
20
20
Fractions 11-17 were combined weight 92 grams, n20/D
1.4521-1.4523.
(b). Into a 3 necked 3 liter flask equipped with stirrer,
condenser and dropping funnel were placed 1 0 0 grams of
magnesium and 1200 cc. of ether.
Methyl bromide was
passed into the solution at such a rate as to keep the
reaction refluxing vigorously.
Within 5 hours praotically
all the magnesium had disappeared.
To the methylmagnesium
31
r
bromide 271 grams (n20/D 1.4644-1.4649) of beta aoid
chloride were added, diluted with 200cc. of ether.
addition was complete in 4 hours.
The
t
The reaction mixture
*
was poured over cracked ice and the magnesium hydroxide
neutralized with HC1.
The ether layer was drawn off and
combined with the ether extract of the water layer.
The
combined layers were washed with water, sodium bicarbon­
ate and finally with water.
After drying over magnesium
sulfate the ether was distilled off and the ketone
fractionated through column A at 3mm.
Gut
Wei ght
5.5
9.5
.
.
3.
4.
5.
12
11
11
6
36
1
2
.
7.
8.
9.
11
12
10.
11.
12.
12
10
10
12
12
12
11
13.
14.
15.
16.
17.
13
16
O.T.
H.T.
n 2 0 /D
96
95
96
96
95
94
95
94
93
95
99
62
60
58
56
53
54
52
56
54
52
53
54
55
54
55
55
56
1.4518
1.4529
1.4531
1.4534
1.4533
1.4533
1.4534
1.4534
1.4534
1.4534
1.4534
1.4534
1.4534
1.4534
1.4534
1.4534
1.4534
100
100
100
98
98
106
Fractions 2-17 were combined and weighed 219 grams.
Fractions 1-17 weighed 225 grams, representing a yield
of 91%.
The increase in yield over a former run may be part­
ly attributed to a 4 to 1 excess of Grignard oveH acid
chloride, and partly to the increased time of stirring as
32
well as to the more active methylmagnesium bromide*
Reactions relating to the structure of methyl betaButleryl ketone.
The ketone did not decolorize boiling
alkaline permanganate solution.
2 ,4 -dinitropbenyl
drazine did not react with the compound.
hy­
It could not
be esterified with acetic anhydride or acetyl chloride.
The enolization of methyl beta-Butleryl ketone was
measured by Dr. L. P. Block.
He found it to be 94%
enolized with 0 .0 $ addition taking place.
Molecular Refraction.
The density of the compound
was determined by weighing it in a pycnometer of known
vo lume •
Volume of pycnometer*------- 3.7521oc.
Weight of ketone
----- --3.2576 grams
Density of ketone----*866
The values for the various groups were taken from L a n g e ’s
handbook.
These values were checked against those calcul­
ated by the Lorenz-Lorentz equation*
Observed M.R.
2 -beta-Butlerylpropylene
60.8
methyl beta-Butleryl ketone
61.2
beta-Butleryldimethyloarbinol
67.0
Calculated M.R.
66.1
62.1
68.0
It may be seen that the closest check is gotten from the
ke to ne •
Attempted ozonolvsis of methyl beta-Butleryl ketone.
In an ozonolysis tube were placed 49 grams of the ketone
and 150oo. of glacial acetic acid.
Very little ozone was
33
'taken up and after 19 hours the ozonolysis was discon­
tinued*
The ozonide was decomposed in the regular ap­
paratus used in this laboratory.
It consists of a
X liter 3 necked flask fitted with a mercury seal stirrer,
dropping funnel, reflux condenser and a down dropping
condenser.
dust,
In the flask were placed *35 mole of zinc
2 0 0 ec.
of water and a crystal of silver nitrate.
The acetic acid solution was added slowly, accompanied
by rapid stirring.
The decomposition products were
steam distilled until no oily layer was left in the flask.
The oil layer was separated and again added to the zinc
and distilled.
The treatment of the water layer with
dimetol showed formaldehyde to be present in very small
quantities.
A mixed melting point with the known deriva­
tive showed no depression.
The oil layer was first dis­
tilled through a Glaisen flask, then fractionated through
column II,
Weight
Cut
C.T.
H.T.
n20/D
Pressure
17mm,
1.4490
93-108
120
.2
.
17
1.4515
103-106
120
.
.4
17
1.4525
106-107
123
3.
1.5
17
1.4530
107
122
4.
1.4
17
1.4529
107
122
5.
3.2
17
1,4529
107
122
6 .
3.6
17
1.4529
108
128
7.
3.4
18
1. 4529
108
128
4.8
a.
18
1.4529
108
128
9.
2 .&
18
1.4529
108
128
10.
2.0
po -6
j.ys
>
0
2b’0
The recovery of the ketone was practically quantitative.
1
2
Attempted bromoform reactions on methyl beta-Butleryl
ketone.
In a 2 necked 2Q0cc. flask equipped with stirrer
34
and dropping funnel were placed 56cc. of water and 9.6
grams of bromine.
The mixture was cooled to 0°C. and
4 grams of ketone added slowly.
The solution was stirred
at ice temperature for one hour and for 4 more at room
temperature.
was formed.
No reaction was observed and no bromoform
The acidification of the water gave no acid.
Another bromoform reaction was attempted with SOcc. of
dioxane added and the stirring continued for 4 days.
The
results were again negative.
To 5cc. o f the ketone, bromine was added in small
portions until no more HBr was given off.
ture did not exceed 60°C. at any time.
The tempera­
The solution was
refluxed with 15$ sodium hydroxide for one hour and then
steam distilled until most of the oily layer had passed
over.
On cooling,
the remaining oil solidified and was
crystallized from ethyl alcohol (m.p. 120°C.)•
Acidifi­
cation of the water layer gave an acid which could not be
crystallized.
Attempted preparation of the oxime of methyl betaButleryl ketone.
In a bomb tube were placed .50 gram
of hydroxylamine hydrachloride, 3cc. of water, 2 cc. of
10$ sodium hydroxide and .20 gram of ketone.
The tube
was sealed off and heated in a steam bath for 3 days.
On oooling the original oil separated out.
A similar
reaction heated in an oven for 36 hours at 160°0. failed
to give the oxime.
35
Oxidation of methyl beta-Butleryl ketone.
tion of 6.7 grams of chromic anhydride in 12co.
A soluof water
was added to 50cc. o f glacial acetic acid and the solu­
tion placed in a small dropping funnel.
Into a 200cc.
3 necked flask fitted with the dropping funnel was placed
10 grams of the ketone and 500cc. of glacial acetic acid.
The oxidizing mixture was added slowly over a period of
3 hours at 20-60°C.
No decoloration occurred and on
dilution of the mixture with water no acid could be de­
tected.
Fine grams of the starting material was recovered.
In a similar oxidation carried out at 90°C., 16*3 grams
of the anhydride was used to 10 grams of the ketone.
After
stirring for 4 hours on a steam bath the mixture was di­
luted with 4O0cc. of water.
Crude beta-Butlerow*s acid
separated out in a
30# yield.
The crude acid was pressed
on a clay plate to
free it of oily matter and crystallized
twice from methyl
alcohol.
(m.p. 127-128 mixed, m.p. 128-
129, m.p. of pure
beta acid 128-129.)
Determination of molecular weight of methyl betaButleryl ketone.
The molecular weight was determined by
the freezing point lowering of benzene.
Trial
M
I
189
II
193
HI
196
The tertiary carbinol expected from the reaction of the
beta acid chloride
with a methyl Grignard reagent is elim­
inated by this determination.
The average checks within
36
3# of the molecular weight of the ketone.
Attempted reductions of methvl beta-Butleryl ketone.
With aluminum iscpronylate.
Into a lOOcc. flask
were placed 7.5 grams of the propylate,
15 grams of the
ketone, and 35cc. of isopropyl alcohol.
This mixture
was refluxed for 4 hours under a column.
No acetone
appeared thus indicating the reaction to have failed.
All of the starting material was recovered.
Hydrogenation with Raney nickel.
It was necessary
to heat the ketone to 357°C. under 3000 pounds of hydro­
gen before hydrogenation took place.
These rigorous
conditions caused splitting of the carbon skeleton.
of the expected secondary alcohol was isolated.
None
The
hydrogenation mixture was fractionated through column II.
Cut
Wei ght
C.T.
.
.
3.
4.
5.
6.
7.
8 .
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
2
2
23
70
72
73
75
82
82
82
82
84
84
84
84
84
84
115
123
125
125
125
1
2
3
4
2
3
4
4
3
3
3
4
4
3
3
2
2
2
3
2
H.T.
Pressure
23
56
65
33-35
35-39
45-49
55
740mm.
740
740
31
36
68
63
6§
63
64
64
60
68
67
67-76
78-80
90
94
22
22
32
25
26
26
30
30
24
24
24
26
25
25
25
n 2 0 /D
gas
1.3996
1.4000
1.4010
1.4030
1.4102
1.4243
1.4294
1.4315
1.4322
1.4322
1.4322
1.4322
1.4322
1.4323
1.4322
1.4486
1.4495
1.4508
1.4514
Cut
21.
22.
23.
Weight
2
3
1
C.T.
124
124
124
H.T.
Pressure
95
95
96
24mm.
24
24
n20/D
1.4515
1.4517
1.4517
Cuts 21-23 were apparently unhydrogenated ketone.
Fractions 10-16 consisted of a hydrocarbon and a carbinol
which made a liquid urethan.
The carbinol part of this
fraction dissolved in concentrated sulfuric while the
hydrocarbon portion did not.
The molecular weight as
determined by the freezing point lowering method of cuts
10-16 was 160.
With sodium and moist benzene.
Into a 1 liter flask
were placed 250cc. of water containing 85 grams of sodium
7 a 9 of
carbonate and 250co. of benzene.
Over a period of three
days 60 grams of finely chopped sodium was added at inter­
vals.
The mixture was stirred very slowly during the
time of addition.
The benzene layer was drawn off, dried
over potassium carbonate, and the benzene stripped off.
Fractionation of the remaining oil gave a quantitative
recovery of methyl beta-Butleryl ketone.
With sodl'ffTn and ethyl alcohol.
To a solution of 20
grams of ketone in 200cc. of 95$ ethyl alcohol in a 500cc.
flask fitted with a condenser was added 30 grams of sodium
in small pieces.
During the time of addition (6 hours)
the solution was kept refluxing.
The alcoholate was
decomposed with water and neutralized with glacial acetic.
This solution was extracted with ether and the ether layer
38
distilled.
None of the carbinol was found.
O n l y the
starting ketone was isolated.
With hydrogen and Adams catalyst.
To 50co. of
dioxane contained in a hydrogenation flask was added
grams (.05 mole) of methyl beta-Butleryl ketone and
10
1
gram of Adams catalyst.
This mixture was shaken at
45 pounds pressure of hydrogen at a temperature of 60°C.
for 5 hours and fractionated through column II at 18mm*
Cut
1.
2*
3.
4*
5.
6*
We ight
1.5
2
3
1.5
2
1
C.T.
H.T.
115
85-95
119
95
119
93
93
119
119
93
residue
Pot
n 2 0 /D
1.4532
ft
1.4533
This fractionation shows the o n l y product obtained to
be unhydrogenated ketone*
With hydrogen and a calcium copper chromite catalyst*
The hydrogenation was carried out by Mr* N. Cook employ­
ing 65 grams of methyl beta-Butleryl ketone in a dioxane
solvent at 3400 pounds hydrogen pressure.
tion bomb was shaken at 230°C.
The hydrogena­
for 40 hours*
The reduc­
tion mixture was fractionated through column II at 3mm*
Cut
Weight
1.
2.
2.5
3.
4.
5.
6.
7.
2.0
.30
2.0
3.5
3.5
4.5
C.T.
75
75
90
89
87
87
87
H.T.
45
45
45-55
67
65
65
66
n 2 0 /D
1.4250
1.4208
1.4212
1.4529
1.4521
1.4526
1.4530
39
Cut
.
9.
8
10.
11.
12.
13.
14.
Weight
5.0
5.0
3.0
5.0
4.0
4.0
3.0
C.T.
H.T
n20/D
91
91
90
91
91
90
90
66
66
66
66
66
66
66
1.4532
1.4532
1.4532
1.4532
1.4532
1.4532
1.4538
The first 4 cuts reacted with bromine and
in HgSO^ in the cold.
this mixture.
No attempt was made to identify
Cuts 5-14 represent unreduced ketone.
Preparation of l.-beta-Butlery 1-2-ethanol.
a.
Preparation of methylmagnesium chloride.
In a 1
liter 3 necked flask were placed 9 grams of magnesium
and 250cc. of ethyl ether.
Methyl chloride was passed
through until the magnesium had disappeared.
b.
Addition of beta-Butie r o w ’s aldehyde to methyl magnes­
ium chloride.
The aldehyde
by Dr. J. S. Whitaker2 9 .
(n20/D 1.4485) was prepared
To the Grignard 46 grams of
aldehyde and lOOcc. of ether were added slowly*
The
addition was complete in an hour and the reaction mixture
stirred for another hour.
The Grignard was decomposed
by pouring it over cracked ice.
Steam distillation separ­
ated the oil layer from the water layer.
was extracted with ether,
The distillate
dried over potassium carbonate,
and fractionated through column II.
Cut
Weight
1
2.
3.6
C.T.
H.T.
79
46-68
69
87
Pressure
4mm.
4
n20/D
1.4384
1.4469
40
Cut
3.
4.
5.
6
7.
8
9.
.
.
10.
Weight
C.T.
H.T.
Pressure
n 2 0 /D
7.3
88
88
88
88
11.2
2.0
1.0
1.0
92
93
95
89
69
69
69
69
74
74
80
80
4mm.
4
4
4
4
4
4
4
1.4480
1.4469
1.4480
1.4475
1.4475
1.4476
1.4618
1.4620
4.5
4.5
6.8
Cuts 9-10 proved to be a carbinol which yielded a phenyl
urethan (m.p, 103-105),
This carbinol was undoubtedly
1-beta-Butleryl-2-ethanol.
however,
Not enough was obtained
for oxidation to the corresponding ketone.
Addition of methyl beta-Butleryl ketone to methyl Grignard,
To 0,3 mole of methyl G-rignard prepared as shown on the
previous page was added 15 grams of ketone.
A slow evolu-
tion of gas and increase in temperature were noted.
A
pyragallol trap was attached to the apparatus to keep
oxygen from the flask.
The ethyl ether was distilled
off after the addition of 150cc. of dibutyl ether.
The
temperature was increased slowly to 150°C. and kept there
for 4 hours.
The Grignard complex was decomposed by pour­
ing over cracked ice.
Following ether extraction the ether
layer was dried over sodium carbonate and distilled
through column XI.
Cut
1.
2.
3.
4.
Weight
.2 grams
2
6
5
P.T.
C.T.
130
130
130
140
109
106
103
105
H.T.
n 2 0 /D
81-88
84
82
1.4515
1.4520
1.4525
1.4525
86
Pressure
9mm.
8
7
8
✓
41
From the reaction 13 grams of unreacted ketone were ob­
tained.
No trace of tertiary carbinol was found.
Treatment of methyl beta-Butleryl ketone with dehydrating
reagents.
To eliminate completely the possibility of
the ketone having a carbinol struoture the following de­
hydration was attempted.
To 17 grams of the ketone (n2 0 /D
1.4531) was added 4 grains of anydrous copper sulfate.
mixture was heated with air bath under column II.
temperature was kept at 150°C. for 1 hour.
tion took place.
The
The
No dehydra­
Two grams of chloronapthelenesulfonio
acid were added and the temperature increased slowly to
210°C.
No water appeared but lower boiling compounds
distilled over indicating that the ketone had been
cracked.
This failure of the compound to dehydrate showed
definitely that it was not a carbinol.
The dehydration
mixture was fractionated through column II at 19mm.
Cut
.
.
3.
4«
5.
1
2
Weight
2
1
2
3
10
C.T.
P.T.
H.T.
75
123
150
155
155
155
63
63-105
105-109
122
122
128
128
110
110
n 2 0 /D
1.4192
1.4290
1.4475
1.4512
1.4517
Fraction 1 and 2 took up rapidly a solution of bromine in
CC1 4 and failed to give ketone derivatives; fractions 4 and
5 represented impure starting material.
Attempted oxidation of methyl beta-Butleryl ketone with
potassium persulfate.
In a 1 liter 3 necked flask equipped
42
with condenser and stirrer were placed 5 grains of ketone
(n20/D 1.4531), 750cc. of 90$ acetic acid,
15 grains of
potassium persulfate and 7.5cc. of concentrated sulfuric
aoid.
The reaction mixture was stirred at room tempera­
ture for 72 hours.
The oxidation mixture was neutralized
carefully with NaOH and extracted with ether.
The ether
was distilled off and 50oc. of methyl alcohol added.
The methyl alcohol solution was refluxed for 1 hour to
decompose any peroxides that might have been formed.
After the addition of 50cc. of 10$ NaOH the mixture was
refluxed for 4 hours.
tracted with ether.
On cooling the solution was ex­
The water layer was acidified but no
acid or oil precipitated.
The ether layer on evaporation
yielded unchanged ketone.
It was hoped that this oxida­
tion would yield methyl beta-Butlerowate.
Prenaration of acetyl-beta-Eutlerowyl-methane.
cc. three necked flask, equipped with stirrer,
Into a 200
condenser
and dropping funnel, was placed .10 mole (2.7 grams) of
magnesium.
To the magnesium .10 mole (12.2 grams) of
ethyl bromide dissolved in 90cc. of ether was added
slowly.
The addition was complete in 1/2 hour.
To the
ethylmagnesium bromide was added . 1 0 mole ( 2 0 grams)
of methyl Butleryl ketone (n20/D 1.4531) dissolved in an
equal volume of anhydrous ethyl ether.
tion, which was completed in 1 0 minutes,
During the addi­
copious quantities
43
of ethane were generated.
On stirring, the reaction
mixture assumed an olive green color.
Thirty minutes
after the addition of the ketone had taken place the
bromomagnesium enolate began to precipitate.
was continued for 45 minutes.
Stirring
Five hundreths mole of
acetyl chloride (3.9 grains of acetyl chloride in 25cc.
of ether) was added over a period of 15 minutes to the
enolate mixture.
An ice salt bath was used to cool the
contents of the flask during the addition and the sub­
sequent stirring, which was stopped at the end of 1 1 / 2
hours.
The reaction mixture was decomposed by pouring over
ioed HC1.
The decomposition products were steam distilled
until nearly all the oil had come over.
solid remained in the flask.
A white oily
The contents of the flask
were extracted with ether; the white solid remained sus­
pended in the ether layer.
A small portion of this solid
burned with a smoky flame and left a MgO residue.
The
white compound was probably the magnesium chelate of the
diketone.
The ether was allowed to evaporate leaving the
undecomposed magnesium salt and some diketone which did
not steam distill.
To prepare the copper derivative of the diketone,
3 grams of Cu(Ac )2 were dissolved in 15cc. of concen­
trated NH4 OH.
This was added to the magnesium chelate
compound which contained some diketone.
shaken and allowed to stand for one hour.
The mixture was
An olive green
44
compound precipitated out.
The solution was filtered
and the precipitate remaining washed until no blue
color was obtained in the filtrate.
The dry salt
weighed 3.5 grams amounting to 25% yield calculated on
the basis of acetyl chloride.
The copper complex o n
crystallizing twice from 95% ethyl alcohol melted at
166-168°C.
The small amount o f white mag n e s i u m complex
was insoluble in alcohol and was decomposed slowly by
6
N.HC1.
Its melting point was over 300°C,
The copper
complex was decomposed b y shaking with ether acidified
with dilute HOI.
A light yellow oil remained after
removal of the ether.
This oil gave an intense reddish
purple color on treatment with alcoholic FeClg.
The
ether extract was fractionated through column II at 3mm,
Cut
Weight
1.
2.
4
4
3.
4.
3
.4
C.T.
90
90
91
140
H.T.
71
75
76
115
n 2 0 /D
1.4531
1.4531
1.4542
1.4789
Fractions 1 and 2 were unreacted methyl beta-Butleryl
ketone while fraction 4 was
the diketone.
A pot residue
of 2.5 grams remained and had a n index of 1.4872.
Frac­
tions 1 and 2 gave no FeCl 3 coloring while 3 gave a slight
test and fraction 4 and the pot residue gave the same in­
tense reddish purple as did the diketone obtained from
the copper complex.
The 2 , 4 -dinitrophenylhydrozones of
fraction 4 , the pot residue,
and the product obtained from
the decomposition of the copper complex were made readi­
ly.
After one crystallization from ethyl alcohol they
all melted at 181-182°C. and their mixed melting points
suffered no depression.
This was proof that all three
products were largely beta-Butlerowyl-acetyl-methane.
The overall yield of diketone amounted to some 71% of the
theoretical while the unreacted ketone was 80% recovered.
Preparation of beta-Butlerowylaeetic acid.
3 necked flask fitted with condenser,
Into a 200cc*
separatory funnel
and stirrer was placed 2.7 grains of -a4Lumi num. turnings.
The system was shut off from the air by a Gilman trap.
To the magnesium was added 11 grams of ethyl bromide dis­
solved in lOOcc. of ether.
The addition was finished in
15 minutes and stirring continued for 1 1 / 2 hours.
To
the ethylmagnesium bromide prepared above was added 2 0
grams (.10 mole) of methyl beta-Butleryl ketone dissolved
in 75cc. of ether.
4 hours.
The reaction mixture was stirred for
Some of the enolate precipitated out when addi­
tion was nearly complete.
Carbon dioxide was bubbled
first through a Gilman trap and them through the reaction
mixture over a period of three days.
The Grignard com­
plex was decomposed by pouring over iced HC1.
The ether
layer was drawn off and extracted twice with a cold solu­
tion of 10% NagCOg.
The IfegCOg extract was acidified
cautiously with cold HC1 and the solid which precipitated
out was filtered off*
Total weight of crude acid. amounted
to 16 grams or 6 6 % of the theoretical, m.p. 104-109°C.
with decomposition*
It was recrystallized "by dissolving
in ether and adding petroleum ether and drawing off tlie
solvent under reduced pressure, m.p. of acid 116-117°C.
with decomposition.
amounted to 6 grams.
The recovery of unreaoted ketone
One gram of the keto acid refluxed,
on the steam bath for 2 hours gave back the starting
ketone,
(n20/D of ketone 1.4531),
(n20/D of ketone recov­
ered from acid 1.4535).
Attempted synthesis of aoetyl-beta-Butlerowyl-methane.
Into a 200cc. 3 necked flask equipped with stirrer and.
condenser were placed lOOco. o f benzene and 20 grams of
ethyl acetoacetate.
To this solution 3.4 grams o f finely
divided sodium was added over a period of 36 hours at­
tended by vigorous stirring.
a thick gelatinous mass.
acid chloride
The enolate settled out as
To the enolate 35 grains of beta
(n20/D 1.4631-1.4636) was added in 2 hours
and stirring continued for 72 hours.
The reaction m i x ­
ture was added to 400cc. of 5% sulfuric acid and the ben­
zene and ethyl acetoacetate distilled off.
The beta aoid
chloride was recovered as beta acid to which it had been
hydrolyzed during the steam distillation.
The contents
of the flask were extracted twice with ether and the
ether layer with 2.0% sodium hydroxide.
O n evaporation o f
47
the ether a small amount
of oil remained.
This residue
failed bo give a copper salt when treated with ammonaical
copper acetate.
Therefore the ketone was assumed not to
have teen present.
Preparation of 1-beta-But lerowvl-3--phenyl-2-ethanol.
a 3 necked SOOoc*
flask equipped with stirrer,
Into
condenser,
and. dropping funnel was placed 2 . 1 grams of magnesium
turnings.
of
To the magnesium was added in 1 hour 10 grams
ethyl, bromide in 90oo. of ethyl ether.
To the ethyl-
magnesium "bromide was added 18 grains of methyl betaButleryl ketone.
After s tirring for one hour the mixture
was treated with 9.1 grains of freshly distilled benzaldehyde.
Stirring was continued overnight.
reaction a white solid precipitated out.
decomposed b y pouring o v e r iced HC1.
During the
The enolate was
The ether layer was
evaporated and steam distilled until it was freed from
unreacted benzaldehyde.
The ether extract of the resi­
due remaining from the
steam distillation was dried over
sodium sulfate and evaporated.
of petroleum ether was added.
earbinol was thrown out,
To the residual oil 5cc.
On cooling, 4 grams of
(m.p. 90°C.).
a Liquid acetate and benzoate.
The carbinol gave
Neither the carbinol nor
the oil from which it was crystallized reacted with brom­
ine in carbon tetrachloride.
benzal was
L
present.
This indicated that no
48
Preparation of beta-Butlerowyl-benzoyl—methane#
In the
usual manner *075 mole of the bromomagnesium enolate of
methyl beta-Butleryl ketone was prepared.
To the lOOoc.
of the ethereal solution of the enolate was added 5 . 4
grams of benzoyl chloride in 2 0 co. o f ether over a period
of 15 minutes.
The addition product was decomposed by
pouring over iced HOI.
The ether was shaken first with
10$ sodium carbonate and then with water.
After drying
over magnesium sulfate the ether was evaporated and the
residue distilled in a Claisen flask at 8 mm.
Cut
Weight
1*
2.
3.
3
6.4
6.8
H.T.
89
89-305
205-210
n20/D
1.4600
1.4773
solid
Fraction 3 contained the diketone.
Yield 59.5$.
Two
crystallizations from ligroin gave a melting point of
87-88.5°C.
187°C.
The 2,4~dinitrophenylhydrazone melted at 186-
The copper derivative made from a saturated ammon-
aical solution of copper acetate and had a melting point
of 135-137°C.
The enol test with ferric chloride was
positive.
Attempted preparation of the pinaool of methyl beta-Butleryl ketone.
To 5 grams of magnesium turnings,
33ce. of
anhydrous ether and 50cc. of benzene contained in a 200cc.
flask, fitted with a condenser, was added 14 grams of
iodine in small portions.
When the solution was colorless
49
it was cooled and to it was added 2 0 grams of methyl
beta-Butleryl ketone*
for 30 minutes.
The flask was stoppered and shaken
The characteristic white presipitate did
not form nor did the reaction mixture proceed through the
red free radical stage.
The solution was filtered, washed
with sodium thiosulfate solution, and washed again with
water and dried over magnesium sulfate*
The ether and
benzene were sucked off with the aid of the water pump.
From the remaining liquid 19 grams of the starting ketone
were recovered.
No reaction had taken place.
The fact
that the reaction had failed is not surprising since the
mechanism of the reaction includes the addition of magnesious iodide to the carbonyl group.
It has been shown
repeatedly that the carbonyl group of methyl beta-Butleryl
ketone does not undergo addition reactions.
Preparation of di-beta-Butlerowyl-me thane.
In a 200cc. 3
necked flask equipped with stirrer, condenser, and drop­
ping funnel was placed 2.7 grams of magnesium,
ethyl ether.
50cc. of
To the magnesium was added 1 2 . 2 grams of
ethyl bromide in 400cc. of ether over a period of 1 hour.
To the mixture 20 grams of methyl beta-Butleryl ketone in
20cc. of ether was added dropwise.
Refluxing was con­
tinued 1 hour after the last gas had been given off.
To
the above enolate 21.8 grams of beta-ButlerowTs acid
chloride was added.
Stirring and refluxing were continued
for 12 hours.
Half of the ether was allowed to hoil off
during this time.
The reaction mixture was decomposed
by shaking with iced HC1.
The ether layer was drawn off
and shaken twice with 1 0 $ sodium hydroxide and twice with
water.
The basic washings after neutralizing with HC1
yielded 11 grams of beta-Butlerow*s acid.
A small por­
tion of the ether layer was shaken with ammonaical copper
acetate.
A dark green color indicated that the copper
derivative was present,
isolate.
but it proved too difficult to
The remaining ether was evaporated and 200ce. of
95$ ethanol added; a thick white precipitate formed
almost immediately.
yield 23$.
Weight of the precipitate,
9 grams,
The diketone gave a blood red color with fer­
ric chloride,
(m.p. 128-130°C. after crystallizing twice
from ethanol).
Preparation of beta-Butlerowyl-triethylacetyl-methane.
The 3,3-diethyl-2-pentanone was obtained from Mr. Lewis
of this laboratory.
To .04 mole of the enolate of 3,3-
diethyl-2-pentanone was added 8.7 grams
beta-Butlerow's qcid chloride.
(.04 mole) of
The reaction mixture was
stirred overnight and decomposed by pouring over iced
HC1.
The ether layer was drawn off and washed with
NaHCOg and water.
The diketone was precipitated as its
copper salt which was crystallized once from benzene.
Decomposition of the copper salt with HC1 gave the white
diketone which melted at 129— 131®C. on being crystallized
from ligroin.
This diketone gave a positive enol test
with ferric chloride.
Preparation of beta-Butlerowyl-alpha-Butlerowyl-methane.
To .075 mole of the enolate of methyl beta-Butleryl ketone
was added 16.3 grams
(.075 mole) of alpha-Butlerow’s acid
oliloride, n20/D 1.4428-1.4455.
The reaction mixture was
stirred overnight and then, evaporated to half volume and
refluxed for 4 hours.
The ether suspension was shaken
with iced HC1 and the ether layer washed with NaEOOg and
water.
After evaporating the ether the remaining liquid
was distilled through a Claisen flask at 33mm.
The
liquid fraction coming over at 120-140°C. represented
methyl ketone and alpha acid.
The liquid left in the
flask solidified when cooled.
Weight 12 grams,
42$,
crystallized from ethanol, m.p. 90°C.
yield
The mixed
m.p. with the compound prepared by Mr. Lester,
using the
beta chloride on the alpha-Butleryl-methyl enolate
showed no depression.
The fact that these two reactions
give the same compound is very good evidence for the
structure of both ketones.
Attempted preparation of alpha-Butlerowyl-beta-Butlerowylaoetyl-methane.
with stirrer,
Into a 250cc. 3 necked flask equipped
condenser,
and dropping funnel was placed
52
.34 gram of* magnesium (.013 mole) and 20cc. of dry ether.
To the magnesium turnings was added a mixture of 1.45 grams
(•013 mole)
of ethyl bromide and 20cc. of dry ether.
When the reaction was completed 5.0 grams
(.013 mole) of
alpha-But le rowyl— beta-Butlerowyl-me thane in 15cc. of ether
was added.
The evolution of ethane was very rapid, and
no more was evolved on heating the solution.
enolate 1 . 2
To this
grams of acetyl chloride was added and the
mixture stirred for 12 hours.
After being decomposed in
the usual fashion only the starting diketone could be''
isolated.
It is possible that the triketone could be
prepared using dibutyl ether as the solvent and by long
refluxing of the solution.
Attempted preparation of 1. 5-di-beta-Butlerowyl-2.4pentandione.
a 50Occ.
a.
Preparation of malonyl chloride.
Into
flask fitted with a condenser was placed 62
grams of malonic acid and 2 1 0 grams of thionyl chloride.
The temperature was kept at 40°C. for 4 days and then
increased to 60°C. for 6 hours.
The thionyl chloride
was removed under vacumn and the remaining liquid dis­
tilled through a Glaisen flask at 30mm.
distilling at 58-60 was kept.
The fraction
Weight 56 grams, yield
76 %.
b.
Addition of malonyl chloride to the enolate
of methyl beta-Butleryl ketone.
To .18 mole of an
enolate suspension of methyl beta-Butleryl ketone was
added 12.0 grams (*08 mole) of malonyl chloride.
A red
color appeared with the addition of the first drop of
chloride, deepening to a brown.
The reaction mixture
was decomposed in the usual manner.
The ether layer
on distillation through a Claisen flask at 20mm. gave
80 grams of unreacted ketone,
b.p. 100°C.
The material
remaining in the flask consisted of 4 grams of a gu m m y
solid.
Crystallization from methano1-ether with bone
blacking produced a light brown solid giving an enol
test with ferric chloride.
This solid decomposed on
melting over a wide range of temperature.
Attempted preparation of the peroxide of methyl betaButleryl ketone.
To .05 mole of ethyl magnesium bromide
was added 10 grams of methyl beta-Butleryl ketone.
solution was stirred for 40 minutes.
The
A few cc. of the
enolate solution was decomposed with iced HC1, and the
ether layer was washed twice with ice water and dried
over sodium sulfate.
The ketone obtained in this man­
ner gave a positive enol test with ferric chloride.
The
remaining enolate solution was decomposed similarly and
diluted to 4 times its volume with petroleum ether.
Oxygen was bubbled through the mixture for 4 hours.
Wo
discharge of iodine was obtained when this solution was
added to HI in glacial acetic acid.
This indicated that
54
the peroxide had not been made*
The recovery of start­
ing material was quantitative.
Synthesis of ethyl beta-Butleryl ketone.
3 necked flask equipped with condenser,
In a 1 liter
separatory
funnel and stirrer were placed 18.6 grams of magnesium.
To this was added 87.2 grams of ethyl bromide dissolved
in 350oc. of ether.
The time of addition was 1 1/2 hours,
with stirring continued for 2 hours.
To the solution of
this Grignard reagent 70.2 grams of beta acid chloride
dissolved in 150cc. of ether was added in 1 1/2 hours
attended by vigorous stirring.
Stirring was continued
for 8 hours and the reaction mixture was decomposed with
iced HC1.
The ether oil layer was steam distilled until
no oil was observable in the distillate.
The solution
remaining undistilled was extracted with ether and the
ether layer added to the ether extract of the steam
distillate.
The ketone was fractionated through column I.
Cut
Weight
C.T.
1.
2.
2 grams
2
1.8
6.8
8
10.8
106
106
106
105
106
108
108
108
108
3.
4.
5.
6.
7.
8.
9.
14.1
15.4
4
H.T.
56-81
81.5
81.5-88
83
83
80
85
85
83
n2 0 /D
1.4540
1.4553
1.4553
1.4551
1.4548
1.4548
1.4549
1.4553
1.4582
Pressure
5mm.
5
5
5
4
5
5
5
5
None of the fradtions gave a test with alcoholic silver
nitrate,
indicating the absence of the acid chloride.
55
Fractions 4-8 were combined as the pure ketone.
Weight
55.9 grams, yield 70%.
In another similar run a yield of* 79% of* pure ethyl
beta-Butleryl ketone was obtained.
This compound made no
ketone derivatives and was similar in this respect to its
methyl homolog.
The enolization of* the ketone was run
by Dr*. L. P. Block.
H e reported 57% enolization and 0.0%
addition.
Preparation of alpha-beta-Butlerowvlpropionic acid.
a 200cc. 3 necked flask,
Into
equipped with stirrer, condenser
and dropping funnel, was placed .60 gram of magnesium.
To the magnesium 3.0 grams of ethyl bromide dissolved in
45cc. of dry dibutyl ether was added.
After stirring
for 1 hour 5.39 grains of ethyl beta-Butleryl ketone in
15cc. of dibutyl ether was added.
The solution was reo
fluxed for 30 minutes at 140 0.
During this treatment a
green color appeared but no precipitation occurred.
The
solution was cooled and dry carbon dioxide bubbled through
for 25 hours.
The green color disappeared and a white
precipitate formed.
The Grignard complex was decomposed
by pouring over iced HOI.
The ether layer was extracted
twice with cold 10% sodium carbonate.
The resulting water
layer was neutralized with cold HC1 and the solid which
formed was filtered off.
yield 48%.
Weight of crude acid 3.0 grams,
The melting point on crystallizing twice from
56
lignoin was 121-123°C.
On heating on a steam bath for
5 hours the acid decomposed into ethyl beta-Butleryl
ketone.
Preparation of beta- Butlerowyl-benzoyl-me thy 1- methane.
Into a 2 0 0 cc. 3 necked flask equipped with stirrer,
condenser, and dropping funner were placed 2 . 4 grams of
magnesium.
To the magnesium 1 1 grams of ethyl bromide
dissolved in lOOcc. of dry ethyl ether, was added over a
period of 20 minutes.
To the ethylmagnesium bromide
solution 21 grams of ethyl beta-Butleryl ketone in 40cc.
o f dry ethyl ether was added.
for 3 hours.
The solution assumed an olive green color
but no precipitation occurred.
7.2
Refluxing was continued
To the enolate mixture
grains of benzoyl chloride in 30cc. of ether was added
i n 15 minutes.
The solution immediately turned orange
which deepened to a dark brown after 4 hours of stirring.
The reaction mixture was decomposed by pouring over iced
HC1.
The ether layer was dried over sodium sulfate; the
ether was evaporated and the oil remaining steam dis­
tilled until solid appeared in the condenser.
On cooling,
the oil left in the flask solidified and after 4 cry­
stallizations from ligroin melted at 115-116°C.
An identical run employing half quantities of mater­
ials was made,
the only difference being that an ice
salt bath was used during the addition of the benzoyl
chloride, and that the resulting oil was fractionated
from a Claisen flask instead of being steam distilled.
Cut
Weight
1.
2.
3.
4r.
5,0
0.4
0.4
6.0
H.T.
gr.123-125
125-127
165
166-169
n20/D
Pressure
1.4582
1.4764
solid
solid
28mm.
28
3
3
Fraction 1 represented recovered ethyl beta-Butleryl
ketone and fraction 4 represents beta-Butlerowyl-benzoylmet hyl-methane.
Yield 43%, m.p. 115-116°C.
No ketone
derivatives, including the copper salt could be made.
The
compound did not give a positive test with ferric
chloride.
This evidence would seem to indicate that
this compound was not a diketone.
periments showed
However,
later ex­
that this evidence was not valid.
Treatment o f beta-Butle rowyl- benzoyl-methyl- me thane with
aIka 11.
a.
One gram of diketone,
.25 gram of sodium
hydroxide and 75cc. of* alcohol were refluxed for 5 hours.
The alcohol
was distilled off and the residue extracted
with sodium hydroxide ether mixture.
Only unsaponified
material was recovered from the ether.
h.
-A mixture of 5cc. of methyl alcohol,
80cc. of
15$ aqueous potassium hydroxide, and 1 gram of diketone
were refluxed for 16 hours.
The reaction mixture was
either extracted and the ether was evaporated.
all of the starting material was recovered.
aoid was found in the alkaline layer.
Practically
No benzoic
From the refusal
of the diketone to saponify,
the possibility of an enol
ester structure would seem doubtful.
Among the compounds that might have been formed
was the 1,3 ketol with the structure
^
c-c-c-c — C - C H - c
c
/I
I
fa-
I
which would have resulted from the action of ethylmagnesium bromide upon beta-Butlerowyl-benzoyl-methylmethane.
This could have readily occurred if the
enolization of the ethyl ketone was incomplete,
thus
leaving some unreacted ethylmagnesium bromide.
That the
compound did not have this structure was shown by the
fact that it could not be dehydrated with 30% sulfuric ac­
id on refluxing for 18 hours, and that it would not
form the chloride on shaking with concentrated HC1.
Preparation of 1-beta-Butlerowyl-1-methyl-3-phenyl-2ethanol.
The bromomagnesium enolate (.076 mole) of
ethyl beta-Butleryl ketone was prepared in the usual
manner.
Dibutyl ether was used as the solvent.
The
speed of the enolization of the ketone at the boiling
temperature of dibutyl ether, as judged from the rapid­
ity of the gas evolved, was considerably greater than in
ethyl ether.
To the lOOcc. of this enolate solution con­
tained in a 200cc. 3 necked flask equipped with stirrer,
condenser, and dropping funnel was added 8 grams of freshly
distilled benzaldehyd© in 35cc.
of dry dibutyl ether.
A white precipitate formed after 10 minutes of stirring.
The reaction was allowed to stir overnight.
The addition
complex was poured over HC1 and the ether layer dried
over potassium carbonate.
The ether was evaporated and
the remaining oil distilled from a 50cc. Claisen flask.
Cut
Weight
H.T.
1.
2.
3.
2.3grams 60-80
6.5
105-106
6.4
-
n20/D
Pressure
1.4980
1.4583
10
8 mm.
Fraction 1 represented benzaldehyde and fraction 2 repre­
sented ketone.
Fraction 3 was undistillable at 10mm.
solidified on cooling.
It
The solid was washed with sodium
carbonate and ether; the solid remaining after evapora­
tion of the ether was crystallized twice from ligroin*
(m.p. 90-92°C.,
yield of crude carbinol 26$.)
In another
similar run the yield was 2 0 $.
Oxidation of 1-beta-Butlerowyl-1-methyl-2-phenyl-2ethanol to beta-Butlerowyl-benzoyl-methyl-methane.
a 50cc. flask containing 13cc. of water,
centrated sulfuric acid and
Into
2.5cc. of con­
.44 grams of potassium di-
chromate was placed 1.19 grams of the above ketol.
compound was rather slow in oxidizing,
The
the first green
appearing 20 minutes after refluxing had begun.
solution was refluxed gently for 4 hours.
The
On cooling
the oil layer solidified and was filtered off.
A yield
1*1 grams of a white solid was obtained.
This re­
presents an almost quantitative conversion of the ketol
to the diketone.
The diketone melted at 11*7-116°C.
after 3 crystallizations from ligroin.
This diketone
was identical with that prepared from the reaction of
benzoyl chloride on the bromomagnesium enolate of ethyl
beta-Butleryl ketone.
A mixed melting point of the com­
pounds prepared by the two different methods showed no
depression.
This oxidation proves that the product
obtained from the reaction of benzoyl chloride on the
ethyl beta-Butleryl enolate was not a n enol ester but a
diketone.
Bromination of ethyl beta-Butleryl ketone.
are those of Bavorsky23.
The directions
Into a 2 0 0 cc. flask were placed
35 grams of ethyl beta-Butleryl ketone,
cium carbonate and 30cc. of water.
11 grams of cal­
This mixture was
heated to 50°C. and 32 grams of bromine were added dropwise over a period of 2 hours.
reaction proceeded smoothly.
stallized.
At this temperature the
On standing the oil cry­
The solid bromide was taken up in ether and
shaken with 50cc. of water, a crystal of sodium thiosulfate, and 1 gram of calcium carbonate.
The ether
layer was washed 3 times with 300cc. portions of water,
dried over sodium sulfate,
and the ether evaporated.
The
solid on crystallizing from a methanol water mixture gave
61
a melting point; of 6 6 — 6 8 ^ 0 .
33 grams,
Weight of crude monobromid©
yield 72%.
Treatment of alpha-bromo-ethyl beta-Butleryl ketone with
alkali.
a.
A solution of 50cc. of 10% aqueous potassium
carbonate, 2 0 oc. of methanol, and 2 grams of bromoketone
were refluxed for 12 hours.
The resulting solution was
extracted with ether and washed twice with water*
Evap­
oration of the ether layer left only the bromoketone;
no carbinol could be isolated.
b.
A. mixture of 2 grams of alpha-brom-ethyl beta-
Bu-fcleryl ketone, 90cc. of absolute ethenol, and lOcc. of
1,2
normal sodium hydroxide was allowed to reflux 1 0
bour 3 .
Recovery of the starting material was quantitative*
Attempted preparation of the acetate of 1-beta-Butlerowyl1-ethanol.
A solution of 2 grams of anhydrous potassium
acetate, 1 gram of alpha-brom-ethyl beta-Butleryl ketone,
and 15c c . of normal butyric acid were refluxed for 5 hours.
No precipitate of potassium bromide was observed.
On
diluting the reaction mixture with water, the starting
bromoketone was recovered quantitatively.
In a similar
attempt using glacial acetic acid as a solvent the re­
action also failed.
It may be seen from the preceding experiments that
the bromine atom a^nd alpha-brom-ethyl beta-Butleryl ketone
Is extremely difficult to replace.
This is also Indicated
62
by the fact that boiling the bromoketone with an al­
coholic solution of silver nitrate gives a very faint
precipitate of silver bromide.
Preparation of isooro-pyl beta-Butleryl ketone.
To 4 9
grams of magnesium placed in a 1 liter 3 necked flask
equipped with stirrer,
condenser, and dropping funnel
was added 246 grams of isopropyl bromide in 500cc. of
ether over a period of 2 hours.
To the isopropyl Grig­
nard reagent 218 grams of beta acid chloride in 140cp.
of dry ether was added in 1 1/2 hours.
The Grignard
complex was decomposed by pouring over iced HC1.
Most
of the oil layer was separated b y steam distillation.
The remaining oil which did not steam distill was ether
extracted and added to the oil separated by steam dis­
tillation.
The combined ether extracts were washed
with 10% sodium hydroxide and water.
After drying over
calcium chloride the ether layer was fractionated through
column II.
Gut
.
.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
1
2
Weight
2
2
2
2
2
C.T*
66
69
96
111
114
5
5
5
4
110
110
110
110
10
12
20
114
115
115
H.T.
40-45
45-69
69
69-86
86-90
71
77
77
71
77
78
79
n 2 0 /D
Pressure
1.3260
1.4436
1.4592
1.4332
1.4555
1.4595
1.4593
1.4601
1.4609
1.4595
1.4591
1.4590
5mm.
5
5
5
5
5
6
6
6
6
6
6
63
Cut
Weight
13.
14.
15.
16.
17.
18.
19.
11
14
14
12
C.T.
H.T.
n 2 0 /D
115
118
118
80
83
83
87
87
87
87
1.4589
1.4589
1.4589
1.4589
1.4589
1.4589
1.4595
120
120
120
120
13
14
18
Pre
6
6
6
6
6
6
6
Fractions 10-19, which were isopropyl beta-Butleryl
ketone, were combined.
pure ketone 58.5$.
impure ketone.
Yield of
Fractions 3,4,5, 6 ,7, 8 , 9 represent
Lower boiling fractions and pot residue
weighed 20 grams.
made.
Weight 130.5 grams.
No derivatives of this ketone could be
No trace of beta-Butlerow*s aldehyde could be de-
tected.
Some of the aldehyde was expected since the
reaction of t-butyl-Grignard reagent with the beta acid
chloride gives a yield of 60$ of b e t a - B u t l e r o w *s aldehyde.
Preparation of alpha-methyl-aloha-beta-Butlerowyl-pro­
pionic acid.
stirrer,
Into a 3 necked 200cc.
condenser,
flask equipped with
and dropping funnel were placed 1.62
grams of magnesium and 25cc. of dry dibutyl ether.
To
the magnesium was added 7.3 grams of ethyl bromide in
40cc. of dibutyl ether over a period of 45 minutes.
ring was continued for 3 hours.
Stir­
To the ether solution of
the ethylmagnesium bromide was added 15 grams of isopropyl
beta-Butleryl ketone.
Very little gas was evolved until
the dibutyl ether was refluxing.
fluxing,
After one hour of re-
ethane had ceased to come over.
This ketone
64
enolized with more difficulty than either its methyl
or ethyl hojitologs.
Its enolizatioo value was found to
be 25fo of the theoretical by Dr, L. P. Block; no addi­
tion took place.
On cooling dry carbon dioxide was bubbled
through the bromomagnesium enolate solution.
At the
end of 2 0 hours the reaction mixture was poured over
iced HC1.
The ether layer was shaken three times with
10% sodium carbonate.
These basic extracts were acidi­
fied with HC1 and the acid which appeared as a solid
was filtered off.
Weight of acid,
15 grams.
It melted
at 100-102°C. after 2 crystallizations from etherligroin.
The starting ketone was regenerated upon re-
fluxing the keto acid for several hours on the steam bath.
Attempted preparation of 1 .1 -dimethyl- 1 -beta-Butlerowyl2 - phenyl- 2 - ethano1.
with stirrer,
Into a 3 necked 500cc. flask equipped
condenser, and dropping funnel was placed
5.2 grams of magnesium in 60cc. of dry dibutyl ether.
To
the magnesium was added 24 grams of ethyl bromide in 100
cc. of dibutyl ether.
Stirring was continued for 1 hour
after the addition was completed.
To the ethylmagnesium
bromide 45 grams of isopropyl beta-Butleryl ketone was
added dropwise.
2
20
The reaction mixture was refluxed for
hours and stirred overnight.
To the enolate mixture
grams of freshly distilled benzaldehyde in 2 0 cc. of
dibutyl ether was added slowly.
Stirring was continued
65
fof 20 hours.
The reaction mixture was decomposed by
pouring into iced HCX.
After washing with sodium car­
bonate solution and then water, the ether layer was dried,
over magnesium suXfate.
The dibutyl ether was distilled
off at atmospheric pressure and the remaining liquid,
distilled from a Claisen flask at 8 mm. pressure.
Cut
1.
2.
3.
Weight
10
H.T.
30-45
45-63
40
85-100
pot residue 2 grams
6
n20/D
1.5513
1.4780
1.4680
1.4610
Fraction 3 and the pot residue represent recovered ketone.
No evidence of a reaction having taken place could be de­
tected.
/
Preparation of the enol benzoate of isooro'pyl beta-Butler­
yl ketone.
In the usual manner .20 mole of the bromo-
magnesium enolate of isopropyl beta-Butleryl ketone wets
prepared.
To the enolate solution 14 grams of benzoyl
chloride in 20ce. of dibutyl ether was added.
and stirring were continued overnight.
Refluxing
The reaction mix­
ture was poured over iced HC1, and the ether layer separ­
ated and washed with sodium carbonate and then water.
After drying the ether solution over calcium chloride
the ether was removed by distillation and the remaining
liquid fractionated from a Claisen flask.
66
Cut
Weight
1.
2»
5 gramsI 35-45
2.5
45-85
3
84
5
84
7
86-88
4
88-95
1.5
95-172
4. 5
172-177
5.5
177-186
11.5
180
3•
4.
5.
6.
7.
8.
9.
10.
H.T.
n20/D
1.4648
1.4658
1.4630
1.4609
1.4630
solid
Tt
tl
ft
ft
Pres
7mm
8
8
a
8
8
8
8
8
8
Fractions 3-6 were recovered ketone and 8-10 were enol
"benzoate.
73$,
Weight of enol benzoate 31.5 grams, yield
crystallized twice from ligroin, m.p. 50-52°C.
The
ester gave no color with ferric chloride nor did it take
up bromine in a bromine carbon tetrachloride solution.
Saponification of the enol benzoate of isopropyl betaButleryl ketone.
hol,
A solution of 75cc. of 95$ ethyl alco­
2 grams of the enol benzoate and 1.0 gram of KOH
were refluxed for two hours.
Most of the alcohol was
distilled off and 15cc. of water was added.
The re­
maining solution was ether extracted twice and the basic
water layer acidified with sulfuric acid.
An acid preci­
pitated out which after crystallizing once from hot water
melted at 120-121°C.
The acid was identified as benzoic
sincie a mixed melting point with a known sample showed
no depression.
The ether layer was washed twice with
water and dried over potassium carbonate.
The liquid
remaining after evaporation of the ether, was isopropyl
beta-Butleryl ketone.
Although diketones sometimes split
67
under comparable conditions, the compound was assumed to
be an enol ester because of* its low melting point in con­
trast to beta-Butlerowyl-benzoyl-methyl-methane.
Preparation of* the peroxide of isopropyl beta-Butleryl
ketone.
To.072 mole of ethylmagnesium bromide contained
in a 500cc. erlenmeyer flask fitted with calcium chloride
tube and dropping funnel was added 8 grains of isopropyl
beta-Butleryl ketone.
The solution was gently refluxed
for 1 hour, diluted with 4 titiies its volume of petroleum
ether and shaken with iced HC1.
The ether-petroleum ether
layer was washed rapidly 3 times with ice water and dried
for 5 minutes over sodium sulfate.
Oxygen was passed
through the solution for 4 hours; at the end of this tiifate
an oil remained with a few finely divided crystals sus­
pended in it.
Half of this oily solution was shaken with
a mixture of HI and petroleum ether.
was drawn off and evaporated,
The petroleum ether
leaving beta-Butlerowfa acid,
which was identified by the method of mixed melting
points.
The remaining half of the oily solution was sha­
ken with 4 0 c c . of glacial acetic acid containing 10 grams
of potassium iodide.
immediately.
hydroxide.
posited.
The discharge of iodine took place
The solution was made basic with sodium
On standing,
crystals of iodoform were de­
68
Preparation of methyldiethylcarbinnl.
into a 5 liter
flask equipped with stirrer, condenser, and dropping fun­
nel were placed 146 grains (6.0 mole^ of magnesium turn­
ings and 400cc. of dry ether.
To the turnings were add­
ed 654 grains (6.0 moles) of ethyl bromide in 1200co. of
ether.
Addition was finished in 3 hours.
continued for 4 hours.
Stirring was
From the dropping funnel 378 grains
(5.25 mole^ of methyl ethyl ketone in 400cc. of ether
was added in 3 hours.
The mixture was stirred overnight.
The Grignard complex was decomposed with 1 kilogram of
cracked ice.
$he ether layer was decanted off and com­
bined with the ether extract of the magnesium hydroxide.
The ether extracts were dried over potassium carbonate
and the ether stripped off.
Preparation of diethylmethylcarbinyl chloride.
All of
the material boiling below 100°C. was stripped from the
carbinol prepared in the foregoing reaction.
The remain­
ing 500cc. was shaken with 1200ec. of concentrated HC1
and allowed to stand for 15 minutes.
The solution was
shaken again and the chloride layer drawn off, washed
with 5% NaHC0 3 and finally with water.
The tertiary
chloride was dried over KgCOg for 48 hours and then
fractionated through column X at atmospheric pressure
(740mm.)•
4
69
Cut
Weight
C.T,
1 .
2#
9 grains
17
17
17
18
17
16
17
16
17
17
16
17
18
17
17
18
16
17
18
17
16
56
61
61
62
62
62
63
63
64
63
63
63
61
61
61
61
61
61
61
61
61
61
61
61
61
3Jk•
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
12
8
10
H.T.
48
55
58
58.5
58.5,
58.5
58.5
n
«
it
it
tt
tt
it
tt
tt
tt
ti
it
n
tt
ti
tt
ti
ti
n20/D
1.4144
1.4150
1.4200
1.4213
1.4213
n
tt
ti
tt
tt
tt
tt
ti
ti
w
tt
tt
tt
tt
tt
tt
tt
w
1.4220
pot residue
Fractions 4-23 weighed 358,5 grams, n 2 0 /D 1.4213, yield
figured from methyl ethyl ketone, 60$#
Preparation of diethylmethyloarbinyl Grignard reagent.
Into a 5 liter pot equipped with stirrer,
condenser and
dropping funnel were placed 73 grams (3.0 mole) of mag­
nesium turnings and 1200ce. of dry ether.
was started with 5cc. of ethyl bromide.
The reaction
Through the
dropping funnel 358 grams of diethylmethylcarbinylchloride in 2 0 0 cc. of dry ether was added over a period of
4 hours.
Stirring was continued overnight.
This Grignard
reagent was given to Mr. Lewis to carbonate; from it he
70
prepared 3-ethyl-3-methyl-2-pentanone.
Attempted preparation of beta-Butlerowoin.
Into a 1
liter 3 necked flask fitted with stirrer and condenser
were placed 57cc. of xylene and 34.5 grams of sodium*
The sodium was melted and stirred vigorously until it
was beaten into small droplets, whereupon the stirrer
was stopped and the solution allowed to cool*
The
xylene was decanted and the powdered sodium washed with
several portions of anhydrous ether.
The flask was
fitted with a dropping funnel and 450cc. of dry ethyl
ether added.
From the funnel 148.5 grams of methyl
beta-Butlerowate (n20/D 1.4451) was slowly run dropwise
into the solution.
tion.
No heat was evolved during the addi­
Refluxing was continued for 72 hours and at the
end of this time no appreciable amount of sodium had
reacted.
The sodium was disposed of by adding 105 grams
of glacial acetic acid over a period of 2 hours.
The
solution was washed twice with water, once with sodium
bicarbonate and finally with water.
dried "over magnesium sulfate,
off.
The ether layer was
and the ether distilled
The remaining solution was subjected to fractionation
through column I*
Out
1
.
.
2
3.
4.
Weight
4
8
12
12
C.T.
96
94
94
96
H.T.
n20/D
62
62
62
60
1.4453
1.4452
1.4452
it
Pressure
5mm.
5
5
5
71
Cut
Weight
5.
13
6.
12
12
12
10
12
7.
.
9*
8
10.
11.
Q
C.T.
96
96
96
96
96
96
96
. H.T
n.20/D
Pressure
60
60
59
60
60
59
60
1-4452
"
5m m .
5
5
4
4
4
5
Fractions 1 - 1 1 were recovered methyl beta-Butlerowate.
No evidence of the beta-Butlerowoin or of the diketone
could be found*
The action of sodium on beta-But le row's aldehyde.
A
mixture of 4 grains of be ta-But le row's aldehyde, .5 grams of
finely divided sodium and 35cc. of ether was refluxed on
the steam bath for 3 days.
Acetyl chloride reacted
vigorously with one cc. of the ether solution.
A white
solid which precipitated during the course of the reaction
proved not to be the sodium salt of beta-Butlerow's acid.
It was insoluble in base and acid.
When recrystallized
once from methanol it melted at 150-152°0.
The remain­
ing ether solution was decanted from the sodium and
shaken with ioed HC1.
The ether layer was washed with
a 10$ sodium carbonate solution.
no precipitate when acidified.
The basic layer gave
The ether layer was evap­
orated and the white solid which was left had a melting
point of 150-152°C.
ol.
after one crystallization from methan­
The compound oxidized readily to beta-Butlerow's
acid when treated with CrOg dissolved in glacial acetic
f
72
acid.
The compound is probably 1,2-di-beta-Butleryl- 1 ,
2 -ethandiol.
H
R - C
'
/
a
-
C
-
K
/
OH oH~
Preparation of methyl iodide.
In a 500cc. flask were
placed 250 grams of sodium iodide, and 150 grams of
acetone.
The solution was shaken for 15 minutes and
then filtered into a 2 necked 500cc. flask.
The flask
was fitted with a condenser and an inlet tube extending
below the surface of the liquid.
The flask containing
the remaining iodide was dried and weighed.
The weight
of sodium iodide in approximately 150 grams of acetone
at 28°C. was 83 grams.
Methyl chloride was passed
through a Gilman trap and into the saturated solution of
sodium iodide.
After 10 minutes a white precipitate
appeared and continued to form for 15 hours.
The con­
tents of the flask were then distilled directly from the
salt through column II,
Cut
1.
2.
3.
4.
5.
6.
Weight
2
4
2
4
3
4
C.T.
30
30-36
36-39
39
39-40.5
42
H.T.
n20/D
29-30
30-36
36-40
40
41
41*5
1,3960
1,4645
1.4610
1.4820
1.4865
1.4887
Pressure
741mm.
73
Cut
Weight
C.T.
H.T.
n30/D
Pressure
7*
Q.
4
2
46
50
41.5
50
1.4930
1.4811
741mm.
Fractions 2-8 represented iihpure methyl iodide, weight
30 grams, yield 25#.
The methyl iodide was identified
by its dimethylanaline addition product.
74
SUMMARY
1*
The following sterically hindered ketones have been
prepared:
3, 5,5-trimethyl-3-t-butyl-2-hexanone, 4, 6 ,6 -
trimethyl- 4- t— butyl-3— heptanone,
2 ,4, 6
,6-tetr«miethyl-4—
t- butyl- 3- hepta no na •
2.
The abnormal properties of these ketones have been
studied,
3.
Reactions of their magnesium etiolates have been
investigated.
New Compounds Prepared
Name
Formula
ci ct
(R is the c-c-crc— group)
c C.-C-C
i
c
1. 3,5,5-trimethyl-3-t-butyl- ^
C-
-
2 -hexanone
2. 4,6,6-trimethyl-4-1-butyl-
T?_ Q- C H x ~ C H ^
3-heptanone
3. 3 ,4 ,6,6-tetramethyl-4-tbutyl-3-heptanone
4
. 3 ,5, 5 - trimethyl-3- 1 -butyl2 -hexanol
5.
6
5 ,7, 7 - trimethyl-5-1-butyl2 ,4-octandione
. 4 ,6 , 6 - trimethyl-4- 1 -butyl3 -keto-heptanoic acid
7. 4 ,6 ,6 - trimethyl-4- 1 -butyl1 -phenyl-1-heptano 1-3-one
C Hs
^
‘‘
-
c
- c H - Cc
^
- C - C
ov\
^
O
— C ^
R - C" C
^
i- j
- S"i
^
HI
C “ <1?
^ ^
75
SUMMARY (continued)
Name
Fo rmula
(R is the c-<L- c.-c -gro up )
c-
8
, 4, 6 ,6 - trimethyl-4-t-butyl1 - phenyl- 1 ,3-heptandione
9. 2, 2, 4,8,10* 10-hexamethyl-4, 8—
di-t~butyl-5, 7-undeoandione
10. 3, 3-die thy 1-7, 9,9-trimethyl-7t-butyl-4, 6 -deoandione
" R - C - C H - C_-a>
11
"*■ v'
o
o
R - C -C.Hu
1\
-C“
H
C
C. - F\
11
~
H
H
11. 2, 2, 8 ,10,10-pentamethyl-4neopentyl-9- 1 -butyl-5,7-undeoandione
12. 2,4, 6 ?*tetramethyl-4-1— butyl3-keto-heptanoic acid
R ~
~
o
o
"K -
^ ~ c," cr~
c
c
c-c-c_
\
O
~CooH
^
c^
13. 1 -phenyl- 2 ,4, 6 ,6 -tetramethyl4-t-butyl-l,3-heptandione
7\ - C - C H - C - C D
w »
n
o CH3 o
W
14. 1 - phenyl- 2 ,4, 6 ,6 -tetramethyl- f\ - C - C H ’ C - <D
4-t-butyl-l-heptanol-3-one
»i 1
*
o
cH3
15. 4, 6,6-trimethyl-4-t-butyl- 2 bromo-3-heptanone
~R - C- CH8^- ^H,^
16. 2,2,4, 6 ,6-pentamethyl-4-tbutyl-3-keto-heptanoic acid
"R- C - C - C - OH
■
M
■
I
17. Enol benzoate of 2 ,4, 6 ,6 tetramethyl-4-t-butyl-3heptanone
u
O
II
II
Q
I
11
^ ^ o
P\- C
< __
^ (c- H3)
_ _
n
O
i
76
BIBLIOGRAPHY
1. Baum, Ber., 28, 3207 (1895)
2. Kohler and Baltzley, J.A.C.S,, 54, 4015 (1932)
3. Fieth and Davis, Ber., 24, 3546 (1891).
4. Meyer,
Ber., 29, 830 (1896)
5. Fuson, Emerson and Gray, J.A.C.S., 61, 4(Jo(1939)
6 . Klages and Allendorf, Ber., 31, 1008 (1898)
7. Fuson and Walker, J.A.C.S., 52, 3269 (1930)
8 . J. G. Aston and J. Newkirk, unpublished work.
9. Klages, Ber., 35, 2635 (1903)
10. F. G. Whitmore, unpublished work.
11. Kohler and Tishler, J.A.C.S., 54, 1594,
(1932)
12. Uianowa, Chem. Zentr., 84, I, 1402 (1913)
13. Schlenk, Hillemann, and Rodloff, Ann., 487, 135 (1931)
14. Fuson,
Fugate and Fisher, J.A.C.S., 61, 2362 (1939)
15. Fuson, Fisher, Ullyot, and Fugate, J. Org. Chem., 4,
111 (1939)
16. Kohler and Johnstin, Am. Chem. J., 33, 45 (1905)
17. Smith and Guss, J.A.C.S.,
18. Kohler*
59, 804 (1937)
Jacobs and Sonnichsen, J.A.C.S., 627, 85 (1940)
19. C. S. Miner, Jr., M.S. thesis.
20. L. P. Block, Ph.D. thesis.
21. Gilman and Jones, J.A.C.S., 63, 1162 (1941)
22. Gomberg and Bachmann, J.A.C.S., 49, 236 (1927)
23. Favorsky, J. Prakt. Chem., 88, 641 (1913)
24. F. C. Whitmore et al», J.A.C.S., 63, 643 (1941)
25. Kohler and Thompson, J.A.C.S., 59, 887 (1937)
26. C. Lewis, unpublished work.
27. Nasarov, Ber. 70 B, 599 (1957)
28. H. H. Johnson, Ph.D. thesis.
29. J. S. Whitaker, Ph.D. thesis.
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