[CONTRIBUTION FROM
THE
GEORGEHERBERT JONES LABORATORY, THE UNIVERSITY OF CHICAl30]
THE REACTION OF SODIUM IN LIQUID AMMONIA WITH ESTERS' M. S. KHARASCH, E. STERNFELD,
AND
F. R. MAY0
Received January 19, 1940 INTRODUCTION
The first thorough work on the reactions of sodium with organic esters was done by Bouveault and Locquin (1). They reported that two molecules of an aliphatic ester in benzene or ether solution at temperatures below 10' condensed to form the corresponding acyloins. Small amounts of diketones were also found as products, and these were assumed to have been formed by atmospheric oxidation of the acyloins. These investigators report,ed that they encountered difficulty in obtaining a good yield of acetoin from ethyl acetate, though the higher esters all gave better than 50% yields of the acyloins. This apparently anomalous behavior of ethyl acetate was ascribed to the reactivity of acetoin and its destruction during hydrolysis and subsequent operations. As a matter of fact, when the sodium compound first formed with ethyl acetate was acetylated, and then the ordinary procedures carried out, acetoin mono- and di- acetates were obtained without any difficulty. The schematic representation of the reaction was written as follows: 0
It
2RCOEt
+ 4Na -+
RCONa
11
RCONa VI
+ 2NaOEt
Wahl (2) obtained a small yield of benzoin by allowing two moles of sodium to react for three days with one mole of ethyl benzoate in ether solution. If the reaction-mixture stood for three months the yield of benzoin was increased to 14'%. Of the other products of the reaction, only benzoic acid was identified. Tingle and Gorsline (3) in the same year carried out a series of experi1 Presented at a Symposium on the Chemistry of Liquid Ammonia Solutions at the Milwaukee Meeting of the American Chemical Society, September, 1938. A preliminary note appeared in the J . Am. Chem. SOC.,61,215 (1939). 362
363
SODIUM AND ESTERS IN LIQUID AMMONIA
ments with ethyl benzoate and sodium in ether and in petroleum ether. They found large amounts of benzoic acid and only traces of benzoin. Chablay (4) treated acetic, butyric, isovaleric, and caproic esters in liquid ammonia with sodium, expecting either the acetoacetic ester or acyloin condensation to take place. He states that ethyl acetate gave acetoacetic ester, whereas the other esters yielded only the corresponding alcohols and amides. Scheibler and Voss (5) proposed a mechanism for the acyloin condensation which involves the formation of an ester enolate and its subsequent reduction by the hydrogen liberated in the reaction. The reactions were written as follows:
0
It
2CHlCOR
2HzC=C
/ONa
\
+ 2Na
+ 2H2
-
-
2CH&
2HzC=C
\
\
/ON,
H\
OR
/ONa
+ Hn
OR
-
CHaCONa
II
CH3CONa
+ 2ROH
OR
VI The difficulty with this mechanism lies in its inability to include in the reaction scheme non-enolizable esters such as ethyl trimethylacetate. This was recognized by Scheibler, and he proposed a special mechanism for non-enolizable esters (6).
0
11 RCOR’
- ONa
Na
/ONa
-+ RC
I\
OR’ I
Na
/
RC
I\
Na OR’
IV
I I
RCONa-
RCONa
11
RCONa
V
VI
There is little evidence to support Scheibler’s formulation of the reactions of the enolizable esters. If hydrogen is formed in the reaction, at least a portion would be expected to escape, and this is contrary to observation. The second mechanism in some aspects is similar to the one favored by us and described in this paper. Blicke (7) observed the formation of a red color and a flocculent precipitate when either one or two atoms of sodium were used with one mole of phenyl benzoate in ether. He isolated phenol and benzoic acid and deduced the presence of benzoin by qualitative tests, but did not isolate
364
KHARASCH, STERNFELD, AND MAY0
either benzil or benzoin. The following equations were proposed for the reaction : 0
II
2c~6coc6H6
1+
2Na
ONa ONa
I 2csH,cocsHs I
I
CsHsCOCsHs
+ * c&scoce& I I
C6RsC=C
I
csH&=o
ONa
+ 2NaOCeHI
I1
I11
I
I
.It H
H
H
H
H
ONa
OCsHHS
/
ONa
The existence of a free radical was postulated from the color of the products for either free radical could be written with a quinoid form. Blicke recognized that benzil was not necessarily an intermediate in the reduction of esters to acyloins, but that, phenyl benzoate and two equivalents of sodium might give
/ONa CsHaC
I\ Na OCdHs
(IV)
SODIUM AND ESTERS IN LIQUID AMMONIA
365
directly, and that this compound would then give the sodium derivative of benzoin. More recent work by Snell and McElvain (8) on aliphatic esters has shown that the reaction-mixtures in ether or benzene need not be kept below 10"during the reaction as recommended by Bouveault and Locquin. Thus, by heating the mixtures to the boiling point of the solvent throughout the reaction, they were able to isolate over 50% yields of the acyloins, except with ethyl acetate, where the yield was only 23%, Trimethylacetic ester gave 32% of the diketone, the other esters yielding less than 10%. The reaction was thought to take place in two steps: (A) The ester reacts with one mole of sodium to form the diketone-sodium ethoxide addition-product :
H
ONa
/
2 R OEt + 2 N a - R C
:a Rp /
\
OEt
I1 (B) The diketone-sodium ethoxide m tion-product is L e n converted by two atoms of sodium to the acyloin: RC/ONa
\
OEt ONa
R
RCONa +2Na-
e
R ONa
+ 2 NaOEt
VI
\
OEt I1
The authors suggested that the diketone-sodium ethoxide addition-product might result from the union of two free radicals as postulated by Blicke
366
KHARASCH, STERNFELD, AND MAY0
(7). They explain the formation of acids by the reactions previously proposed by Scheibler and Marhenkel (9).
8
R OEt
/ONa + NaOEt --+RC-OEt
\
OEt
0
R -0Et
ONa
/ RC-OEt \
OEt
+ HzO
P
+ EtOH + NaOH
0
" RE -0Na + 2EtOH
Evidence for this mechanism was obtained by treating ethyl butyrate with sodium ethoxide. Upon hydrolysis, the mixture yielded nearly 50% butyric acid. DISCUSSION
It seemed that further work on the reactions of liquid ammonia sodium solutions with esters would prove profitable, in that such a solution gives the ester an opportunity to react rapidly and completely with the sodium. Furthermore, the primary reaction is known to be over upon the disappearance of the characteristic blue color of the solution. Ethyl acetate, propionate, isobutyrate, trimethylacetate, phenylacetate, diphenylacetate, and benzoate were allowed to react with either one or two moles of sodium in liquid ammonia. The following general observations were made during the course of the reactions: (a) Only half a mole of ester was required to discharge the color of one mole of sodium if the ester ww added to the liquid ammonia solution of sodium. (b) No hydrogen gas was evolved when any of the esters reacted with either one or two moles of sodium nor was there any evolution of hydrogen gas when the reaction-mixtures were treated with ammonium bromide, regardless of the presence or absence of benzene as solvent for the ester. These facts imply that the carbonyl group of the ester is directly attacked, without a preliminary enolization. The products of the various reactions are summarized in Table I. The Table shows that in some instances reduction of ester to alcohol takes place to a considerable extent. In these experiments, however, roughly equivalent quantities of acid and amide are also formed. This is in agreement with our statement that only 0.50 (A.05) mole of ester per mole of sodium is required to discharge the color of a sodium solution. If direct reduction of ester t o alcohol were possible, only one-fourth mole of ester would be
367
SODIUM AND ESTERS IN LIQUID AMMONIA
TABLE I REACTION OF SODIUM WITH ESTERS YImD8' OP IDBNTIFIIDD PBODVCPB
Diketoni fig --
Acetic. ...........
2
ester 25% Acetic acid 83% Acetoin diacetate
2
Acetic. . . . . . . . . . . . Propionic. . . . . . . . .
2
Propionic. . . . . . . . .
1
Isobutyric. . . . . . . .
2
Isobutyric. . . . . . . .
2
Trimethylacetic.
.
2
Trimethylacetic.
.
2
Phenylacetic.. . . . .
2
Diphenylacetic. . .
2
11%
Benzoic. . . . . . . . . . .
2
14%
Benzoic. . . . . . . . . . .
2
Benzyl chloride 15%
Benzoic. . . . . . . . . . Benzoic. . . . . . . . . . . Benzoic. . . . . . . . . . .
2 2 1
Ethyl bromide W% t-Butyl bromide 20%
0
8% p-Aminocrotonic
25%
Acetic. . . . . . . . . . . .
Acetyl chloridc Trace
1
Based on ester used. them tars.
Other products
22% 18%
12% Ethyl bromide
28%
29%
Ethyl bromide
22%
30%
24% Propyl alcohol 10% Propionamide 30% Propionic acid 46% Propionic acid 12% Propionamide 10% Isobutyl alcohol 25% Isobutyric acid 8% Isobutyramide 32% Ethyl isopropyl ketone 15% &Butyl carbinol 6% Trimethylacetic acid 10% Trimethylacetamide 33% Ethyl t-butyl ketone 27% Phenylethyl alcohol 31% Phenylacetamide 36% Diphenylethyl alcohol 18% Benzophenone 32y0 Diphenylacetic acid 9% Benzamide 12% Benzoic acid 5% Desoxybenzoin 10% Isobenzamarone 8% Dibenzyl 15% Benzoic acid 34% Propiophenone 30% Valerophenone 28% Benzilic acid 25% Benzoic acid
In all case8 there were unidentified substances, some of
368
KHARASCH, STERNFELD, AND MAY0
required to react with one mole of sodium. Experiments with esters in the absence of sodium, but in the presence and absence of sodamide, show that the formation of amide is not due to ammonolysis of the ester. The formations of alcohol and amide are apparently related, and an obvious possibility is that both come from the disproportionation of an intermediate. Reaction of esters with one equivalent of sodium. An attempt to obtain diacetyl by reacting ethyl acetate with one equivalent of sodium was partially successful in that a product was obtained which boiled at 78-95' and gave the characteristic green ring test with thiophene-containing benzene and concentrated sulfuric acid. The diketone itself, however, was not isolated. In one experiment a few milligrams of yellow needles which resembled dimethylquinone (from the condensation of two molecules of diacetyl) were obtained, but these were contaminated with a nitrogenous impurity which rendered their analysis worthless. Experiments with ethyl propionate were more successful in yielding diketones. Dipropionyl was distilled with steam and identified by means of its 2,4dinitrophenylhydrazone. When ethyl benzoate was treated with one equivalent of sodium in liquid ammonia a deep red-purple color developed. Hydrolysis of the mixture yielded either benzil or a mixture of benzil and benzilic acid, depending upon the treatment of the reaction-mixture. It seemed probable that the monosodium ethyl benzoate compound can exist as a free radical in equilibrium with its dimer, similar to the metal ketyls. Some evidence for this hypothesis was obtained when oxygen was passed through the ammonia solution of monosodium ethyl benzoate. The color of the solution was black at first, then brown. Benzoic acid was the only product that was isolated, although an effort was made to obtain other products. The non-crystallizable material was a tar which exploded upon heating, indicating that peroxides may have been formed from free radicals in solution. Benzil was added to two equivalents of sodium ethoxide in liquid ammonia to test the reversibility of the reaction: ONa
2 CsH&
/ONa
I\
\
OEt ONa
OEt
I 'OEt
I1
SODIUM AND ESTERS IN LIQUfD AIdMdNIA
369.'
A purple color developed which could be instantly discharged by neutralizing the solution with ammonium bromide. This suggests that the sodium ethoxide addition-product of b e n d may dissociate into free radicals in much the same way as the sodium salt of benzpinacol, although the concentration of free radicals is probably small. Reaction of esters with two equivalents of sodium. In accordance with previous investigations, it was found difficult to obtain clear-cut results from the reduction of ethyl acetate with two atoms of sodium. Attempts to isolate pure acetoin resulted in low yields, but acetoin diacetate was formed in good yield if, upon evaporation of the ammonia, but before hydrolysis, the sodium compound was treated with acetyl chloride. The formation of pure acetoacetic ester claimed by Chablay as a result of the reaction of ethyl acetate with sodium in liquid ammonia has not been substantiated. We obtained, instead, a small amount of /3-aminocrotonic ester. This product was formed by a Claisen condensation of two molecules of ethyl acetate and subsequent ammonolysis of the product by the solvent, as shown by the fact that acetoacetic ester, when dissolved in liquid ammonia, gave better than an 80% yield of the amino ester. Ethyl propionate behaved like ethyl acetate except that it gave no evidence of a Claisen condensation under the conditions used; the same was true of the other esters investigated by us. Ethyl isobutyrate differed from ethyl acetate and ethyl propionate in that its sodium derivative was spontaneously inflammable in air; this suggested that the compound had a structure involving a sodium-to-carbon linkage according to the classical formulation (IV) .2 Further support for this formula was obtained by hydrolysis of the inflammable substance to isobutyraldehyde. 0
i-Pr-C
/ONa2
I\
+ 2 HzO -+
Na OEt
II
i-Pr-CH VI11
+ 2 NaOH + EtOH
IV
* Throughout this paper, as in this case, such formulas will be written as though the sodium ethoxide were an integral part of the molecule, though there is no evidence t o show whether the sodium ethoxide is free or associated with the reduced ester. If the sodium ethoxide is not an integral part of the molecule then the structure 0
II
R-C-Na
(V)
is more elegantly represented as a resonance hybrid of the following forms
[R:Cj@:]-Na+
and [R:C:O:]-Nst
370
K€IA#ASCH, STERNFgLD, AND MAY0
Formulation of the reaction of esters and sodium to give compounds of types IV or V has been postulated previously. Additional evidence of the existence of such compounds was obtained by treating the intermediate with ethyl bromide, and isolating ethyl isopropyl ketone from the reactionmixture: ONa ONa
/ \
+ EtBr -+
i-Pr-C-OEt
+ NaBr
Et
Na
IV ONa
/ i-Pr-C-OEt \
/ \
i-Pr-C-OEt
0
+ He0 -+
i-Pr-
e
-Et
+ NaOH + EtOH
VI1
Et
The simultaneous presence of isobutyrddehyde and isobutyroin, obtained as such and as the diacetate upon hydrolysis, suggests an equilibrium of the type given below:
/
ONa
i-Pr-C-ONa
2 i-Pr-C-OEt
\
i-PrNa
e
-0Na
+
2NaoEt
VI
IV Similar observations were made with trimethylacetic ester. Some aldehyde was obtained from ethyl phenylacetate by treatment with sodium in liquid ammonia. The corresponding acyloin, however, could not be isolated, though the high-boiling fraction, obtained as a syrup, reduced Fehling’s solution in the cold. This reaction, however, may have been due to an aldehyde polymer. Diphenylacetic ester with two equivalents of sodium gave a strong yellow color, deeper than the yellow from ethyl isobutyrate or phenylacetate. Instead of yielding diphenylacetaldehyde it gave benzophenone and a greater proportion of alcohol (diphenylethanol in this case) than any of the other esters. Further work would be necessary to determine the mode of formation of benzophenone. Striking results were obtained with ethyl benzoate and sodium in liquid ammonia. When the ester was treated with two equivalents of sodium a deep red solution resulted which resembled in color a solution of triphenylmethylsodium in liquid ammonia. Upon evaporation of the ammonia and hydrolysis of the red solid, benzaldehyde waa obtained in good yield. Treatment of the red solution with benzyl chloride gave desoxybenzoin
371
SODIUM AND ESTERS IN LIQUID AMMONIA
and isobenzamarone. This indicates a sodium-to-carbonlinkage analogous to that in triphenylmethylsodium. ONa /ONa / CsH&H2Cl-+ C6H&-OEt NaCl CsH&-0Et
\
+
+
\
Na IV ONa
CH2CsHs
0
Isobenzamarone is formed by the reaction of benzaldehyde and desoxybenzoin (10). Further indication of the structure of the sodium ethyl benzoate compound is furnished by the formation of propiophenone and valerophenone by treatment of the red solution with ethyl bromide and n-butyl bromide respectively. The reactions are similar to the one in which benzyl chloride is involved. That the sodium compound (IV or V) is presumably in equilibrium with the sodium salt of benzoin (VI) and sodium ethoxide is indicated by the following reactions. A red solution resulted when benzoin, suspended in liquid ammonia, was treated with sodium ethoxide and sodamide. The color was similar to that obtained from sodium and ethyl benzoate in liquid ammonia, but less intense. Upon hydrolysis of the reactionmixture, benzaldehyde was obtained, and upon addition of ethyl bromide and subsequent hydrolysis, propiophenone. These reactions indicate the identity of this red solution with that obtained from two moles of sodium and ethyl benzoate. The lower yield of aldehyde and less intense color when starting with benzoin may be due in part to differences in the state of suspension or solution of the reactants. C.~HH,C~
cas-c
C&&ONa
11
+2NaNH,-+
H ‘
+2NHa
C&CONa VI
M
0 CsHsCONa
11
CeHsCONa VI
+ 2 NaOEt
/ONa 2 C&C--OEt
\ IV
II
t-
2 CJLCOEt
Na
I
1
0 Ha0
~
II
CsHsC-H VI11
+ 4 Na
372
KHARASCH, STERNFELD, AND MAY0
We have been unable to secure evidence that diketones can be formed by the following sequence of reactions since the disodium ethyl benzoate compound in liquid ammonia did not yield a diketone when treated with ethyl benzoate2: ONa
When the reaction-mixtures were allowed to stand for a short time little reaction took place. On longer standing, tars were obtained. It seems appropriate at this point to discuss what relation the compounds formed by the action of sodium on ethyl benzoate bear to those obtained from benzil and sodium or potassium. Staudinger and Binkert (11) claim that the red compound from bensil and two atoms of potassium is the dipotassium salt of stilbenediol, in spite of the fact that the esters and ethers of stilbenediol are colorless. Their reason is that the ultraviolet absorp tion of salts of phenols and enols is much stronger and of a different type than that of the ethers and esters. These investigators did not consider the possibility of an equilibrium of the salts of the stilbenediol with benzoylsodium : 0 CaHSCONa
A
GHs ON& VI
*
A
2CsHs Na V
That such an equilibrium actually exists has been demonstrated by treating the reaction-product of benzil and sodium (the so-called stilbenediol salt) with ethyl bromide. Propiophenone in good yield was isolated from the reaction-mixture. It is conceivable, therefore, that the color of the compound is not due to the salts of the stilbenediol per se but rather to its equilibrium partners. The series of reactions which occurs when sodium reacts with esters is, in our opinion, best summarized by the scheme depicted in Figure I. As
373
SODIUM AND ESTERS IN LIQUID ~LMMONIA
indicated in the literature review, all of the compounds in Figure I have been isolated or suggested by previous workers. Our work presents better evidence for the existence of the free radical (I) and the “sodium-tocarbon” compound (IV) or (V). It indicates strongly the existence of 0
II
+ 2Ns
2RCOR’
ONa
I
1
/ RC \
OR’
/ONB 2RC-OR’
I
RC-O
*
I
ONs
R
/ \
I
+
2NsOR‘
O I11
RC
OR’
I1
1’”
7 , 0 2RC-OR‘
\
*
I
2RCNa
+
RCONs 2NaOR’
11
+
2NsOR‘
RCONs
Ns
RC=O
RCOAc
RC
RCOAc
0
0
II
RCR”
II 2RCH
VI1
VI11
\
I
H
IX
X
FIQIJRE 1.-The reaction of sodium with esters
one equilibrium between (I), (11), and (111) and another between (IV), (V), and (VI). We have also shown that liquid ammonia is a convenient solvent for study of the indicated reactions because they take place very rapidly in a homogeneous solution at low temperature.
374
KHARASCH, STERNFELD, AND MAY0 EXPERIMENTAL PART
Procedure I . Reaction of esters with two equivalents of sodium. The sodium was dissolved in 100-500 g. of liquid ammonia contained in a clear glass Dewar flask equipped with a stirrer, dropping-funnel, and escape valve. The ester, in pure form or in dry benzene solution, was then added t o the ammonia solution drop by drop until the blue color of the sodium was entirely discharged. The reaction was very vigorous at first, more so with ethyl isobutyrate, trimethylacetate, and benzoate than with ethyl acetate or propionate, but abated in violence as the sodium was consumed. The mixture was then forced over into a filter flask under its own pressure and the liquid ammonia evaporated by suction. Ice and water were added along with an organic solvent, either benzene or ether. The hydrolyzed mixture was separated into aqueous and organic portions, the aqueous solution extracted rapidly with three or four successive portions of benzene or ether, acidified, and again extracted thoroughly. In a number of experiments this procedure was reversed, the original mixture being hydrolyzed with sulfuric or acetic acid and then made basic for the extraction of nitrogenous compounds. No significant difference in the results was noted. The basic and acidic organic solutions were washed twice with a saturated salt solution, then dried over anhydrous sodium sulfate and distilled. Procedure II. Reaction of esters with one equivalent of sodium. The liquid ammonia solution of sodium prepared as above was forced under its own pressure into a previously cooled round-bottomed flask containing the ester and equipped with an escape valve and stirrer. The ester could not be added to the sodium solution directly, as all the sodium would react when only half the ester had been added. The reaction-mixture was then evaporated and treated as above. Reaction of ethyl acetate with sodium. When treated according to Procedure I (2 equivalents of sodium), 9 g. of ethyl acetate gave 1.2 g. of acetoin, b.p. 147-153", identified as the phenylhydrazone, m.p. 82-84' (12). Anal. Calc'd for C10H14N20:N, 15.73. Found: N, 15.51. p-Aminocrotonic ester, b.p. 103" a t 15 mm., was identified as the copper salt, m.p. 182". Evaporation of the basic water solution and acidification yielded 1.5 g. of acetic acid, b.p. 118". To obtain the acetoin diacetate, the dry solid left from the sodium-ester reaction after evaporation of the ammonia i n vacuo, was treated with a slight excess of acetyl chloride in benzene with strong cooling. The sodium chloride was collected and washed several times with benzene. The filtrate and washings were combined and distilled. Nineteen grams of ethyl acetate yielded 14 g. of acetoin diacetate which boiled a t 203", and 3 g. of a liquid which boiled at 203-214". A distinct odor of acetic acid suggested that some of the ester had decomposed, and treatment of a small portion of the lower-boiling liquid with semicarbazide gave the semicarbazone of acetoin monoacetate, m.p. 163-164'. The liquid was therefore redistilled i n vacuo. Almost all of the product boiled at 103-105" at 20 mm. Anal. Calc'd for C8H1204: C, 51.72; H, 6.89. Found: C, 51.54; H, 6.63. Acetyl determinations on this substance gave no conclusive results : short periods of hydrolysis with aqueous sodium hydroxide gave one acetyl group per molecule, whereas long periods of refluxing gave more than two, due t o the decomposition of acetoin into acid products. When ethyl acetate was treated with one equivalent of sodium as outlined in Procedure 11, i t gave mostly unidentified high-boiling products and tar. A portion
SODIUld AND EBTaRS IN LIQUID AMMONIA
375
was subjected t o distillation and the fraction of b.p. 78-95', when mixed with thiophene-containing benzene and treated with concentrated sulfuric acid, gave the green ring test characteristic of diacetyl. Semicarbazide, phenylhydrazine, and 2,4-dinitrophenylhydrazine,however, all failed to yield any identifiable derivative. The lack of yellow color in the fraction itself showed that i t was a t most a very dilute solution of the diketone. Approximately 0.1 g. of yellow needles melting a t 123-125" separated from the portion of the product not subjected to distillation. The color and melting point suggested that they might be 2,5-dimethylquinone (m.p. 124-125') from condensation of diacetyl, but analysis showed that they contained 14% of nitrogen. Reaction of ethyl propionate with sodium. Twenty grams of ethyl propionate was added t o 9.2 g. (2 equivalents) of sodium in liquid ammonia as in Procedure I. The following products were isolated: 1.3 g. of propionamide, m.p. 76-78', 3 g. of propyl alcohol, b.p. 97-100"; 4.5 g. of propionic acid, b.p. 129-135"; and 2.6 g. of propioin, b.p. 67-72' a t 18 mm. This yielded a 2,4-dinitrophenylhydrazonewhich melted a t 154'. Anal. Calc'd for C I ~ H ~ B N ~N, O S18.92. : Found: N, 18.96. Ten grams of ethyl propionate treated with one equivalent of sodium as in Procedure I1 yielded 8.5 g. of light yellow liquid, b.p. 85-110". This wide fraction was collected because the yellow color began t o appear when the temperature of the distilling vapors was as low as 85". The distillate gave the green ring test for 1,2diketones and precipitated the 2,4-dinitrophenylhydrazone of dipropionyl, m.p. 145-145.5'. AnaE. Calc'd for C12H14"406: N, 19.06. Found: N, 19.20. The quantity of hydrazone which was isolated corresponded t o a weight of 1.3 g. of dipropionyl in the original mixture. Reaction of ethyl isobutyrate with sodium. Twelve grams of ethyl isobutyrate was added t o 4.6 g. (2 equivalents) of sodium in liquid ammonia as in Procedure I. Two grams of a liquid, b.p. 110-112", was identified as isobutyl alcohol by its 3,5-dinitrobenzoate, m.p. 63-64". Anal. Calc'd for CllHsNzOe: N, 10.56. Found: N , 10.63. From the acidified aqueous solution were extracted 3.7 g. of isobutyramide m.p. 128', and 0.8 g. of isobutyric acid, identified as the ammonium salt, m.p. 118". Twelve grams of ethyl isobutyrate in 50 cc. of benzene was added to 4.6 g. (2 equivalents) of sodium in liquid ammonia and treated as in Procedure I. The fraction boiling a t 58-67' gave 2 g. of isobutyraldehyde, calculated from the weight of its 2,4-dinitrophenylhydrazone,m.p. 181". One gram of isobutyl alcohol was collected a t 109-112' and 1 g. of isobutyroin distilled a t 80" (20 mm.). It was identified as the oxime, m.p. 109". Anal. Calc'd for CBHlrNOz: N, 8.50. Found: N, 8.63. Twelve grams of ethyl isobutyrate was added to 4.6 g. (2 equivalents) of sodium in liquid ammonia. To the resulting mixture was added 11 g. of ethyl bromide, and the reaction-mixture was worked up as in Procedure I. The fraction boiling a t 116-118" (3 g.) was pure ethyl isopropyl ketone as indicated by the quantitative isolation of its 2,4-dinitrophenylhydrazone, which melted a t 168-169". Anal. Calc'd for C12H18N404:N, 20.00. Found: N, 20.04. Reaction of ethyl trimethylacetate with sodium. Thirteen grams of ethyl trimethylacetate was added t o 4.6 g. (2 equivalents) of sodium in liquid ammonia. After treatment as in Procedure I, the fraction of the distillate boiling up to 80" was treated with 2,4-dinitrophenylhydrazine,whereupon the 2,4-dinitrophenylhydra-
376
RRARASCH, STERNFELD, AND MAY0
zone of trimethylacetaldehyde separated. The melting point after crystallization from ethyl alcohol was 210" (12). Anal. Calc'd for CIIHI;NIO~:N, 21.13. 'Found: N, 20.96. Of the remaining liquid, which had a marked camphor-like odor, 1.3 g. boiled a t 110-114°, solidifying when cooled, and melting a t 47". It was identified as t-butyl carbinol. Two and one-half grams of pivaloin was obtained. It boiled a t 92-103" (30 mm.), m.p. 77-80". Approximately 1 g. of trimethylacetamide, m.p. 178", remained in the distilling flask. From the aqueous layer upon acidification was obtained about 0.5 g. of trimethylacetic acid, m.p. 3235". Eight grams of ethyl trimethylacetate was added to 3 g. (2 equivalents) of sodium in liquid ammonia, and 8 g. of ethyl bromide was added to the mixture. The mixture, upon hydrolysis, yielded 2.5 g. of ethyl t-butyl ketone, b.p. 120-126'. Further confirmation was obtained by the preparation of the 2,4-dinitrophenylhydrazone, m.p. 175". Anal. Calc'd for C I I H ~ ~ N N, ~ O19.05. ~: Found: N, 18.90. Reaction of ethyl phenylacetate with sodium. Sixteen grams of ethyl phenylacetate was added to 4.6 g. (2 equivalents) of sodium in liquid ammonia. The following products were isolated: 3 g. of 8-phenylethyl alcohol b.p. 115-120" (25 mm.), identified as the phenylurethane, m.p. 80"; 4 g. of phenylacetamide, m.p. 155", identified by its mercury salt, m.p. 205-207"; 0.8 g. of phenylacetaldehyde, identified as the 2,4-dinitrophenylhydrazone, m.p. 240" (13). Anal. Calc'd for CI&&~N~O(: N, 18.68. Found: N, 18.41. Reaction o j ethyl diphenylacetate with sodium. Seventeen grams of ethyl diphenylacetate was added to 3 g. (2 equivalents) of sodium in liquid ammonia. The mixture, upon hydrolysis, yielded 5.1 g. of 2,2-diphenylethanol, m.p. 64-65", and 2.3 g. of benzophenone, b.p. 275-280". The alcohol, upon analysis, gave the following results : Anal. Calc'd for c14&40: C, 84.85; H, 7.07. Found: C, 84.92; H, 6.94. It was further identified as the oxalate, m.p. 159.5-160" (14). The benzophenone was identified as the 2,4-dinitrophenylhydrazone,m.p. 238". Anal. Calc'd for CloH14N404:N, 15.47. Found: N, 15.48. That portion of the organic layer which did not distill up to 310" was crystallized from methyl alcohol. A solid wm obtained which melted a t 100". It reduced Fehling's solution upon heating for five minutes in boiling water, but failed to yield a hydrazone. Analysis suggests that the compound is tetraphenylacetoin. This compound is not described in the literature and no effort was made t o characterize i t further. C, 85.74; H, 6.12. Anal. Calc'd for C&&: Found: C, 86.02; H, 6.40. From the basic water solution, upon acidification, 4.4 g. of diphenylacetic acid, m.p. 146", was obtained. Reaction o j ethyl benzoate with sodium. Fifteen grams of ethyl benzoate in 50 cc. of dry benzene was added to 4.6 g. (2 equivalents) of sodium in liquid ammonia. After treatment as in Procedure I, the following products were isolated: 5 g. of benzaldehyde, b.p. 174-BO", identified as the 2,4-dinitrophenylhydraeone,m.p. 236", and 1.2 g. of impure benzoin, m.p. 128-130", b.p. 220-230" (40mm.). The pure 2,4-dinitrophenylhydrazoneof benzoin was obtained after several crystallizations from methyl alcohol. It melted sharply at 234" (12). The yield of benzoin was increased t o So% by the following procedure: t o 14 g. (0.1 mole) of ethyl benzoate in liquid ammonia was added 4.6 g. (0.2 atom) of sodium
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377
in small slices. A violent reaction occurred with the addition of each slice. After the usual treatment (in this case the mixture was acidified immediately after evaporation of the ammonia), 5 g. of benzoin, m.p. 129-130", crystallized from ether solution. Fifteen grams of ethyl benzoate was added to 4.6 g. (2 equivalents) of sodium in liquid ammonia. The mixture was stirred for a short time and 12.6 g. of benzyl chloride was added slowly. After treating as in Procedure I, 7.5 g. of material which boiled a t 195-280" (8 mm.) was collected. On repeated crystallizations of the distillate from ether and petroleum ether, two products were obtained: 1.5 g. of dibenryl, m.p. 50", and 0.3 g. of isobenzamarone, m.p. 179". Anal. Calc'd for C&2,02: C, 87.67; H, 5.63. Found: C, 87.58; HI 5.69. The mother liquors were evaporated t o dryness and the residue was extracted with cold methanol. Upon refluxing the methanol extract with 2,4-dinitrophenylhydrazine, the hydrazone of desoxybenzoin was obtained] contaminated with some of the 2,4-dinitrophenylhydrazone of benzoin. After three crystallizations from methyl alcohol the pure hydrazone of desoxybenzoin was obtained. It melted at 181" and its melting point was not depressed by the addition of a known sample. The methanol-insoluble residue was dissolved in hot ethyl alcohol and yielded, upon addition of 2,4-dinitrophenylhydrazine, the hydrazone of benzoin, m.p. 232-234". Extraction of the residue which was insoluble in cold methanol with very dilute alkali, and acidification, yielded 2.6 g. of benzoic acid, m.p. 121". To the red mixture from 15 g. of ethyl benzoate and 4.6 g. (2 equivalents) of sodium in liquid ammonia was added 11 g. of ethyl bromide. The red color faded t o light brown. The material was hydrolyzed in the usual manner, and upon distillation gave 4.4 g. of propiophenone, b.p. 198-218". Three grams of benzoin was obtained by crystallization of the residue. Other high-boiling compounds not identified may represent mono- or di- ethyl ethers of benzoin. The propiophenone was identified as the 2,4-dinitrophenylhydrazone,which was found not t o depress the melting point of an authentic sample. To the red mixture from 15g. of ethyl benzoate and 4.6 g. (2 equivalents) of sodium in liquid ammonia was added 13 g. of n-butyl bromide. After the usual treatment] the mixture upon distillation yielded 4.7 g. of valerophenone, b.p. 135-152" (30 mm.). The valerophenone was further characterized by the preparation of its 2,4-dinitrophenylhydrazone, m.p. 154", and by analysis. Anal. Calc'd for C1,HlsNIOI: N, 16.87. Found: N, 17.02. Of the remaining organic material, 7.5 g. boiled a t 185-320" at 30 mm., partly solidifying in the receiver. Two grams was identified as benzoin (the 2,4-dinitrophenylhydrazone melted at 234'). The remainder, unidentified, may represent mono- or di- butyl ethers of benzoin or their decomposition-products. Two and one-half grams (0.8 equivalent) of sodium in liquid ammonia was added to 20 g. of ethyl benzoate according to Procedure 11. Four grams of benzil distilled at 120-130" at 3 mm. and was characterized by the preparation of the 2,4-dinitrophenylhydrazone, m.p. 184-185" (13), and analysis. Anal. Calc'd for CeoHlrN,Os: N, 14.30. Found: N, 14.21. In a similar experiment, the alkaline water layer was shaken several times with the organic layer and allowed to stand for some period before separation. Under these conditions 2 g. of benz-il was isolated and identified as the 2,4-dinitrophenylhydrazone. Three grams of benzilic acid, identified by its deep red color in concentrated sulfuric acid solution and its neutralization equivalent, was obtained upon acidification of the aqueous solution.
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Reaction of benzoin with sodium ethoxide and sodamide i n liquid ammonia. T o 2.3 g. of sodium dissolved in liquid ammonia were added a few crystals of anhydrous ferric nitrate. After the sodium had reacted completely, 2.3 g. of absolute alcohol was added dropwise. Five grams (0.024 mole) of benzoin was then added in small portions. A red color developed, lighter in shade than that from ethyl benzoate and sodium. Subsequent treatment as in Procedure I gave 1.2 g. of benzaldehyde 2,4-dinitrophenylhydrazone, m.p. 236'. Four grams of benzoin, m.p. 135-137', was recovered. A few drops of a viscous liquid distilled above 340", and a little tar remained in the distilling-flask. Five grams of benzoin was added to a mixture of sodium ethoxide and sodamide prepared as above. The red mixture was then treated with 11 g. of ethyl bromide, the red color becoming light brown. When hydrolyzed, the mixture upon distillation yielded 1.6 g. of propiophenone, b.p. 198-220" (2,4-dinitrophenylhydrazone, m.p. 190"). One and one-half grams of benzoin was recovered; the remainder of the material (3 g.) was a t a r which decomposed upon attempted distillation. Reaction of benzil with sodium i n liquid ammonia. Ten grams of benzil in 100 cc. of dry ether was added to 2 g. (2 equivalents) of sodium in liquid ammonia and the red solution treated with 15 g. of ethyl bromide. The usual procedures of hydrolysis and distillation yielded 1.5 g. of propiophenone, b.p. 190-206', 2,4-dinitrophenylhydrazone, m.p. 188-190". The melting point of the hydrazone was not lowered by the addition of an authentic sample. The water solution, upon acidification, yielded 2 g. of benzoic acid, m.p. 119-120". SUMMARY
1. Equilibria and intermediate products in the acyloin condensation have been investigated in liquid ammonia, an excellent solvent for this purpose. 2. New evidence is presented that the action of one and two equivalents of sodium with an ester gives respectively a free radical and a very reactive organo-sodium compound. 3. It is shown that similar compounds can be obtained by the combined action of sodamide and sodium ethoxide on a diketone or an acyloin. CHICAGO, ILL. REFERENCES
(1) BOUVEAULT AND LOCQUIN, Bull. SOC. chim., (3) 36, 629 (1906). (2) WAHL,Bull. SOC.chim., (4)3, 947 (1908);Compt. rend., 147, 74 (1908). (3) TINGLE AND GORSLINE, Am. Chem. J.,40, 84 (1908). (4) CHABLAY, Ann. chim., (9) 8 , 205 (1917). (5) SCHEIBLER AND Voss, Ber., 63, 388 (1920). AND EMDEN, Ann., 434, 265 (1923). (6) SCHEIBLER (7)BLICKE,J. Am. Chem. Soc., 47, 229 (1925). (8) SNELLAND MCELVAIN, J. Am. Chem. Soc., 63, 750 (1931). (9) SCHEIBLER AND MARHENKEL, Ann., 468, 8 (1927). (10) KNOEVENAGEL AND WEISSGERBER, Ber., 26, 437 (1893). (11) STAUDINGER AND BINKERT, Helv. Chim. Acta, 6 , 703 (1922). (12) PECHMANN AND DAHL,Ber., 23, 2421 (1890). (13) ALLEN, J. Am. Chem. SOC.,62, 2955 (1930). AND CLAPP, J . erg. Chem., 3, 359 (1938). (14) KHARASCH
