RESEARCH
In Brief from the 147th ACS National Meeting Stable oxapentadienyl dianion radicals and trianions, oxabutadienyl trianion radicals, and oxapropenyl dianion radicals have been made by Dr. Nathan L. Bauld of the University of Texas, Austin. Stepwise electronation of certain organic anions by alkali metals in tetrahydrofuran (THF) gives the deeply colored species. The electrons enter low-energy vacant molecular orbitals to form the anion radicals. They are formed in high yield (quantitative in some cases) and are stable under nitrogen, Dr. Bauld told the Division of Organic Chemistry. The enolate of dibenzoylmethane (which is the anion of the 2,4-diphenyl1,5-dioxapentadienyl system) reacts with one equivalent of potassium in THF at —78° C. to give a deep-green pentadienyl dianion radical. A second equivalent of potassium converts the dianion radical into the blue trianion. The dianion radical is paramagnetic; the trianion diamagnetic. Both species are reoxidized to the starting enolate by nickel chloride in 9 0 % yield. Excess potassium converts the red 2,3-diphenyl-l,4-dioxabuta-' dienyl (benzil) dianion to a purple trianion radical. The blue 2-phenyl-l-oxapropenyl dianion radical (the dianion radical of the enolate of acetophenone) is stable for several days at room temperature. It is distinctly different from the known, unstable amber ketyl of acetophenone. Glyoxal, a-keto acids, and pyruvic aldehyde are degradation products produced in plastic building materials exposed to carbon-arc or solar radiation. Identification of these compounds was made by chemists at the National Bureau of Standards, Washington, D.C. The NBS study centered on two plastics widely used in the building industry—polymethyl methacrylate and cellulose acetatebutyrate. Exposed samples of the plastics were dissolved in acetic acid, and the solutions added to phenylenediamine solution to produce a pronounced color. Ultraviolet and visible spectra of these solutions show the presence of the degradation products, NBS' V. E. Gray and Dr. J. R. Wright told the Division of Organic Coatings and Plastics Chemistry. Formation of hemimlcelles by alkyl surfactant ions at solid-liquid interfaces has been verified by chemists at the University of California, Berkeley. Hemimicelles, which are two-dimensional clusters of associated ions, begin to appear when adsorbed ions reach a certain critical concentration at the interface. Basis for this formation is the van der Waals interaction between the alkyl chains of adjacent adsorbed ions, Dr. Thomas W. Healy of the university's department of mineral technology told the Kendall Award Symposium of the Division of Colloid and Surface Chemistry. The system studied by Dr. D. W. Fuerstenau and co-workers Dr. Healy and Dr. P. Somasundaran was silica in aqueous solutions of alkylammonium ace42
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tates. Evidence for hemimicelle formation was obtained by determining the effects of chain length on the electrokinetic potential of the system. From this study, the Berkeley research workers obtained a value of the van der Waals cohesive energy per methylene group of 0.97 kT, or 580 calories per mole. This agrees very closely with the energy value determined from properties of solutions of alkyl surfactants. According to Dr. Healy, this agreement substantiates the hemimicelle hypothesis, and adds weight to the validity of electrokinetic techniques.
A unique scission of the nitrogen-nitrogen bond of the symmetrical dialkylhydrazine, l-(2-diethylaminoethyl)-2-(amethylphenethyl) hydrazine, occurs in acid. Products of the scission are dl-amphetamine and diethylaminoethylamine. Mechanism of the reaction isn't known, but a cyclic intermediate may form during the cleavage, Dr. Edward F. Elslager, Dr. Enta A. Weinstein, and Dr. Donald F. Worth of Parke-Davis told the Division of Medicinal Chemistry. The hydrazine compound is stable in alkali. Salts of 1-alkyl and aralkyl-2-(a:-methylphenethyl) hydrazine are stable in acid. This suggests that the cleavage reaction depends on the proximity of the protonated tertiary amine of the hydrazine.
Several 2,2-dialkyl-A'isoflavens can block secretion of pituitary gonadotropin hormone. This hormone controls production of male and female sex hormones. Some antigonadotropic compounds have been used to treat hormone-linked cancers. Surprisingly, the 2,2-dialkyl-A'5isoflavens tested so far have relatively little estrogenic activity, Dr. C. E. Cook, Dr. M. E. Wall, and R. C. Corley of Research Triangle Institute (Durham, N.C.) told the Division of Medicinal Chemistry. Some 2-alkyl-A"*-isoflavens have estrogenic activity approaching that of diethylstilbestrol. But the compounds are difficult to make. The RTI scientists have developed methods for making the closely related dialkyl compounds easily in large quantities from commercial chemicals.
A new antidepressant affects only the amygdala of the brain of test animals. The specific activity of 5-(2-dimethylaminoethyl)-2,3-dihydro-2-phenyl-1,5- benzothiazepin-4(5H)-one hydrochloride (SQ 10496) may help define functions of certain areas of the brain, Dr. John Krapcho and Dr. Chester F. Turk of The Squibb Institute for Medical Research told the Division of Medicinal Chemistry. The amygdala is part of the limbic system of the brain which is involved with emotional and defense reactions.
Photoisomerization Depends On Concentration Photolysis of high concentrations of difuryl and dithienyl ethylene gives trans isomer NATIONAL
MEETING
Organic Chemistry Photolysis of difuryl ethylene and dithienyl ethylene at high concentra tions gives the more stable trans iso mer, according to studies made by Dr. C. M. Orlando, Jr., Dr. A. A. Zimmerman, and Dr. M. H. Gianni of Esso Research and Engineering Co. (Linden, N.J.). This is contrary to the general rule that photoisomeriza tion of olefins favors the less stable cis isomer. The general rule appears to be based on studies made at low concentrations, the Esso Research workers say. How ever, they find a concentration depend ence of photostationary states for the difuryl and dithienyl ethylene systems at concentrations ranging from 1M to about 1 0 - 3 M . The Esso Research results agree with recent work done with 4-nitro3'-methoxystilbene by Dr. D. SchulteFrohlinde, Dr. H. Blume, and Dr. H. Gusten of Kernforschungszentrum Karlsruhe, Strahlen Chemisches Laboratorium, Karlsruhe, West Germany. These workers also find a dependence of photostationary states on concen tration. The photolyses done by the Esso Research group were run on degassed benzene solutions of the cis and trans isomers of difuryl and dithienyl ethyl ene at 30° C. using a 275-watt sun lamp. Composition at equilibrium was determined by capillary gas chroma tography with a 150-foot silicone col umn. The percentage of trans isomer rela tive to cis increases markedly at high concentrations. For example, at 0.001M difuryl ethylene, there is 39% trans isomer present at the photosta tionary state. At 1M, 97% trans isomer is present. With dithienyl ethylene, the percentages of 'trans isomer present at the photostationary state increase from 9% at 0.01 Ai to 69% at 0.54M. The three Esso Research chemists
propose two competing mechanisms to account for the dependence of the photostationary states on concentra tion. The isomerization path for the cis-to-trans conversion involves vibra tional^ excited ground state molecules arising from the first excited singlet state via internal conversion. Com peting with this mechanism is a series of reactions for the trans-to-cis conver
sion involving an electronically excited triplet intermediate. At high concentrations of olefin, quenching reactions interfere with the mechanism involving the electronically excited triplet state. Thus the singlet mechanism predominates, reducing the trans-to-cis interconversion at these concentrations, favoring formation of trans isomer.
Cis, Trans Photoequilibriurrι Is a Function of Olefin Concentration DIFURYL ETHYLENE Molar concentration % Trans*
10°
% Cis*
97 70 49 39
10- 1 ΙΟ"2 ΙΟ-3
DITHIENYL ETHYLENE Molar concentration % Trans* 1
3 30 51 61
% Cis*
31 70 87 91
69 30 13 9
5.4 X 103 X 10-»
ίο- 1 io-2
* At equilibrium after photolysis.
100 A Difuryl ethylene
f\·
• 4-Nitro-3'-methoxystilbene
90
• Dithienyl ethylene -
80
• \
>v
70
κη
\
\ \
en CD
ACS
% Trans somer
147TH
40
\ \
!
*>. ^
\β
\
^
_
i *••"
\ \
30
1
\
^ ^ *
\v \
•
2oJ
•
.
.
\V
·
Ίι
v^.\^
10
0 10°
ίο- 2
io- 3
Molar concentration
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43
Ketones Cleaved at Room Temperature Cleavage of nonenolizable ketones is done with potassium tert-butoxide in dimethyl sulfoxide 147TH
ACS
NATIONAL
MEETING
Organic Chemistry
Nonenolizable ketones can be cleaved to acids and hydrocarbons at room temperature by treating the ketones with a dimethyl sulfoxide (DMSO) solution of potassium ier£-butoxide. Camphenilone, nortricyclanone, 7-ketonorbornene, benzopinacolone, and dehydronorcamphor give the cor responding acids in yields ranging from 9 to 80%, according to studies made by Dr. Paul G. Gassman and Frank V. Zalar of The Ohio State Uni versity, Columbus. The cleavage of ketones to acids with base generally requires high tem peratures and strongly basic media (such as fusion with potassium hy droxide or heating with potassium hy droxide in ethylene glycol). However, the Ohio State work provides a cleav age reaction under fairly mild condi tions (at room temperature, for in stance). Treatment of nortricyclanone with a dimethyl sulfoxide solution of potas sium terf-butoxide at room tempera ture gives bicyclo[3.1.0]hexane-3-carboxylic acid and a nortricyclanone-dimethyl sulfoxide addition product. The yield of acid depends on time, base concentration, and molar equiva lents of base. Under optimum condi tions, the acid can be obtained in 67% yield. The cleavage doesn't give an isomerization of the carboxyl group. The mechanism of the reaction is uncertain. Formally, the reaction in volves the addition of water to the ketone. However, the reaction can be carried out under anhydrous condi tions. Attack by any of three anionic species—tert-butoxide ion or dimethyl sulfoxide anion with either a nucleophilic carbon or with a nucleophilic oxygen—can be proposed, the Ohio State workers say. Their experiments indicate that the presence of tertbutoxide ion isn't necessary for the re action to take place. The production of the addition product of nortricycla none and dimethyl sulfoxide indicates that the dimethyl sulfoxide anion con 44
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taining a nucleophilic carbon is actu ally present during the cleavage reac tion. However, its role or that of the addition product in the cleavage is not known. Dehydronorcamphor gives an 80% yield of A 3 -cyclopentenylacetic acid when treated with four equivalents of potassium ierf-butoxide in DMSO (di luted with 0.8 equivalent of water) at room temperature. Previously, this cleavage had been carried out by treat ing dehydronorcamphor with sodamide (in 33%? yield to give the amide of A 3 -cyclopentenylacetic acid) and with potassium teri-butoxide in refluxing tert-butyl alcohol by Dr. S. J. Cristol and Dr. Peter K. Freeman at the University of Colorado, Boulder, [JACS, 83, 4427 (1961)]. The major product was a 3 1 % yield of a conden sation product; the acid was obtained in 19% yield.
Treatment of 7-ketonorbornene with potassium ferf-butoxide in DMSO gives a mixture of two acids in 50% yield. One of the acids is A:i-cyclohexenecarboxylic acid (32% ), and the other is A^cyclohexenecarboxvlic acid (18%). An instantaneous red color is formed when benzopinacolone is added to a DMSO solution of potassium tert-bu toxide. The color stems from the cleavage of the ketone to the triphenylmethyl anion. A quantitative yield of the anion is obtained. The reaction is 97% complete in 135 seconds at room temperature. Dehydronorcamphor, 7-ketonor bornene, and benzopinacolone all form stabilized anions when cleaved, thus providing a driving force for the re action. A ketone which doesn't pro vide such a driving force is camphenil one. This ketone also undergoes cleavage with potassium terf-butoxide, but gives β-dihydrocamphoceenic acid in only 9% yield. Formation of a large yield of DMSO-camphenilone adduct seems to be the cause of the low yield, according to the two Ohio State chemists.
Cleavage Gives Acids, Hydrocarbons
amp em one •Adduct products aren't shown *Under optimum conditions
*A?-Cyclohexenecarboxylic acid e 1 A -CycIohexenecarboxylic acid d Triphenylmethane yield is quantitative
Evidence Points to Two Competing Reactions N-OTs H
çf
ThMsBr 4-tert-Butylcyclohexanone oxime tosylate
Evidence obtained
4-tcrt-Butylcyclohexanone anil
with analogous compounds
5-terl-Butyl-2-phenyl1-azacycloheptene
.. .
OTs
M*&r*
Ο II
CH3c=N-C2H5
OTs
H" H2o
ThMpT
I
Ν II CH3C-CM2CH3_
C2H5ON-CH3
CK 3 -c-Ph + CoHc-C-Ph *
*
OTs
Methyl ethyl ketone oxime tosylate
II
ο
NJ-PH
Th. M g ~ C H 3 - c - C * H 5 . . . Indicates mechanism
•phNH.
^
with two competing
reactions
"N-OTs
-,
N-Ph n
Addition-elimination
N-OTs "PhMgBr
+ ?h2Mg
^
Direct substitution sub
V [TSÎ*T^Î,CH3^SOZ~]
Oxime Tosylates React with Grignards Reactions with phenylmagnesium bromide give rearranged Schiffs bases in about 80% yield 147TH
ACS
NATIONAL
MEETING
Organic Chemistry Oxime tosylates react with Grignard reagents via a molecular rearrangement which gives Schiffs bases in about 80% yield. This observation stems from research done at the University of New Hampshire (Durham) by Stanford S. Pelosi, Jr., and Dr. Robert E. Lyle. Reactions of oximes and oxime derivatives with Grignard reagents
generally give poor yields of ethylene imines. α-amino alcohols, and amines. Usually, unreached starting oxime is recovered. Such reactions fail to proceed in high yield because of the negative charge on the oxygen. This negative charge results from the loss of the proton from the oxime during its initial reaction with the Grignard re agent. Therefore, the New Hampshire workers predicted that replacement of the oximino hydrogen by a substituent unreactive to the Grignard reagent would allow the reactions to proceed
in good yield. This is the case, for example, with the O-tosyl derivatives of oximes. Tosylate is a good leaving group and thus allows formation of a reactive electron-deficient nitrogen. For example, 4-/
