Potassium T-butoxide In T-butyl Alcohol Research Articles

The Conversion of Ethyl Dienol Ether and Dienyl Pivalate Derivatives of Hagemanns Ester Into Bicyclic Enones

The cyclization of compounds obtained from ethyl dienol ether and dienyl pivalate derivatives of Hagemann's ester has been examined. The carbanions of methyl phenyl sulfone and methyl phenyl sulfoxide react with the methylated dienol ether (4) to give the β-keto sulfone (8) and sulfoxide (9), the former of which was converted into the oxabicyclo[4.3.0]non-1-en-3-one (16). The iodide (17) with potassium t-butoxide in t-butyl alcohol gave the octahydronaphthalenone (18). With lithium ethoxide in tetrahydrofuran the octahydronaphthalenedione (22) was obtained from the dienyl pivalate (24). Both reactions involve the generation and intramolecular cyclization of a dienolate produced by cleavage of the pivaloyl group in each of (17) and (24). The scope and limitations of these reactions are briefly discussed.

Synthesis and photochemistry of 5-hydroxy-5β-cholest-3-en-6-one

Reaction of 3β-benzyloxy-5-hydroxy-5α-cholestan-6-one (1) with potassium t-butoxide in t-butyl alcohol gives 5-hydroxy-5β-cholest-3-en-6-one (2), which on direct irradiation (300 nm) in hexanes gives the B-seco steroid 9 and the indenacetaldehyde derivative 10.

Bicyclo[3.3.0]octenones in synthesis. A new synthesis of (±)-cedrene using sequential inter- and intra-molecular Michael reactions

A new synthetic approach to cedrene (1) based on sequential inter- and intra-molecular Michael reactions using the bicyclo[3.3.0]octenone (21) as the key intermediate is described.Michael addition of the enolate derived from (21) to 2-nitrobut-2-ene, led to a mixture of diastereoisomers of the nitro ketone (22), which was then converted into the 1,4-dione (23). Treatment of (23) with potassium t-butoxide in t-butyl alcohol resulted in smooth intramolecular Michael reaction leading to a mixture of α-(24a; major) and β-isomers of thetricyclo[5.3.1.01,5]undecanedione (24) in a combined yield of 73%. The undecanedione (24) was then converted into (±)-cedrene (1) and the corresponding methyl epimer (31a)via the intermediates (25), (26), (27) and (28).

Condensed cyclic and bridged-ring systems. Part 10. Alumina-induced regioselective intramolecular alkylations of cis- and trans-4a-(2-methylsulphonyloxyethyl)-3,4,4a,9,10,10a-hexahydrophenanthren-2(1H)-ones

The synthesis and intramolecular alkylations of cis- and trans-4a-(2-methylsulphonyloxyethyl)-3,4,4a,9,10,10a-hexahydrophenanthren-2(1H)-ones (5a) and (6a), and the respective 6- and 5-methoxy analogues (5b) and (5c), and (6b) and (6c), are described. While alumina-induced alkylation of the cis-isomers (5a) and (5b) is shown to give, in each case, a mixture of the corresponding regioisomeric bridged-ketones, cis-3,4,4a,9,10,10a-hexahydro-1,4a-ethanophenanthren-2(1H)-one (23a) and cis-3,4,4a,9,10,10a-hexahydro-3,4a-ethanophenanthren-2(1H)-one (24a), and the 6-methoxy derivatives (23b) and (24b) in a ratio of ca. 3–4 : 1, the trans-isomers (6a–c) produce exclusively the respective trans-hexahydro-3,4a-ethanophenanthren-2(1H)-ones (26a–c). Alkylation of the cis-ketone (5a) with sodium hydride in benzene gives a 3 : 1 mixture of isomers (23a) and (24a), whereas with potassium t-butoxide in t-butyl alcohol the only isolable product is cis-3-hydroxy-4a,9,10,10a-tetrahydro-1,4a-ethanophenanthren-2(1H)-one (25)[arising from the concomitant autoxidation of the major alkylated product (23a)]. Using sodium hydride or potassium t-butoxide as the base, the trans-ketone (6a) gives trans-3,4,4a,9,10,10a-hexahydro-3,4a-ethanophenanthren-2(1H)-one (26a) as the sole product. The attempted preparation of the 5-methoxy-methanesulphonate (5c) from the corresponding cis-keto-alcohol (21c) led to cis-3,4,4a,9,10,10a-hexahydro-5,4a-(epoxy-ethano)phenanthren-2(1H)-one (27)via elimination of the aromatic methoxy methyl group.

Irreversible E1cb mechanism in the syn eliminations from 1,2-dihalogenoacenaphthenes promoted by potassium t-butoxide in t-butyl alcohol

The lack of a significant leaving group effect and the preferential departure of the ‘poorer’ leaving group suggest an irreversible E1cb mechanism for the title reactions.

ChemInform Abstract: CARBON‐CARBON BOND FORMATION BY USE OF CHLOROIODOMETHANE AS A C1 UNIT. I. FORMATION OF CHLOROMETHYLTRIPHENYLPHOSPHONIUM IODIDE AND ITS APPLICATION FOR THE WITTIG CHLOROMETHYLENATION OF ALDEHYDES AND KETONES

AbstractAus dem Phoshoniumiodid (III) ‐ zugänglich aus (I) und (II) ‐ wird mit KO‐tBu in tBu‐OH das Phosphoran (IV) erzeugt, das in situ mit den Ketonen (V) bzw. den Aldehyden (VIII) unter Chlormethylenierung (Wittig‐Reaktion) zu E/Z‐Gemischen der Chlorolefine (VI) bzw. (IX) reagiert; als Nebenprodukte entstehen die Olefine (VII) bzw. die Acetylene (X); aus den Aldehyden (VIIIa)‐(VIIIc), (VIIIe) und (VIIIf) bilden sich zusätzlich die entsprechenden Styrole R3‐CH=CH,.

Eine ungewöhnliche Chlorwasserstoff‐Abspaltung: syn‐Eliminierung aus einem sterisch behinderten, aber freidrehbaren Halogenkohlenwasserstoff

An Unusual Dehydrochlorination: syn‐Elimination from a Sterically Hindered, but Free Rotating Halogenated HydrocarbonDepending on the solvent, the meso‐3, 4‐dichloro‐2,2,5,5‐tetramethylhexane undergoes base‐promoted dehydrochlorination in a syn‐ or anti‐periplanar manner, thus affording (Z)‐3‐chloro‐2,2,5,5‐tetramethyl‐3‐hexene and the thermodynamically less stable (E)‐isomer, respectively. Alcoholate aggregates of different size (presumably, dimers and trimers or tetramers) are alternatively involved in these stereochemically distinct conversions, at least when potassium t‐butoxide in t‐butyl alcohol or tetrahydrofuran serves as a base/solvent system.

Carbon-Carbon Bond Formation by Use of Chloroiodomethane as a C1 Unit. I. Formation of Chloromethyltriphenylphosphonium Iodide, and Its Application for the Wittig Chloromethylenation of Aldehydes and Ketones

Abstract Chloromethyltriphenylphosphonium iodide has been prepared by the reaction of chloroiodomethane with triphenylphosphine. Upon treatment with potassium t-butoxide in t-butyl alcohol, the phosphonium iodide was converted into chloromethylenetriphenylphosphorane; this in turn was used for the Wittig reaction of aldehydes and ketones into the corresponding chloroolefins of the type RCH=CHCl and RR′C=CHCl in good to moderate yields. The configurations of these chloroolefins were assigned on the basis of NMR spectral studies. Direct conversion of benzaldehyde into phenylacetylene was also achieved using the phosphonium salt and excess potassium t-butoxide.

Kinetic study of elimination from 3α-chloro-3β-methyl- and 3β-chloro-3α-methyl-5α-cholestane promoted by potassium t-butoxide in t-butyl alcohol

Elimination from 3α-chloro-3β-methyl-(1) and 3β-chloro-3α-methyl-5α-cholestane (2) to give 3-methylene-5α-cholestane (exo-olefin) and 3-methyl-5α-cholest-2-ene (endo-olefin) has been investigated in ButOK–ButOH solution. The exo:endo olefin ratio is affected by the ButOK concentration but does not depend significantly upon the conformation of the chlorine substituent. This also holds for the reaction rates since the endo-olefin is formed at 100° only 1.7 fold faster from (1)(axial chlorine) than from (2)(equatorial chlorine). In contrast, elimination from 3α-chloro-5α-cholestane (3) is ca. 500 fold faster than from the equatorial isomer (4). The small difference between (1) and (2) in the rate of formation of the endo-olefin is due to compensation between enthalpy and entropy factors. A similar situation is also observed when the exo-olefin forming reactions from (1) and (2) are considered. The kinetic data and the activation parameters support the hypothesis that both olefins are formed from (2) in an anticoplanar process involving a skew-boat conformation.

Studies related to penicillins. XIV. Oxidations of (4R,5R)-11,11-dimethyl-4-phenoxyacetamido-6-thia-2,9,10-tirazatricyclo(6.3.0.02,5)-undec-8-en-3-one.

The adduct (13)[or (16)], obtained from the reaction of 4-isopropylidene-3-oxo-7β-phenoxyacetamidocepham (1) with hydrazine, readily undergoes dehydration to give the title pyrazoline (2). N-Bromosuccinimide converts the derivative (2) into the 8-bromo-pyrazoline (6), which is transformed into the 8-methoxy-pyrazoline (7) by silver(I) perchlorate in methanol. The 8-acetoxy-pyrazoline (8), formed by the action of lead tetra-acetate on the pyrazoline (2), affords the 8-hydroxy-pyrazoline (9) in the presence of methanolic triethylamine or potassium t-butoxide in tetrahydrofuran. With potassium t-butoxide in t-butyl alcohol, it yields the epimeric alcohol (16). Compounds (7)–(9) lose nitrogen when irradiated to give the cyclopropyl derivatives (18)–(20), respectively, Iron(III) chloride converts the cyclopropanol (20) into the carbinolamine (24).

Stereochemistry of the electrophilic addition of bromine to dibenzo[b,f]thiepin and its 5,5-dioxide

The dibromide formed by kinetically controlled bromine addition to dibenzo[b,f]thiepin (3) is the trans-isomer (5). Treatment of this product with methanolic sodium methoxide gives the bromo-ene (1) together with products resulting from substitution and rearrangement reactions, but the reaction with potassium t-butoxide in t-butyl alcohol gives only the bromo-ene (1). Bromine addition to the sulphone (2) in carbon tetrachloride gives the cis-dibromide whereas in acetic acid the trans-dibromide is obtained. The acid-catalysed dehydration and rearrangement of 9-hydroxymethylthioxanthen (18) proceeds abnormally under anhydrous conditions in toluene giving 10,11-dihydro-10-p-tolyldibenzo[b,f]theipin (19).

The origin of high ortho:para-reactivity ratios in the reactions of fluoronitrobenzenes with potassium t-butoxide in t-butyl alcohol

Kinetic data for fluorine substitution of 1-fluoro-2- or 1-fluoro-4-nitrobenzene by potassium methoxide in methyl alcohol in the presence or absence of added dicyclohexyl-18-crown-6 or by potassium t-butoxide in t-butyl alcohol in the presence of the crown ether are reported. The crown ether has a negligible influence on the kinetics of the reactions of potassium methoxide where the ortho:para-activation ratio is around unity. In sharp contrast, comparison with previous data for the reactions of the same substrates with potassium t-butoxide in t-butyl alcohol shows that on addition of the crown ether (in equimolar quantities to the nucleophile, with consequent nearly total removal of potassium cation from the bulk system), the rate of reaction of the o-nitro-substituted substrate is increased by only a factor of three while that of the p-nitro-substituted substrate is increased by a factor of nearly 2000. Consequently, the ortho:para-ratio changes from 3·6 × 102 in the absence to ca. 1 in the presence of the crown ether. These results show that the high value of the ortho:para-ratio obtained in t-butyl alcohol in the absence of addenda can be attributed mainly to specific stabilization of the transition state of the reaction of the o-nitro-substituted substrate by potassium cation bridging between the nucleophile and nitro-group oxygen atoms. This intramolecular assistance is a consequence of the low polarity and low dissociating ability of the medium used, t-butyl alcohol, and does not appear when the medium is more polar and dissociating, like methyl alcohol.

Acetylene–allene isomerisations. Part I. Base catalysis by potassium t-butoxide in t-butyl alcohol

Isomerisation of hex-1-, -2-, and -3-yne, and hexa-1,2- and -2,3-diene catalysed by potassium t-butoxide in t-butyl alcohol (concentrating on the first 20% or so of isomerisation of the pure compounds) is reported. The experimental results are discussed as better evidence for the accepted stepwise acetylene–allene isomerisation than has been previously reported. Kinetic acidity of protons and stability of carbanions in this system is discussed.

A BASE-INDUCED CARBANIONIC ELIMINATION REACTION OF PHENYLSULFONYLACETATES

Abstract 1,2-Diphenylethyl phenylsulfonylacetate underwent predominantly a syn β-elimination with potassium t-butoxide in t-butyl alcohol. A carbanion intermediate and a six-membered cyclic transition state are suggested.

Some elimination reactions of hydroxy tosylates in the bornane series

The reaction of cis-bornane-2,3-diol monotosylates with potassium t-butoxide in t-butyl alcohol gives exclusively the corresponding born-2-ene epoxide; trans-bornane-2,3-diol monotosylates give a ketone in addition to the epoxide.

Axial:Equatorial Rate Ratios. 1. Eliminations Leading to the Exocyclic Methylene Group

Phenyl cis-4-t-butylcyclohexanemethyl sulfoxide (4) thermolyzes to 1-t-butyl-4-methylenecyclohexane (5) at 116 and 130° about five to six times faster than its trans (equatorial) epimer 6. cis-4-t-Butylcyclo-hexanemethyl bromide (7) undergoes elimination with potassium t-butoxide in t-butyl alcohol at 100° about nine times faster than its trans (equatorial) epimer 8. The rate difference found for the sulfoxides 4 and 6 is the first clear demonstration of steric acceleration (without any contribution from any reagent repulsion effect) in the formation of an exocyclic carbon–carbon double bond in a simple anchored cyclohexane System. The faster elimination from 7 (vs. 8) is ascribed primarily to steric acceleration; the experiment neither requires nor excludes the influence of non-bonding repulsions between the substrate and the attacking base.

Base-catalyzed Dehydrobromination of Several α-Bromoacetals

Base-catalyzed dehydrohalogenation with potassium t-butoxide in t-butyl alcohol of the acetals obtained from homologues of α-bromoacetaldehyde and ethylene glycol[2-(α-bromoalkyl)-1,3-dioxo-lanes] or 1,3-propanediol[2-(α-bromoalkyl)-1,3-dioxane] provides the corresponding ketene acetal, in some cases exclusively and in others as the major product along with a smaller proportion of the α,β-unsaturated acetal. In contrast, similar dehydrohalogenation conditions convert the acetals obtained from homologues of α-bromoacetaldehyde and monohydroxy alcohols, to the α,β-unsaturated acetals, in some cases exclusively, and in others as the major product accompanied by a smaller proportion of the corresponding ketene acetal.The preference for the ketene acetal formation from the 2-(α-bromoalkyl)-1,3-dioxolanes (the ethyleneacetals) is believed due to greater ease of approach by base to the methine proton as a result of the restricted shape of the 1,3-dioxolane ring. Approach by base to the methine proton of the α-bromoalkyl dialkylacetals is more hindered by the two alkoxy groups, which cause preferred attack by base at the β proton to provide the α,β-unsaturated acetal.The proportion of α,β-unsaturated acetal obtained from base-catalyzed dehydrohalogenation of 2-(α-bromoalkyl)-1,3-dioxolanes can be greatly increased if the reaction is carried out in dimethyl sulfoxide. This marked change in proportion of products is thought to be due to a change in mechanism occasioned by the dimethyl sulfoxide.

Structures of the sulphones formed in the oxidation of the products of thiol addition to chloronorbornadienes and related compounds

The sulphides formed by the respective additions of ethanethiol and benzenethiol to some chloronobornadienes are converted into the corresponding sulphones without change in stereochemistry. The only exceptions are the oxidation, with hydrogen peroxide in acetic acid, of 1,4,5,6,7,7-hexachloronorborn-5-en-2-endo-yl phenyl sulphide to afford the 2-exo phenyl sulphone, and of 1,2,3,5-endo,6,6-hexachloronoborn-2-en-7-syn-yl phenyl sulphide to give an epimeric mixture of the corresponding 7-syn and 7-anti phenyl sulphones. Product sulphones have been treated with potassium t-butoxide in t-butyl alcohol in an effort to effect epimerisation, and to provide evidence about the thermodynamic stability of individual sulphones. It is probable that in the presence of potassium t-butoxide in t-butyl alcohol, many of the derived carbanions have complete configurational stability, and hence the sulphones are not epimerised.

Mechanisms of elimination reactions. Part III. Rate coefficients for elimination from substituted 2-phenylethyl arenesulphonates with potassium in t-butyl alcohol

The rate coefficients for elimination from 24 substrates in the series 2-Z-phenylethyl p-Y-arenesulphonate with potassium t-butoxide in t-butyl alcohol at 40 °C have been correlated with the Hammett equation. The reaction constants ρz decrease linearly with the electronic properties of the group Y only for the most electron-withdrawing substituents, indicative of a shift to transition states with less carbanion character. The reaction constants ρY become less positive as Z becomes more electron-withdrawing, suggesting that increased Cβ–H bond breaking is accompanied by decreased Cα–X bond breaking, and a shift to a transition state with greater carbanion character. This result supports earlier secondary deuterium isotope studies in establishing a new interpretation of the reactivity ratio kOTs/kBr as a measure of C–X bond breaking.

Synthesis and Elimination Reaction of O-Methyl Derivatives of Methyl (Methyl α-d-Glucopyranosido)uronate

Abstract Several methyl ethers [2,3,4-tri-O-methyl- (1), 4-O-methyl- (2), 3-O-methyl- (3), and 2-O-methyl- (4)] of methyl (methyl α-d-glucopyranosido)uronate were used as model compounds for the examination of β-elimination reaction. 1 was purely synthesized from methyl α-d-glucopyranoside and both 3 and 4 were newly synthesized via the corresponding methyl ethers of methyl α-d-glucopyranoside. The condition of β-elimination reaction was examined using 1 as a model compound. It was shown that β-elimination reaction occurred only when an alkoxide was used as a base. The yield of the unsaturated product, i. e., methyl (methyl 4-deoxy-2,3-di-O-methyl-β-l-threo-hex-4-enopyranosido)uronate (13) was about 40–50% by sodium methoxide in methanol at 60–70°C, and 70–80% by potassium t-butoxide in t-butyl alcohol even at room temperature. In both cases the reaction was completed within several minutes. The β-elimination reaction was followed by UV spectra using the molecular extinction coefficient of purely isolated 13, and the reaction products were examined by gas-liquid chromatography. The β-elimination product of 2 was also obtained in good yield, but that of 3 in very poor yield.