Potassium T-butoxide In Dimethyl Sulphoxide Research Articles

Syntheses of the aphid pigment derivatives quinone A, quinone A′, and deoxyquinone A as racemates

3-Acetyl-5-methoxy-1,7-bisisopropoxy-4-naphthol (11) was converted in a number of high yielding transformations into the title quinones. Key steps were the stereospecific base-induced cyclisation in almost quantitative yield of 2-allyl-4,7-bisbenzyloxy-3-(1-hydroxyethyl)-1,5-dimethoxynaphthalene (18) into 7,10-bisbenzyloxy-3,4-dihydro-5,9-dimethoxy-trans-dimethyl-1H-naphtho[2,3-c]pyran (20) followed by the oxygenation of (20) to afford its two C-4 hydroxy epimers (23) and (26) in high combined yield, by potassium t-butoxide in dimethyl sulphoxide in the presence of oxygen. The efficient conversion of the major pseudoequatorial hydroxy compound (23) into the minor pseudoaxial hydroxy epimer (26)via the corresponding pseudoaxial chloro derivative was useful in providing increased quantities of precursors to quinone A′.

Reactions of coordinated ligands: IX. chromium(0)-promoted intramolecularnucleophilic substitution of an aryl halide: a preparation of chroman

When treated with potassium t-butoxide in dimethyl sulphoxide the chromium tricarbonyl complex of 3-(2-fluorophenyl)propan-1-ol underwent a rapid intramolecular nucleophilic substitution to give the corresponding complex of chroman, from which the heterocycle was obtained by oxidation with iodine. With metal alkoxides the chromium tricarbonyl complex of 2-(2-fluorophenyl)ethanol gave either mixtures (from which the product of intramolecular nucleophilic substitution was not isolated) or the products of intermolecular nucleophilic substitution.

ChemInform Abstract: NOVEL SYNTHESES OF 1,6‐METHANO(10)ANNULENE AND 4‐METHYLAZULENE

AbstractDas Dichlortricycloundecadien (Ia) ergibt in Gegenwart von Base ein Gemisch aus 1,6‐Methano‐ [10]annulen (II) und 4‐Methylazulen (III).

Heterocyclic compounds with bridgehead nitrogen atoms. Part 9. Synthesis in the pyrrolo[2,1,5-de]quinolizine ([2.3.3]cyclazine) series starting from indolizines

Pyrrolo[2,1,5-de]quinolizines may be obtained from various 3-substituted derivatives of 5-methyl-2-phenyl- and 2,5-dimethyl-indolizine by base-catalysed condensation of the 5-methyl group with a carbonyl group in the β-position of the 3-substituent. The 1,3-diethoxalyl derivatives of these indolizines were converted, by treatment with sodium ethoxide or methoxide, into mixtures of pyrrolo[2,1,5-cd]indolizines ([2.2.3]cyclazines) and 4-hydroxy-3H-pyrrolo[2,1,5-de]quinolizin-3-ones. Under similar conditions, 5-methyl-2-phenyl-3-pyruvoyl-indolizine gave a low yield of 4-methyl-2-phenyl-3H-pyrrolo[2,1,5-de]quinolizin-3-one. When the 3-substituent was a 2-oxopropano- or 2-oxo-2-phenylethano-hydroximoyl group, cyclisation was effected with potassium t-butoxide in dimethyl sulphoxide, and the resulting 3-hydroxyimino-3H-pyrrolo[2,1,5-de]quinolizines were cleanly converted into the corresponding pyrroloquinolizinones by treatment with silver(I) oxide. 4-Methyl-2-phenyl-3H-pyrrolo[2,1,5-de]quinolizin-3-one was converted into the corresponding thione and thence, by methylation, into a methylthiopyrrolo[2,1,5-de]quinolizinylium salt.

Synthesis of the mangostins

Acylation of 5,7-bisbenzyloxy-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran (10c) with 6,8-dimethoxy-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-5-carboxylic acid (9b) in the presence of trifluoroacetic anhydride gave 5,7-dibenzyloxy-3,4-dihydro-2,2-dimethyl-2H-1- benzopyran-8-yl, 3,4-dihydro-6,8-dimethoxy-2,2-dimethyl-2H-1-benzopyran-5-yl ketone (8c), which was converted, in three steps, into dimethyl-1-isonormangostin (7). Reaction of (7) with boron trichloride resulted in the cleavage of the two terminal pyran rings to give 1,7-bis-(3-chloro-3-methylbutyl)-2,8-dihydroxy-3,6-dimethoxyxanthen-9-one (6a). Selective methylation of (6a) afforded the known 1,7-bis-(3-chloro-3-methylbutyl)-8-hydroxy-2,3,6-trimethoxyxanthen-9-one (6b). Whereas dehydrochlorination of the methoxycarbonyloxy derivative (6c) of (6b) with lithium chloride in dimethylformamide gave a mixture from which dimethylmangostin (1d) and 1,7-bis-(3-methylbut-3-enyl)-8-hydroxy-2,3,6-trimethoxyxanthen-9-one (22c) were isolated by preparative high pressure liquid chromatography, that of (6b) with potassium t-butoxide in dimethyl sulphoxide gave a mixture from which β-mangostin (1b) was obtained, by the same technique.

Novel syntheses of 1,6-methano[10]annulene and 4-methylazulene

Reaction of 11, 11-dichlorotricyclo [4.4.1.01,6]-undeca-3, 8-diene (4) with potassium t-butoxide in dimethyl sulphoxide affords 1,6-methano[10]annulene (9) and 4-methylazulene (10); similar treatment of the dibromopropellane (5) yields the azulene (10), the mono-bromopropellane (11), but diminished yields of the annulene (9).

The allyl ether as a protecting group in carbohydrate chemistry. Part 11. The 3-methylbut-2-enyl (‘prenyl’) group

The ‘prenyl’ group in ally 3,4,6-tri-O-benzyl-2-O-(3-methylbut-2-enyl)-α-D-galactopyranoside was stable to the action of chlorotris(triphenylphosphine)rhodium(I) during 24 h, whilst the allyl group was isomerised within 1 h. Previous work has shown that the but-2-enyl group is completely isomerised within 24 h by the rhodium catalyst. Thus an allyl group can be removed without affecting a ‘prenyl’ group in the same molecule. The ‘prenyl’ group is cleaved at about the same rate as a but-2-enyl group by potassium t-butoxide in dimethyl sulphoxide. The isomerisation of the allyl group by the rhodium catalyst gives a mixture of cis- and trans-prop-1-enyl ethers.

The allyl ether as a protecting group in carbohydrate chemistry. Part 10. Synthesis of 3-O-(β-D-galactopyranosyl 3-sulphate)-2-O-hexadecanoyl-1-O-hexadecyl-L-glycerol, ‘seminolipid’

3-O-Allyl-L-glycerol was converted, by way of the 1-O-trityl derivative, into 3-O-allyl-2-O-(but-2-enyl)-L-glycerol, which was alkylated with hexadecyl bromide and sodium hydride in NN-dimethylformamide. The product was converted, by the action of potassium t-butoxide in dimethyl sulphoxide, into 1-O-hexadecyl-3-O-(prop-1-enyl)-L-glycerol which was alkylated with ‘crotyl bromide’ and the product was hydrolysed to give 2-O-(but-2-enyl)-1-O-hexadecyl-L-glycerol. This was condensed with acetobromogalactose to give the β-galactoside which was converted into crystalline 2-O-(but-2-enyl)-1-O-hexadecyl-3-O-(3,4-O-isopropylidene-β-D-gaiactopyranosyl)-L-glycerol. This, on benzylation followed by acidic hydrolysis, gave 3-O-(2,6-di-O-benzyl-β-D-galactopyranosyl)-2-O-(but-2-enyl)-1-O-hexadecyl-L-glycerol which was converted, by way of the O-dibutylstannylidene derivative, into 3-O-(3-O-ally) 2,6-di-O-benzyl-β-D-galactopyranosyl)-2-O-(but-2-enyl)-1-O-hexadecyl-L-glycerol. Benzylation of this compound and subsequent treatment with potassium t-butoxide in dimethyl sulphoxide gave 3-O-[2,4,6-tri-O-benzyl-3-O-(prop-1-enyl)-(β-D-galactopyranosyl]-1-O-hexadecyl-L-glycerol which was acylated with hexadecanoyl chloride in pyridine. The prop-1-enyl group was cleaved by the action of mercury(II) chloride to give crystalline 3-O-(2,4,6-tri-O-benzyl-β-D-galactopyranosyl)-2-O-hexadecanoyl-1-O-hexadecyl-L-glycerol. This compound was sulphated with the pyridine–sulphur trioxide complex and the benzyl groups were removed by catalytic hydrogenolysis in glacial acetic acid to give ‘seminolipid’ with properties similar to those reported for the natural material. ‘Desulphato-seminolipid’[3-O-(β-D-galactopyranosyl)-2-O-hexadecanoyl-1-O-hexadecyl-L-glycerol] was also prepared by catalytic hydrogenolysis of 3-O-(2,4,6-tri-O-benzyl-β-D-galactopyranosyl)-2-O-hexadecanoyl-1-O-hexadecyl-L-glycerol.

Studies in the synthesis of 7,8-benzo[5]metacyclophane

Compound 5 reacted with silver perchlorate in anhydrous benzene to give 3a and in wet acetone to give a mixture of 9 and 10; treatment of 9 with potassium t-butoxide in dimethyl sulphoxide gave 11.

ChemInform Abstract: REACTION OF 5‐CHLOROALKYL‐3‐PHENYL‐4,5‐DIHYDROISOXAZOLES WITH STRONG BASE. AN UNEXPECTED NEW SYNTHESIS OF THE 2‐OXA‐3‐AZABICYCLO(3,1,0)HEX‐3‐ENE RING SYSTEM

Reaction of 5-chloromethyl-3-phenyl-4,5-dihydroisoxazole with potassium t-butoxide in dimethyl sulphoxide gives 4-phenyl-2-oxa-3- azabicyclo[3,1,0]hex-3-ene in high yield and reaction of the 5-(1?- chloroethyl) homologue gives high yields of the diastereoisomeric 6- methyl derivatives of the bicyclic system. Some unsuccessful attempts to convert these bicyclic compounds into substituted cyclo-propanols and cyclopropenes are described.

Synthesis of 3-O-(α-D-glucopyranosyl)-1,2-di-O-stearoyl-L-glycerol, a ‘glucosyl diglyceride’

3-O-(3,4-Di-O-benzyl-α-D-glucopyranosyl)-1,2-O-isopropylidene-L-glycerol was converted into 3-O-(α-D-glucopyranosyl)-1,2-di-O-stearoyl-L-glycerol, a ‘glucosyl diglyceride.’ 1,6-Anhydro-2,3,4-tri-O-benzyl-β-D-glucopyranose was converted by acetyl chloride and hydrogen chloride into 6-O-acetyl-2,3,4-tri-O-benzyl-D-glucopyranosyl chloride, which was condensed with 1,2-di-O-(but-2-enyl)-L-glycerol under conditions shown previously to give predominantly 1,2-cis-glycosidic linkages. The product was treated with potassium t-butoxide in dimethyl sulphoxide to give crystalline 3-O-(2,3,4-tri-O-benzyl-α-D-glucopyranosyl)-L-glycerol, which was also prepared from 3-O-(3,4-di-O-benzyl-α-D-glucopyranosyl)-1,2-O-isopropylidene-L-glycerol. 3-O-(2,3,4-Tri-O-benzyl-α-D-glucopyranosyl)-L-glycerol was converted into the ‘glucosyl diglyceride’ and also into 3-O-(2,3,4-tri-O-benzyl-α-D-glucopyranosyl)-1,2-di-O-stearoyl-L-glycerol, which should serve as an intermediate for the syntheses of a ‘glucuronosyl diglyceride,’ the ‘plant sulpholipid.’ and one of the phosphorylated ‘glucosyl diglycerides’ of Streptococci.

Syntheses of 1,3,3-trimethyl-2-oxabicyclo[2.2.2]oct-5-ene (2,3-didehydro-1,8-cineole), 6,6-dimethyl-2-methylene-7-oxabicyclo[3.2.1]octane (isopinol), 2,6,6-trimethyl-7-oxabicyclo[3.2.1]oct-2-ene (pinol), and 1-(3-lsopropylidenecyclopentyl)ethanone (pinolone) from hydroxy- and bromo-derivatives of cineole

Treatment of (+)-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6-one p-tolylsulphonylhydrazone with n-butyl-lithium gave, in a low yield. 1,3,3-trimethyl-2-oxabicyclo[2.2.2]oct-5-ene (1), a terpene recently found in Laurus nobilis oil. Dehydration of the 1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6-ols (an equilibrated endo–exo-mixture) with phosphoryl chloride–pyridine yielded mainly pinolone (5). The 1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6-ols gave the 6-bromo-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octanes (endo–exo mixtures) in 60 : 40 ratio with phosphorus tribromide–pyridine and in 80 : 20 ratio with triphenylphosphine dibromide. From treatment of the latter mixture with 1,5-diazabicyclo[5.4.0]undec-5-ene, (+)-pinol and a new terpenoid. (–)-isopinol, were obtained: with potassium t-butoxide in dimethyl sulphoxide, however, three products were obtained, namely the didehydrocineole (1), (+)-pinol, and (–)-isopinol. The structure of (–)-isopinol(6,6-dimethyl-2-methylene-7-oxabicyclo[3.2.1]-octane) and those of the other new compounds reported were determined from i.r., n.m.r., and mass spectral data.

Phenyloxazoline derivatives of amino-sugars. Part 3. Preparation of intermediates for the synthesis of sphingoglycolipids

1,2-Dideoxy-5,6-O-isopropylidene-2′-phenyl-α-D-glucofuranoso[2,1-d]-Δ2′-oxazoline (1) was readily converted into allyl 2-benzamido-2-deoxy-5,6-O-isopropylidene-βD-glucofuranoside (4) by the action of the pyridine salt of toluene-p-sulphonic acid in allyl alcohol–pyridine at reflux. This method is superior to acid alcoholysis for the conversion. The mesylate of the alcohol (4) was converted into allyl 2,3-dideoxy-5,6-O-isopropylidene-2′-phenyl-β-D-allofuranosido[2,3-d]-Δ2′-oxazoline (9) by hot aqueous triethylamine. The isopropylidene group of compound (9) was hydrolysed preferentially in anhydrous methanol and the allo-diol (12) produced was converted into the talo-anhydride (17), which was hydrolysed to give the talo-diol (18). The allo-diol and the talo-anhydride are potential intermediates for the synthesis of sphingosine. The isomerisation of the allyl group of compound (9) to a prop-1-enyl group, without affecting the phenyloxazoline group, was accomplished by the action of commercial potassium t-butoxide in dimethyl sulphoxide containing t-butyl alcohol or preferably by the action of chloro(tristriphenylphosphine) rhodium (I).

Reaction of 5-Chloroalkyl-3-phenyl-4,5-dihydroisoxazoles with strong base. An unexpected new synthesis of the 2-Oxa-3-azabicyclo[3,1,0]hex-3-ene ring system

Reaction of 5-chloromethyl-3-phenyl-4,5-dihydroisoxazole with potassium t-butoxide in dimethyl sulphoxide gives 4-phenyl-2-oxa-3- azabicyclo[3,1,0]hex-3-ene in high yield and reaction of the 5-(1?- chloroethyl) homologue gives high yields of the diastereoisomeric 6- methyl derivatives of the bicyclic system. Some unsuccessful attempts to convert these bicyclic compounds into substituted cyclo-propanols and cyclopropenes are described.

Reactions of the 1-halo-7-(2-hydroxyethoxy)cycloheptenes and the 3-halo-4-(2-hydroxyethoxy)bicyclo[3.2.1]oct-2-enes with potassium t-butoxide

Reactions of 1 - bromo - 7 - (2 - hydroxyethoxy)cycloheptene 2 and its chloro analogue 3 with potassium t-butoxide in dimethyl sulphoxide or tetrahydrofuran gave cycloheptatriene and cis - 8,11 - dioxabicyclo[5.4.0]undec - 2 - ene 18 as the major products together with small amounts of the trans-isomer 17,8,11-dioxabicyclo[5.4.0]undec - 1(7) - ene 14, 8,11 - dioxabicyclo[5.4.0] - undec - 1 - ene 19, cyclohept - 2 - enone ethylene ketal 15, cyclohept - 3 - enone ethylene ketal 16, and 1- and 2 - t - butoxycyclohepta - 1,3 - diene 20. Similar reactions of 3 - bromo - and 3 - chloro - 4 - (2 - hydroxyethoxy)bicyclo[3.2.1]oct - 2 - ene 4 and 5 gave 4,7 - dioxatricyclo[7.2.1.0 3,8]dodeca - 2 - ene 26 as the major product together with small amounts of 3,6 - dioxatricyclo[7.2.1.0 2,7]dodeca - 2(7) - ene 27 and bicyclo[3.2.1]oct - 3 - ene - 2 - one ethylene ketal 28. Mechanisms for these transformations are discussed.

The allyl ether as a protecting group in carbohydrate chemistry. Part IX. Synthesis of derivatives of 1,6-anhydro-β-D-galactopyranose

1,6-Anhydro-2,3-di-O-benzyl-β-D-galactopyranose was prepared by four different methods and isolated and characterised as the crystalline p-nitrobenzoate. (a) Allylation of 1,6-anhydro-2-O-benzyl-β-D-galactopyranose gave a mixture of di- and mono-allyl derivatives. The mono-allyl derivatives were benzylated and the allyl group was removed. (b) Phenyl 4-O-allyl-2,3-di-O-(but-2-enyl)-β-D-galactopyranoside was treated with potassium t-butoxide in dimethyl sulphoxide, which removed the but-2-enyl groups, isomerised the allyl group, and converted the phenyl 4-O-(prop-1-enyl)-β-D-galactopyranoside formed into 1,6-anhydro-4-O-(prop-1-enyl)-β-D-galactopyranose. Benzyl chloride was then added to the solution to give the 2,3-di-O-benzyl derivative and the prop-1-enyl group was subsequently hydrolysed. (c) 1,6:2,3-Dianhydro-β-D-talopyranose was converted into the 4-O-allyl derivative, which was hydrolysed with base to give 4-O-allyl-1,6-anhydro-β-D-galactopyranose. This was benzylated and the allyl group was removed. (d) Tritylation of 1,6-anhydro-2-O-benzyl-β-D-galactopyranose gave predominantly 1,6-anhydro-2-O-benzyl-4-O-trityl-β-D-galactopyranose, which was benzylated and the trityl group was removed. The 1,6-anhydro-2,3-di-O-benzyl-β-D-galactopyranose was condensed with 2,3,4-tri-O-benzyl-6-O-(but-2-enyl)-D-galactopyranosyl chloride, under conditions shown previously to give predominantly 1,2-cis-glycosidic linkages, to give a disaccharide derivative which was converted into crystalline 1,2,3,6-tetra-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl)-α-D-galactopyranose. 1,6-Anhydro-2-O-benzyl-4-O-trityl-β-D-galactopyranose was converted into crystalline 3-O-allyl-1,6-anhydro-2-O-benzyl-4-O-trityl-β-D-galactopyranose, an intermediate for the synthesis of 1,6-anhydro-2,4-di-O-benzyl-β-D-galactopyranose. 1,6:2,3-Dianhydro-4-O-benzyl-β-D-talopyranose was converted into 1,6-anhydro-2-azido-4-O-benzyl-2-deoxy-β-D-galactopyranose, which was isolated and characterised as the crystalline p-nitrobenzoate. Preliminary investigations on the conversion of 1,6-anhydro-2,3-di-O-benzyl-4-O-p-nitrobenzoyl-β-D-galactopyranose into 6-O-acetyl-2,3-di-O-benzyl-4-O-p-nitrobenzoyl-D-galactopyranosyl chloride by the action of acetyl chloride in the presence of hydrogen chloride (‘chloracetolysis’) and on the reaction of N-bromosuccinimide with 6-O-allyl-1,2:3,4-di-O-isopropylidene-α-D-galactopyranose are also reported.

Synthesis of 3-O-[6-O-(α-D-galactopyranosyl)-β-D-galactopyranosyl]-1,2-di-O-stearoyl-L-glycerol, a ‘digalactosyl diglyceride’

2,3,4,-Tri-O-benzyl-6-O-(but-2-enyl)-α-D-galactopyranosyl chloride was condensed with 1,2-O-isopropylidene-3-O-(2,3,4-tri-O-benzyl-β-D-galactopyranosyl)-L-glycerol, under conditions shown previously to lead to 1,2-cis-glycosides, to give crystalline 1,2-O-isopropylidene-3-O-[2,3,4-tri-O-benzyl-6-O-(2,3,4-tri-O-benzyl-6-O-but-2-enyl-α-D-galactopyranosyl)-β-D-galactopyranosyl]-D-glycerol. Removal of the but-2-enyl group, by the action of potassium t-butoxide in dimethyl sulphoxide, gave the corresponding crystalline alcohol. The alcohol was benzylated and the isopropylidene group was removed by hydrolysis; subsequent acylation with stearoyl chloride and hydrogenolytic removal of the benzyl groups gave the title compound.

ChemInform Abstract: THE ALLYL ETHER AS A PROTECTING GROUP IN CARBOHYDRATE CHEMISTRY, ISOMERISATIONS WITH TRISTRIPHENYLPHOSPHINERHODIUM(I) CHLORIDE

AbstractDas Galaktopyranosid (I) liefert bei der Behandlung mit Tris‐(triphenylphosphimrhodium(l)‐chlorid die Umlagerungsprodukte (II) und (III), die mit Quecksilber(II)‐ chlorid in die Verbindungen (V) bzw. (IV) übergeführt werden.

Permethylation for mass spectrometry: rearrangements of ester linkages and use of potassium t-butoxide.

Thirteen selected compounds were permethylated with potassium t-butoxide in dimethyl sulphoxide and methyl iodide, a simpler procedure than those using sodium hydride but equally effective. From mass spectrometric study of the products. it emerged that carboxylic esters of methanol and of o-diphenols were at least partially rearranged, whereas those of benzyl alcohol and of a monophenol, as well as fully acylated carbohydrate-like substances, were largely not. Some anamalies of C-methylation and N-methylation were encountered.

Base-catalysed rearrangement and hydrogen isotope exchange reactions of tricyclo[7.1.0.02,7]deca-2(7),3,5-triene (cyclopropindene) and related compounds

The rates of rearrangement and hydrogen isotope exchange of the title compound, catalysed by potassium t-butoxide in dimethyl sulphoxide or by potassium t-pentoxide in t-pentyl alcohol have been measured, and compared with the exchange rates for model hydrocarbons. It is tentatively suggested that the kinetic results taken together with the low stereoselectivity in the deprotonation step may be consistent with the participation of a tricyclodecatrienyl (homoindenyl) anion intermediate possessing a small degree of homoaromatic character. Exchange in benzylcyclopropane was only slightly faster than that in isobutylbenzene, indicative of the absence of substantial stabilisation of a benzylic carbanion by an α-cyclopropyl substituent.