Base-promoted Reaction Research Articles

A one-pot, non-catalytic approach to 1,2,4-benzothiadiazine-1,1-dioxides

Condensations of o-halo-substituted benzenesulfonyl chlorides with 2-aminopyridines and amidines may give the corresponding 1,2,4-benzothiadiazine-1,1-dioxides under mild, non-catalytic conditions in nearly quantitative yields. The successful one-pot cyclization depends on three factors: (i) the nature of the o-halogen, (ii) the electronic character of the benzene ring substituent, and (iii) the steric load around the amidine unit. O-Fluorobenzenesulfonyl chlorides bearing methylcarboxyl- or nitro-group and o-chloro- and o-bromobenzenesulfonyl chlorides bearing nitro-group are reactive enough to give the desired 1,2,4-benzothiadiazine-1,1-dioxides in a one-pot base-promoted reaction. In all other cases, open-chain sulfonylated amidine intermediates are isolated. The latter are converted to the title compounds either in the presence of potassium carbonate or upon the addition of a copper(I) catalyst.

Base-Promoted Reaction of 5-Hydroxyuracil Derivatives with Peroxyl Radicals

Addition of millimolar amounts of a weak base (pyridines) dramatically accelerates the reaction with peroxyl radicals of two biologically relevant uracil derivatives, 5-hydroxyuracil (HU) and 5-hydroxy-6-methyluracil (HMU). This is due to the formation of small amounts of the deprotonated form (pK(a) = 8.1-8.5 in water), which reacts with peroxyl radicals much faster than the parent undissociated form, via formal H-atom transfer from the OH in the 5 position.

ChemInform Abstract: Novel Base-Promoted Addition-Elimination Reaction of Electron- Deficient Benzylidene Derivatives with N-Phenyl-1,2,4-triazole-3,5- dione (PTAD).

The reaction of electron-deficient benzylidene derivatives with PTAD afforded the double Diels–Alder product and the Diels–Alder ene product; the latter underwent novel base-induced elimination of phenyl urazole via a stable carbanion.

Base-promoted elimination reactions of (E)- and (Z)-arylaldehyde O-benzoyloximes. Effects of stereochemistry, β-aryl group and base-solvent on the nitrile-forming transition states

Base-promoted elimination reactions of (E)- and (Z)-arylaldehyde O-benzoyloximes. Effects of stereochemistry, β-aryl group and base-solvent on the nitrile-forming transition states

ChemInform Abstract: Lewis Base Promoted Reactions of Alkyne-Dicobalt Hexacarbonyls

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A catalytic approach to the base-promoted reaction of epoxides with activated methylenes

Abstract This contribution reports the results obtained in the definition of a catalytic method for the nucleophilic ring opening of epoxides by activated methylenes promoted by a polymer-supported base. The attention has been focused on the use of polymer supported bases and the best results have been obtained by using 4-(dimethylamino)pyridine (PS-DMAP) and 2- tert -butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,3,2-diazaphosphorine both on polystyrene (PS-BEMP). Solvent-free conditions has been essential for reaching a sufficient reactivity to realize this process, in fact when a reaction medium is used, the processes are almost unfeasible.

A Novel and Expedient Synthesis of 7‐Pyrimidinylpyrimido[4,5‐d]pyrimidinones

AbstractA novel and efficient procedure for the synthesis of new 7‐pyrimidinylpyrimido[4,5‐d]pyrimidinone derivatives was elaborated via the base‐promoted cyclodimerization reaction of 5‐[(dimethylamino)methylidene]‐6‐iminopyrimidine‐2,4(1H,3H)‐dione hydrochlorides. In an analogous manner, a 2‐thioxo analog was prepared starting with the corresponding 2‐thioxopyrimidin‐4‐one.

Unusual base-catalyzed exchange in the synthesis of deuterated PF-2413873

The preparation of deuterated PF-2413873 (4-[3-cyclopropyl-1-(methanesulfonylmethyl)-5-methyl-1H-pyrazol-4-yl]oxy-2,6-dimethylbenzonitrile, 1) is described for use as a bioanalytical standard in clinical trials. Two strategies were investigated. The sulfone-containing substituent was labelled by base-catalyzed exchange, but unacceptable deuterium loss was noted under assay conditions. Alternatively, labelling 4-cyano-3,5-dimethylphenol was achieved by heating with deuterium oxide over platinum oxide. After building up the pyrazole ring we discovered that, during the subsequent alkylation to attach the methylthiomethyl group, the base, potassium t-butoxide, caused unwanted scrambling of deuteriums on the aromatic portion and the methylthiomethyl group. Thus, it was necessary to remove all base-labile hydrogens to prevent their exchange. This was accomplished by alkylating the pyrazole with per-deuterated chloromethyl methylsulfide, oxidation to the sulfone, and selective removal of its deuteriums by treatment with sodium hydroxide. The unusual sensitivity and selectivity of these base-promoted exchange reactions are discussed. Thus, 4-[3-cyclopropyl-1-(methanesulfonylmethyl)-5-methyl-1H-pyrazol-4-yl]oxy-[2H6]2,6-dimethyl-[3,5-2H]benzonitrile (17) was obtained, labelled with eight deuterium atoms and an acceptable D0/D8 ratio. Copyright © 2009 John Wiley & Sons, Ltd.

Base-Promoted Reactions of Dichlorocarbene Adducts of Cyclic Enamines: A New Route to Annulated Pyrroles

Treatment of the gem-dihalogenocyclopropanes 1-5 with potassium tert-butoxide or LDA results in the formation of the corresponding and annulated pyrroles 13-17, respectively.

Impressive changeover of reaction course in ring expansion of styrylbenzocyclobutenol under alkoxide-forming conditions

Impressive changeover of the reaction course was observed in the rearrangement of styrylbenzocyclobutenol derivative 1. While the thermal reaction gave naphthalene 2, the base-promoted reaction gave the isomeric product 3 in high yield.

Base-Promoted Reactions in Ionic Liquid Solvent: Synthesis of Butenolides

Base-Promoted Reactions in Ionic Liquid Solvent: Synthesis of Butenolides

Facile Synthesis of 4-Arylsulfanylcoumarin Library through Reaction of 4-Tosyloxycoumarins with Thiols on Solid Phase

Abstract Diversified 4-arylsulfanylcoumarins were generated under extremely mild conditions on solid phase with a silyl linker based macro-beads by base-promoted reaction of 4-tosyloxycoumarins with thiols.

A Direct One‐Pot Synthesis of Naphtho[2,3‐b]furan‐4,9‐dione Derivatives via C,O‐Dialkylation of β‐Dicarbonyl Compounds by 2,3‐Dichloro‐1,4‐naphthoquinones.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A Direct One-Pot Synthesis of Naphtho[2,3- b ]furan-4,9-dione Derivatives via C,O-Dialkylation of β-Dicarbonyl Compounds by 2,3-Dichloro-1,4-naphthoquinones

Base-promoted reactions of acyclic and cyclic β-dicarbonyl compounds (3) with 2,3-dichloro-1,4-naphthoquinone (1) and 4a,6,7,8a-tetrachloro-1,4-methanonaphthalene-5,8-dione (2) resulted in C,O-dialkylation of 3 to give 2,3-disubstituted naphtho[2,3-b]furan-4,9-diones (4) and 5,8-methanonaphtho[2,3-b]furan-4,9-diones (6) respectively in moderate to high yields.

Synthesis of hexabromo, hydroxy, epoxy, methoxy and nitroxy derivatives of tetralins and naphthalenes

Stereoselective synthesises are described for naphthalene and tetralin derivatives. Hexabromo 2 and 3, monomethoxy 7, dimethoxy 6, dihydroxy 4 and dinitroxy 10 derivatives of tetralin have been obtained. Base-promoted elimination reactions of 6 and 4 provided monomethoxy 8 and 9 and diepoxy 5 naphthalenes respectively. The structures of these products were determined by 1H and 13C NMR spectra, mass spectra and micro analysis.

Base-promoted reactions of bridged ketones and 1,3- and 1,4-haloalkyl azides: competitive alkylation vs azidation reactions of ketone enolates.

The reactions of 1,3- and 1,4-haloalkyl azides with enolates of 2-norbornanone (and a ring-expanded analog) afford polycyclic 1,2,3-triazolines in good yields. The reaction occurs by the initial azidation of the ketone enolate, followed in order by triazoline formation and O-alkylation. An interesting element of this process is the preferential reaction of the alkyl azide with an enolate anion as opposed to the more familiar reaction of the alkyl halide (including Cl and I derivatives). Reactions of acyclic or monocyclic enolates generally lead to 1,2,3-triazoles but none of the alternative C-alkylation product.

Stevens Rearrangement of a Cyclic Hemiacetal System: Diastereoselective Approach to Chiral α-Amino Ketone

The base-promoted reaction of ammonium ylide la, which forms a cyclic hemiacetal structure, is shown to afford the anti-hemiacetal 3a in high diastereopurity, via the Stevens rearrangement followed by efficient thermodynamic epimerization.

Nucleoside H-phosphonates. Part 19: Efficient entry to novel nucleotide analogues with 2-pyridyl- and 4-pyridylphosphonothioate internucleotide linkages

Synthetic and 31P NMR spectroscopy studies resulted in the development of efficient protocols for the stereospecific synthesis of a novel type of nucleotide analogues, 2-pyridyl- and 4-pyridylphosphonothioates. The underlying chemistry involves formation of the P–C bond via a base-promoted reaction of suitably protected dithymidine H-phosphonothioates with N-methoxypyridinium tosylate in acetonitrile, or with trityl chloride in pyridine, to produce high yields of nucleotide analogues with a 2-pyridyl- or 4-pyridyl moiety directly bound to the phosphorus centre.

Transition-metal-based Lewis acid and base ambiphilic catalysts of iridium hydride complexes: multicomponent synthesis of glutarimides.

Mutual destruction of reagents in acid- and base-promoted reactions in the same container is now avoidable with the iridium polyhydride complex [IrH5(PiPr3)2] (1), which is an ambiphilic Lewis acid and base catalyst. By using catalyst 1, a three-component reaction of nitriles, olefins, and water proceeds efficiently to give glutarimides, which are pharmacologically important (see scheme).

Divergent Regioselectivity in the Base‐Promoted Reactions of Cyclic Eight‐Membered α‐Ketols with Activated Halides.

AbstractFor Abstract see ChemInform Abstract in Full Text.