Reaction Of Dichloroketene Research Articles

Multigram Synthesis of C4/C5 3,3-Difluorocyclobutyl-Substituted Building Blocks

An approach for the multigram synthesis of 3,3-difluorocyclobutyl-substituted building blocks (including carboxylic acid, amines, alcohols, azide, trifluoroborate ketone) is described. It is shown that, in most cases, ethyl 3,3-difluorocyclobutanecarboxylate is a convenient common synthetic intermediate to obtain the target derivatives. For preparation of 3,3-difluorocyclobutanol or -cyclobutanone, an alternative pathway via reaction of dichloroketene and tert-butyl or benzyl vinyl­ ether should be applied.

Entropic Intermediates and Hidden Rate-Limiting Steps in Seemingly Concerted Cycloadditions. Observation, Prediction, and Origin of an Isotope Effect on Recrossing

An unusual intramolecular kinetic isotope effect (KIE) in the reaction of dichloroketene with cis-2-butene does not fit with a simple asynchronous cycloaddition transition state, but it can be predicted from trajectory studies on a bifurcating energy surface. The origin of the KIE is related to a high propensity for transition state recrossing in this system, with heavier masses recrossing less. The KIE can also be predicted by a statistical model that treats the cycloaddition as a stepwise mechanism, the rate-limiting second step being associated with an entropic barrier for formation of the second carbon-carbon bond. The relevance of this stepwise mechanism to other asynchronous but seemingly concerted cycloadditions is suggested by examination of organocatalytic Diels-Alder reactions.

Highly diastereoselective electrophilic additions to the vinylcyclopropane moiety of a homotropylidene system

The acid catalyzed addition of AcOH and MeOH to the vinylcyclopropane moiety of tetracyclo[5.3.2.0 2,10 .0 3,6 ]dodeca-4,8,11-triene ( 1 ) afforded kinetic mixtures of 9-acetoxy and, respectively, 9-methoxytricyclo[4.3.3.0 2,5 ]dodeca-3,7,10-trienes in which the β derivatives are always, even when sterically more congested, highly prevalent over their α counterparts. Studies with deuterated acetic acid showed that there was not any relationship between the stereochemistry of the deuteron (proton) attack and that of the nucleophilic trapping of the intermediate carbocation. These findings can be rationalized on the basis of a two step process i) proton attack to the homotropylidene moiety of 1 with formation of a cyclopropylcarbinyl carbocation ii) opening of its cyclopropane ring under tight assistance by the nucleophilic solvent to give the final products with high β diastereoselectivity. By contrast, the reaction of dichloroketene, a strong uniparticulate electrophile, involved only the cyclobutene system of 1 . Graphic

Free radical annulation of dichlorocyclobutanones with sequential ring expansion

A new synthetic sequence that adds the elements of ketene across the termini of a 1,5-diene is described. Dichlorocyclobutanone adducts from reaction of dichloroketene with 1,5-dienes undergo intramolecular free radical annulation. Lewis acid-promoted ring-opening of the cyclized cyclobutanones then yields novel ring expansion products. Reaction of (R)-carvone provides an unusual example leading to the formation of a tricyclic dione. The carbonyl group of carvone enhances the radical cyclization and influences the ring-opening pathway.

Steroidal cyclobutanones. Part 2. Diastereofacial selection in the cycloaddition of dichloroketene and 3β-acetoxy-20a-homopregna-5,20-diene. Crystal structure of the cycloadduct, (20S)-3β-acetoxy-20,24-cyclo-22,22-dichlorochol-5-en-23-one

The reaction of dichloroketene and 3β-acetoxy-20a-homopregna-5,20-diene 1 is shown to give one diastereoisomeric cycloadduct 2 arising from attack at the rear side of the preferred rotamer 1b of the steroid skeleton. The structure of dichlorocyclobutanone 2 was determined by X-ray crystallography. Reduction of 2 gives chlorocyclobutanone 3 and cyclobutanone 4. Examination of the cyclobutanones by CD, 1H and 13C NMR spectroscopy demonstrates that these techniques can be used for the determination of the configuration of 2 and 3.

On the Interesting Course of Dichloroketene Addition to 1,5-Dimethyl-1,5-cyclooctadiene

Abstract Reaction of dichloroketene with 1,5-dimethyl-1,5 COD 6 charters an eventful course to furnish novel tricyclic ketone 10, through the intermediacy of tricyclic hydroxy olefin 9, in which the two carbon atoms of dichloroketene form a bridge across the eight mem-bered ring.

ChemInform Abstract: Stereoselective Formation of a Steroidal 20‐Hydroxy‐24‐oic Lactone by a Novel Reaction of Dichloro Ketene with an Epoxy Olefin.

AbstractReaction of the pregnene derivative (I) with dichloro ketene (II), generated in situ from the trichloroacetyl chloride and zinc dust, leads unexpectedly to the formation of the dichloro lactone (III) which is reduced to the monochloro derivative (IV).

Stereoselective formation of a steroidal 20-hydroxy-24-oic lactone by a novel reaction of dichloroketene with an epoxy olefin

Stereoselective formation of a steroidal 20-hydroxy-24-oic lactone by a novel reaction of dichloroketene with an epoxy olefin

ChemInform Abstract: SYNTHESIS AND PHOTOBIOLOGICAL ACTIVITY OF N,N‐DISUBSTITUTED 4‐AMINO‐3‐CHLORO‐2H‐THIENO(2,3‐H)‐1‐BENZOPYRAN‐2‐ONES, 7‐THIOISOSTERS OF 4‐AMINO‐3‐CHLOROANGELICINS

A convenient synthesis of a series of N,N-disubstituted 4-amino-3-chloro-2H-thieno[2,3-h]-1-benzopyran-2-ones (IV), which are 7-thioisosteres of 4-amino-3-chloroangelicins, was accomplished via dehydrochlorination and dehydrogenation of the 1,4-cycloadducts obtained by reaction of dichloroketene with N,N-disubstituted (E)-5-aminomethylene-6,7-dihydrobenzo-[b]thiophen-4(5H)-ones . Some aspects of the photobiological activity of these thioangelicins were studied; three of them (IV a, e, f) appeared to inhibit DNA synthesis in Ehrlich ascites tumor cells. The most active compound, namely 3-chloro-4-morpholino-7-thioangelicin (IV e), afforded 70% of the antiproliferative effect of 8-MOP, but unlike this reference compound was unable to induce erythema on guinea pig skin. However, compounds (IV a, f) produced a slight erythema, thus suggesting that a relationship between antiproliferative and phototoxic effects does not exist.

Reaction of dichloroketene and sulfene with N,N‐disubstituted α‐aminomethyleneketones. Synthesis of pyrano[2,3‐e]indazole and 1,2‐oxathiino[6,5‐e]indazole derivatives

AbstractThe polar 1,4‐cycloaddition of dichloroketene to N,N‐disubstituted (E)‐5‐aminomethylene‐1,5,6,7‐tetrahydro‐(1‐methyl)(1‐phenyl)‐4H‐indazol‐4‐ones V, prepared from 1,5,6,7‐tetrahydro‐(1‐methyl)(1‐phenyl)‐4H‐indazol‐4‐ones via the 5‐hydroxymethylene derivatives, gave in good yield N,N‐disubstituted 4‐amino‐3,3‐dichloro‐4,5,6,7‐tetrahydro‐(7‐methyl)(7‐phenyl)pyrano[2,3‐e]indazol‐(3H)ones VI, which are derivatives of the new heterocyclic system pyrano[2,3‐e]indazole. Dehydrochlorination of VI with DBN afforded N,N‐disubstituted 4‐amino‐3‐chloro‐6,7‐dihydro(7‐methyl)(7‐phenyl)pyrano[2,3‐e]indazol‐2(5H]‐ones VII generally in satisfactory yield. Full aromatization with DDQ of VII was tried only in the case of dimethylamino derivatives, giving a moderate yield of 3‐chloro‐4‐dimethylamino(7‐methyl)(7‐phenyl)pyrano[2,3‐e]indazol‐2(7H)‐ones. Cycloaddition of sulfene to V occurred only in the case of aliphatic N‐substitution to give in moderate yield 4‐dialkylamino‐4,5,6,7‐tetrahydro‐(7‐methyl)(7‐phenyl)‐3H‐1,2‐oxathiino[6,5‐e]indazole 2,2‐dioxides, which are derivatives of the new heterocyclic system 1,2‐oxathiino[6,5‐e]indazole.

Studies on ketene and its derivatives. CXIII. Reaction of dichloroketene with aromatic amine N-oxides.

Reaction of dichloroketene with pyridine 1-oxide (1) gave four products, namely, 2-dichloromethylpyridine (2), 4-dichloromethylpyridine (3), 3, 3, 7-trichloro-6-dichloroacetyl-2-oxo-2, 3, 3a, 6, 7, 7a-hexahydrofuro [2, 3-c] pyridine (4), and 3, 3-dichloro-6-dichloroacetyl-7-hydroxy-2-oxo-2, 3, 3a, 6, 7, 7a-hexahydrofuro [2, 3-c] pyridine (5). Reaction of dichloroketene with 1, followed by treatment with abs. methanol gave 3, methyl 2, 2-dichloro-2-(2-pyridyl) acetate (6), and methyl 2, 2-dichloro-2-(4-pyridyl) acetate (7). Similar reaction of dichloroketene with methylpyridine 1-oxides gave the corresponding 2-dichloro and 4-dichloro methylpyridines. On the other hand, reaction of dichloroketene with 2, 6-dimethylpyridine 1-oxide (18), followed by treatment with abs. methanol gave 4-dichloromethyl-2, 6-dimethylpyridine (19) and bis (2, 6-dimethyl-4-pyridyl) dichloromethane (21). Dichloroketene also reacted with quinoline 1-oxide (24) and isoquinoline 2-oxide (29) to give the corresponding dichloromethyl derivatives (25 and 26, and 30, respectively).

Studies on ketene and its derivatives. CXVII. Reaction of dichloroketene with ethyl N-(2-pyridyl)formimidates.

The reaction of dichloroketene with ethyl N-(2-pyridyl)formimidates (1) gave ethyl 2, 2-dichloro-3-ethoxy-3-(2-pyridylamino)propionates (3) and 3-chloro-2-ethoxypyrido[1, 2-a]pyrimidin-4(4H)-ones (4), together with 3, 3-dichloro-4-ethoxy-1-(2-pyridyl)-2-azetidinone (2). Compound 3b, on standing at room temperature, was transformed into ethyl 2-ethoxy-8-methylimidazo[1, 2-a]pyridine-3-carboxylate (6).

The reaction of dichloroketene with 4-methylene- spiro[2,4]heptane

The reaction of dichloroketene with 4-methylene- spiro[2,4]heptane

Reaction of ketenes with N,N‐Disubstituted 2‐Aminomethylenecycloalkanones III. Synthesis of N,N‐Disubstituted 3,3‐Diehloro‐4‐amino‐5,6‐polymethylene‐3,4‐dihydro‐α‐pyrones

AbstractThe reaction of dichloroketene with N,N‐Disubstituted 2‐aminomethylenecyclopentanones, cyclohexanones, cycloheptanones and cyclooctanones gave the 1,4‐cycloadducts, namely N,N‐Disubstituted 3,3‐dichloro‐4‐amino‐5,6‐polymethylene‐3,4‐dihydro‐α‐pyrones. The structures of these products were determined by uv, ir and nmr spectral data, as well as by dehydrochlorination of the adduct, 3,3‐dichloro‐4‐diphenylamino‐5,6‐tetramethylene‐3,4‐dihydro‐α‐pyrone, which led to 3‐chloro‐4‐diphenylamino‐5,6‐tetramethylene‐α‐pyrone.The by‐product of the cycloaddition reaction was the N,N‐Disubstituted dichloroacetamide, the formation of which varies according to the substituents on the nitrogen atom.