Synthesis of some novel chloro-/aryl-substituted-5,5-dimethyl-2-cyclohexenones

Abstract

Two novel structural isomers: the dihalo-5,5-dimethyl-2-cyclohexenones were synthesized. Regioselective Suzuki-Miyaura cross coupling reaction of the isomers with nine different aryl boronic acids afforded eighteen novel compounds: the 2-aryl-3-chloro-5,5-dimethyl-2-cyclohexenones and the 3-aryl-2-chloro-5,5-dimethyl-2-cyclohexenones in 90–95% yields, which were characterized spectroscopically by IR, NMR and MS. The single crystal X-Ray diffraction ORTEP views of four representative compounds unambiguously confirm the formation of substituted cyclohexenones.     

Unequivocal syntheses of 6-methyl- and 6-phenylisoxanthopterin

Although 6-methyl- ( 1 ) and 6-phenylisoxanthopterin ( 2 ) have previously been synthesized, the requirement of high purity necessary for immunological testing has necessitated our development of the first reported synthesis of these compounds by unequivocal methods. In the process of so doing four new pyrazines, ethyl 3-amino-5-chloro-6-methyl-2-pyrazinecarboxylate ( 11 ), N,N-dimethyl-N'-(6-chloro-3-cyano-5-phenylpyrazin-2-yl)methanimidamide ( 16 ), 2-amino-3-ethoxycarbonyl-5-phenylpyrazine 1-oxide ( 19 ), and ethyl 3-amino-5-chloro-6-phenyl-2-pyrazinecarboxylate ( 20 ) were synthesized. Four new pteridines, 7-methoxy-6-methyl-2,4-pteridinediamine ( 7 ), 7-methoxy-6-phenyl-2,4-pteridinediamine ( 17 ), 2-amino-7-ethoxy-6-methyl-4(3H)-pteridinone ( 12 ), and 2-amino-7-ethoxy-6-phenyl-4(3H)-pteridinone ( 21 ) have also been synthesized enroute to these isoxanthopterins.     

Nucleotide. XV. Synthese und Eigenschaften von 2′-O-t-Butyldimethylsilyl-5′-O-monomethoxytritylribonucleosid-3′-phosphotriestern,Ausgangssubstanzen für Oligonucleotid-Synthesen

Nucleotides. XV. Synthesis and Properties of 2′O-t-Butyldimethylsilyl-5′-O-monomethoxytritylribonucleoside-3′-phosphotriesters, Starting Materials for Oligonucleotide Syntheses The syntheses of two types of fully blocked ribonucleoside 3′-phosphotriesters 6–14 have been achieved in excellent yields from 2′-O-t-butyldimethylsilyl-5′-O-monomethoxytrityl-ribonucleosides 1–5 by phosphorylation with 2-chloro- and 2,5-dichlorophenylphosphorodichloridate respectively and subsequent treatment by cyanoethanol to 6 , 8 , 10 , 12 and 14 and by p-nitrophenylethanol to 7 , 9 , 11 and 13 . These phosphotriesters are valuable starting materials for oligonucleotide syntheses due to the fact that the corresponding phosphotriesters 15–23 with free HO? C(5′) could be obtained by detritylation and the 3′-phosphodiester triethylammonium salts 24–32 by deblocking of the cyanoethyl and the 2,5-dichlorophenyl group respectively. All newly synthesized compounds have been characterized by UV.-and NMR.-spectra as well as C, H, N elementary analyses.     

Synthesis of nucleoside analogs of 1,4-oxathiane, 1,4-dithiane,and 1,4-dioxane

The two regioisomers 6-chloro-9-(1, 4-oxathian-3-yl)-9H-purine ( 5 ) and 6-chloro-9-(1,4-oxathian-2-yl)-9H-purine ( 6 ) were obtained when 3-acetoxy-1,4-oxathiane ( 3 ) was subjected to the acid-catalyzed fusion procedure; compound 3 was prepared by a Pummerer reaction with 1,4-oxathiane 4-oxide ( 2 ). The nucleoside analog 6 could he converted into the adenine derivative 7 and 9-(1,4-oxathian-2-yl)-9H-purine-6(1H)thione ( 8 ). The following nucleoside analogs have also been synthesized: 6-chloro-9-(1,4-dithian-2-yl)-9H-purine ( 13 ), 9-(1,4-dithian-2-yl)adenine ( 14 ), 9-(1,4-dithian-2-yl)-9H-purine-6(1H)thione ( 15 ), and 6-chloro-9-(1,4-dioxan-2-yl)-9H-purine ( 18 ).     

Synthesis and calcium channel antagonist activity of new symmetrical and asymmetrical 4-[2-chloro-2-(4-chloro-6-methyl-2-oxo-2H-pyran-3-yl)vinyl]-substituted 1,4-dihydropyridines

New symmetrical 4-[2-chloro-2-(4-chloro-6-methyl-2-oxo-2H-pyran-3-yl)vinyl]-substituted 1,4-di-hydropyridines were synthesized in moderate to good yields via the modified Hantzsch reaction of β-dicarbonyl compounds with (Z)-3-chloro-3-(4-chloro-6-methyl-2-oxo-2H-pyran-3-yl)acrolein in the presence of an excess amount of NH₄OAc. Also, the reaction of β-dicarbonyl compounds with (Z)-3-chloro-3-(4-chloro-6-methyl-2-oxo-2H-pyran-3-yl)acrolein in the presence of enamino esters and ketones was performed, and asymmetrical 4-[2-chloro-2-(4-chloro-6-methyl-2-oxo-2H-pyran-3-yl)vinyl]-substituted 1,4-dihydropyridines were obtained in moderate to good yields at room temperature. The calcium channel blocking activity of these compounds was assessed. They demonstrated moderate to weak effects, although one compound had a comparable effect (IC₅₀ =1.40×10⁻⁷ M) with respect to the reference drug Nifedipine.     

Halogenation of N-Substituted p-Quinonimines and p-Quinone Oxime Esters: II. Chlorination and Bromination of 4-Aroyl(arylsulfonyl)oxyimino-2-methyl-2,5-cyclohexadienones

Halogenation of 4-aroyl(arylsulfonyl)oxyimino-2-methyl-2,5-cyclohexadienones yields Z,E-isomeric 4-aroyl(arylsulfonyl)oxyimino-5,6-dihalo-2-methyl-2-cyclohexenones and (E)-4-aroyl(arylsulfonyl)oxyimino-5,6-dihalo-6-methyl-2-cyclohexenones. Further chlorination leads to formation of (Z,E)-4-aroyl(arylsulfonyl)oxyimino-2,5,6-trichloro-6-methyl-2-cyclohexenones.     

Synthesis and Photochemical Behaviour of 2-Amino-1,3-Cyclohexadienes

The reaction of the 4,4-dialkylated 2-cyclohexenones 1 or 2 with a twofold excess of a secondary amine 3 affords the 2-amino-1,3-cyclohexadienes 4 and 5 , respectively. Irradiation (λ ≧ 300 nm) of the morpholino derivative 4a yields a mixture of the isomeric 3-morpholino-6-methyl-1,3,5-heptatrienes 6 and 7 , while 5 gives only one corresponding product 8 . The reaction of enone 1 with an equimolar amount of pyrrolidine ( 3c ) affords the bis-enamine 9 which is converted to the unsaturated diketone 10 by oxidative hydrolysis.     

Design,synthesis, and pesticidal activities of novel pyrimidin-4-amine derivatives containing trifluoroethyl sulfide moiety

In order to overcome the problem of pesticide resistance, it is necessary to discover novel pesticides with new mechanisms of action. Herein, a series of novel pyrimidin-4-amine derivatives containing trifluoroethyl sulfide moiety were designed and synthesized. Bioassays indicated that the title compounds synthesized possessed excellent acaricidal activity against Tetranychus urticae and fungicidal activity against Erysiphe graminis and Puccinia sorghi. Especially, the acaricidal activity of 5-chloro-6-(difluoromethyl)-N-(2-(2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl)thio)phenoxy)ethyl)pyrimidin-4-amine (compound T4 , LC₅₀ = 0.19 mg/L) against T. urticae was close to commercial acaricide cyenopyrafen, and the fungicidal activity of 5-chloro-6-(difluoromethyl)-2-methyl-N-(2-(3-((2,2,2-trifluoroethyl)thio)phenoxy)ethyl)pyrimidin-4-amine (compound T15 , EC₅₀ = 1.32 mg/L) against P. sorghi. was superior to commercial fungicide tebuconazole. The synthesis and characterization of these compounds were given and the structure–activity relationships were discussed.     

Intramolecular [2 + 2]-Photocycloadditions of 6-Allyl-2-cyclohexenones. Formation of Tricyclo[3.3.1.02,7]nonan-6-ones and Tricyclo[4.2.1.03,8]nonan-7-ones

Alkylation of 4,4,6-trimethyl-2-cyclohexenone ( 1 ) in toluene in the presence of sodium bis(trimethylsilyl)amide proceeds smoothly to give high yields of compounds 2 . Irradiation (λ= 366 nm) of the 6-allyl-4,4,6-trimethyl-2-cyclohexenones 2a–c yields mixtures of the isomeric tricyclo-nonanones 3 and 4 , the product ratio depending on the substituent R' of the allylic side chain and on the solvent. The quantum yields for the cyclizations are given.     

Pteridines. Part XCVII. Synthesis and properties of 6-thioxanthopterin and 7-thioisoxanthopterin

6-Thioxanthopterin ( 13 ) was synthesized in four steps starting from 2-amino-4-(penthyloxy)pteridine ( 3 ) via the 8-oxide 4 , its subsequent interconversion to the 6-chloro ( 7 ) and 6-thio derivative ( 12 ) and final hydrolysis of the pentyloxy group. 7-Thioisoxanthopterin ( 15 ) was derived analogously from 2-amino-4-(pentyloxy)pteridine-7(8H)-thione ( 14 ) by alkaline hydrolysis. The various 6- and 7-thiopteridines were methylated to give the corresponding 6- ( 10, 11 ) and 7-(methylthio) derivatives ( 16, 17 ). The newly synthesized compounds have been characterized by elemental analyses, their UV spectra, and the determination of the acidic and basic pK_a values. The spectral relationships are discussed in detail.     

Kinetics of the reactions of cyclopropane derivatives. V. The gas-phase unimolecular reactions of 1 α-chloro-2α,3α-dimethylcyclopropane and 1α-chloro-2α,3β-dimethylcyclopropane

Thermolysis of the “all-cis” compound 1α-chloro-2α,3α-dimethylcyclopropane (A) at 550–607 K and 6–115 torr is a first-order homogeneous non-radical-chain process giving penta-1,3-diene (PD) and HCl as products. The Arrhenius parameters are log₁₀A(sec^?1) = 13.92 ± 0.08 and E = 199.6 ± 0.9 kJ/mol. The isomer with trans-methyl groups, 1α-chloro-2α,3β-dimethylcyclopropane (B) reacts by two parallel first-order processes giving as observed products trans-4-chloropent-2-ene (4CP) and PD + HCl, with log₁₀A(sec^?1) = 14.6 and 13.8, respectively, and E = 199.5 and 190.2 kJ/mol, respectively. The 4CP undergoes secondary decomposition to PD + HCl (as investigated previously). Comparison of the results for compounds (A) and (B) with those for other gas-phase and solution reactions leads to the conclusion that the gas-phase thermolyses proceed by rate-determining ring opening to form olefins which may decompose further by thermal or chemically activated reactions, and that the ring opening is a semiionic electrocyclic reaction in which alkyl groups in the 2,3-positions trans to the migrating chlorine semianion move apart, with appropriate consequences for the rate of reaction and the stereochemistry of the products.     

Synthesis and three-dimensional structure of 4-hydroxy-4-methyl-3-chloro-6-alkyltetrahydropyrans

A method has been developed for the preparation of 4-hydroxy-4-methyl-3-chloro-6-alkyltetrahydropyrans based on the cycloalkylation of 4-hydroxy-2-methyl-3-chloro-1-butene with aldehydes. Dehydrochlorination of these compounds furnished the corresponding oxiranes of the tetrahydropyran series. The chlorine atoms in these newly synthesized chlorotetrahydropyranols have been found to favor equatorial positions.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1457–1460, November, 1986.     

Umlagerung von α-Halogen- in α′-Halogen-cyclobutanone,Schlüsselstufe einer variationsreichen Synthese von Pyrethroiden

Rearrangement of α-Halogen- to α′-Halogen-cyclobutanones, Key Step of a Highly Versatile Synthesis of Pyrethroids α-Halogenocyclobutanones, which are readily available by [2 + 2]-cycloaddition of haloketenes to terminal olefins (e. g. 5 → 6 ), undergo an efficient and stereoselective cine-rearrangement to α′-halogenocyclobutanones in the presence of catalysts such as tertiary amines, HX acids or quaternary ammonium salts (e. g. 6 → 7 , Table 1). Preparative as well as mechanistic aspects of the cine-rearrangement are discussed. The 2,4-cis-disubstituted cyclobutanones 7–32 thus formed represent valuable intermediates in a new synthesis of pyrethroids 1 . The X-ray structure of 2-chloro-4-(2,2,2-trichloroethyl)-3,3-dimethylcyclobutanone ( 7 ), the most important precursor of cis- 3 (X = Cl) shows the following features: a puckered cyclobutanone ring (dihedral angle 31°), 2,4-cis-di-pseudoequatorial arrangement of the chloro and trichloroethyl substituents, and an endo-deviation (0.225 Å; 11°) of the carbonyl O-atom from the plane formed by C(1), C(2) and C(4) (Fig. 2).     

Synthesis of 1,8-, 1,6- and 3,6-dichloro-9H-thioxanthen-9-ones

Cyclization of 2-chloro-6-[(3-chlorophenyl)thio]benzoic acid ( 2 ) gave a mixture of 1,8-, 3 , and 1,6-dichloro-9H-thioxanthen-9-ones 4 . The mixture was converted to 1,8-diamino- 7 , and 1-amino-6-chloro-9H-thioxanthen-9-ones 8 , from which 3 and 4 were prepared separately, respectively. From a mixture of 4 and 3,6-dichloro-9H-thioxanthen-9-one ( 11 ) obtained by cyclizing 4-chloro-2-[(3-chlorophenyl)thio]benzoic acid ( 10 ) was separated 11 by conversion of 4 to 8 .     

Pyrimidines. 65. Synthesis of 6-substituted thieno[2,3-d]pyrimidine-2,4(1H,3H)-diones

Several 6-substituted thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione derivatives were synthesized. 6-Ethoxycarbonyl derivatives 3 and 7 were prepared by treatment of 6-chloro-5-formyluracil 1 and 6-chloro-5-cyanouracil 6 with ethyl 2-mercaptoacetate in the presence of a base. Electrophilic substitution reactions (Vilsmeier-Haack reaction, bromination, and nitration) of 5,6-unsubstituted thieno[2,3-d]pyrimidine 9 , prepared by condensation of 6-mercaptouracil 8 with chloroacetaldehyde, afforded the corresponding 6-formyl-, 6-bromo-, and 6-nitrothieno[2,3-d]pyrimidines 10, 15 and 16 , respectively.     

Photochemical Synthesis and Some Reactions of 7-Oxa-and 7-Thiatricyclo[3.2.1.03,6]octan-2-ones

Irradiation (λ = 350 nm) of newly synthesized 2-acetyl- or 2-methyl-2-(alk-2-enyl)furan-3(2H)-ones 1 and 2-acetyl- or 2-methyl-2-(prop-2-enyl)thiophen-3(2H)-ones 2 affords the corresponding 1-acetyl- or 1-methyl-substituted 7-oxa- and 7-thiatricyclo[3.2.1.0^3,6]octan-2-ones 10 and 11 , respectively, via regioselective intramolecular [2 + 2] photocycloaddition in 65–95% yield (Scheme 2). The 1-acetyl-substituted O-derivatives 10b and 10c undergo ring opening on treatment with MeONa in MeOH at–78° to afford stereoselectively methyl 3-exo-acetyl-2-oxabicyclo[3.2.0]heptane-7-endo-carboxylates 12b and 12c , respectively, while a 2:1 diastereoisomeric mixture of methyl 3-acetyl-2-thiabicyclo[3.2.0]heptane-7-endo-carboxylates 13 and 14 is obtained from the corresponding S-derivative 11b . The outcome of the Huang-Minlon reduction of the 1-methyl-substituted ketones 10a and 11a is again influenced by the heteroatom in the tricycle. While 1-methyl-7-oxatricyclo[3.2.1.0^3,6]-octane ( 15 ) is the only product from the corresponding oxatricyclooctanone 10a , a 1:2 mixture of 1-methyl-7-thiatricyclo[3.2.1.0^3,6]-octane ( 16 ) and 3-methylbicyclo[3.1.1]hept-2-ene-6-endo-thiol ( 17 ) is obtained from the analogous S-compound 11a , both products stemming from a common carbanion precursor.     

Synthesis and antimicrobial agents of thiazolidinone derivatives from benzocyclohepetenone

A series of benzosuberone coupled piperazin-1-yl thiazolidin-4-one derivatives 6a-j were synthesized from 3-(2-[9-chloro-2,3-dimethyl-6,7-dihydro-5H-benzo[7]annulen-8-yl]-4-oxothiazolidin-3-yl)propanoic acid ( 4 ) and substituted piperazines/secondary amines 5a-j using 1-hydroxy benzotriazole, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and triethyl amine in good yields and their structures were characterized by ¹H NMR, ¹³C NMR, IR, and Mass spectra. The newly synthesized compounds were evaluated for their antimicrobial activity against bacterial strains and a fungal strain. Compounds 6f and 6g were indicated promising and broad spectrum antibacterial activity.     

High‐temperature catalysts for the production of α‐olefins based on iron(II) and iron(III) tridentate bis(imino)pyridine complexes modified by nitrilo group

Series of Fe(II) and Fe(III) tridentate bis(imino)pyridine complexes without nitrilo groups 2–6 and with nitrilo groups 7–13 were synthesized. According to X‐ray analysis, the introduction of nitrilo groups in para‐ and ortho‐positions tends to result in shorter axial Fe? N bonds. Both types of complexes, 2–6 and 9–13 , afforded very productive catalysts for the production of α‐olefins with higher K values and better linearity of Schultz–Flory distribution α‐olefins than the parent methyl substituted Fe(II) complex 1 . Noticeably, the complexes functionalized with a para‐nitrilo group 9–13 tend to make α‐olefins with higher K values of the Schultz–Flory distribution, more ideal distributions, and less of the heavier insoluble fractions of α‐olefins than corresponding nonsymmetrically substituted complexes without para‐nitrilo groups 2–6 . Statistically significant correlations were obtained between % solids of total α‐olefins and the blocked solid angle fraction in the +z hemisphere ( = 51.3%, p = 0.012) and between catalyst productivity and total blocked solid angle fraction ( = 43.5%, p = 0.023). The modest values of show that, while steric effects are significant, they are not the sole factor determining catalyst performance. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 585–611, 2008     

Reactions of epoxy-1,1,2-trichloroethane with nudeophiles

Epoxy-1,1,2-triehloroethane (1) was synthesized by the autuoxidation of trichloroethylene and was characterized. It was shown to react readily with 2-mercaptobenzirnidazole (2), 1 -melhyl-2-mercaptoimidazole ( 3 ), p-nitrolhiophenol ( 4 ), and 3,4-dichlorolhiophenol ( 5 ) forming 2-chloro-2-(benzirnidazole-2-thio)acelie acid ( 6 ), 2-ehloro-2-(1-methylirnidazole-2-thio)aeetic acid (characterized as methyl ester ( 8 )), 2-chloro-2-(4-nitrolhiothiophenoxy)-4-nilrophenylthioaeetate (9), and 2-chloro-2-(3,4-dichlorothiophenoxy)-3,4-dichlorophenylthioaeetale ( 10 ), respectively. Base hydrolysis of 9 yielded 2,2-di(4-nilrothiophenoxy)acetie acid ( 11 ). Adducl 9 decomposed on silica gel yielding p-nitrophcnyldisulfide ( 12 ).     

Zur Synthese sulfonierter Derivate von 2,3-Dimethylanilin und 3,4-Dimethylanilin

On the Synthesis of Sulfonated Derivatives of 2,3-Dimethylaniline and 3,4-Dimethylaniline Baking the hydrogensulfate salt of 2,3-dimethylaniline ( 1 ) or of 3,4-dimethylaniline ( 2 ) led to 4-amino-2,3-dimethylbenzenesulfonic acid ( 4 ) and 2-amino-4,5-dimethylbenzenesulfonic acid ( 5 ), respectively (Scheme 1). The sulfonic acid 5 was also obtained by treatment of 2 with sulfuric acid or by reaction of 2 with amidosulfuric acid. 3-Amino-4,5-dimethylbenzenesulfonic acid ( 3 ) and 5-Amino-2,3-dimethylbenzenesulfonic acid ( 6 ) were prepared by sulfonation of 1,2-dimethyl-3-nitrobenzene ( 9 ) to 3,4-dimethyl-5-nitrobenzenesulfonic acid ( 11 ) and of 1,2-dimethyl-4-nitrobenzene ( 10 ) to 2,3-dimethyl-5-nitrobenzenesulfonic acid ( 12 ), respectively, with subsequent Béchamp reduction (Scheme 1). Preparations of 2-amino-3,4-dimethylbenzenesulfonic acid ( 7 ) and of 6-amino-2,3-dimethylbenzenesulfonic acid ( 8 ) were achieved by the sulfur dioxide treatment of the diazonium chlorides derived from 3,4-dimethyl-2-nitroaniline ( 24 ) and from 2,3-dimethyl-6-nitroaniline ( 31 ) to 3,4-dimethyl-2-nitrobenzenesulfonyl chloride ( 29 ) and 2,3-dimethyl-6-nitrobenzenesulfonyl chloride ( 32 ), respectively, followed by hydrolysis to 3,4-dimethyl-2-nitrobenzenesulfonic acid ( 30 ) and 2,3-dimethyl-6-nitrobenzenesulfonic acid ( 33 ), and final reduction (Scheme 3). Compound 7 was also synthesized by reaction of 4-chloro-2,3-dimethylaniline ( 23 ) with amidosulfuric acid to 2-amino-5-chloro-3,4-dimethylbenzenesulfonic acid ( 20 ) and subsequent hydrogenolysis (Scheme 2). 4′-Bromo-2′, 3′-dimethyl-acetanilide ( 13 ) and 4′-chloro-2′, 3′-dimethyl-acetanilide ( 14 ) on treatment with oleum yielded 5-acetylamino-2-bromo-3,4-dimethylbenzenesulfonic acid ( 17 ) and 5-acetylamino-2-chloro-3,4-dimethylbenzenesulfonic acid ( 18 ), respectively. Their structures were proven by hydrolysis to 5-amino-2-bromo-3,4-dimethylbenzenesulfonic acid ( 21 ) and 5-amino-2-chloro-3,4-dimethylbenzenesulfonic acid ( 22 ), followed by reductive dehalogenation to 3 .