Reactions of 4-Methoxy-3-quinolinyl and 1,4-Dihydro-4-oxo-3-quino-linyl Sulfides Aiming at the Synthesis of 4-Chloro-3-Quinolinyl Sulfides

The preparation of 1,4-dihydro-4-oxo-3′-alkylthio-3,4′-diquinolinyl sulfides 3 or 1,4-dihydro-4-oxo-3-(alkylthio)quinolines 4 by acid catalysed hydrolysis of 4-methoxy-3′-alkylthio-3,4′-diquinolinyl sulfides 1 or 4-methoxy-3-(alkylthio)-quinolines 2 is described. The reactions of 4-methoxy-3′-alkylthio-3,4′-diquinolinyl sulfides 1 or 1,4-dihydro-4-oxo-3′-alkylthio-3,4′-diquinolinyl sulfides 3 with phosphoryl chloride in DMF afforded 4-chloro-3′-alkylthio-3,4′-diquinolinyl sulfides 5 . Treatment of the title compounds 1 or 3 with boiling phosphoryl chloride systems:leads to 4-chloro-3-(alkylthio)quinolines 6 and thioquinanthrene but those of alkoxy- or oxo-quinolines 2 or 4 lead to 4-chloro-3-(alkylthio)quinolines 6 . The reactions of N-methyl-4(1H)-quinolinones 3n and 4n with phosphoryl chloride directed to 4-chloro-3-(alkylthio)quinolines 6 were studied as well.     

α,ω-Bis(4-substituted-3-quinolinylthio)alkanes from reactions of thioquinanthrene with alkoxides

The reaction of thioquinanthrene 1 with sodium alkoxides and α,ω-dihaloalkanes leads to the formation of α,ω-bis[4-(4-methoxy-3-quinolinylthio)-3-quinolinylthio]alkanes 4 . The yield depends on the nature of α,ω-dihalo-alkanes. The effect of α,ω-dihaloalkanes of the following types: XCH₂X (X = Cl,Br,I), X(CH₂)₂X (X = Cl,Br,I), Br(CH₂)₃Br and Br(CH₂)₆Br were studied. The preparation of 4-alkoxy-3′-(ω-bromoalkylthio)-3,4′-diquinolinyl sulfide 3 and their transformation to α,ω-bis(4-alkoxy-3-quinolinylthio)alkanes 6 were studied as well.     

Diastereo‐ and Enantioselective Intramolecular [2+2] Photocycloaddition Reactions of 3‐(ω′‐Alkenyl)‐ and 3‐(ω′‐Alkenyloxy)‐Substituted 5,6‐Dihydro‐1H‐pyridin‐2‐ones

3‐(ω′‐Alkenyl)‐substituted 5,6‐dihydro‐1H‐pyridin‐2‐ones 2 – 4 were prepared as photocycloaddition precursors either by cross‐coupling from 3‐iodo‐5,6‐dihydro‐1H‐pyridin‐2‐one ( 8 ) or—more favorably—from the corresponding α‐(ω′‐alkenyl)‐substituted δ‐valerolactams 9 – 11 by a selenylation/elimination sequence (56–62 % overall yield). 3‐(ω′‐Alkenyloxy)‐substituted 5,6‐dihydro‐1H‐pyridin‐2‐ones 5 and 6 were accessible in 43 and 37 % overall yield from 3‐diazopiperidin‐2‐one ( 15 ) by an α,α‐chloroselenylation reaction at the 3‐position followed by nucleophilic displacement of a chloride ion with an ω‐alkenolate and oxidative elimination of selenoxide. Upon irradiation at λ=254 nm, the precursor compounds underwent a clean intramolecular [2+2] photocycloaddition reaction. Substrates 2 and 5 , tethered by a two‐atom chain, exclusively delivered the respective crossed products 19 and 20 , and substrates 3 , 5 , and 6 , tethered by longer chains, gave the straight products 21 – 23 . The completely regio‐ and diastereoselective photocycloaddition reactions proceeded in 63–83 % yield. Irradiation in the presence of the chiral templates (?)‐ 1 and (+)‐ 31 at ?75 °C in toluene rendered the reactions enantioselective with selectivities varying between 40 and 85 % ee. Truncated template rac‐ 31 was prepared as a noranalogue of the well‐established template 1 in eight steps and 56 % yield from the Kemp triacid ( 24 ). Subsequent resolution delivered the enantiomerically pure templates (?)‐ 31 and (+)‐ 31 . The outcome of the reactions is compared to the results achieved with 4‐substituted 5,6‐dihydro‐1H‐pyridin‐2‐ones and quinolones.     

A novel synthesis of precocenes. Efficient synthesis and regioselective O-alkylation of dihydroxy-2,2-dimethyl-4-chromanones

The reactions of trihydroxybenzenes 1a-c and 3-methylbut-2-enoic acid ( 2 ) in a zinc chloride/water/phosphoryl chloride system afford either the new trihydroxyphenylbutenone derivatives 3b,c or dihydroxy-2,2-dimethyl-4-chromanones 4a-c in good yields. Compounds 3b,c can be cyclized in high yields to 4b,c in 5% sodium hydroxide solution. Regioselective O-alkylation of 4a-c leads to 5a-f in good yields. O-Alkylation of 5a-f , followed by reduction and dehydration, results in the formation of precocene 3 ( 7d ) and its regioisomer 7a-c,e,f . Methylation of 4a-c gives 6g-i . Subsequent reduction and dehydration affords precocene 2 ( 7h ) and its regioisomers 7g,i .     

A convenient synthesis of novel pyridazino[3,4-b]quinoxalines

Novel 4-chlorophenylhydrazono-3-oxo-1,2,3,4-tetrahydropyridazino[3,4-b]quinoxalines 10a-c were synthesized by the cyclization of the α-hydrazonohydrazides 8a-c. The chlorination of 10a with phosphoryl chloride afforded 3-chloro-4-[2-(o-chlorophenyl)hydrazino]pyridazino[3,4-b]quinoxaline 12.     

Asymmetric Alkylations of a Sultam-Derived Glycine Equivalent: Practical preparation of enantiomerically pure α-amino acids

Alkylation of the chiral glycine derivative 2 with “activated” organohalides under ultrasound-assisted phasetransfer catalysis or with activated and nonactivated organohalides in anhydrous medium provides (mostly crystalline) alkylation products 3 . Acidic hydrolysis of the pure products 3 gives (aminoacyl)sultams 4 which by mild saponification furnish pure α-amino acids 5 in good overall yields from 2 , along with recovered auxiliary 1 (Scheme 1). Pure ω-protected α,ω-diamino acids and α-amino-ω-(hydroxyamino)acids 12–16 are readily accessible from (ω-haloacyl)sultams 3 via reaction with N-nucleophiles followed by acidic and basic hydrolyses (Scheme 2). A reliable determination of the enantiomeric purity of α-amino acids using HPLC analysis of their N-(3,5-dinitrobenzoyl)prolyl derivatives 17 is presented.     

A facile synthesis of novel 1-aryl-1H-pyrazolo[3,4-b]quinoxalines

The reactions of 3-methyl-2-oxo-1,2-dihydroquinoxaline 3 with chlorophenyl diazonium salts afforded the hydrazones 4a-c , whose chlorinations with phosphoryl chloride gave the dichlorides 5a-c . Refluxing of the dichlorides 5a-c and base in N,N-dimethylformamide provided the 1-aryl-1H-pyrazolo[3,4-b]quinoxalines 6a-c .     

Reaktionen von α-Chlorcarbonsäurechloriden mit Trialkylaminen

The condensation of α,α-dichloropropionyl chloride (IVa) and of trichloroacetyl chloride (IVb) with α-chloropropionyl chloride (Ia) in the presence of triethylamine led to two acid chloride enol-esters, both as mixtures of cis- and trans-isomers, namely 1, 2-dichloropropenyl α,α-dichloropropionate (Va) and 1, 2-dichloropropenyl trichloroacetate (Vb). A mixture of triethylamine and trichloroacetyl chloride produced an oxidation-reduction reaction to give 48% 1, 2, 2, 2-tetrachloroethyltrichloroacetate (VIII) and 69% 1-diethylamino-4, 4, 4-trichloro-1-butene-3-one (IX). Basic hydrolysis of IX led to 43% of glutaconic acid (XIII). Tripropylamine reacted in the same way with trichloroacetyl chloride to yield 1-dipropylamino-2-methyl-4, 4, 4-trichloro-but-1-ene-3-one (XIX) which was readily hydrolyzed in acid solution to α-trichloroacetyl-propionaldehyde (XX).     

Facile synthesis of fused purines from 8-aminotheophylline

Fused purines 3a-f were prepared by one-step from 8-aminotheophylline ( 1 ) and α,ω-dibromoalkanes in N, N-dimethylformamide in the presence of sodium hydride. Reaction of 3c-e with chloroacetyl chloride followed by treatment with dimethylamine gave 6a-c . A one-step reaction of 1 with ethyl bromopropionate gave 1,3-dimethyl-1,2,3,4,6,7,8,9-octahydropyrimido[2,1-f]purine-2,4,8-trione ( 7b ). Facile syntheses of 7a, c, d from 1 were also carried out.     

Preparation and thermal degradation of α,ω-alkylene bis[5-(1,2,3,4-thiatriazolyl)] sulfides

Syntheses of some extremely shock sensitive α,ω-alkylene bis[ 5-(1,2,3,4-thiatriazolyl)] sulfides via reaction of sodium 1,2,3,4-thiatriazoline thionate (1) and α,ω-dihaloalkanes are described. Dichloromaleic imide reacted analogously with 1 to give 3,4-bis(5-(1,2,3,4-thiatriazolyl)thio)maleic imide. The compounds decompose thermally in solution with formation of α,ω-alkylene bis(thio-cyanates), nitrogen and sulfur. The infrared spectra are discussed.     

Michael addition of benzoylacetonitrile to chiral α-cyanoacrylates derived from enantiomerically pure α-hydroxyaldehydes: Synthesis of 3-alkoxycarbonyl-4-alkyl-2-amino-5-cyano-6-phenyl-4H-pyrans

We describe the Michael addition of benzoylacetonitrile to α-cyanoacrylates 4a-c and 5a obtained from readily available chiral α-hydroxyaldehydes 1a-c . The resulting polyfunctionalized 4-alkyl-2-amino-4H-pyrans 6a-c, 7a have been obtained in good yield and moderate diastereoselectivity.     

α,ω-Dihydroxyalkan-α,α-diphosphonsäuren durch Desaminierung von ω-Aminoalkandiphosphonsäuren

α,ω-Dihydroxyalkane-α,α-diphosphonic Acids by Desamination of ω-Aminoalkanediphosphonic Acids The title compounds represent a new group of complexing diphosphonic acids which are synthesized by desamination of ω-amino-α-hydroxyalkane-α,α-diphosphonic acids. In case of α,ω-dihydroxypropane-α,α-diphosphonic acid ( 1 ) a phosphonylated phostone is formed by dehydration. In contrast, the ω-phenyl drivative of ( 1 ) yields in a smooth reaction under the same conditions 2-hydroxy-5-phenyl-3-phosphono-1.2-oxaphosphol-3-en-2-oxide ( 6 ).     

Substituted γ-Lactones. 35 . Reduction of 4-aroyl-3-hydroxy-2(5H)-furanones

The reduction of 4-aroyl-3-hydroxy-2(5H)-furanons 1a-c was investigated using different reducing agents. Sodium borohydride reacts with type 1 compounds by loss of water to yield 4-(arylmethylene)-2,3(4H,5H)-furandiones 2a-c . Platinum or charcoal supported by pallodium chloride transforms 1a to 4-benzyl-3-hydroxy-2(5H)-furanone ( 3). Compounds 2a and 2b react with o-phenylenediamine to give 3-(E-(1′-hydroxymethyl-2′-aryl)ethenyl]-2-quinoxalinones 4a and 4b . The lactone 3 under the same conditions splits out formaldehyde and forms 3-(2′-phenylethyl)-2-quinoxalinone ( 6 ). The structure assignments of the novel compounds are based on elemental analysis and nmr as well as ir spectroscopic data.     

Functional polymers and sequential copolymers by phase transfer catalysis. 18. Synthesis and characterization of α,ω-bis(2,6-dimethylphenol)–poly(2,6-dimethyl-1,4-phenylene oxide) and α,ω-bis(vinylbenzyl)–poly(2,6-dimethyl-1,4-phenylene oxide) oligomers

A novel and convenient synthetic method for the preparation of α,ω-bis(2,6-dimethylphenol)–poly(2,6-dimethyl-1,4-phenylene oxide) (PPO-2OH) is presented. It is based on the oxidative copolymerization of 2,6-dimethylphenol (DMP) with 2,2′-di(4-hydroxy-3,5-dimethylphenyl propane) (TMBPA) in a mixture of water–methanol or chlorobenzene–methanol. By using a 4/1 mole ratio of DMP to TMBPA and different solvent mixtures, it was possible to obtain bifunctional PPO-2OHs with number average molecular weights between 1000 and 5000. A phase-transfer-catalyzed etherification of PPO-2OH chain ends with a mixture of m- and p-chloromethylstyrene was used to synthesize α,ω-bis(vinylbenzyl)-poly(2,6-dimethyl-1,4-phenylene oxide)s (PPO-2VBs). The thermal polymerization of the PPO-2VBs was studied by differential scanning calorimetry, and has demonstrated a very high thermal reactivity for this new class of reactive oligomers.     

6-Substituted thioquinanthrenes. Reaction of thioquinanthrene with radicals formed from DMF

Reaction of bis-hydrogen sulfate of thioquinanthrene with DMF-ferrous sulfate-hydroxylamine-O-sulfonic acid system took place at the α-quinolinyl position and led to 6-monosubstituted thioquinanthrene derivatives 1 (42%) and 2 (11%).     

Study of the synthesis of poly(isobutylene-b-amide-11) by polycondensation of α,ω-dianhydride oligoisobutylene with α,ω-diamino oligoamide-11. I. Study of amine–anhydride and amide–anhydride reactions on low molecular weight models and on oligomers and polymers

The side reactions connected with the polycondensation of α,ω-diamino oligoamides and α,ω-dianhydride oligoisobutylenes are studied on low and high molecular weight models. Models for amine and anhydride end groups are dodecylamine and (2-dodecene-1-yl) succinic anhydride, respectively; their reaction is studied in the bulk (170°C) and in solution (142, 152, and 162°C); the products are analyzed by ¹H-, ¹³C-, and ¹H-¹³C-NMR and GPC. Some of these products and the junctions between the blocks are prepared independently. Models of amide groups in the chain are N-dodecyldodecanamide and N-dodecyloctadecanamide; their reaction with anhydride model results in cleavages with formation of imide groups. The results obtained from low molecular weight models are confirmed by studies on oligomers. They show unambiguous by that crosslinking which accompanies the block polycondensation originates from the reaction of amino-end groups with the intermediary acid groups resulting from the amine-anhydride reaction.     

Reactions of 3-Benzylidene-3H-1,2-dithioles and 3-Alkyl-1λ4,2-dithiol-1-ylium Salts with Isonitriles: A Synthesis of 1,6aλ4-Dithia-6-azapentalenes

1,6aλ⁴-Dithia-6-azapentalenes ( 7a )–( 7h ), ( 12a ), and ( 12b ) have been synthesized by the reaction of 5-aryl-3-benzylidene-3H-1,2-dithioles with isonitriles in the presence of phosphoryl chloride and by the reaction of 3-benzyl- and 3-methyl-1λ⁴, 2-dithiol-1-ylium salts with isonitriles. Possible mechanisms for these reactions are discussed. © 1997 John Wiley & Sons, Inc. Heteroatom Chem 8 : 479–485, 1997     

Copolymeric cyclodextrin polysiloxane stationary phases prepared from 6A,6C- and 6A,6D-dialkenyl-substituted β-cyclodextrin

The syntheses of four new β-cyclodextrin-hexasiloxane copolymers from heptakis(2,3-di-O-methyl)-β-cyclodextrin (2) by multi-step processes are described. 6^A,6^C-Di-O-[p,p'-methylenebis(benzenesulfonyl)]hetakis(2,3-di-O-methyl)β-cyclodextrin (3) , which was prepared by the reaction of 2 with p,p'-methylenebis-(benzenesulfonyl chloride), is a key intermediate for the preparation of permethylated 6^A,6^C-bisalkenyl-β-cyclodextrins 5, 6 , and 9. Permethylated 6^A,6^C-bissulfonate ester 4 , which was obtained from 3 by a methylation reaction under mild conditions, was reacted with sodium allyloxide or sodium ω-undecenyloxide to produce permethylated 6^A,6^C-bisallyl- (or bis-ω-undecenyl)-β-cyclodextrin 5 or 6 or was hydrolyzed with 2% sodium amalgam in methanol to yield diol 7. Compound 7 was oxidized with periodinane, followed by Wittig's reaction with methyltriphenylphosphonium iodide to give permethylated 6^A,6^C-dideoxy-6^A,6^C-dimethylene-β-cyclodextrin (9). Treatment of 2 with p,p'-methylenebis(benzenesulfonyl chloride) or p,p'-biphenyldisulfonyl chloride gave bissulfonate esters 10 or 11 , respectively. Both of them were treated with sodium p-allyloxy-phenoxide in DMF, followed by methylation, to form permethylated 6^A,6^D-di-O-(p-allyloxyphenyl)-β-cyclo-dextrin (16). Bisalkenes 5, 6, 9 and 16 were copolymerized with α,ω-dioctyldecamethylhexasiloxane by a hydrosilylation process to give the cyclodextrin-containing copolymers 17–20.     

Ammoniakverlust aus α,ω-Alkandiaminen im Massenspektrometer. 22. Mitteilung über das massenspektrometrische Verhalten von Stickstoffverbindungen

Loss of ammonia from α,ω-alkanediamines in the mass spectrometer . Under electron impact α,ω-alkanediamines lose ammonia from the molecular ion. This fragmentation reaction is explained in the case of 1.4-butanediamine ( 1 ) on the basis of the spectra of homologues and deuteriated derivatives. The reaction proceeds via neighbouring group participation; the mechanism is given in Scheme 1.     

Synthesis and antimicrobial activity of new 1,2,4-triazole, 1,3,4-oxadiazole, 1,3,4-thiadiazole,thiopyrane, thiazolidinone,and azepine derivatives

4-oxo-4-phenylbutanehydrazide 3 was reacted with aryl or alkyl isothiocyanates to give the corresponding N-substituted-2-(4-oxo-4-phenylbutanoyl) hydrazine-1-carbothioamide 4a-c . Cyclization of thiosemicarbazides 4a-c with sodium hydroxide led to the formation of 3-(4-sub-5-thioxo-1,2,4-triazol-3-yl)-propanone 5a-c . Desulfurization of thiosemicarbazides 4a-c by mercuric oxide afforded 3-(5-(sub-amino)-1,3,4-oxadiazol-2-yl)-propanone 6a-c . The reaction of 4a-c with phosphorus oxychloride gave 3-(5-(sub-amino)-1,3,4-thiadiazol-2-yl)-propanone 7a-c . Treatment of 4a-c with ethyl-bromoacetate or α-bromopropionic acid gave N′-(3-sub-thiazolidin-2-ylidene)-butanehydrazide 8a-c and (N′-(3-sub-oxothiazolidin-2-ylidene)-butanehydrazide 9a-c . Chlorination of oxothiazolidine-hydrazide 9a-c by phosphorus oxychloride afforded N-(3-sub-4-oxothiazolidine)-butane-hydrazonoyl-chloride 10a-c . The reaction of 10a-c with mercaptoacetyl-chloride yielded 2-((4-benzoyl-thiopyrane) hydrazono)-3-sub-thiazolidinone 11a-c . Also, reacted of 10a-c with hydrazine hydrate afforded N″-(3-sub-oxothiazolidine)-butane-hydrazon-hydrazide 12a-c . The 3-sub-2-((pyridazine) hydrazono) thiazolidinone 13a-c was obtained by cyclization of 12a-c via refluxing in DMF. The reaction and cyclized of 9a-c with chloroacetyl-chloride in ethanolic KOH afforded 1-((3-sub-4-oxothiazolidine) amino)-azepine-dione 14a-c . The chemical structures of the new compounds have been confirmed by diverse spectroscopy analyses such as IR, NMR, MS, and elemental analysis. The synthesized compounds were tested for their antimicrobial activity and these compounds were considered (Pyridazin-hydrazono-thiazolidinone 13a-c , oxothiazolidin-azepinedione 14a-c , N-thiazolidin-hydrazon-hydrazide 12a-c , and thiopyran-hydrazono-thiazolidinone 11a-c ) the most effective as antimicrobial activity.