An Efficient Method for the Synthesis of N-Acylsulfonamides: One-pot Sulfonylation and Acylation of Primary Arylamines under Solvent-Free Conditions

Summary. The preparation of N-acylsulfonamides is described using primary amines, arylsulfonyl chlorides and acyl chlorides. Reaction of primary aryl amines with arylsulfonyl chlorides in the presence of NaHCO₃ produced N-arylsulfonamides, which reacted in situ with benzoyl chloride furnishing the corresponding N-benzoyl-N-arylsulfonamides in 72–96% yields. Accordingly, 4-nitrobenzoyl chloride and 3,5-dinitrobenzoyl chloride were used as acylating agents. All the reactions were carried out under solvent-free conditions at room temperature and the products were isolated after simple work-up in high yields and purity.     

Chloracylierung und Bromacylierung von Carbonylverbindungen. IV. Bildungsmechanismus von Carbonsäure-(1-halogenalkyl)estern

Chloroacylation and bromoacylation of carbonyl compounds IV. Investigations of the reaction mechanism The kinetics of the Lewis acid catalyzed reaction between acyl chlorides and carbonyl compounds (especially aldehydes) is investigated by ¹H-NMR.-spectroscopy. With acetyl chloride as starting material a second order reaction is observed; the rate of the reaction increases in polar solvents as well as with increasing electron-donating capacity of the aldehyde. - With benzoyl chloride as starting material the reaction is first order with respect to benzoyl chloride, but zero order with respect to the aldehyde. The reaction rate is strongly influenced by the substituents of the benzoyl chloride. - Two polar reaction mechanisms which are in accord with these results are outlined and discussed.     

Etude de l'acylation de l'acétyl-3 acétoxy-8 indolizine par action de chlorures d'acide en présence de chlorure d'aluminium

Study of acylation of 3-acetyl-8-acetoxyindolizine by miscellaneous acid chlorides in the presence of aluminium chloride shows that this reaction is either limited to a transesterification (in the case of benzoyl chloride) or leads to introduction of an acyl group in position 1 with simultaneous liberation of the phenol function in position 8. When acylation takes place, acetyl chloride resulting from the cleavage of the acetoxy group competes with the acid chloride used in the reaction. Predominant acylation by the latter is observed when the reaction is performed with ethoxalyl chloride or with non branched aliphatic acid chlorides; by contrast solely acetylation takes place when pivaloyl or phenylacetyl chloride is used. These results are tentatively explained by a process related to the Fries rearrangement. The hypothesis of intramolecular transfer of an acyl group from the ester function in position 8 can be discarded by the observed results.     

Reactions of atomic carbon with acyl chlorides

Reactions of arc-generated carbon atoms with acyl chlorides proceed by two distinct mechanistic pathways depending on the nature of the alkyl group in the substrate. Acetyl chloride affords vinyl chloride from the putative chloromethylcarbene produced by deoxygenation, whereas pivaloyl chloride gives t-butyl chloride as the predominant product via a chain reaction from the initially generated pivaloyl radical. When the alkyl group is isopropyl, both pathways are implicated.     

Structural features of <Emphasis Type="Italic">N</Emphasis>-acylcytisines

N-Acyl cytisine derivatives were synthesized by acylation with acetic anhydride; benzoyl and o-bromo- and p-nitrobenzoyl chlorides; and crotonyl and cinnamoyl chlorides. The structures of the synthesized compounds were studied using IR, PMR, and x-ray structure analysis (XSA). PMR spectra of the N-acylcytisines in solution typically had two rotational isomers around the N12–CO bond. Conformational analysis was performed using XSA for the position of the acyl group relative to the cytisine core. Bond lengths and angles of the acyl groups involved in the conjugation were analyzed.     

Rearrangement reactions of aziridinylbenzaldoximes

Reactions of 2,2-dimethylaziridine with benzohydroximoyl chlorides [ArC(Cl)?NOH] give aziridinylbenzaldoximes 1 . It has been found that the aziridine ring in these compounds undergoes ring opening in hydrogen chloride-dioxane solution to give (Z)-N-hydroxy-N′-(2-chloro-2-methylpropyl)benzenecarboximidamides [ArC(NHCH₂CR¹R²Cl)?NOH, 4 ]. Treatment of 1 with hydrochloric acid followed by neutralization with aqueous sodium hydroxide gave 6,6-dimethyl-3-aryl-1,2,4-oxadiazines 2. Reaction of 4 with sodium hydride in dioxane gave 5-isopropyl-3-aryl-4,5-dihydro-1,2,4-oxadiazoles 5. Reaction of the 4,5-dihydro-1,2,4-oxadiazoles 5 with N-chlorosuccinimide gave the heteroaromatic 1,2,4-oxadiazoles 6 . It is suggested that reactions of 4 with sodium hydride in dioxane solution involve the conjugate base of 4 which undergoes a 1,2-hydride shift that is concerted with loss of chloride ion. In aqueous sodium hydroxide solution it is suggested that the conjugate base of 4 undergoes ionization of the chlorine atom followed by nucleophilic attack by the oximate anion.     

Simple,High Yield Preparation of N-Benzylacetamides by Lewis Acid-Catalyseed Reaction of Benzyl Chlorides or Benzyl Methyl Ethers with Acetonitrile

Reaction of either benzyl chlorides or benzyl methyl ethers with hydrated ferric chloride in acetonitrile results in smooth Ritter reaction and formation of N-benzylacetamides in excellent yield.     

About the synthesis of [1,2]diazepinoindole derivatives from ethyl 2-(1-methylindole)acetate, 2-indole and 3-indoleacetohydrazones

The Vilsmeier-Haack reaction with ethyl 2-(1-methylindole)acetate and N,N-Dimethylamides/phosphorus oxychloride gave (65–85%) of ethyl 2-(3-acyl-1-methylindole)acetates 2 , which when boiled with hydrazine yielded about 90% of 4,5-dihydro-6-methyl-4-oxo-3H[1,2]diazepino[5,6-b]indoles 3. The attempted cyclization of 2-(1-methylindole)acetohydrazones 6 with acyl (acetyl and benzoyl) chlorides/triethylamine, to [1,2]diazepino[5,6-b]indole derivatives was fruitless and the bis(acyl)hydrazones 9 were obtained. Several transformations of 9 are reported. Similarly, the attempted cyclization of 3-indoleacetohydrazones 14 with acetyl chloride/triethylamine to [1,2]diazepino[4,5-b]indole derivatives was also fruitless and the bis(acyl)hydrazones 16 were again obtained.     

Competitive proton and hydride transfer reactions via ion‐neutral complexes: fragmentation of deprotonated benzyl N‐phenylcarbamates in mass spectrometry

The gas‐phase chemistry of deprotonated benzyl N‐phenylcarbamates was investigated by electrospray ionization tandem mass spectrometry. Characteristic losses of a substituted phenylcarbinol and a benzaldehyde from the precursor ion were proposed to be derived from an ion‐neutral complex (INC)‐mediated competitive proton and hydride transfer reactions. The intermediacy of the INC consisting of a substituted benzyloxy anion and a phenyl isocyanate was supported by both ortho‐site‐blocking experiments and density functional theory calculations. Within the INC, the benzyloxy anion played the role of either a proton abstractor or a hydride donor toward its neutral counterpart. Relative abundances of the product ions were influenced by the nature of the substituents. Electron‐withdrawing groups at the N‐phenyl ring favored the hydrogen transfer process (including proton and hydride transfer), whereas electron‐donating groups favored direct decomposition to generate the benzyloxy anion (or substituted benzyloxy anion). By contrast, electron‐withdrawing and electron‐donating substitutions at the O‐benzyl ring exhibited opposite effects. Copyright © 2015 John Wiley & Sons, Ltd.     

DMSO-catalyzed chlorination of alcohols using N-phenylbenzimidoyl chloride

N-phenylbenzimidoyl chloride has been demonstrated as an efficient chlorination reagent catalyzed by dimethyl sulfoxide (DMSO) in conversion of alcohols to corresponding chlorides. The reaction conditions were mild, and most of the substrates gave satisfactory yields. The configuration inversion of the chlorination was proved using optically active phenyl alcohols. The amount of DMSO can be as low as 0.001 eq without reducing the efficiency of the chlorination. A plausible mechanism for the reaction was proposed and proved by experiments. The reaction is stereoselective and potentially chemoselective among primary benzyl alcohols, secondary benzyl alcohols, and unactivated aliphatic alcohols.     

Dendritic poly(benzyl ether)‐b‐poly(N‐vinylcaprolactam) block copolymers: Self‐organization in aqueous media,thermoresponsiveness and biocompatibility

Four generations of new amphiphilic thermoresponsive linear‐dendritic block copolymers (LDBCs) with a linear poly(N‐vinylcaprolactam) (PNVCL) block and a dendritic poly(benzyl ether) block are synthesized by atom transfer radical polymerization (ATRP) of N‐vinylcaprolactam (NVCL) using dendritic poly(benzyl ether) chlorides as initiators. The copolymers have been characterized by ¹H NMR, FTIR, and GPC showing controlled molecular weight and narrow molecular weight distribution (PDI ≤ 1.25). Their self‐organization in aqueous media and thermoresponsive property are highly dependent on the generation of dendritic poly(benzyl ether) block. It is observed for the LDBCs that the self‐assembled morphology changes from irregularly spherical micelles, vesicles, rod‐like large compound vesicles (LCVs), to the coexistence of spherical micelles and rod‐like LCVs, as the generation of the dendritic poly(benzyl ether) increases. The results of a cytotoxicity study using an MTT assay method with L929 cells show that the LDBCs are biocompatible. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 300–308     

Synthesis and Some Reactions of New N-[Aryl(Benzyl,Cyclohexyl, Propyl)sulfonyl]-4-azatricyclo[5.2.1.02,6]dec-8-enes

A synthesis was accomplished of 4-azatricyclo[5.2.1.02,6]dec-8-ene by aminolysis of bicyclo[2.2.1]hept-2-ene-endo,endo-5,6-dicarboxylic acid anhydride followed by transformation of amidoacid into imide that was subsequently reduced by lithium aluminum hydride. The reaction of the key tricyclic amine with sulfonyl chlorides afforded N-[aryl(benzyl, cyclohexyl, propyl)sulfonyl]-4-azatricyclo[5.2.1.02,6]dec-8-enes.The sulfonamides were subjected to epoxidation with perphthalic acid. By reaction of sulfonamides with p-nitrophenyl azide triazolines were obtained. The structure of compounds synthesized was confirmed by IR, ^1Hand ¹³ NMR spectra.     

Synthesis and characterization of new poly(azomethine ester)s having phenylthiourea units

New polyesters having azomethine and phenylthiourea groups in the polymer backbone were synthesized by interfacial polycondensation method. The dihydroxy monomer N-(4-hydroxy-3-methoxybenzal) N′-(4′-hydroxyphenyl)thiourea was condensed with six diacid chlorides: terephthaloyl, isophthaloyl, azeloyl, suberoyl, pimeloyl and adipolyl chlorides. The resulting polyesters were characterized by viscosity, IR, NMR and TGA analysis. The wholly aromatic poly(azomethine ester) derived from terephthaloyl chloride when blended with polyaniline/NH₄OH, polyaniline/HCl and pure polyaniline shows conductance in the range 3.2 × 10⁻³-0.91 × 10⁻¹ S cm⁻¹.     

Synthesis of antifols related to 2,4-diamino-6,7-dihydro-5H-pyrrolo[3,4-d] pyrimidine. Enhancement of antiparasitic selectivity by nitrogen-linked mono- and dichlorobenzoyl groups or the 3,4–dichlorophenylthiocarbamoyl group

Improved procedures have been developed for the synthesis of 2,4-diamino-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidine ( 2a ), its 7-mcthyl derivative ( 2b ), and 6-(chloro-substituted phenyl) derivatives of 2,4-diamino-6,7-dihydro-5H-pyrrolo[3,4-d]pyritnidine ( 4 ). Direct acylation of compounds 2a or 2b with acid chlorides or mixed anhydrides derived from chloro-substituted benzoic or cinnamic acids gave 6-(chloro-substituted benzoyl or cinnamoyl) derivatives. Lithium aluminum hydride reduction of 6-(chloro-substituted benzoyl) derivatives under controlled conditions permitted preparation of 6-(chloro-substituted benzyl) derivatives (3). Compound 2a also reacted with aryl isothiocyanates to yield 6-arylthiocarbamoyl derivatives. Antimalarial assays for in vivo activity against murine malaria (P. berghei) and avian malaria (P. gallinaceum) revealed that a somewhat enhanced in vivo antiparasitic effect above that of parent compound 2a without any evident increase in host toxicity was conferred by introduction of certain of the 6-chloro-substituted benzoyl groups or the 6-(3,4-dichlorophenylthiocarbamoyl) group. Corresponding 6-(chloro-substituted benzyl) derivatives more frequently displayed host toxicity.     

Acylation of salts of dinitromethane

Conclusions When the ambient anion of dinitromethane is reacted with acyl chlorides (acetyl or benzoyl chloride) the acylation of this anion occurs only at the oxygen atom, with the formation of the O-acyl derivatives of dinitromethane. The latter, being very reactive compounds, undergo a number of further transformations during the reaction process.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2045–2049, September, 1971.     

Synthesis and characterization of novel nano size electroactive poly 4,4′‐diaminodiphenyl sulphone

The modification of electrodeposited polyaniline film by subsequent electrodeposition of 4,4′‐diaminodiphenyl sulfone (DDS) leads to a new material having nanostructure. The coated polymer films were treated with various pH solutions. The film adherent characteristics and surface morphology were studied using SEM. The electrochemically synthesized polyDDS revealed good redox behavior. The DDS was also polymerized by the chemical oxidation method using potassium persulphate. The polymer was characterized by UV‐Vis and FTIR spectral studies. The formation of polymer through the N? H group was understood from the single N? H stretching vibrational frequency at 3459 cm^?1. The X‐ray diffraction studies revealed the formation of nano sized (28 nm) crystalline polymer. The conductivity of the polymer was determined to be 1.07 × 10^?4 S.cm^?1. The solubility of the chemically polymerized powder was ascertained, and polyDDS showed good solubility in DMF and DMSO. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 1702–1707, 2005     

Synthesis and biological properties of 3-methyl-10-propargyl-5,8-dideazafolic acid

The synthesis of N³-methyl-10-propargyl-5,8-dideazafolic acid ( 1b ) is described. Ring closure of methyl-5-methylanthranilate with chloroformamidine hydrochloride gave a high yield of pure 2-amino-4-hydroxy-6-methylquinazoline treatment of which with iodomethane/sodium hydroxide provided the corresponding 3-methylquinazoline (6) which was converted to its 2-pivaloylamino derivative. This synthetic approach, next involving functionalisation of the 6-methyl group, was not further pursued because of difficulty encountered in removing the pivaloyl group. Methyl 5-methylanthranilate was treated with p-toluenesulfonyl chloride and the product then N-methylated. The tosyl group was cleaved with hydrogen bromide/phenol and the resulting methylamine ring-closed with chloroformamidine hydrochloride to provide 2-amino-1,4-dihydro-1,6-dimethyl-4-oxoquinazoline ( 11 ). The 2-pivaloylamino derivative of 11 was prone to hydrolytic deamination when attempts were made to remove the pivaloyl group and further elaboration of this heterocycle, with the intention of obtaining N¹-methyl-10-propargyl-5,8-dideazafolic acid was, too, not attempted. Di-t-butyl N-(4-propargylamino)benzoyl)-L-glutamate was therefore prepared and coupled with 2-amino-6-bromomethyl-4-hydroxyquinazoline hydrobromide. The resulting antifolate diester was N-monomethylated. Removal of the t-butyl groups with trifluoracetic acid afforded the target compound 1b and its structure was proved by degradation to the quinazoline 6 . Its IC₅₀ for L1210 thymidylate synthase (TS) was 26 μM; the control value for 10-propargyl-5,8-dideazafolic acid ( 1a ) was 0.02 μM. Thus the substitution of the lactam hydrogen in 1a by a methyl group reduced the TS inhibition by 1300-fold. Compound 1b was poorly cytotoxic to L1210 cells in culture (ID₅₀ > 100 μM). An unperturbed lactam group in this class of antifolate is important for binding to TS.     

Acylation des β-énaminoesters: Regio et stéréoformation des β-énaminoesters N- ou C-acylés

The reaction of acyl chlorides with cyclic five-membered β-enaminoesters gave exclusively N-acylated products while reaction of acyl chlorides with cyclic seven-membered β-enaminoesters gave only C-acylated products. In the case of cyclic six-membered β-enaminoesters, the reaction of acyl chlorides gave a mixture of N-acylated and C-acylated products.     

Reactions of 4-aminocycloheptimidazoles with alkyl iodides,acyl chlorides,and α-haloketones

The reactions of 4-amino-2-phenylcycloheptimidazole with alkyl iodides and α-bromoketones gave respectively 1-alkyl- and 1-acetonyl- (or 1-phenacyl)-substituted cycloheptimidazol-4(1H)-ones, while the reactions with acyl chlorides gave 4-arylamino-2-phenylcycloheptimidazoles. On the other hand, 2,4-diaminocycloheptimidazole were benzoylated with benzoyl chloride on the amino group at the 2- and/or 4-position and reacted with α-haloketones to give tricyclic 2-substituted 9-aminocyclohept[d]imidazo[1,2-a]imidazoles.     

Reactions of 2,3-dihydro-1H-cyclohepta[b]pyrazines with acyl halides

2 When3-dihydro-1H-cyclohepta[b]pyrazine ( 3 ) was treated with acetyl chloride under the Friedel-Crafts conditions, its pyrazine ring opened to afford 2-[N'-acetyl-(2-aminoethyl)amino]tropone. Reactions with propionyl and butyryl chloride also gave similarly ring-opened products. On the other hand, aromatic benzoyl chlorides reacted with compound 3 to afford N-benzoyl-substituted 2,3-dihydro-1H-cyclohepta[b]pyrazines, in addition to ring-opened compounds.