Fluorinated N-[2-(haloalkyl)phenyl]imidoyl chloride, a key intermediate for the synthesis of 2-fluoroalkyl substituted indole derivatives via Grignard cyclization process

Fluorinated N-[2-(haloalkyl)phenyl]imidoyl chloride, which was readily available from the corresponding anilines by using Uneyama's one-pot synthesis of fluorinated imidoyl chloride, was found to be a key intermediate for the facile synthesis of 2-fluoroalkyl substituted indole derivatives via the Grignard cyclization process. The bromination of 3-methyl group of 3-methyl-2-trifluoromethyl indole with NBS/CCl₄ led to the formation of 3-bromomethyl substituted indole which can be further utilized to synthesize some new and biologically interested indole derivatives.     

Selective hydrogen transfer reactions from alcohols to ketones promoted by rhodium complexes with 1,10-phenanthroline and related ligands

Substituted cyclohexanones are effectively reduced to the corresponding alcohols using propan-2-ol as hydrogen source and Rh(I) complexes with 1,10-phenanthroline (phen) and substituted derivatives as catalyst precursors.Rh(I) derivatives with phen, 4,7-Ph₂phen and 4,7-Mc₂phen (chel/Rh ⩾ 2) promote the preferential formation of the axial alcohol (substrate = 4-t-butylcyclohexanone), while the 4,7-(MeO)₂phen derivative gives in higher yield the equatorial isomer. Hindered substrates such as 2-methylcyclohexanone and 3,3,5-Me₃cyclohexanone are reduced to the corresponding axial alcohol with a selectivity ⩾ 98% (chel = 4,7-Me₂phen).     

Oxidative addition of substituted arsines and stibines with bis(trifluoromethyl)nitroxyl

Reactions of bis(trifluoromethyl)nitroxyl with a number of methyl- and trifluoromethyl- substituted arsines and stibines at room temperature lead to the formation of pentavalent arsenic and antimony derivatives, namely (CH₃)_3?n(CF₃)_nM[ON(CF₃)₂]₂ (M = As, n = 0, 1, 2; M = Sb, n = 0, 1). The derivatives yield bis(trifluoromethyl)- hydroxylamine and the corresponding dichlorides on treatment with hydrogen chloride. A free radical mechanism is proposed for the oxidative addition reactions.     

Synthesis of new biheterocycles containing a 1,4-benzodioxane fragment

The reaction of 1,4-benzodioxane-2-carbonyl chloride with 5-(4-aminophenyl)-1,3,4-oxa- and -thiadiazole-2-thiols afforded new biheterocyclic compounds which were converted into the corresponding S-benzyl derivatives by treatment with benzyl chloride. 5-(4-Aroylaminophenyl)-1,3,4-oxa(thia)diazole-2-thiols reacted with 2-bromomethyl-1,4-benzodioxane to give compounds in which the 1,4-benzodioxane nucleus and fivemembered heterocycle are linked through a CH₂S bridge.     

Synthesis of 2-selenothieno[2,3-d]pyrimidine derivatives

Intramolecular cyclization of 2-(N-acylselenoureido)-3-carbethoxy-4,5,6,7-tetrahydrobenzo[b]thiophenes in alkaline media leads to the formation of the potassium salt (I) of 2-seleno-4-oxo-3,4,5,6,7,8-hexahydrobenzo[b]thieno[2,3-d]pyrimidine, acidification of which yielded the corresponding base in free form. Some pyrimidine compounds containing a selenium atom in the side chain were obtained by reaction of potassium salt I with halo derivatives (ClCH₂CH₂COOCH₃ and ClCH₂CH₂OH).Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 753–754, June, 1977.     

Formation of Platinum–Tin Bond by Tin(II)Chloride Insertion

The first ¹¹⁹Sn NMR evidence for the presence of direct platinum–tin bond in solution has been obtained for PtCl(SnCl₃)(bdpp) complex (bdpp = (2S,4S)-2,4-bis(diphenylphosphino)pentane). Various PtCl₂(L₂) complexes (L₂ = heterobidentate P–P, P–O, P–N, P–S chelating ligands) have been reacted with tin(II)chloride resulting in the formation of the corresponding PtCl(SnCl₃)(L₂) derivatives. Tin(II)chloride has been inserted into the Pt–Cl bond transto the harder donor atom of the L₂ ligand.     

Reaction of 3-Amino-2H-azirines with 2-Amino-4,6-dinitrophenol (Picramic Acid): Synthesis of Quinazoline- and 1,3-Benzoxazole Derivatives

The reaction of 3-(dimethylamino)-2H-azirines 1a–c and 2-amino-4,6-dinitrophenol (picramic acid, 2 ) in MeCN at 0° to room temperature leads to a mixture of the corresponding 1,2,3,4-tetrahydroquinazoline-2-one 5 , 3-(dimethylamino)-1,2-dihydroquinazoline 6 , 2-(1-aminoalkyl)-1,3-benzoxazole 7 , and N-[2-(dimethylamino)phenyl]-α-aminocarboxamide 8 (Scheme 3). Under the same conditions, 3-(N-methyl-N-phenyl-amino)-2H-azirines 1d and 1e react with 2 to give exclusively the 1,3-benzoxazole derivative 7 . The structure of the products has been established by X-ray crystallography. Two different reaction mechanisms for the formation of 7 are discussed in Scheme 6. Treatment of 7 with phenyl isocyanate, 4-nitrobenzoyl chloride, tosyl chloride, and HCl leads to a derivatization of the NH₂-group of 7 (Scheme 4). With NaOH or NaOMe as well as with morpholine, 7 is transformed into quinazoline derivatives 5 , 14 , and 15 , respectively, via ring expansion (Scheme 5). In case of the reaction with morpholine, a second product 16 , corresponding to structure 8 , is isolated. With these results, the reaction of 1 and 2 is interpreted as the primary formation of 7 , which, under the reaction conditions, reacts with Me₂NH to yield the secondary products 5 , 6 , and 8 (Scheme 7).     

Rh(I)-catalyzed conjugate addition of alkenylzirconocene chloride: stereoselective formation of carbocycles through cascade reaction

Stereoselective formation of carbocycles was carried out through [RhCl(cod)]₂-catalyzed reactions of alkenylzirconocene chloride to ω-carbonyl-α,β-ene carbonyls (ketone, ester, and amide) or to bis-enone derivatives. The Rh(I)-catalyzed reaction of alkenylzirconocene chloride with ω-carbonyl-α,β-enoyl amide, which is derived from Oppolzer’s sultam, showed high diastereoselectivity to yield an carbocycle (95% yield, >95% de).     

A Convenient Synthesis of Type IV Glycosyl Donors from Type I Disaccharides

ABSTRACT

The synthesis of 4,6-di-O-acetyl-3-O-(tetra-O-acetyl-ß-D-galactopyranosyl)-2-deoxy-2-phthalimido-α,ß-D-galactopyranosyl chloride 1 4 and its 6-O -benzyl derivative 1 2 was achieved in a 5-step sequence starting from the readily available type I disaccharide derivative 3. The key step in the synthesis involved the preparation of trifluoromethanesulfonate (triflate) derivatives 7 and 9 and their subsequent SN₂ displacement by acetate ion for conversion of 2-deoxy-2-phthalimido-ß-D-glucopyranosyl moiety to the corresponding galacto configuration.     

Preparation of tetrahydrocyclopenta[b]indoloquinones

The nitration of N-acyl-7-methyl-1,3a,4,8b-tetrahydrocyclopenta[b]indole with a mixture NH₄NO₃-(CF₃CO)₂O afforded 5-nitro derivatives whose reduction with Fe(OH)₂ in H₂O led to the formation of 5-amino derivatives. The oxidation of the 5-amino derivatives with Fremy’s salt gave the corresponding indoloquinones.     

Reactions of tert-butyl N,N-diethyl-N′-(4-phenylthiazol-2-yl)-phosphorodiamidite with electrophilic reagents

Previously unknown amidophosphorous acid derivatives were prepared by transamidation of tert-butyl N,N-diethyl-N′-(4-phenylthiazolyl)phosphorodiamidite with 2-amino-4-phenylthiazole, and their reactions with acetyl and benzoyl chloride were studied. These reactions are shown to proceed regioselectively according to the Arbuzov scheme to give the corresponding ketophosphonates. The reaction of the phosphorodiamidite with acetyl chloride in a 1:2 molar ratio involves formation of acetophosphonate that reacts in the enol form to give the corresponding (1-acetoxy)vinylphosphonate.     

Synthetic transformations of higher terpenoids: XVII. Intramolecular cyclization of N-furfuryl amides of the labdane series

16-(Benzylaminomethyl)lambertianic acid methyl ester reacts with 2-methylprop-2-enoyl chloride to give unsaturated amide which readily undergoes intramolecular [4 + 2]-cycloaddition with formation of terpenoid derivatives of 10-oxa-3-azatricyclo[5.2.1.0^1,5]decenone. Acetylation of lambertianic acid methyl ester with acetic anhydride occurs preferentially at the 2-position of the furan ring and is accompanied by migration of the exocyclic double bond. Reductive amination of 16-acetyl-15,16-epoxylabda-8(9),13,14-triene and subsequent reaction of the resulting amine with 2-methylprop-2-enoyl chloride give intramolecular cyclization products in high yield without isolation of intermediate furfurylacryloyl derivative. Reactions of methyl 16-(benzylaminomethyl)-15,16-epoxylabda-8(9),13,14- and -8(17),13,14-trien-18-oates with maleic anhydride lead to the formation of the corresponding 10-oxa-3-azatricyclo[5.2.1.0^1,5]dec-8-ene-6-carboxylic acid derivatives as mixtures of diastereoisomers.     

Heterocyclic variants of the 1,5-benzodiazepine system. V. Derivatives of 2-(ortho-R1-anilino)-4-(p-R2-phenyl)-3H-1,5-benzodiazepines

Mono-N-methylation of 2-(ortho-R₁-anilino)-4-(p-R₂-phenyl)-3H-1,5-benzodiazepines IV is achieved in moderate yield with sodium hydride in methyl iodide. Reaction of the N-methyl derivatives I with methoxyacetyl chloride gave the compounds II and III . The structure of all products was confirmed by ir, ¹H-nmr and mass spectrometry.     

Phase-transfer catalyzed alkoxylation of 2-(dichloromethyl) furan by alcohols in the presence of potassium hydroxide

Reaction of 2-(dichloromethyl)furan (I) with KOH in a CH₂Cl₂ medium and in the presence of alcohols (methanol, ethanol, and n-butanol) and a catalytic amount of triethylbenzylammonium chloride (TEBAC) results in the formation of 2-chloro-methylene-5-alkoxy-2, 5-dihydrofurans (II) (mixtures of Z- and E-isomers) and 2-dialkoxymethylfurans (III), in overall yields of up to 96%. Reaction with isopropyl and tert-butyl alcohols gave only the corresponding products (II), in 21 and 12% yield, respectively.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 6, pp. 1403–1407, June, 1991.     

Catalysis by zeolite leading to the construction of thiazole ring: an improved synthesis of 4-alkynyl substituted thiazoles

Zeolite H-beta facilitated the reaction of α-chloro acetyl chloride with 1,2-bis-trimethyl silyl acetylene to give 1-chloro-4-(trimethylsilyl)but-3-yn-2-one which on treatment with thioacetamide afforded 2-methyl-4-[(trimethylsilyl)ethynyl]thiazole. l-Proline on the other hand facilitated the coupling reaction of 2-methyl-4-[(trimethylsilyl)ethynyl]thiazole with (hetero)aryl halides (modified Sonogashira reaction) under Pd-Cu catalysis in the presence of aqueous K₂CO₃ affording an improved method for the synthesis of corresponding 4-alkynyl substituted thiazole derivatives.     

Synthesis of 1,3-Bis[3-X-2-(X-acetoxy)propyl]-6-methyl- 1,2,3,4-tetrahydropyrimidine-2,4-diones

A procedure was developed for synthesizing nitrogen-and-sulfur-containing pyrimidine derivatives by reactions of 1,3-bis(3-chloro-2-hydroxypropyl)-6-methyluracil with 1-butanethiol and chloroacetyl chloride, followed by treatment of the resulting 1,3-bis[3-chloro-2-(chloroacetoxy)propyl]-6-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dione with 1-butanethiol, morpholine, and piperidine. Oxidation of the sulfur-containing products with NaIO₄ gave the corresponding sulfoxides.     

Synthesis of Derivatives of the Optically Active β‐Amino Acids from (+)‐Car‐2‐ene

The reaction of (+)‐car‐2‐ene ( 4 ) with chlorosulfonyl isocyanate (=sulfuryl chloride isocyanate; ClSO₂NCO) led to the tricyclic lactams 6 and 8 corresponding to the initial formation both of the tertiary carbenium and α‐cyclopropylcarbenium ions (Scheme 2). A number of optically active derivatives of β‐amino acids which are promising compounds for further use in asymmetric synthesis were synthesized from the lactams (see 16, 17 , and 19 – 21 in Scheme 3).     

Alkylation,amino(hydroxy)methylation,and cyanoethylation of 5-substituted 4-phenyl-4<Emphasis Type="Italic">H</Emphasis>-1,2,4-triazole-3-thiols

Reactions of 1,2,4-triazole-3-thiols with 2-bromopropionic acid, 2-bromocaproic acid, ethylene chlorohydrine, chloroacetamide, 3-bromo-4-methoxybenzyl chloride, 2-methoxy-5-acetylbenzyl chloride, and 2-(2-chlorophenoxy)ethyl chloride in the presence of KOH have afforded new 3-sulfanyl-1,2,4-triazoles in high yields. Aminomethylation of 1,2,4-triazole-3-thiols in the presence of formaldehyde has given the corresponding 2-aminomethyl-2H-1,2,4-triazole-3(4H)-thiones. Interaction of triazole-3-thiols with formalin and acrylonitrile has resulted in the formation of N²-hydroxymethyl- and 3-(2-cyanoethyl)sulfanyl derivatives.     

Synthesis of heterocycles. Part II. New routes to acetylthiadiazolines and alkylazothiazoles

Methylglyoxalyl chloride arylhydrazones (III) react with an ethanolic solution of thiourea to give 2-amino-4-methyl-5-arylazothiazoles (XII) instead of the expected 2-acetyl-4-aryl-5-imino-Δ²-1,3,4-thiadiazolines (V) which were obtained from III and potassium thiocyanate. 3-Thiocyanato-2,4-pentanedione (IV) coupled with diazotized anilines to give V. The postulated routes to formation of V and XII from III are given. Nitrosation of V gave the corresponding N-nitroso derivatives (VI) which decomposed upon refluxing in dry xylene to give 2,4-disubstituted-Δ²-1,3,4-thiadiazolin-5-ones (VII). Boiling of either V or VI with hydrochloric acid gave the hydrochloride salt (VIII). The thiadiazolines V gave the respective N-acyl derivatives (IX) and (X) with acetic anhydride and benzoyl chloride in pyridine.     

Synthesis of some new spiroindoline derivatives incorporated with pyrazoloheterocycles

Indole-2,3-dione ( 1 ) was treated with malonic acid ( 2 ) in a mixture of ethanol/pyridine to afford 1-[3-(2-oxoindolinylidene)]acetic acid ( 3 ). Compound 3 reacted with thionyl chloride to give the corresponding acid chloride ( 4 ). The acid chloride 4 reacted with arenes in the presence of AlCl₃ to yield 3-(2-oxoindolinylidene)acetophenones 5a–c . Compounds 5a–c reacted with 3-methylpyrazolin-5-one derivatives 6a , b to give 3-aracyl-3-[4′-(3′-methylpyrazolin-5-onyl)]-indoline-2-one derivatives 7a–f . Compounds 7a–f were treated with phosphorus pentoxide in phosphoric acid, with ammonium acetate or methanolic methylamine and with phosphorus pentasulfide to give spiro[indoline-3,4′-(pyrazolo[4,5-b]pyran)]-2-ones 8a–f , spiro[indoline-3,4′-(pyrazolo[4,5-b]-dihydropyridine)]-2-ones 9a–f , 10a–f and spiro[indoline-3,4′-(pyrazolo[4,5-b]thiopyran)]-2-ones 10a–f , respectively. All of the synthesized spiroheterocycle derivatives were identified by conventional spectroscopic methods (IR, ¹H NMR) and elemental analyses. © John Wiley & Sons, Inc.