Heterocyclic variants of the 1,5-benzodiazepine system. VIII. Reaction of 4(7)-aminobenzimidazole with ethyl 2-alkylmalonates

Reaction of 4(7)-aminobenzimidazole with ethyl 2-alkylmalonates gave the novel 4,5,6,7-tetrahydro-5-alkyl-imidazo[1,5,4-ef][1,5]benzodiazepine-4,6-diones, and the 2-alkyl-4(7)-(2′-ethoxycarbonyl)acetamido-benzimidazoles. The structure of all the products was corroborated by ir, mass spectrometry and ¹H-nmr.     

Research for new antichagasic drugs.

A series of ten 1-[(5-nitrothenylidene)amino]azoles has been synthesized by the reaction of 5-nitrothiophene-2-carbaldehyde with 1-aminopyrazole, 1-aminoimidazole, 1- and 4- amino-1,2,4-triazoles, 1-aminoindole, 1- and 2-aminoindazoles, 1-aminobenzimidazole and 1- and 2-aminobenzotriazoles. Physical data, spectroscopic characteristics and biological properties of all the derivatives have been examined. The antiprotozoal activity has been tested against Trypanosoma cruzi, comparative to Nifurtimox (Lampit).     

以水作溶剂微波法合成1,4-二氢苯并咪唑并[1,2-a]嘧啶类衍生物

以芳香醛、2-氨基苯并咪唑和丙二腈为原料,用传统法和微波辐射法三组分一锅煮法合成1,4-二氢苯并咪唑并[1,2-a]嘧啶类化合物。反应均在无催化剂条件下以水作反应溶剂进行。结果表明,采用微波辐射优于常规方法,三组分摩尔比n(2-氨基苯并咪唑)∶n(丙二腈)∶n(取代苯甲醛)=1∶1.1∶1,辐射功率400 W,时间为6～8 min时,1,4-二氢苯并咪唑并[1,2-a]嘧啶的收率在85%以上,反应速率比常规加热条件下提高70倍。通过荧光发射光谱研究证实,该系列化合物具有明显的荧光性质,其荧光发射峰位于480～550 nm。     

Nucleotides. Part LV. Synthesis and application of a novel linker for solid-phase synthesis of modified oligonucleotides

Various bifunctional amino-protecting groups such as the phthaloyl, succinyl, and glutaryl group were investigated as potential linker molecules for attachment to solid-support materials. Pentane-1,3,5-tricarboxylic acid 1,3-anhydride ( 16 ) offered the best properties and reacted with the amino groups of differently sugar-protected adenosine (see 20 and 22 ), cytidine (see 29 ), and guanosine derivatives (see 32 ) to the corresponding 2-(2-carboxyethyl)glutaryl derivatives 23 , 24 , 30 , and 33 . The usefulness of the new linker-type molecules was demonstrated by the solid-support synthesis of the potentially antivirally active 3′-deoxyadenylyl-(2′–5′)-2′-adenylic acid 2′-{2-[(adenin-9-yl)methoxy]ethyl} ester ( 38 ) starting from the 2′-end with N⁶,N⁶-[2-(2-carboxyethyl)glutaryl]-9-{{2-[(4,4′-dimethoxytrityl)ethoxy]methyl}adenine ( 12 ).     

Synthesis and characterization of new benzimidazole derivatives using 2-substituted 1,3-bis(dimethylamino)-trimethinium salts

Novel benzimidazole derivatives are synthesized by the reaction of 2-substituted 1,3-bis(dimethylamino)-trimethinium salts with 2-aminobenzimidazole in the presence of acetic acid or triethylamine in acetonitrile as the solvent. The ultraviolet spectral behavior of these compounds is examined in DMSO.     

Copper-catalyzed synthesis of 2-aminobenzimidazoles from carbonimidoyl dichlorides and amines

A new protocol for the synthesis of a variety of 2-aminobenzimidazole derivatives has been developed. O-haloaryl carbonimidoyl dichloride reacted with anilines to generate an o-haloaryl guanidine intermediate, which underwent copper catalyzed ring closure to afford 2-aminobenzimidazole derivative in moderate yields     

超声波促进离子液体中Biginelli一锅法合成苯并咪唑并[2,1-b]喹啉-6-酮

在超声波辐射下, 芳香醛、1,3-环己二酮和2-氨基苯并咪唑3组分在离子液体([bmim]Br)介质中经Biginelli反应“一锅煮”合成了一系列新型苯并咪唑并[2,1-b]喹啉-6-酮衍生物. 2-氨基苯并咪唑的使用是对经典的Biginelli反应的发展, 并且该方法具有反应条件温和、产率较高(65%～86%)及环境友好等优点. 产物经IR, ¹H NMR和元素分析确证了结构.     

Acyl Derivatives of 2-Aminobenzimidazole and Their Fungicide Activity

Procedures have been developed for the preparation of methyl 2-benzimidazolylcarbamate, 2-acetylaminobenzimidazole, 2-benzoylaminobenzimidazole, 2-(3,5-dibromo-2-hydroxybenzoylamino)benzimidazole, 1-(3,6-dichloro-2-methoxybenzoyl)-2-aminobenzimidazole, 2-(3,5-dichloro-2-hydroxybenzoylamino)benzimidazole, 2-(3,5-dichloro-2-methoxybenzoylamino)benzimidazole, and 1-(3,5,6-trichloro-2-methoxybenzoyl)-2-aminobenzimidazole. The synthesized compounds have been tested for fungicide activity.     

Transformed steroids. 141. Iodosobenzene diacetate for theα-hydroxylation of [17,16a]-2′-methyloxazoline derivatives of 20-ketosteroids

Using the [17,16a-d]-2′-methyloxazoline derivatives of 3β-hydroxypregn-5-en-20-one (I) as an example, the α-hydroxylation reaction has been studied with the use of rodosobenzene diacetate in a methanolic solution of NaOH as the α-hydroxylating reagent. The reaction took place successfully through the stage of the formation and isolation of the corresponding [17,16a-d]-2′-methyloxazoline derivative of 20, 20-dimethylpregn-15-ene-3β,21-diol (II), the dimethyl acetal protection of which was eliminated by acid hydrolysis in methanol. The results of physicochemical investigations and biological trials of the [17,16a-d]-2′-methyloxazoline derivatives of 21-hydroxy-21-acetoxy-20-ketosteroids obtained are given.     

Enolethers. XXI. Synthesis of 5,5′-disubstituted 4,4′-bipyrimidines

1,6-Dialkoxy-3,4-diones 3 are easily accessible by acylation of enol ethers 1 with oxalyl chloride and subsequent elimination of hydrogen chloride using triethylamine. The open-chain 2,5-dimethyl derivative 3b is converted with amidines 4a-c and S-methylisothiourea (4d) , respectively, to give 2,2′-disubstituted 5,5′-dimethyl-4,4′-bipyrimidines 5a-d . The dihydrofuran and dihydropyran derivatives 3c and 3d , however, react with benzamidine (4c) in dimethylformamide only in the presence of calcium hydride as condensation agent yielding 5,5′-bis(2-hydroxyethyl)- and 5,5′-bis(3-hydroxypropyl)-2,2′-diphenyl-4,4′-bipyrimidine 6a and b.     

Synthesis of novel aza-heterocyclic derivatives from diester and diacid chlorides having the dibenzobarrelene skeleton

When attempting to synthesize the symmetric aza-heterocyclic-substituted dibenzobarrelene derivatives from the 2-aminobenzimidazole (or 2-aminoimidazoline) with diacid chlorides and diester in the presence of various organic bases, different products were isolated in high yield. NMR spectroscopic analysis proved these products to be dibenzobarrelene-substituted fused benzimidazodiazepine, imidazolinediazepine, and dicarboxamides derivatives. Cyclic or noncyclic dicarboxamides with the dibenzobarrelene skeleton have been synthesized for the first time using these methods.     

Heterocyclic β-Enamino esters. 28. The reaction of heterocyclic β-Enamino esters and nitriles with cyclic amidines. A simple route to azolopyrimidines

Whereas 2-amino-3-ethoxycarbonyl-4,5-dihydrofurans Ia-c condense with 5-membered amidine derivatives, via elimination of ethanol to afford the azolopyrimidines IIIa,b, XI, and XIVa,b, the 2-amino-3-cyano-4,5-dihydrofurans Id,e give with the same reagents, under elimination of ammonia, the novel ring systems of furo-azolopyrimidines XVIII and XXa,b. 2-Amino-3-ethoxycarbonyl-5,6-dihydro-4H-thiopyrane (XXI) reacts with 5-amino-1,2,4-triazole (II) to yield the triazolo[1,5-a]pyrimidine XXII, and with 2-aminobenzimidazole to XXIII. The mechanism of these reactions is discussed. XIVb and VIIb are cyclized in a secondary step to give the novel furo[2,3-d]benzimidazo[1,2-a]pyrimidine XXVI, and furo[2,3-d]-1,2,4-triazolo[1,5-a]pyrimidine XXVIII respectively, besides the acetoxy derivatives XVII and XXIX.     

Nonglycoside analogs of nucleotides

N¹-(2′,3′-Dihydroxypropyl)uracil, -thymine, -cytosine, and N⁹-(2′,3′-dihydroxypropyl)adenine were synthesized by alkylation of nucleic bases with 2,3-O-isopropylideneglycerol chlorohydrin, subsequent separation of the resulting mixtures, and removal of the protective groupings. Phosphorylation of these compounds or of their selectively substituted derivatives gave 2′(3′)-monophosphates, which were converted to 2′,3′-cyclophosphates by reaction with N,N′-dicyclohexylcarbodiimide. Thionation of the corresponding cytosine derivatives gave N¹-(2′,3′-dihydroxypropyl)-4-thiouracil and its 2′(3′) phosphate.     

Saturated heterocycles. Part 209. Synthesis of 1-cyclohexyl-substituted isoquinoline derivatives

In contrast with earlier literature data [7], both acrylic esters and acrylonitrile underwent Michael addition to l-methyl-3,4-dihydroisoquinolines 1-4 to yield the diesters 5-9 or the dinitrile 10 , respectively. Compounds 5-10 were converted by Claisen condensation to 1-[(3′-methoxycarbonyl- or 1-[(3′-ethoxycarbonyl-4′-oxo)-l'-cyclohexyl]-3,4-dihydroisoquinoline derivatives 11-16 . Several derivatives of 12 were prepared. The new compounds possess various pharmacological actions.     

Ketene S,S-acetals in the synthesis of some new fused pyrimidine derivatives

Condensation of ketene dithioacetal derivatives with some aminoazoles (5-aminotetrazole monohydrate, 2-aminobenzimidazole, 2-aminobenzothiazole, and 2-aminothiazole) in the presence or absence of triethylamine gave the corresponding tetrazolopyrimidines, benzimidazopyrimidines, benzothiazolopyrimidines, and thiazolopyrimidines. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 469–473, March, 2007.     

Cyclocondensation of 2-Aminobenzimidazole with Dimedone and Its Arylidene Derivatives

The reactions of 2-aminobenzimidazole with substituted benzaldehydes and dimedone, 2-arylidene derivatives of dimedone, 9-arylhexahydro-1H-xanthene-1,8(2H)-diones and also with dimedone and DMF have been studied. The direction of formation of the pyrimidine ring has been established and discussed. An X-ray structural investigation of 2,2-dimethyl-2,3-dihydrobenzimidazo[1,2-a]quinazolin-4(1H)-one has been carried out.     

Nucleosides. Part LIX. The 2-(4-nitrophenyl)ethylsulfonyl (Npes) Group: A New Type of Protection in Nucleoside Chemistry

The 2-(4-nitrophenyl)ethylsulfonyl (npes) group is developed as a new sugar OH-blocking group in the ribonucleoside series. Its cleavage can be performed in a β-eliminating process under aprotic conditions using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as the most effective base. Since sulfonates do not show acyl migration, partial protection of 1,2-cis-diol moieties is possible leading to new types of oligonucleotide building blocks. A series of Markiewicz-protected ribonucleosides 1–10 is converted into their 2′-O-[2-(4-nitrophenyl)ethylsulfonyl] derivatives 29–38 in which the 5′-O? Si bond can be cleaved by acid hydrolysis forming 39–45 . Subsequent monomethoxytritylation leads to 46–50 , and desilylation affords the 5′-O-(monomethoxytrityl)-2′-O-[2-(4-nitrophenyl)ethylsulfonyl]ribonucleosides 51–55 . Acid treatment to remove trityl groups do also not harm the npes group (→ 56–58 ). Unambiguous syntheses of fully blocked 2′-O-[2-(4-nitrophenyl)ethylsulfonyl]ribonucleosides 96–102 are achieved from the corresponding 3′-O-(tert-butyl)dimethylsilyl derivatives. Furthermore, various base-protected 5′-O-(monomethoxytrityl)- and 5′-O-(dimethoxytrityl)ribonucleosides, i.e. 59–77 , are treated directly with 2-(4-nitrophenyl)ethylsulfonyl chloride forming in all cases a mixture of the 2′,3′-di-O- and the two possible 2′- and 3′-O-monosulfonates 107–148 which can be separated into the pure components by chromatographic methods. The npes group is more labile towards DBU cleavage than the corresponding base-protecting 2-(4-nitrophenyl)ethyl (npe) and 2-(4-nitrophenyl)ethoxycarbonyl (npeoc) groups allowing selective deblocking which is of great synthetic potential.     

Condensation of o-aminophenol and α-dicarbonyl compounds. Part 2. Dibenzoxazolines

The study of 2′-aryl-2,2′-dibenzoxazolines (II), obtained together with 2-hydroxy-(2H)-1,4-benzoxazines (1) by condensation of o-aminophenol with a series of phenylglyoxal derivatives, emphasized that these compounds are an equilibrium mixture of dibenzoxazolines and related tautomeric ketimine forms. This behaviour was widely investigated by ir, uv and pmr spectroscopy. J. Heterocyclic Chem., 14, 957 (1977)     

Nucleotides. Part XLV. Synthesis of new (2′–5′)adenylate trimers,containing 5′-amino-5′-deoxyadenosine residues at the 5′-end of the oligoadenylate chain,and of its analogues,carrying a 9-[(2-hydroxyethoxy)methyl]adenine residue at the 2′-terminus

The 5′-amino-5′-deoxy-2′,3′-O-isopropylideneadenosine ( 4 ) was obtained in pure form from 2′,3′-O-isopropylideneadenosine ( 1 ), without isolation of intermediates 2 and 3 . The 2-(4-nitrophenyl)ethoxycarbonyl group was used for protection of the NH₂ functions of 4 (→7) . The selective introduction of the palmitoyl (= hexadecanoyl) group into the 5′-N-position of 4 was achieved by its treatment with palmitoyl chloride in MeCN in the presence of Et₃N (→ 5 ). The 3′-O-silyl derivatives 11 and 14 were isolated by column chromatography after treatment of the 2′,3′-O-deprotected compounds 8 and 9 , respectively, with (tert-butyl)dimethylsilyl chloride and 1H-imidazole in pyridine. The corresponding phosphoramidites 16 and 17 were synthesized from nucleosides 11 and 14 , respectively, and (cyanoethoxy)bis(diisopropylamino)phosphane in CH₂Cl₂. The trimeric (2′–5′)-linked adenylates 25 and 26 having the 5′-amino-5′-deoxyadenosine and 5′-deoxy-5′-(palmitoylamino)adenosine residue, respectively, at the 5′-end were prepared by the phosphoramidite method. Similarly, the corresponding 5′-amino derivatives 27 and 28 carrying the 9-[(2-hydroxyethoxy)methyl]adenine residue at the 2′-terminus, were obtained. The newly synthesized compounds were characterized by physical means. The synthesized trimers 25–28 were 3-, 15-, 25-, and 34-fold, respectively, more stable towards phosphodiesterase from Crotalus durissus than the trimer (2′–5′)ApApA.