Synthesis of novel N2-adamantyl derivatives of 2-amino-6-methyl-4(3H)-pyrimidinone as potential activators of tumor necrosis factor (TNF) release

A method has been developed for the synthesis of N²-adamantyl-2-amino-6-methyl-4(3H)-pyrimidinones based on the reaction of (adamant-1-yl)alkylamine with 2-(ethylsulfanyl)-6-methyl-4(3H)-pyrimidinone which can lead to the corresponding derivatives in which the exocyclic nitrogen atom and the adamantyl radical are separated by a hydrocarbon fragment. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1541–1544, October, 2006.     

Synthesis of 4-substituted 2-carenes in novel imidazolinium ionic liquids

4-Acetyl-, 4-acetoxymethyl-, and 4-hydroxymethyl-2-carenes were synthesized using novel ionic liquids. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 114–116, March–April, 2007.     

Synthesis of new derivatives of 1,5,9,13-tetraaza[16]annulene using 2-substituted vinamidinium salts

New 7,15-dibromo-, 7,15-di(bromomethyl)-, and 7,15-di[4-(bromomethyl)phenyl]-1,5,9,13-tetraaza[16]annulene derivatives are synthesized via the condensation reaction of 2-substituted vinamidinium salts [2-substituted 3-(dimethylamino)-N,N-dimethyl-2-propen-1-aminium salts] with 1,8-diaminonaphthalene in acetonitrile/acetic acid. The ultraviolet spectral behavior of these compounds is examined in DMSO.     

Synthesis of novel 3-(1,3-thiazol-2-yl)-7,8-dihydroquinoline-2,5(1H,6H)-diones

An efficient method for the synthesis of novel 3-(1,3-thiazol-2-yl)-7,8-dihydroquinoline-2,5(1H,6H)-diones from various 2-dimethylaminomethylidenecyclohexane-1,3-diones, (1,3-thiazol-2-yl)acetonitriles, and dimethylformamide dimethyl acetal was developed. These transformations proceeded through intermediate 2-[2-(4-aryl-1,3-thiazol-2-yl)-2-cyanoethenyl]-3-oxocyclohex-1-en-1-olates. They were isolated as piperidinium salts and used in further heterocyclization reactions with aromatic amines, giving novel 1-aryl-3-(1,3-thiazol-2-yl)-7,8-dihydroquinoline-2,5(1H,6H)-diones. These compounds were also obtained by preparative three-step “one pot” synthesis under controlled microwave irradiation. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 412–417, February, 2008.     

A novel and convenient route for the construction of 5-((1H-1,2,4-triazol-1-yl)methyl)-1H-indoles and its application in the synthesis of Rizatriptan

In this study, a novel and convenient route for the construction of 5-((1H-1,2,4-triazol-1-yl)methyl)-1H-indoles (8) is presented starting from (1H-1,2,4-triazol-1-yl)methanol (5) and indolines (6) under 98% H₂SO₄ at room temperature for 4–24 h, followed by deacetylation and dehydrogenation. Based on this finding, a novel route to synthesize Rizatriptan starting from tryptamine was designed and accomplished with 48.5% overall yield in 6 steps. Compared with operational art, the new route afforded higher yield and more pure products requiring no chromatographic purification, which may further be applied in industrialization.     

A novel method for the synthesis of 5-substituted 1H-tetrazole from oxime and sodium azide

A simple and efficient protocol is developed for the synthesis of 5-substituted 1H-tetrazoles from various oximes and sodium azide (NaN₃) by using copper acetate as a catalyst.     

A novel intramolecular Ugi 3CC for the synthesis of N-alkyl-3-oxo-2-aryl-1,2,3,4-tetrahydropyrazino[1,2-a]indole-1-carboxamides

An intramolecular Ugi reaction of 2-(2-formyl-1H-indol-1-yl)acetic acid with aryl amines and isocyanides has been developed to produce a novel class of N-alkyl-3-oxo-2-aryl-1,2,3,4-tetrahydropyrazino[1,2-a]indole-1-carboxamides in good yields. This is the first report on intramolecular Ugi three component reaction of 2-(2-formyl-1H-indol-1-yl)acetic acid, aryl amine, and isonitrile.     

Nickel complexes bearing 2-(1H-benzimidazol-2-yl)-phenoxy ligands: Synthesis, characterization and ethylene oligomerization

A series of 2-(1H-benzimidazol-2-yl)-phenols and their nickel complexes have been synthesized and characterized by elemental and spectroscopic analysis. The molecular structures of ligand L4 and complex C5 were confirmed by X-ray diffraction analysis. X-ray crystallographic analysis revealed that complex C5 has a six-coordinated distorted octahedral geometry. Upon activation with Et₂AlCl, these nickel(II) complexes showed good activity for ethylene oligomerization. When PPh₃ was added as an auxiliary ligand to the catalytic system, an increased activity as high as 1.60 × 10⁷ g mol⁻¹ (Ni) h⁻¹ was observed. The ligand environment and reaction conditions remarkably affected the catalytic behavior of these nickel complexes.     

Synthesis of 6-substituted 3-cyano-5-nitropyridine-2(1H)-thiones

The reactions of 1-substituted 2-nitro-3-phenylaminoprop-2-en-1-ones with cyanothioacetamide afforded the corresponding 6-substituted 3-cyano-5-nitropyridine-2(1H)-thiones, which were used for the synthesis of 6-substituted 3-cyano-2-methylthio-5-nitropyridines and 7-substituted 4-hydroxy-8-nitropyrido[2",3":4,5]thieno[2,3-b]pyridin-2(1H)-ones.     

Anodic formation of 3,6-diaryl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles and 2(3-aryl-5-methyl-1H-[1,2,4]triazol-1-yl)-5-aryl-1,3,4-thiadiazoles

3,6-Disubstituted 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles together with the unknown systems 2-(3-aryl-5-methyl-1H-[1,2,4]triazol-1-yl)-5-aryl-1,3,4-thiadiazoles were obtained by anodic oxidation, under aprotic conditions, of aryl aldehyde N-(5-aryl-1,3,4-thiadiazol-2-yl) hydrazones. Mechanistic proposals are given.     

Synthesis of 9-arylamino- and (Z)-9-arylimino-9H-pyrrolo[1,2-a]indoles by reactions of 2-(pyrrol-1-yl)benzaldehydes with aryl amines

Heating mixtures of 2-(pyrrol-1-yl)benzaldehydes and aryl amines under argon afforded 9-arylamino-9H-pyrrolo[1,2-a]indoles, via cyclization of the resulting 2-(pyrrol-1-yl)benzaldimine intermediates. Heating in the presence of oxygen afforded (Z)-9-arylimino-9H-pyrrolo[1,2-a]indoles, which were successfully hydrolyzed with hydrochloric acid to give pyrrolo[1,2-a]indol-9-ones.     

1-[5-(1,3-二氧-4,5,6,7-四氢-1H-异吲哚-2-基)苯基]-3-取代脲衍生物的合成与除草活性研究

为了寻找高效低毒的原卟啉原氧化酶抑制剂(protox)类除草剂, 设计并合成了一系列1-[5-(1,3-二氧-4,5,6,7-四氢-1H-异吲哚-2-基)苯基]-3-取代脲类衍生物4a～4d和5a～5g. 化合物4a～4d经异氰酸酯法合成, 收率、纯度高; 化合物5a～5g利用固体光气一锅法合成, 反应时间短.所得化合物结构经¹H NMR, IR, 质谱和元素分析表征. 初步生物活性测试表明: 化合物4c, 5a, 5b, 5c在有效成分75 g/hm² 剂量下对苘麻、马刺苋、凹头苋等双子叶杂草表现出90%以上的防效.     

Microwave assisted synthesis of novel imidazo [2,1-b]thiazole derivative attached to quinoxalinones

3-(6-Phenylimidazo[2,1-b]thiazol-5-yl)quinoxalin-2(1H)-ones (qunoxalinone) (6a-q) have been synthesized by the reaction of ethyl 2-oxo-2-(6-phenylimidazo[2,1-b]thiazol-5-yl)acetates (4a-e) with suitably substituted o-phenylenediamines (5a-f) under microwave heating. The ethyl 2-oxo-2-(6-phenylimidazo[2,1-b]thiazol-5-yl)acetates (4a-e) were prepared by the reaction of 6-phenylimidazo[2,1-b]thiazoles (3a-e) with ethyl chlorooxoacetate in refluxing 1,4-dioxane whereas the thiazoles (3a-e) were synthesized by the reaction of 2-bromo-1-phenylethanones (2a-e) with thiazol-2-amine in refluxing acetone.     

Synthesis and structural revision of naturally occurring ayapin derivatives

The synthesis of three highly oxygenated naturally occurring coumarins, 8-methoxy-6,7-methylenedioxycoumarin, 5-methoxy-6,7-methylenedioxycoumarin and 5,8-dimethoxy-6,7-methylenedioxycoumarin is described for the first time, together with a new method for the preparation of ayapin (6,7-methylenedioxycoumarin). Comparison of the spectroscopic data of the synthetic tetraoxygenated coumarin 5,8-dimethoxy-6,7-methylenedioxycoumarin with literature reports resulted in the structural revision of several natural coumarins. Two coumarins, both identified as 5,8-dimethoxy-6,7-methylenedioxycoumarin must have other structures, while the structure of another coumarin, described as the isomeric 7,8-dimethoxy-5,6-methylenedioxycoumarin has to be revised to 5,8-dimethoxy-6,7-methylenedioxycoumarin.     

Quinoxalines. Part 12: Synthesis and structural study of 1-(thiazol-2-yl)-1H-pyrazolo[3,4-b]quinoxalines—the dehydrogenative cyclization with hydroxylamine hydrochloride

Starting with 2-acetylquinoxaline a novel class of heterocyclic compounds, the 1-(thiazol-2-yl)-1H-pyrazolo[3,4-b]quinoxalines 4, were prepared by following two different synthetic procedures: 2-acetylquinoxaline reacted with thiosemicarbazide to the thiosemicarbazones 1a which was (i) cyclized with α-halogeno ketones to the thiazoles 3. These compounds were dehydrogenated in acidic medium to the title compounds 4. (ii) The thiosemicarbazone 1a could be also dehydrogenated using NH₂OH·HCl to the thioamide 5a and these, finally, were cyclized with α-halogeno ketones to the title compounds 4. Only thiazole 3a was isolated, the other thiazoles 3 were dehydrogenated in a one-pot procedure. From the thioamide 5a also both the compounds 9, by reacting with dibromodiacetyl, and 10, by treatment with dimethyl acetylenedicarboxylate, were obtained. The analysis of both the ¹H and ¹³C NMR spectra was not straightforward but could be attained finally by employing the whole arsenal of 1D and 2D NMR spectroscopy.     

1-(3,5-二甲基苯基)-1-[(1S,4S)-1,7,7-三甲基双环[2.2.1]庚烷-2-基]肼的合成工艺改进

以3,5-二甲基苯胺和2-莰酮为起始原料,在微波促进下,经缩合反应制得N-(3,5-二甲基苯基)-1-(1S,4S)-1,7,7-三甲基二环[2.2.1]庚烷-2-亚胺(1);1经硼氢化钠还原后再与羟胺-O-磺酸经胺化反应合成了1-(3,5-二甲基苯基)-1-[(1S,4S)-1,7,7-三甲基双环[2.2.1]庚烷-2-基]肼,总收率70.4%,其结构经1H NMR和ESI-MS确证。     

Synthesis of l-azaisotryptophan and its analogs: a general access to new 2-substituted azaindoles

l-(N-Cbz)-7-azaisotryptophan, l-(N-Cbz)-1a, a new isostere of tryptophan, was synthesized by reacting Li₂-(N-Boc)-2-amino-3-picoline, Li₂-(N-Boc)-2a, with appropriately protected l-aspartic acid followed by simple functional group manipulation. This synthetic success led us to access a set of analogs of azaisotryptophan (4a–c; 6a–c) as well as a new class of chiral amines (7a–c; 8a–c) for future application in asymmetric synthesis and design of homochiral ligands. Further, we have generalized the method substantiating a variety of new azaindol-2-yl derivatives (10aa–10lc) with functionalized substituents. In a preliminary luminescence characterization, l-(N-Cbz)-1a has exhibited about 30 nm bathochromic shifted fluorescence emission compared to tryptophan and (N-Cbz)-tryptophan.     

Synthesis of 5-substituted 1H-tetrazoles catalyzed by ytterbium triflate hydrate

Various 5-substituted 1H-tetrazoles were synthesized from aryl nitriles, alkyl nitriles, and vinyl nitriles reacting with sodium azide. The tetrazoles were recovered in high yield under mild conditions when the reaction was catalyzed by ytterbium triflate hydrate in dimethylformamide. Other rare-earth and post-transition metal catalysts were also investigated.     

New silatranes possessing urea functionality: Synthesis, characterization and their structural aspects

The present work aims at the synthesis of various novel silatranes bearing substituted urea functionality. Nucleophilic addition of various amines (morpholine, aniline, ethylenediamine and 3-aminopropyltriethoxysilane) to 3-isocyanatopropyltriethoxysilane resulted in the four triethoxysilanes; N-[3-(triethoxysilyl)propyl]morpholine-4-carboxylic acid amide (1), 1-[3-(triethoxysilyl)propyl]-3-phenylurea (2), 1,2-bis{N′-[3-(triethoxysilyl)propyl]ureido}-ethane (3) and N-[3-(triethoxysilyl)propyl]-N′-[3-(triethoxysilyl)propyl]urea (4), respectively. In the presence of a base the resulting silanes undergo transesterification reaction with triethanolamine, thus forming the corresponding silatranes, N-(3-silatranylpropyl)morpholine-4-carboxylic acid amide (5), 1-(3-silatranylpropyl)-3-phenylurea (6), 1,2-Bis[N′-(3-silatranylpropyl)ureido]-ethane (7) and N-(3-silatranylpropyl)-N′-(3-silatranylpropyl)urea (8), respectively. Among these are four novel compounds (5-8), which were characterized by elemental analysis, IR, multinuclear (¹H, ¹³C and ²⁹Si) NMR and mass spectroscopy. Structures of compounds 5 and 6 were deduced by X-ray crystallography. Single crystal X-ray studies revealed distorted trigonal bipyramidal coordination about Si in 5 and 6 with Si-N bond distance of 2.121(1) Å and 2.189(2) Å, respectively.     

Synthesis of a novel tetracyclic azaindolo[2,1-c][1,4]benzoxazine ring system

Synthesis of a series of novel fused tetracyclic mono- and diazaindolo[2,1-c][1,4]benzoxazine heterocyclic compounds 3a-o has been achieved in a two-step one-pot reaction set up starting from commercially available or easily accessible inputs. For example, reaction of di-lithiated (N-Boc)-2-amino-3-methylpyridine Li₂-2a with Weinreb amide of 2-(2,4-difluorophenoxy)-2,2-dimethylacetic acid 1a, followed by TFA treatment furnished the tetracyclic compound 3a, which is essentially a fusion of 7-azaindole and 3,4-dihydro[1,4]benzoxazine, in 70% isolated yield. A competitive elimination by-product 4a was also observed (24% isolated yield) in this case. Based on our initial results, a structural basis and molecular mechanism have been suggested to explain these two parallel reactions. Consequently, with appropriate structural tuning of 1, formation of the individual products can be controlled.