Organische Phosphorverbindungen XXVIII. Die α-Aminoalkylierung von elementarem weissem Phosphor. Eine einfache Methode zur Darstellung von tertiären Phosphinoxiden,Phosphinsäuren und Phosphonsäuren [1]

White phosphorus reacts with N-hydroxymethyl-dialkylamines to give mainly three products, i.e., tris(dialkylaminomethyl) phosphine oxides, bis(dialkylamino-methyl) phosphinic acids, and dialkylaminomethyl phosphonic acids, according to the equation: The yield of the various products depends mainly upon the ratio of the reactants, the pH, and the solvents used.     

A new intramolecular recyclization in water‐base cleavage reaction of 2,2‐dialkyl‐4‐hydroxymethylbenz[f]iso indolinium bromides and chlorides

The water‐base cleavage reaction of 2,2‐dialkyl‐4‐hydroxymethylbenz[f]isoindolinium bromides and chlorides (2b‐g) and (4a‐g) was investigated. It was established that the above‐mentioned salts in water‐base cleavage reaction undergo intramolecular recyclization. As a result 1,3‐dihydro‐4‐dialkylaminomethyl‐naphto[1,2‐c]furans (5a‐g) are obtained in 62‐72% yields. The same products in 65‐70% yields may be obtained by step cyclization cleavage reaction of dialkyl‐4‐hydroxybutyn‐2‐yl‐(3‐phenylpropargyl) ammonium salts (1b‐g) and (3a‐g) , as well. The structure of the resulting amines 5a‐g are determined and approved by X‐ray diffraction, nmr and ir spectroscopic methods.     

2-Bromomethyl derivatives of benzofuran and indole and their reactions with some nucleophilic reagents

The corresponding 2-bromomethyl derivatives of benzofuran and indole were obtained by bromination of 2-methyl-3-carbethoxy-5-methoxybenzofuran and 1,2-dimethyl-3-earbethoxy-5-methoxyindole with N-bromosuccinimide. A number of alkyl(aryl)thiomethyl and dialkylaminomethyl derivatives were obtained by reaction of the 2-bromomethyl derivatives with nucleophilic reagents.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 308–311, March, 1973.     

Sterically hindered 3-pyridinols

Summary 2,6-Dialkyl-4-(dialkylaminomethyl)-3-pyridinols were synthesized and their structures established by the PMR method. It was shown to be possible to aminomethylate 2,6-dialkyl-3-pyridinols in the 4-position.The authors thank N. M. Émanuél' for constant interest in the work.     

Modified Coumarins. 11. Synthesis and Biological Activity of Mannich Bases of Substituted 1,3-Dihydrocyclopenta[c]chromen-4-ones

Mannich bases containing the dialkylaminomethyl group in the 6- and 8-positions of 2,3-di-hydrocyclopenta[c]chromen-4-ones were prepared by condensation of 7- and 9-hydroxy-2,3-dihydrocyclopenta[c]chromen-4-ones with substituted 1,1-diaminomethanes. The effects of 8-chloro-7-hydroxy-6-(1-pyrrolidinylmethyl)-2,3-dihydrocyclopenta[c]chromen-4-one and 8-chloro-7-hydroxy-6-(morpholinomethyl)-2,3-dihydrocyclopenta[c]chromen-4-one on the central and peripheral nervous systemwere defined and enable the presence of tranquilizing and neuroleptic properties to be predicted.     

Modified Coumarins. 7. Synthesis and Biological Activity of Mannich Bases of Substituted 7,8,9,10-Tetrahydrobenzo[c]chromen-6-ones

Condensation of 1- and 3-hydroxy-7,8,9,10-tetrahydrobenzo[c]chromen-6-ones with substituted 1,1- diaminomethanes produced Mannich bases containing a dialkylaminomethyl group in the 2- and 4-positions of 7,8,9,10-tetrahydrobenzo[c]chromen-6-one. Pharmacological screening of 2-chloro-3-hydroxy-4-(1- pyrrolidinylmethyl)-7,8,9,10-tetrahydro-6H-benzo[c]chromen-6-one in Wistar rats showed that it possesses low toxicity and acts as a stimulant of the central and peripheral nervous systems with indications of neuroleptic and tranquilizing activities.     

Synthesis of 5-(5-R-2-furyl)thiazole derivatives by the reaction of 2-(5-R-furfuryl)thiuronium salts with acetic anhydride

2-Acetamide-4-methyl-5-(5-R-2-furyl)thiazoles were obtained by the reaction of 2-(5-R-furfuryl)thiuronium salts with acetic anhydride. The reaction intermediates — 2-(5-R-furfuryl)-1,3-diacetylthioureas — were isolated and characterized.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 557–562, April, 1990.     

A convenient synthetic route from isatin N-Mannich bases to nitrogen-containing derivatives of isoindigo

Abstract  

The reaction of aminomethylisatins (isatin N-Mannich bases) with hexaethylphosphorous triamide leads to the formation of 1,1′-bis(dialkylaminomethyl)-3,3′-bis(indolin-3-ylidene)-2,2′-diones and 1,1′-bis(1,3-dioxo-1,3-dihydroisoindol-2-ylmethyl)-1H,1′H-[3,3′]bisindolylidene-2,2′-dione.     

Synthesis of 4-substituted 3-[3-(dialkylaminomethyl)indol-1-yl]maleimides and study of their ability to inhibit protein kinase C-α, prevent development of multiple drug resistance of tumor cells and cytotoxicity

A series of 3-[3-(dialkylaminomethyl)indol-1-yl]maleimides containing the indole, dihydroindole, mercaptophenol, or tetrahydroquinoline residues at position 4 of the maleimide ring, as well as 3-(dialkylaminomethyl)indole derivatives have been synthesized. Their ability to inhibit in vitro protein kinase C-α (PKC-α) has been studied. Cytotoxicity of new compounds and their ability to constrain activation of multiple drug resistance (MDR) have been studied in the human tumor cell line. Both the toxic and the low-toxic PKC-α inhibitors prevent the activation of MDR in the tumor cells. Among compounds under study, a number of substances have been found that prevent the activation of MDR but do not inhibit PKC-α. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1977–1985, September, 2008.     

5-氟脲嘧啶的β-D-半乳吡喃糖苷的合成

5-氟脲嘧及其衍生物是目前临床上广泛使用的抗代谢类抗癌药物, 主要适用于消化道癌、乳腺癌、肺癌等, 但具有一定的毒性, 主要表现为骨髓抑制和胃肠道反应。我们以Koenigs-Knorr法和相转催化法合成了5-氟脲嘧啶的两种类型(-N型, -O型)的半乳吡喃糖苷。这些糖苷类化合物在体内糖苷的作用下, 有可能缓慢地分解释放出5-氟脲嘧啶, 降低其毒性, 提高抑瘤效果。     

Direct synthesis of 5-substituted naphthoquinones

Peri-metalation of 4-(dimethylamino)-1-tert-butyldimethylsilyloxynaphthalene (5) followed by reaction with an electrophile and Jones' oxidation affords 5-substituted naphthoquinones.     

Reaction of (dialkylaminomethyl)trimethylsilanes with benzyne

Reactions of (dialkylaminomethyl)trimethylsilanes [dimethylamino-, diethylamino-, pyrrolidino- and morpholino-] with benzyne in THF gave two types of aniline derivatives: N-alkyl-N-(1-trimethylsilylalkyl)anilines and N-alkyl-N-trimethylsilylmethylanilines. From (piperidinomethyl)trimethylsilane, however, unexpected 1-(α-trimethylsilylbenzyl)piperidine was obtained together with N-(4-pentenyl)-N-trimethylsilylmethylaniline.     

Synthesis of 4-aroyl-5-nitro-1H-imidazoles and 4-aroyl-5-aminoimidazoles

The reaction of α-(aryl)-4-morpholineacetonitriles (masked aroyl anion equivalents) with N-protected 4(5)-bromo-5(4)-nitro-1H-imidazoles gave 4-aroyl-5-nitroimidazoles which were reduced to afford 4-aroyl-5-aminoimidazoles.     

α-Metallierte amine durch deprotonierung aliphatischer N-methylamine

Aliphatic N-methylamines can be deprotonated directly by means of s-butyllithium/potassium t-butoxide to give dialkylaminomethyl potassium or after metal exchange the more nucleophilic dialkylaminomethyl lithium.     

Preparation of 1-Trifluoroethyl-4-methoxy-5-chloropyridazin-6-one: Methyl Shift of 4-Methoxy-5-chloropyridazin-6-one

N1-Trifluoroethyl-4-methoxy-5-chloro-3-pyridazone (4) was synthesized by the substitution reaction of 4methoxy-5-chloro-3-pyridazone (1) with trifluoroethyl trifluoromethanesulfonate (A) at basic condition. In the most of reaction conditions, N1-methyl-4-methoxy-5-chloro-3-pyridazone (2) was obtained as a major by-product, which means that the methyl group in the 4-methoxy shifted to N-1 position inter-molecularly aided by A or trifluoroethyl methanesulfonate (B). We obtained N1-methyl-4-trifluoro-ethoxy-5-chloro-3-pyridazone (3) in the reaction of 1 with B at higher temperature in different solvents with different yield (Table 1 ), which mechanism was shown in Figure 1. When we tried to synthesize 4 in the reaction of 1 with trifluoroethyl toluenesulfonate under basic condition, 6 was obtained (Figure 2). All the detailed mechanisms are undergoing investigated.     

3-碘-5-甲基-1,5-苯并硫氮杂(艹卓)-4(5H)-酮的合成

以2-甲基硫代苯胺为原料,通过酰化反应、碘环化反应合成了3-碘-5-甲基-1,5-苯并硫氮杂(艹卓)-4(5H)-酮,总收率86.3%,其结构经NMR,IR和MS表征.     

Dialkylaminoethylation of Trimethylsilyl Esters of Trivalent Phosphorus Acids

Abstract

Dialkylaminomethylation of trimethylsilyl esters of trivalent phosphorus acids using bis(dialkylamino)methanes was carried out for the first time. This reaction is a convenient method for preparation of quaternary coordinated phosphorus compounds, including dialkylaminomethyl and functional groups. Thus trimethylsilylphosphites and -phosphonites of various structures react with bis(dialklamino)-methanes according to Arbuzov reaction in the presence of zinc chloride as a catalyst, when heated to 120°C, resulting in formation of phosphonates and phosphinates (I)     

Enhancement of the Rate of Mannich Reactions in Aqueous Media

The rate of Mannich reaction of phenols and of ketones with secondary amines is greatly increased in aqueous compared with alcoholic or hydrocarbon solvents. Two phase systems are present and a phase transfer catalysis may be operative. With phenols and excess co-reactants the products are mono- or isomeric disubstituted dialkylaminomethyl derivatives dependent upon the reaction time.     

Synthesis of the Derivatives of 4-(5-Aryl-3-methylfuran-3-yl)-1,2,3-thiadiazole and Functionalization of 5-Aryl-2- methylfuran via Reactions of Thiadiazole Ring

By arylation of 2-methyl-3-acetylfuran via the Gomberg–Bachmann reaction 5-(4-ethoxycarbonylphenyl)-, 5-(2-nitrophenyl), and 5-(4-nitrophenyl)-2-methyl-3-acetylfurans were synthesized. Carboethoxyhydrazones of 2-methyl-5-phenyl-3-acetylfuran and its phenyl-substituted analogs when treated with thionyl chloride form 4-(5-aryl-2-methylfuran-3-yl)-1,2,3-thiadiazoles by the Hurd–Mori reaction. Thermal stability of obtained compounds increases with the increase in electron-acceptor action of substituent in phenyl ring. Opening of thidiazole ring in the compounds synthesized under the action of potassium tert-butylate in THF in the presence of alkyl iodides leads to the corresponding alkylthioethynylfurans. Performing the reaction with potassium carbonate in DMF in the presence of excess morpholine permits the preparation of (2-methyl-5- arylfuran-3-yl)thioacetylmorpholides.     

Stereoselective Syntheses of the Isomeric 5, 10-Pentadecadienals

The four isomeric 5, 10-pentadecadienals 1 , 2 , 3 and 4 were prepared by stereo-selective routes from acetylenic precursors. Two of them, 2 and 4 , were also made by Wittig reaction from 2-hydroxytetrahydropyran (29) . 2-Hydroxytetrahydropyran (29) yields (Z)-5-alkenols efficiently by Wittig reaction, and (Z)-4-hexenol was similarly made from 2-hydroxytetrahydrofuran (66) .