- Regio- And Stereoselective (S N2) N -, O -, C - And S -Alkylation Using Trialkyl Phosphates
-
Bimolecular nucleophilic substitution (S N 2) is one of the most well-known fundamental reactions in organic chemistry to generate new molecules from two molecules. In principle, a nucleophile attacks from the back side of an alkylating agent having a suitable leaving group, most commonly a halide. However, alkyl halides are expensive, very harmful, toxic and not so stable, which makes them problematic for laboratory use. In contrast, trialkyl phosphates are inexpensive, readily accessible and stable at room temperature, under air, and are easy to handle, but rarely used as alkylating agents in organic synthesis. Here, we describe a mild, straightforward and powerful method for nucleophilic alkylation of various N -, O -, C - and S -nucleophiles using readily available trialkyl phosphates. The reaction proceeds smoothly in excellent yield, and quantitative yield in many cases, and covers a wide range of substrates. Further, the rare stereoselective transfer of secondary alkyl groups has been achieved with inversion of configuration of chiral centers (up to 98% ee).
- Banerjee, Amit,Hattori, Tomohiro,Yamamoto, Hisashi
-
-
- Preparation of alkylated compounds using the trialkylphosphate
-
[Problem] trialkylphosphate strong base used reaction agent, a carboxylic acid, a ketone, an aldehyde, amine, amide, thiol, ester or Grignard reagent to a variety of substrates, and/or high efficiency to generate a highly stereoselective alkylation reaction, the alkylated compounds capable of producing new means. [Solution] was used as the alkylating agent in the alkylation of compound trialkylphosphate, strongly basic reaction production use. [Drawing] no
- -
-
Paragraph 0184-0185; 0209
(2021/11/02)
-
- PROCESS FOR THE SYNTHESIS OF N-SUBSTITUTED LACTAMS AND AMIDES
-
A process for the synthesis of N-alkylated lactams via reductive alkylation. The process of the present disclosure may be conducted by the addition of an aldehyde to a lactam in the presence of a catalyst under a reducing atmosphere.
- -
-
Paragraph 0034
(2021/06/22)
-
- A new route to N-aromatic heterocycles from the hydrogenation of diesters in the presence of anilines
-
The hydrogenation of dicarboxylic acids and their esters in the presence of anilines provides a new synthesis of heterocycles. [Ru(acac)3] and 1,1,1-tris(diphenylphosphinomethyl)ethane (triphos) gave good to excellent yields of the cyclic amines at 220 °C. When aqueous ammonia was used with dimethyl 1,6-hexadienoic acid, ?-caprolactam was obtained in good yield. A side reaction involving alkylation of the amine by methanol was suppressed by using diesters derived from longer chain and branched alcohols. Hydrogenation of optically pure diesters (dimethyl (R)-2-methylbutanedioate and dimethyl (S)-2-methylbutanedioate) with aniline afforded racemic 3-methyl-1-phenylpyrrolidine in 78% yield.
- Shi, Yiping,Kamer, Paul C. J.,Cole-Hamilton, David J.,Harvie, Michelle,Baxter, Emma F.,Lim, Kate J. C.,Pogorzelec, Peter
-
p. 6911 - 6917
(2017/10/05)
-
- Copper-catalyzed N-methylation of amides and O-methylation of carboxylic acids by using peroxides as the methylating reagents
-
The copper-catalyzed N-methylation of amides and O-methylation of carboxylic acids by using peroxides as the methylating reagent are described. Various amides and carboxylic acids were methylated affording N-substituted amides and esters. Tentative mechanistic studies suggest that this reaction is likely to involve a radical process.
- Xia, Qinqin,Liu, Xiaolong,Zhang, Yuejiao,Chen, Chao,Chen, Wanzhi
-
supporting information
p. 3326 - 3329
(2013/07/26)
-
- Direct conversion of polyamides to ω-hydroxyalkanoic acid derivatives by using supercritical MeOH
-
We examined the decomposition of polyamides such as nylon-6 and nylon-12 by using supercritical MeOH as the reaction media. The treatment of waste nylon-6 with supercritical MeOH resulted in smooth depolymerization, forming caprolactam as the first product which was then converted to a mixture of methyl 6-hydroxycapronate and methyl 5-hexenoate in a ratio of approximately 1:1. The reaction progress was traced using gas chromatography (GC) analyses, and precise product distribution was estimated. During the decomposition of nylon-6, N-methylcaprolactam and methyl 6-(N,N-dimethylamino)capronate were detected as intermediates. The sum of the all detectable products and intermediates exceeded 80%. In addition, we examined the decomposition reaction initiating from caprolactam, N-methylcaprolactam, and methyl N,N-dimethylcapronate under similar reaction conditions, and observed that the final two products were formed in similar yields and ratios. Kinetic analyses by using a simulation study based on the experimental data were performed, and kinetic parameters for each step were estimated. Nylon-12 underwent similar conversion to produce methyl 12-hydroxydodecanoate in good yield. Because methyl ω-hydroxyalkanoate is known to be an important intermediate in the chemical industry, the present method has the potential for producing valuable compounds from waste material. Thus, the first upgrade in the chemical recycling of plastics was accomplished.
- Kamimura, Akio,Kaiso, Kouji,Suzuki, Shuzo,Oishi, Yusuke,Ohara, Yuki,Sugimoto, Tsunemi,Kashiwagi, Kohichi,Yoshimoto, Makoto
-
experimental part
p. 2055 - 2061
(2011/10/09)
-
- PROCESS FOR PRODUCING 6-HYDROXYCAPROIC ESTER AND PROCESS FOR PRODUCING TRIALKYLAMINE
-
A process for producing a 6-hydroxycapoic ester and a process for producing a trialkylamine in both of which nylon-6, ε-caprolactam, which is a monomer therefore, etc. are used as a raw material. The processes are intended to make nylon-6 wastes reusable in various applications without consuming a large quantity of energy. The process for producing a 6-hydroxycarpoic ester and process for producing a tiralkylamine are characterized by reacting amide compounds basically comprising ε-caprolactam with an alcohol in a supercritical state to obtain a 6-hydroxycaproic ester and a trialkylamine.
- -
-
Page/Page column 3-6
(2008/12/04)
-
- PROCESS FOR THE PRODUCTION OF LACTAMS
-
A homogeneous process for the hydrogenation of dicarboxylic acid and/or derivative thereof with an amine in the presence of a catalyst comprising: (a) ruthenium or osmium; and (b) an organic phosphine; and wherein the hydrogenation is carried out in the presence of water.
- -
-
Page/Page column 11
(2008/06/13)
-
- Inhibitors of histone deacetylase
-
The invention relates to the inhibition of histone deacetylase. The invention provides compounds and methods for inhibiting histone deacetylase enzymatic activity. The invention also provides compositions and methods for treating cell proliferative diseases and conditions.
- -
-
-
- N-(DIMETHYLALKOXYSILYLMETHYL)- AND N-(DIMETHYLARYLOXYSILYLMETHYL)LACTAMS
-
A comparison is made of conditions and preparative possibilities of synthesizing Si-substituted N-(dimethylsilylmethyl)lactams with oxygen-containing substituents (alkoxides, aryloxides, benzoates, and triflates) by several methods: by reactions of N-(dimethylchlorosilylmethyl)lactams with sodium alkoxides and with alcohols in the presence of triethylamine, by exchange reactions with trimethylsilyl derivatives of alcohols, phenols, benzoic and trifluoromethylsulfonic acids, and also by a one-pot technique using lactam, dimethylchloromethylchlorosilane, and triethylamine with subsequent addition to the reaction mixture of the alcohol and triethylamine. In the reaction of N-(dimethylchlorosilylmethyl)lactams with sodium alkoxides, concurrently with the replacement of halogen by an alkoxy group the Si-C bond is split to form N-methyllactams, which can also be prepared by the reaction of the initial chlorides with potassium hydroxide. According to IR spectroscopy, intramolecular O->Si coordination is observed in aryloxy-, benzoyloxy-, and trifluoromethylsulfonyloxy derivatives of N-(dimethylsilylmethyl)lactams, whereas the corresponding alkoxy derivatives lack this interaction. The structure of 1-(dimethylsilylmethyl)-2-pyrrolidone phenoxide and benzoate, 1-(dimethylpentafluorophenoxysilylmethyl)perhydro-2-azepinone, and 1-(dimethyltrifluoromethylsulfonyloxymethyl)-2-piperidone was studied by x-ray structural analysis. The lengths of the axial (C=)O->Si and Si-O bonds are, respectively, 2.367 and 1.711(2) Angstroem for the first, 2.228 and 1.711(2) Angstroem for the second, 2.078 and 1.787(2) Angstroem for the third, and 1.753 and 2.785(2) Angstroem for the fourth compound. Variations in the bond lengths are due to the properties of the Si-substituent and to the size of the lactam rings. The ease of formation of the Si-substituted N-(dimethylsilylmethyl)lactams with oxygen-containing substituents via the exchange reaction of N-(dimethylchloromethyl)lactams with the corresponding trimethylsiloxy derivatives correlates with the strength of the silicon-oxygen coordination in the reaction products.
- Artamkina, O. B.,Kramarova, E. P.,Shipov, A. G.,Baukov, Yu. I.,Macharashvili, A. A.,et al.
-
p. 1590 - 1597
(2007/10/02)
-
- An alternative efficient method for transformation of thiocarbonyl to carbonyl group using trifluoroacetic anhydride
-
A simple and efficient procedure for the rapid and mild conversion of thiocarbonyls to carbonyls in high yields is described.
- Masuda, Ryoichi,Hojo, Masaru,Ichi, Tadaaki,Sasano, Shigetoshi,Kobayashi, Tatsuya,Kuroda, Chihiro
-
p. 1195 - 1198
(2007/10/02)
-
- New 5-nitroimidazoles bearing lactame nucleus: Synthesis and antibacterial properties
-
New 5-nitroimidazoles bearing a trisubstituted ethylenic double bond in position 2 were prepared by reacting various 1-alkyl-2-chloromethyl-5-nitroimidazole with 3-nitrolactam anions by S(RN)1 mechanism in phase-transfer catalysis conditions. These compounds showed in vitro and in vivo antianaerobic activity which was clearly greater than that of metronidazole. Structure-activity relationships have been discussed.
- Jentzer,Vanelle,Crozet,Maldonado,Barreau
-
p. 687 - 697
(2007/10/02)
-
- A simple, one-flask transformation of ketones to N-methyl lactams
-
A one-flask conversion of cyclic ketones to N-methyl lactams is described. Reaction of the ketone with triethylorthoformate generates an acetal which is reacted in situ with N-(((p-nitrobenzene)sulfonyl)oxy methylamine 2a(CH3NH-OSO2C6H4NO2). Dealkylation of the resulting O-ethyl imidate with sodium iodide gives the lactam. A variety of lactams, including macrocyclic lactams, are produced simply and in good yields.
- Hoffman, Robert V.,Salvador, James M.
-
p. 2429 - 2432
(2007/10/02)
-
- EFFICIENT SYNTHESIS OF N-SUBSTITUTED LACTAMS FROM (N-ARYLSULFONYLOXY)AMINES AND CYCLIC KETONES
-
A new method is reported for the direct preparation of N-substituted lactams from cycloalkanones.N-(p-nitrobenzenesulfonoxyl) methylamine 1a (CH3NH-OSO2C6H4NO2) was reacted with a series of cycloalkanones to give good yields of N-methyl lactams.An addition-rearrangement pathway accounts for the ring-expanded lactam products.A series of N-alkyl-N-arylsulfonoxyl amines were generated in situ and reacted with cyclobutanone to give N-alkyl pyrrolidinones in high yields.
- Hoffman, Robert V.,Salvador, James M.
-
p. 4207 - 4210
(2007/10/02)
-
- Process for the preparation of N-alkylated caprolactams
-
This invention relates to a process for the preparation of N-alkylated caprolactams by the cyclization of N-alkylated caproic acids.
- -
-
-
- Composition comprising an oxygenated cholesterol and use thereof for topical treatment of diseases
-
The invention is directed to a pharmaceutical composition comprising an oxygenated cholesterol and a penetration-enhancing agent which is useful for topical application to the skin of a patient suffering from a proliferative skin disease characterized by geminative cells having a rapid rate of replication, e.g. psoriasis. The composition comprises an effective amount for the inhibition of germinative cell mitosis of an oxygenated cholesterol, e.g. 26-hydroxycholesterol, or a pharmaceutically effective derivative thereof e.g. an ester or ether. The invention is further directed to a method of treating a patient suffering from said skin disease comprising applying to the effected skin said therapeutic composition. The invention is also directed to the topical application of these compositions to the skin to decrease inflammation.
- -
-
-
- Process for the preparation of 1-substituted aza-cycloalkan-2-ones
-
A process for the preparation of 1-substituted azacycloalkan-2-ones of the formula I STR1 in which R, m and n have the meanings indicated by reaction of corresponding 1-trimethylsilylazacycloalkan-2-ones with alkali metal alcoholate or alkali metal oxide and then alkylation of the alkali metal salts which are formed.
- -
-
-
- Method of improved pest control
-
The disclosure describes a method for improved plant pest control comprising contacting a plant or plant pest with a composition comprising an effective amount of a plant pesticide and an effective delivery enhancing amount of compound having the structural formula STR1 wherein R' is H or a lower alkyl group having 1-4 carbon atoms, m is 3-7, n is 0-17 and R is --CH3, STR2 where R" is H or halogen, with the proviso that if m is 3 and R is CH3, then n is 5-17. Typical plant pesticides include insecticides, fungicides, herbicides, rodenticides, nematicides molluscicides and acaricides. The preferred penetration enhancing compound is 1-n-dodecylaza cycloheptan-2-one.
- -
-
-
- N-ALKYLATION OF AMIDES AND N-HETEROCYCLES WITH POTASSIUM FLUORIDE ON ALUMINA
-
Alumina coated with potassium fluoride promotes smooth N-alkylation of carboxamides, lactams, and other N-heterocycles with alkyl halides or dialkyl sulfate under mild conditions.
- Yamawaki, Junko,Ando, Takashi,Hanafusa, Terukiyo
-
p. 1143 - 1146
(2007/10/02)
-
- Vehicle composition containing 1-substituted azacycloheptan-2-ones
-
There is disclosed an improved method for topically administering a physiologically active agent to a human or animal by dissolving an effective amount of the agent in a carrier containing suitable amounts of 1-substituted-azacycloheptan-2-one, as defined herein, and contacting the skin or other membranes of the human or animal with the resulting composition, whereby penetration of the skin or membranes is enhanced.
- -
-
-
