- Direct Evidence for the Hydroxide Extraction Mechanism in the Phase Transfer Catalyzed Cyclopropanation of 4-Halobutyronitrile in a Solid-Liquid System
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The Hoffman degradation reaction is proposed as an unequivocal proof for the validity of the extraction mechanism in Phase Transfer Catalysis (PTC) in the presence of solid NaOH. 4-Chlorobutyronitrile is found to yield cyclopropyl cyanide via an extraction route while 4-bromobutyronitrile reacts to form the same product by the prevalent interfacial mechanism.
- Cohen, Shlomo,Zoran, Ami,Sasson, Yoel
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Read Online
- Novel method for synthesizing cyclopropyl cyanide
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The invention discloses a novel method for synthesizing cyclopropyl cyanide, which comprises the following steps: carrying out denitrification cyclization reaction on acrylonitrile serving as a raw material and diazomethane in a solvent under the catalytic action of Pd (oAc) 2 to obtain a cyclopropyl cyanide crude product, and carrying out acid pickling, filtration layering and normal-pressure rectification to obtain a pure product with the content of 99.5% or more and the yield of 95% or more. The synthetic route has the advantages of high yield, few byproducts, high purity and environmental friendliness, and is more suitable for industrial amplification.
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Paragraph 0003; 0012-0017
(2022/03/27)
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- Novel method and technology for synthesizing cyclopropyl ammonia
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The invention discloses a synthesis process route of a cyclopropane synthetic route. In the process route, cyanocyclopropane 1 - formic acid (-1 -) and (1) are subjected to hydrolysis under the action of a strong base to generate 1-cyanocyclopropane 1 - formic acid (-1 -), (2) decarboxylation to generate cyclopropanecarboxamide (2 3), and (4 4 3) subjected to Hoffman rearrangement to obtain the target product cyclopropysite. The process route is longer than the production process in the present stage, the reaction route is long, the use of high-temperature and high-pressure is avoided, the danger is reduced, and the safety is improved. The requirement of the reaction equipment is reduced, the used raw materials are easy to obtain, operation is easy, safety and environmental protection are achieved, and industrial production can be realized.
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Paragraph 0017
(2021/09/21)
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- Corresponding amine nitrile and method of manufacturing thereof
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The invention relates to a manufacturing method of nitrile. Compared with the prior art, the manufacturing method has the characteristics of significantly reduced using amount of an ammonia source, low environmental pressure, low energy consumption, low production cost, high purity and yield of a nitrile product and the like, and nitrile with a more complex structure can be obtained. The invention also relates to a method for manufacturing corresponding amine from nitrile.
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Paragraph 0143-0147; 0158; 0180; 0191; 0213; 0224
(2017/10/22)
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- Synthetic method of cyclopropanecarbonitrile
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The invention discloses a synthetic method of cyclopropanecarbonitrile. Cyclopropanecarbonitrile is prepared from a 4-halogenated butyronityile compound under the action of dihydric alcohol and sodium. The method has the advantages of simplicity in operation, fast reaction and high yield, solves the problem of simple and fast synthesis of the cyclopropanecarbonitrile compound, and can be used to prepare cyclopropanecarbonitrile.
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Paragraph 0018; 0019; 0020; 0021; 0022; 0023
(2017/08/25)
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- Simple Copper Catalysts for the Aerobic Oxidation of Amines: Selectivity Control by the Counterion
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We describe the use of simple copper-salt catalysts in the selective aerobic oxidation of amines to nitriles or imines. These catalysts are marked by their exceptional efficiency, operate at ambient temperature and pressure, and allow the oxidation of amines without expensive ligands or additives. This study highlights the significant role counterions can play in controlling selectivity in catalytic aerobic oxidations.
- Xu, Boran,Hartigan, Elizabeth M.,Feula, Giancarlo,Huang, Zheng,Lumb, Jean-Philip,Arndtsen, Bruce A.
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supporting information
p. 15802 - 15806
(2016/12/16)
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- A cyclopropyl armor cyanogen method for preparing derivatives of
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The invention relates to a preparation method of a cyclopropyl methyl cyanide derivative with a general formula I. The preparation method is as below: first synthesizing cyclopropyl formonitrile by using cyclopropanecarboxamide as raw material, then synthesizing a halogenated butyronitrile derivative, and finally synthesizing the target product cyclopropyl methyl cyanide derivative. The invention provides a complete process route, and carefully investigates and researches raw materials and process conditions in each step, so that the method provided by the invention is more efficient and secure, and low in energy consumption and cost, and applicable to large-scale industrialized production.
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Paragraph 0035; 0036
(2016/12/22)
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- SUBSTITUTED NAPHTHYRIDINES AND THEIR USE AS SYK KINASE INHIBITORS
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The invention relates to new substituted naphthyridines of formula (1), as well as pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof, wherein R1 is selected from among -O-R3 or -NR3R4, R3 is C1-6-alkyl which is substituted by R5 and R6 R5 is selected from hydrogen, branched or linear C1-6-alkyl, C2-6-alkenyl, -C1-6-alkylen-O-C1-3-alkyl, C1-3-haloalkyl, R6 is ring X wherein n is either 0 or 1, and Formula (I) is a either a single or a double bond and wherein A, B, D and E are each independently from one another selected from CH2, CH, C, N, NH, O or S and wherein ring X is attached to the molecule either via position A, B, D or E, wherein said ring X may optionally be further substituted by one, two or three residues each selected individually from the group consisting of -oxo, hydroxy, -C1-3-alkyl, -C1-3-haloalkyl, -O-C1-3-alkyl, -C1-3-alkanol and halogen, and wherein R4, R2, R7, R8, R9, R10, R11 and Q may have the meanings as given in claim 1, as well as pharmaceutical compositions containing these compounds.
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Page/Page column 45
(2011/08/21)
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- COMPOSITIONS FOR TREATMENT OF CYSTIC FIBROSIS AND OTHER CHRONIC DISEASES
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The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.
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- Looking for heteroaromatic rings and related isomers as interstellar candidates
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Finding complex organic molecules in the interstellar medium (ISM) is a major concern for understanding the possible role of interstellar organic chemistry in the synthesis of prebiotic species. The present interdisciplinary report is a prospective study aimed at helping detection of heteroaromatic compounds or at least of some of their isomers in the ISM. The thermodynamic stabilities of the C4H5N, C4H4O, C4H4S families were calculated using density functional theory (DFT). It was found that pyrrole, furan and thiophene are unambiguously the most stable isomers at the 10-50 K temperatures of the ISM. Several of the less stable isomers were synthesized and flash vacuum thermolysis experiments were performed on these species. Although the detection of pyrrole in the pyrolysis of many compounds has been reported in the literature, we observed that none of its isomers led to pyrrole in these conditions, which suggests that other formation routes are to be considered. On the other hand, these three aromatic compounds present a very high stability, few % been decomposed at 1500 K by flash vacuum thermolysis; these experiments also show a great stability of crotonitrile that is the most stable compound that can be formed in these conditions. The rotational constants, dipole moments and IR frequencies of the low-lying isomers are given to encourage laboratory experiments on these prototype molecules.
- Lattelais,Ellinger,Matrane,Guillemin
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experimental part
p. 4165 - 4171
(2011/08/02)
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- New reactions of γ-halocarbanions: Underestimated reactive intermediates in organic synthesis
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Short-lived γ-halocarbanions can be trapped by active electrophiles such as aldehydes, imines, and Michael acceptors to give anionic adducts, which undergo intramolecular substitution to give substituted tetrahydrofurans, pyrrolidines, and cyclopentanes. This has underlain a new method for the synthesis of these valuable ring systems. We have determined the acidity of the γ-halocarbanion precursors and have shown that the halogen atoms in the γ-position relative to the carbanion center exert a significant stabilizing effect on the carbanion.
- Barbasiewicz,Judka,Makosza
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p. 1846 - 1858
(2007/10/03)
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- Process for producing cyclopropanecarbonitrile
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A process for producing cyclopropanecarbonitrile involves reacting cyclopropanecarbaldoxime with acetic anhydride to obtain a mixture containing acetic acid and cyclopropanecarbonitrile. The acetic acid can be removed from the mixture through azeotropic distillation of acetic acid with a solvent that forms with acetic acid an azeotropic mixture having an azeotropic point lower than the boiling point of the cyclopropanecarbonitrile.
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- New reactions of γ-halocarbanions: Simple synthesis of substituted tetrahydrofurans
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The treatment of 4-chlorobutyronitrile, 3-chloropropyl phenyl sulfone, and other related compounds with a base afforded γ-halocarbanions that undergo fast intramolecular substitution of the halogen to produce substituted cyclopropanes. We found that these short-lived carbanionic intermediates can be trapped with active external electrophilic partners, such as aldehydes, to give the aldol anions. These anions then undergo rapid intramolecular substitution of chloride to produce 2,3- disubstituted tetrahydrofurans. Under the right conditions, yields of tetrahydrofurans are excellent. Similar reactions with ketones gives 2,2,3-trisubstituted furans, but this process is usually less efficient. Ratios between the rates of intramolecular and intermolecular processes were qualitatively estimated by competitive experiments. It was shown that y-halo and y-trimethylammonium substituents substantially increase the kinetic CH acidity of alkane nitriles and sulfones.
- Makosza, Mieczyslaw,Judka, Marek
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p. 4234 - 4240
(2007/10/03)
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- Process for the manufacture of cyclopropylnitrile
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An improved manufacturing procedure for the preparation and isolation of cyclopropylnitrile is provided. 4-Halobutyronitrile is reacted with an alkali metal base in the presence of an aprotic polar solvent, an inorganic salt and a catalytic amount of water at an elevated temperature. The reaction product cyclopropylnitrile is isolated by azeotropic distillation.
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- 4-(1H-PYRROL-1-YL)IMIDAZOLES WITH ANGIOTENSIN II ANTAGONIST ACTIVITY
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Novel substituted 4-(1-H-pyrrol-1-yl)imidazoles are disclosed as well as methods of preparing them, pharmaceutical compositions containing them, and methods of using them. Novel intermediates useful in the preparation of the compounds of the invention are also disclosed and synthetic methods for preparing the novel intermediates. The compounds are useful as antagonists of angiotensin II and thus are useful in the control of hypertension, hyperaldosteronism, congestive heart failure, glaucoma, vascular smooth muscle proliferation associated with atherosclerosis, and with postsurgical vascular restenosis.
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- 4-(1H-PYRROL-1-YL) IMIDAZOLES WITH ANGIOTENSION II ANTAGONIST ACTIVITY
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Novel substituted 4-(1-H-pyrrol-1-yl)imidazoles are disclosed as well as methods of preparing them, pharmaceutical compositions containing them, and methods of using them. Novel intermediates useful in the preparation of the compounds of the invention are also disclosed and synthetic methods for preparing the novel intermediates. The compounds are useful as antagonists of angiotensin II and thus are useful in the control of hypertension, hyperaldosteronism, congestive heart failure, glaucoma, vascular smooth muscle proliferation associated with atherosclerosis, and with postsurgical vascular restenosis.
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- Deamination Reactions, 54. - Decomposition of 1-Cyano-1-propanediazonium Ions
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The nitrous acid decomposition of 2-aminobutanenitrile (9) was studied with regard to product distribution and stereochemistry.The formation of 2-(hydroxyimino)butanenitriles (21, 22; 8-28percent) indicates the intervention of 1-cyanopropyl radicals (24) that are captured by NO.The polar reactions lead mainly to elimination (10-13) and nucleophilic substitution (14-16), rearrangement playing a minor role. (R)-9 was prepared from (R)-2-aminobutanoic acid.The nitrous acid deamination of (R)-9 afforded the cyanohydrin 16 with 81percent net inversion.Owing to destabilization of the carbocation 26 by CN, the SN2 route of nucleophilic displacement is preferred over SN1.The influence of CN is shown to be smaller than that of CF3. Key Words: α-Cyanodiazonium ions / α-Cyanoalkyl radicals / Carbocations, destabilized / Substitution, nucleophilic / Deamination reactions / Diazonium ions / Radicals
- Bunse, Michael,Kirmse, Wolfgang
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p. 1499 - 1502
(2007/10/02)
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- The Synthetic Potential of the Isocyanide-Cyanide Rearrangement
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Excellent chemical and optical yields (>96percent retention) of cyanides are achieved by vapor phase thermolysis or short contact flow thermolysis of isocyanides. trans-2-Butenyl isocyanide rearranges without concomitant allylic isomerization to trans-2-butenyl cyanide.Optically active 1-(formyloxymethyl)-2-phenylethyl cyanide is obtained from optically active L-phenylalanine as a new type of chiral pool synthon.
- Meier, Michael,Ruechardt, Christoph
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- The Isonitrile-Nitrile Rearrangement. A Reaction without a Structure-Reactivity Relationship
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Reproducible rates of isomerisation of aliphatic isonitriles to nitriles in solution can be measured by GLC or IR when free-radical inhibitors are added to suppress a competing radical chain reaction.The reactivities of 19 primary, secondary, tertiary, cyclic, bicyclic, bridgehead, benzyl, substituted-benzyl, α-carbomethoxymethyl, and triphenylmethyl isocyanides in this rearrangement reaction vary by only a factor of 67 in rate or by +/- 2 kcal mol-1 in ΔG(excit.).This is explained by a tight hypervalent three-membered cyclic transition state in agreement with a previous prediction by ab initio calculation.The slower rate of 9-triptycyl isocyanide is proposed to be due to steric hindrance by the three peri hydrogens.Aromatic isocyanides isomerize about 10 times faster independent of polar para substituents and bulky ortho substituents.A hypervalent orthogonal transition state with retention of the aromatic sextet is proposed in contrast to the popular phenonium-type transition states for aryl migration in other 1,2-rearrangements.The reactivity data and the transition-state structures are discussed in context with other cationotropic 1,2-shifts.
- Meier, Michael,Mueller, Barbara,Ruechardt, Christoph
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p. 648 - 652
(2007/10/02)
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- FACILE CONVERSION OF CARBOXAMIDES TO NITRILES
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Alkyl, aralkyl, aryl, heteroaryl carboxamides bearing various functionalities are readily converted to the corresponding nitriles in good yields using the liquid "diphosgene", trichloromethyl chloroformate, as dehydrating agent.In many cases, the procedure does not require extraction, and hence offers a very simple work-up.
- Mai, Khuong,Patil, Ghanshyam
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p. 2203 - 2206
(2007/10/02)
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- Reactions of Cyclopropyl Sulfonates with Nucleophiles: SN2 Displacements at Cyclopropanes with Inversion
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Treatment of cyclopropyl trifluoromethanesulfonate (3) with tributylhexadecylphosphonium azide (QN3) in aprotic solvents almost quantitatively afforded cyclopropyl azide (6) in a second-order reaction.Nucleophilic displacements with ring preservation were also achieved using QCN or QBr.The analogous reactions of the epimeric 2-methylcyclopropyl trifluoromethanesulfonates (16, 17) with QN3 highly stereospecifically yielded the 2-methylcyclopropyl azides (24, 25) with inversion in addition to the allylic azides 27, 28, and 29.The product fraction of cyclic azides decrea sed with growing steric hindrance in the order 3 > 16 > 17.The experimental results show that SN2 displacements take place with clean inversion at the cyclopropane carbon atom.
- Banert, Klaus
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p. 1564 - 1574
(2007/10/02)
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- Synthesis of Cyclopropane Derivatives from Electron-deficient Olefins and Dichloromethane via Copper(I) Catalysed Photochemical Addition followed by an Electroreductive Dehalogenation Reaction
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The CuCl-catalysed photochemical reaction of electron-deficient olefins with dichloromethane gave 1,3-dichloro compounds, which then afforded cyclopropane derivatives by electrochemical reduction.
- Mitani, Michiharu,Yamamoto, Yasuo,Koyama, Kikuhiko
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p. 1446 - 1447
(2007/10/02)
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- Cyclopropanation of Electron-deficient Olefins with Dibromomethane by Ni(0) Complexes and Zinc
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A new method for the synthesis of cyclopropane derivatives is described. It involves treatment of electron-deficient olefins with dibromomethane in the presence of Ni(0) complex/zinc/Lewis acid (or alkali halide) systems. Ni(PPh3)4/Zn/ZnBr2 system was effective for the cyclopropanation of methyl acrylate and acrylonitrile, but was ineffective for that of methyl vinyl ketone and acrylaldehyde. Ni(COD)2/Zn/NaI system was applicable to the cyclopropanation of methyl vinyl ketone as well as to that of methyl acrylate and acrylonitrile. Alternative catalytic systems which were easy to handle were exploited, involving in situ generated Ni(0) complexes prepared from NiBr2(PPh3)2 and zinc, or nickel bromide, sodium iodide, zinc, and an olefin. Catalytic amounts of nickel compounds are sufficient for the cyclopropanation of methyl acrylate, acrylonitrile, and methyl vinyl ketone, but a 1:2 nickel:acrylaldehyde mole ratio results in the best yield. A mechanism is proposed which involves metallacyclobutane as an intermediate.
- Kanai, Hiroyoshi,Hiraki, Nobuyuki,Iida, Shigeki
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p. 1025 - 1029
(2007/10/02)
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- Process for the preparation of cyclopropylmethyl-n-propylamine
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A process for preparing cyclopropylmethyl-n-propylamine from the reaction of cyclopropylmethylamine with propionitrile is described. The reaction takes place in the presence of a hydrogenation catalyst, preferably a mixture of rhodium on carbon and platinum on carbon. The process is particularly useful as it consumes the cyclopropylmethylamine by-product from another scheme for the synthesis of cyclopropylmethyl-n-propylamine.
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- Oxonium Ions. Solvation by Single Acetonitrile Molecules in the Gas Phase and by Bulk Solvents
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The standard free energy of formation of gaseous complexes between monoprotonic oxonium ions and acetonitrile have been obtained by using the ion cyclotron resonance equilibrium constant method for exchange of acetonitrile between the ions.The results show that the "solvation" by a single molecule of acetonitrile in the gas phase reproduces the important diverse effects of molecular structure on oxonium ion solvation by bulk water.It is estimated from the present results that the effects of solvation by bulk water are only about three times as great as the corresponding effects of "solvation" by a single water molecule in the gas phase.Internal charge delocalization from the protonic site of the oxonium ions may be reversed by differential solvation, both with single H-bonding molecules in the gas phase and with bulk solvent.Further evidence for the site of preffered protonation of esters and amides is provided.
- Bromilow, J.,Abboud, J. L. M.,Lebrilla, C. B.,Taft, R. W.,Scorrano, G.,Lucchini V.
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p. 5448 - 5453
(2007/10/02)
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- Derivatives of cyclopropane
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Compounds of the formula STR1 wherein A is oxygen or --NH--, and R is straight or branched alkyl of 2 to 22 carbon atoms or straight or branched alkenyl of 3 to 18 carbon atoms, And acid addition salts thereof; the compounds as well as the salts are useful as acaricides.
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