- Hydrolysis of Trimethyl Orthocyclopropanecarboxylate: A Change in Rate-Determining Step
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The rate constant for the hydronium ion catalyzed hydrolyis of trimethyl orthocyclopropanecarboxylate measured in dilute aqueous HCl, kH+=5300 M-1s-1, was found to be different from that measured in buffer solutions at pH 6-8, kH+=81 00 M-1s-1.This difference is similar to that observed for cyclic ortho esters and is taken as evicence for a change in the reaction mechanism from rate-determining conversion of ortho ester to a dialkoxycarbonium ion intermediate at high pH to rate-determining decomposition of the hydrogen ortho ester formed by hydration of this ion at low pH.Discovery of this mechanistic change in this acyclic system suggests that this is a general phenomenon common to all ortho esters substituted with carbication-stabilizing groups at their pro-acyl carbon atoms.
- Burt, R. A.,Chiang, Y.,Kresge, A. J.,McKinney, M. A.
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- Direct quantitation of fatty acids present in bacteria and fungi: Stability of the cyclopropane ring to chlorotrimethylsilane
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The stability of the cyclopropane ring and the fatty acid composition of microbial cells were determined using chlorotrimethylsilane as reagent with three different conditions 80°C for 1 h, 60°C for 1 h, and 60°C for 2 h. Chlorotrimethylsilane permits a simultaneous extraction and derivatization of fatty acids. A basic method was used as reference. The bacteria, Escherichia coli, Burkholderia cepacia, and Lactobacillus brevis, and fungi Aspergillus niger and Gibberella fujikuroi were used. The stability of the cyclopropane ring on acidic conditions was tested using the cyclopropanecarboxylic acid and a commercial mixture of bacteria fatty acid methyl esters (BAME). Fisher's least significant difference test showed significant differences among the methods. The method using chlorotrimethylsilane and 1-pentanol for 1 h at 80°C gave the best results in cyclopropane, hydroxyl, and total fatty acid recoveries. This procedure allows the fast and easy one-step direct extraction derivatization.
- Eras, Jordi,Oro, Robert,Torres, Merce,Canela, Ramon
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- Method for preparing cyclopropylamine intermediate cyclopropanecarboxylate from methyl ether
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The invention discloses a method for preparing cyclopropylamine intermediate cyclopropanecarboxylate from methyl ether, and belongs to the technical field of synthesis of medical intermediates, wherein the method comprises the steps: by taking butyrolactone, dimethyl ether and concentrated sulfuric acid as initial raw materials, carrying out ring-opening reaction on butyrolactone under the action of dimethyl ether to generate methyl 4-methoxybutyrate; and carrying out cyclization reaction on the generated methyl 4-methoxybutyrate under the catalytic action of sodium methoxide to generate methyl cyclopropanecarboxylate and methanol. The method has the advantages that the production process is simple, the raw materials are cheap and easy to obtain, the atom utilization rate is high, the raw material and power cost is greatly reduced in the technological preparation process, and the reaction conditions are mild; and the reaction byproduct is methanol, treatment and recovery are convenient, the reaction yield can reach 75.54%-98.18%, and the production cost of the cyclopropylamine intermediate methyl cyclopropanecarboxylate is greatly reduced.
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Paragraph 0020-0060
(2021/07/31)
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- Preparation method of cyclopropylamine intermediate cyclopropanecarboxylic acid methyl ester
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The invention relates to a preparation method of a cyclopropylamine intermediate methyl cyclopropanecarboxylate, and solves the technical problems that an existing preparation method is unreasonable, high in requirements on reaction equipment, complicated to operate, low in yield and unsuitable for industrial production. With methyl acetate and 1,2-dihaloethane as raw materials, and under the action of potassium carbonate and a phase transfer catalyst, alkylation reaction is carried out to obtain methyl cyclopropanecarboxylate. The method can be widely applied to the technical field of synthesis of medical intermediates.
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Paragraph 0020-0048
(2021/05/15)
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- mCPBA-mediated dioxygenation of unactivated alkenes for the synthesis of 5-imino-2-tetrahydrofuranyl methanol derivatives
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A mCPBA-mediated, metal-free, intramolecular dioxygenation reaction of unactivated alkenes is reported. In the presence of m-chlorobenzoic peracid, different unsaturated amide substrates could be cyclized via epoxide intermediates, producing the corresponding 5-imino-2-tetrahydrofuranyl methanol products in up to 94% yield at room temperature.
- Deng, Xiaojun,Zhang, Luwen,Liu, Huixia,Bai, Yu,He, Wei
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supporting information
(2020/11/24)
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- Preparation method of methyl cyclopropanecarboxylate
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The invention relates to a preparation method of methyl cyclopropanecarboxylate. The technical problems that an existing preparation method is unreasonable, by-products are unsalable, the requirementfor air tightness of a production device is high, and the existing preparation method is not suitable for industrial production are solved. According to the method, gamma-butyrolactone is used as a starting raw material, dimethyl sulfate and gamma-butyrolactone are subjected to transesterification ring opening under the action of a catalyst potassium carbonate, and cyclization is performed under the strong alkaline condition to generate methyl cyclopropanecarboxylate. The method can be widely applied to the technical field of medical intermediate synthesis.
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Paragraph 0022-0060
(2020/08/22)
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- Method for preparing cyclopropylamine midbody cyclopropanecarboxylic acid methyl ester
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The invention discloses a method for preparing cyclopropylamine midbody cyclopropanecarboxylic acid methyl ester. First in a sealed reaction kettle, methanol is added dropwise into calcium carbide, togenerate calcium methoxide and acetylene; gamma-chloro methyl butyrate is added into calcium methoxide at 60-120 DEG C, the temperature is controlled to be constant in the reaction process, methanolgenerated in the process is collected, and the cyclopropanecarboxylic acid methyl ester is obtained through distillation. The method is simple in process, types of raw materials necessary for production are fewer, some of the raw materials can be reused, the yield is high, the quality is good, and the method is safe and environmentally friendly.
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Paragraph 0005; 0019-0032
(2018/03/26)
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- Practical synthesis of a heterocyclic immunosuppressive vitamin D analogue
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1α,25-Dlhydroxyvitamin D3 (calcitrioi) 1 and synthetic analogues thereof are highly potent compounds with a wide range of pharmacological activity making them of great interest for the pharmaceutical industry. Herein we report an improved synthesis of the calcitriol analogue 2, which features a novel oxazole-containing side chain. The crucial part of the synthesis was the development of a practical route to the β-keto phosphonate 28, allowing an easy introduction of the unnatural side chain by a Wittig Horner reaction.
- Westermann, Juergen,Schneider, Matthias,Platzek, Johannes,Petrov, Orlin
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p. 200 - 205
(2012/12/26)
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- Carbocation-forming reactions in ionic liquids
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A number of trifluoroacetates, mesylates, and triflates have been studied in ionic liquids. Several lines of evidence indicate that all of these substrates react via ionization to give carbocationic intermediates. For example, cumyl trifluoroacetates give mainly the elimination products, but the Hammett ρ+ value of -3.74 is consistent with a carbocationic process. The analogous exo-2-phenyl-endo-3-deutero-endo-bicyclo-[2.2.1]hept-2-yl trifluoroacetate gives an elimination where loss of the exo-hydrogen occurs from a cationic intermediate. 1-Adamantyl mesylate and 2-adamantyl triflate react to give simple substitution products derived from capture of 1- and 2-adamantyl carbocations by the residual water in the ionic liquid. The triflate derivative of pivaloin, trans-2-phenylcyclopropylcarbinyl mesylate, 2,2-dimethoxycyclobutyl triflate, the mesylate derivative of diethyl (phenylhydroxymethyl)-thiophosphonate, and Z-1-phenyl-5-trimethylsilyl-3-penten- 1-yl trifluoroacetate all give products derived carbocation rearrangements (kΔ processes), anti-7-Norbornenyl mesylate gives products with complete retention of configuration, indicative of involvement of the delocalized 7-norbornenyl cation. 1,6-Methano[10]annulen-11-yl triflate reacts in [BMIM][NTf2] to give 1,6-methano[10]annulen-11-ol, along with naphthalene, an oxidized product derived from loss of trifluoromethanesulfinate ion. Analogous loss of CF3SO2- can be seen in reaction of PhCH(CF3)OTf. Ionic liquids are therefore viable solvents for formation of carbocationic intermediates via kc and k Δ processes.
- Creary, Xavier,Willis, Elizabeth D.,Gagnon, Madeleine
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p. 18114 - 18120
(2007/10/03)
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- Processes for the preparation of cyclopropanecarboxylic acid and derivatives thereof
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Disclosed is a process for the preparation of cyclopropanecarboxylic acid by the non-catalytic, oxidation of cyclopropanecarboxaldehyde using molecular oxygen as the oxidant. Also disclosed are processes for the preparation of amides, esters and acid chlorides from cyclopropanecarboxylic acid.
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- The Mechanism of RuO4-Mediated Oxidations of Ethers: Isotope Effects, Solvent Effects and Substituent Effects
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The mechanism of the RuO4-mediated oxidation of ethers to esters has been investigated.Oxidation of cyclopropylmethyl methyl ether gave methyl cyclopropanecarboxylate.No rearranged products were observed.On RuO4 oxidation of benzyl methyl ether and p-methoxybenzyl methyl ether in CCl4 with NaIO4 as stoichiometric oxidant, no chlorinated products were observed.A series of 4-substituted benzyl methyl ethers was oxidized with RuO4-NaIO4.A correlation of the rate of the reaction with Hammett ?-values gave a ρ of -1.7, indicating only a moderate charge separation in the transition state (TS).Benzyl methyl ether (1) was oxidized in a series of acetone-water mixtures.From these experiments, a Grunwald-Winstein m-value of 0.11 was obtained, indicating a non-polar TS for the reaction.PhCHDOCH3 (2) and PhCD2OCH3 (3) were oxidized and two deuterium isotipe effects, one of 6.1+/-0.4 and another of 1.3+/-0.1 were obtained.If one assumes a one-step reaction mechanism, the value of 1.3 would be a large α-secondary isotope effect, indicating a change in the hybridization of the benzylic carbon during the reaction. α-Methylbenzyl methyl ether (4) was oxidized at a seventh of the rate of 1, despite the fact that 4 would have given a more stable carbocation than 1.These conflicting pieces of evidence are difficult to rationalise with a hydride or hydrogen abstraction mechanism.Instead it is proposed that the reaction proceeds by either a concerted reaction or by a reversible oxidative addition of the ether to RuO4 followed by a slow concerted step to give the product.
- Bakke, Jan M.,Froehaug, Astrid E.
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p. 615 - 622
(2007/10/02)
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- Photolysis of 2-Alkoxy-Δ3-1,3,4-oxadiazolines. A New Route to Diazoalkanes
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2-Alkoxy-2,5,5-trialkyl-Δ3-1,3,4-oxadiazolines (2), when photolyzed in solution with 300-nm light, afford the appropriate diazoalkane (3) and ester (4) in high yield.The diazoalkanes undergo intermolecular reaction, giving rise to azines (5), or they can be trapped in situ with 1,3-dipolarophiles to afford cycloadducts (7 or 11), which can in turn be photolyzed to the corresponding cyclopropenes (8) and cyclopropanes (12), respectively.
- Majchrzak, Michael W.,Bekhazi, Michel,Tse-Sheepy, Irene,Warkentin, John
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p. 1842 - 1845
(2007/10/02)
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- ALKYLATION REACTIONS OF PROPARGYL ALCOHOL; IMPROVED ROUTES TO PROSTAGLANDIN α-SIDE CHAIN PRECURSORS
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Alkylation reactions of the dilithio derivative of propargyl alcohol and the lithio derivative of tetrahydropyranyl protected propargyl alcohol have been explored in order to develop improved synthetic routes to the key prostaglandin α-side chain precursor methyl 7-hydroxyhept-5-ynoate (5).The use of methyl 4-bromobutanoate or the lithium salt of 4-bromobutanoic acid in these reactions did not produce the required products whereas alkylation using trimethyl ortho-4-bromobutanoate (15) gave methyl 7-hydroxyhept-5-ynoate (5) or the corresponding THP ether (4) in good yield after orthoester hydrolysis.Procedures are also described for the transformation of alcohol (5) and THP (4) into methyl 7-bromohept-5-ynoate (1).Alcohol (5) can also be converted into methyl (Z)-7-bromohept-5-enoate (2) using literature procedures.
- Casy, Guy,Furber, Mark,Richardson, Kevan A.,Stephenson, Richard G.,Taylor, Richard J.K.
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p. 5849 - 5856
(2007/10/02)
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- Process for the manufacture of cyclopropylamine
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A modified novel process for preparing cyclopropylamine from γ-butyrolactone is described. The γ-butyrolactone ring is cleaved with a hydrohalide in the presence of a novel catalyst comprising an aqueous sulfuric acid solution. The 4-chlorobutyric acid, thus formed is converted into a hindered chlorobutyrate ester. The hindered ester based on secondary and tertiary alkanols of eight or less carbon atoms, is cyclized to form the hindered cyclopropanecarboxylate ester by a novel reaction medium consisting of solid caustic in a water-immiscible solvent and a phase transfer catalyst. The hindered cyclopropanecarboxylate ester is ammoniated to form cyclopropanecarboxamide by a novel catalyst comprising an alkali metal salt of a polyol having hydroxy groups on adjacent carbons. The carboxamide formed in substantially quantitative yields is converted to cyclopropylamine by a modified Hofmann reaction utilizing continuous degradation of the intermediate with simultaneous distillation.
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- Process for cyclizing upsilon-chlorocarboxylic acids
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γ-chlorocarboxylic acid methyl or ethyl esters are cyclized to the corresponding cyclopropane carboxylic acid esters by employing the sodium or potassium alcoholate of methanol or ethanol in the presence of the same alcohol at a temperature above the boiling point of the alcohol employed.
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- Scope, Limitation, and Mechanism of the Homoconjugate Electrophilic Addition of Hydrogen Halides
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Hydrogen halides (HCl, HBr, HI) add by a homoconjugate 1,5 mechanism to cyclopropanes carrying certain electron-withdrawing substituents.When the substituent is COCH3, COC6H5, CO2H, or CN, the reaction gives the 1,3-disubstituted propane in high yield.Addition of DCl gives a product with deuterium only in the position α to the substituent.The order of rates is not in agreement with a mechanism whereby the cyclopropane ring is protonated initially, since the rate of such a process should be slowed by electron-withdrawing groups.The ketones, however, react much more rapidly than benzylcyclopropane, a model for the direct protonation mechanism.The homoconjugate mechanism involves rapid protonation of the side chain, followed by nucleophilic attack on the cyclopropane ring.The reaction is limited to substrates that can be protonated on the side chain to produce an intermediate with charge ajacent to the cyclopropane ring.This charge must be able to be transmitted by resonance to the unsubstituted ring positions in order to facilitate the nucleophilic step.
- Lambert, Joseph B.,Napoli, James J.,Johnson, Katharine Kappauf,Taba, Kalulu N.,Packard, Beverly Sue
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p. 1291 - 1295
(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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