- A CaMnAl-hydrotalcite solid basic catalyst toward the aldol condensation reaction with a comparable level to liquid alkali catalysts
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In a number of heterogeneous catalysis processes, the promotion effect toward active sites is of vital importance and remains a challenge to obtain largely-improved catalytic performance. Herein, rehydrated Ca4MnxAl-layered double hydroxides (denoted as re-Ca4MnxAl-LDH) were prepared based on a structure memory effect of LDH precursors, which exhibited extremely high heterogeneous catalytic performance for the aldol condensation reaction, with the assistance of the promotion effect of Mn. A combination study including XRD, EXAFS, XPS, CDCl3-FTIR and DFT calculations confirms that re-Ca4MnxAl-LDH samples with Ca-O-MnIV structure show a highly-exposed Ca2+ s-orbital and strengthened coordination between Ca2+ with 7-fold OH-, providing a weakened Br?nsted basic site compared with the reference sample re-Ca4Al-LDH. The optimized re-Ca4Mn0.5Al-LDH catalyst exhibits prominent catalytic performance toward the condensation of isobutyraldehyde (IBD) and formaldehyde (FA) to produce hydroxypivaldehyde (HPA), with a HPA yield of 70.3%. This is significantly higher than re-Ca4Al-LDHs (63.3%) and even comparable to the level of liquid alkali catalysts (73.2%). Studies on the structure-property correlation reveal that the weakened basic site originating from Ca-O-MnIV serves as a promoted active center, which accelerates the product desorption and thus largely improves HPA selectivity. This promoted re-Ca4Mn0.5Al-LDH catalyst can be potentially applied as a promising candidate in heterogeneous aldol condensation reactions.
- Zheng, Lirong,Bing, Weihan,Wang, Huimin,Zheng, Lei,Rao, Deming,Yang, Yusen,Wang, Bin,Wang, Yangdong,Wei, Min
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Read Online
- Asymmetric synthesis of (R)-3,3-dimethyl-2-hydroxy-γ-butyrolactone en route to the formal synthesis of calcium D-pantothenate
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An efficient asymmetric protocol for the synthesis of (R)-3,3-dimethyl-2- hydroxy-γ-butyrolactone, a crucial intermediate for the synthesis of calcium D-pantothenate and several other compounds is described, where the requisite chirality is incorporated by Sharpless asymmetric epoxidation reaction.
- Rama Rao,Mahender Rao,Sharma
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Read Online
- Poly(ethylene glycol) with Multiple Aldehyde Functionalities Opens up a Rich and Versatile Post-Polymerization Chemistry
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Two novel epoxide monomers 3,3-dimethoxy-propanyl glycidyl ether (DMPGE) and 3,3-dimethoxy-2,2-dimethylpropanyl glycidyl ether (DDPGE) were developed for the introduction of multiple aldehyde functionalities into the poly(ethylene glycol) (PEG) backbone. The acetal protecting group for the aldehyde functionality is stable against the harsh, basic conditions of the anionic ring-opening polymerization. Both monomers could be homopolymerized as well as copolymerized randomly with ethylene oxide (EO) in a controlled fashion. Copolymers with molecular weights (Mn) in the range of 4500-20100 g/mol and low dispersity (Mw/Mn) between 1.06 and 1.14 were obtained. The polymers were characterized by size exclusion chromatography, 1H NMR spectroscopy, and by differential scanning calorimetry regarding their thermal properties. The controlled character of the copolymerization was verified by MALDI-TOF. To study the distribution of the acetal-protected aldehyde functionalities at the polyether chains, the copolymerization with EO was monitored by in situ 1H NMR kinetics experiments for both monomers. These measurements revealed almost ideally random distribution of the comonomers with reactivity ratio pairs rEO = 0.96, rDMPGE = 1.04 and rEO = 1.20, rDDPGE = 0.83. The acetal functionalities of DMPGE polymers were successfully addressed by hydrazone formation. In addition, DDPGE copolymers were successfully deprotected in acidic media, and various transformations yielded aldehyde-, ester-, and nitrile-functionalized PEG while maintaining a dispersity below 1.1. Consequently, these monomers represent promising building blocks for the synthesis of multifunctional PEG for a variety of biomedical purposes.
- Blankenburg, Jan,Maciol, Kamil,Hahn, Christoph,Frey, Holger
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Read Online
- Calcium pantothenate. Part 2. Optimisation of oxynitrilase-catalysed asymmetric hydrocyanation of 3-hydroxy-2,2-dimethylaldehyde: Synthesis of (R)-pantolactone
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The synthesis of (R)-pantolactone via oxynitrilase-catalysed asymmetric hydrocyanation of 3-hydroxy-2,2-dimethylaldehyde has been investigated. (R)-Oxynitrilases from almonds as well as from apple and plum kernels were employed as catalysts in the form of defatted meal. A number of factors influencing the hydrocyanation process have been studied and the conditions optimised using statistical methods. (R)-Pantolactone with 74% yield and 30% ee has been synthesised.
- Synoradzki, Ludwik,Rowicki, Tomasz,Wlostowski, Marek
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Read Online
- Preparation method of hydroxypivalaldehyde and application of hydroxypivalaldehyde in preparation of neopentyl glycol
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The invention provides a preparation method of 2,2-dimethyl-3-hydroxypropanal and application thereof in preparation of neopentyl glycol. The 2,2-dimethyl-3-hydroxypropanal is prepared from an epoxy compound by a hydroformylation method. The method has the advantages of good atom economy, low raw material cost, no wastewater generation, and high yield. The invention also provides the application of the 2,2-dimethyl-3-hydroxypropanal in preparation of the neopentyl glycol. The application method circumvents the disadvantages of the conventional methods in the prior art, the reaction system is simple, and the industrial application prospect is excellent.
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Paragraph 0039-0041; 0044-0046; 0049-0051
(2021/02/09)
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- Preparation method of DL-pantoic acid lactone
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The invention discloses a preparation method of DL-pantoic acid lactone, which comprises the following steps: reacting formaldehyde with isobutyraldehyde in the presence of a basic catalyst, slowly dropwise adding the reaction solution into sodium cyanide, adding an acid solution after the reaction is finished, and carrying out esterification reaction to obtain the DLpantoic acid lactone. The reaction is carried out in a water system, high-temperature and high-pressure reaction conditions are not needed, the process safety performance is high, the energy-saving and consumption-reducing effectsare obvious, and a high-content target product is obtained at a high yield, so that the production cost is reduced, and the method is a safe and simple DL-pantoic acid lactone production method.
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Paragraph 0042-0045; 0048-0051; 0054-0057
(2021/02/06)
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- Method for improving selectivity of aldol condensation reaction
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The invention provides a method for improving selectivity of aldol condensation reaction. The method comprises the following steps: introducing C1-C5 aldehyde participating in the reaction and an aqueous solution of an alkaline compound into a coiled tube type reactor in a parallel flow manner, forming a continuous phase under a turbulence condition by the aqueous solution of the alkaline compound, and dispersing the C1-C5 aldehyde in the continuous phase in a droplet form. The C1-C5 aldehyde is selected from one or two of formaldehyde, acetaldehyde, propionaldehyde, n-butyraldehyde, isobutyraldehyde, n-valeraldehyde and isovaleraldehyde; the alkaline compound is selected from at least one of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate,ammonia water, trimethylamine, triethylamine and diisopropylamine. The invention also provides preparation of 1, 3-butanediol by condensation of acetaldehyde and an inorganic alkali compound and preparation of hydroxypivalaldehyde by condensation of formaldehyde, isobutyraldehyde and a trimethylamine aqueous solution. With application of the coiled tube type reactor, the reaction temperature, thematerial ratio and the retention time can be accurately controlled, side reactions are effectively reduced, and the reaction efficiency, the reaction stability and the product selectivity are improvedby adopting the reaction process.
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Paragraph 0028-0030; 0037-0040
(2020/09/16)
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- Preparation method of hydroxyaldehyde and method for resolving optical isomer by using electrodialysis technology
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The present invention provides a process for preparing hydroxyaldehydes using an immobilized catalyst, wherein the immobilized catalyst comprises a solid support and a tertiary amine-based functionalgroup. The invention also provides a method for preparing a polyhydroxy alcohol compound and a polyhydroxy acid compound. The invention further provides a method for splitting the optical isomer fromthe raceme through electrodialysis.
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Paragraph 0232-0250
(2020/12/15)
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- METHOD FOR PRODUCING HYDROXYPIVALALDEHYDE
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There is provided a method for producing hydroxypivalaldehyde (HPA), including steps (i) to (iii) below in this order, Step (i): a reaction step of reacting IBAL with FA to produce a reaction solution containing HPA, step (ii): an extraction step of extracting the reaction solution with an aldehyde solvent represented by formula (1) under basicity to obtain an extract containing HPA, and step (iii): a distillation and collection step of distilling the extract and then collecting HPA from the residue, wherein R represents a saturated alkyl group having 3 or more and 7 or less carbon atoms, further wherein the distillation step of the step (iii) is a step of distilling an extract in the presence of water, and an amount of the water which is subjected to the distillation is 100 parts by mass or more and 2,000 parts by mass or less, with respect to a total amount, 100 parts by mass, of isobutyraldehyde (IBAL) derived from a raw material and an aldehyde solvent represented by formula (1) in an extract which is subjected to the distillation. The method enables HPA to be mass-produced and the collecting ratio of HPA to be improved while selectively removing impurities other than water contained in HPA, specifically IBAL and the like. According to the method for producing HPA as mentioned above, it is possible to reduce the content of neopentyl glycol-isobutyrate, isobutylaldehyde-hydroxypivalaldehyde-acetal, and isobutylaldehyde-hydroxypivalaldehyde-aldol as specific impurities byproduced from HPA.
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Paragraph 0155; 0188
(2019/02/05)
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- METHOD FOR PRODUCING DIOL HAVING CYCLIC ACETAL SKELETON
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The present invention provides a method for producing a diol having a cyclic acetal skeleton, in which the method include an acetalization reaction step of obtaining a diol having a cyclic acetal skeleton by subjecting raw material hydroxypivalaldehyde and at least pentaerythritol and/or trimethylolpropane to an acetalization reaction under an acid catalyst and the raw material hydroxypivalaldehyde can contain a prescribed amount of at least one impurity selected from the group consisting of formaldehyde, neopentyl glycol, an ester compound having a neopentyl glycol skeleton represented by formula (III), and isobutyraldehyde.
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Paragraph 0154; 0155; 0156
(2019/02/28)
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- A D - (-) - pantoic acid lactone synthesis method
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The invention discloses a vitamin B5 synthesis of key intermediate D - (-) - pantoic acid lactone synthetic method, using (R)- (+) - α - phenethylamine hydrochloride or sulfate as a chiral reagent with a racemic pantoic acid alkali metal salt reaction, filtering to remove the inorganic salt, the mother liquor is concentrated to get pantoic acid - (R)- phenethylamine diastereomers salt, by the re-crystallization or beating of the diastereoisomer of the double salt method to carry out the purification, filtering to obtain (D)- pantoic acid - (R)- phenethylamine salt, and (L)- pantoic acid - (R)- phenethylamine salt is dissolved in the solvent, (D)- pantoic acid - (R)- phenethylamine salt and then subjected to a decomposition, acidified cyclization to obtain D - (-) - pantoic acid lactone.
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Paragraph 0029
(2019/03/24)
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- Development of 5-Aminopyrazole-4-carboxamide-based Bumped-Kinase Inhibitors for Cryptosporidiosis Therapy
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Cryptosporidium is a leading cause of pediatric diarrhea worldwide. Currently, there is neither a vaccine nor a consistently effective drug available for this disease. Selective 5-aminopyrazole-4-carboxamide-based bumped-kinase inhibitors (BKIs) are effective in both in vitro and in vivo models of Cryptosporidium parvum. Potential cardiotoxicity in some BKIs led to the continued exploration of the 5-aminopyrazole-4-carboxamide scaffold to find safe and effective drug candidates for Cryptosporidium. A series of newly designed BKIs were tested for efficacy against C. parvum using in vitro and in vivo (mouse infection model) assays and safety issues. Compound 6 (BKI 1708) was found to be efficacious at 8 mg/kg dosed once daily (QD) for 5 days with no observable signs of toxicity up to 200 mg/kg dosed QD for 7 days. Compound 15 (BKI 1770) was found to be efficacious at 30 mg/kg dosed twice daily (BID) for 5 days with no observable signs of toxicity up to 300 mg/kg dosed QD for 7 days. Compounds 6 and 15 are promising preclinical leads for cryptosporidiosis therapy with acceptable safety parameters and efficacy in the mouse model of cryptosporidiosis.
- Huang, Wenlin,Hulverson, Matthew A.,Choi, Ryan,Arnold, Samuel L. M.,Zhang, Zhongsheng,Mccloskey, Molly C.,Whitman, Grant R.,Hackman, Robert C.,Rivas, Kasey L.,Barrett, Lynn K.,Ojo, Kayode K.,Van Voorhis, Wesley C.,Fan, Erkang
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supporting information
p. 3135 - 3146
(2019/03/26)
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- Method for continuously synthesizing neopentyl glycol monoester hydropivalicate by gas phase method
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The invention belongs to the field of organic chemistry, and particularly relates to a method for continuously synthesizing neopentyl glycol monoester hydropivalicate by a gas phase method. The methodcomprises the following specific steps: fixing a supported catalyst A on a filler layer of a reaction rectifying tower A, putting formaldehyde and isobutyraldehyde into the reaction rectifying towerA, carrying out heating, and carrying out reacting under catalysis of a catalyst A to generate hydroxyl pivalaldehyde; sending the hydroxyl pivalaldehyde generated in the rectifying tower A to a reaction rectifying tower B from a tower kettle to carry out a reaction to generate a neopentyl glycol monoester hydropivalicate crude product, wherein a supported catalyst B is fixed in the reaction rectifying tower B; and feeding the neopentyl glycol monoester hydropivalicate crude product generated in the rectifying tower B into the rectifying tower C from the tower bottom, carrying out rectification and purification, and extracting the neopentyl glycol monoester hydropivalicate from the tower top. The method improves the yield of the neopentyl glycol monoester hydropivalicate, reduces cost andis worthy of industrial promotion.
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Paragraph 0016-0018
(2019/11/28)
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- Synthetic method of D,L-pantolactone
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The invention belongs to the field of chemical technology, and more specifically relates to a synthetic method of D,L-pantolactone. The synthetic method of D,L-pantolactone comprises following steps:paraformaldehyde and isobutyraldehyde are subjected to aldol condensation reaction under the effect of an alcohol solvent and an alkaline catalyst, and an obtained reaction solution is directly used in a next step treatment without separation; hydrocyanic acid is added, reaction is carried out to generate 2, 4-dihydroxyl-3, 3-dimethylbutyronitrile; 2, 4-dihydroxyl-3, 3-dimethylbutyronitrile is subjected to esterification reaction under acidic conditions to obtain 2, 4-dihydroxyl-3, 3-dimethyl butyrate; an alkali is added for neutralizing of excess acid, and solid liquid separation is carried out to obtain a side product ammonium salt; liquid evaporation is carried out for alcohol recycling, and rectification is carried out to obtain D,L-pantolactone product. The synthetic method of D,L-pantolactone is capable of preparing a target product high in content and yield, reducing acid and alkali using amount, avoiding using of organic solvents in production extraction, reducing generated waste water greatly, saving energy, protecting the environment, and reducing cost.
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Paragraph 0056-0058
(2019/12/09)
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- Enhancing the photo-efficacy of an organic visible-light-activated chromophore (alizarin red S) on zinc oxide with a Ag-Na electrolyte to photo-transform aromatic and aliphatic alcohols
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The development of an aqueous silver-sodium/alizarin red sensitised zinc oxide system has been reported to oxidise a range of both aromatic and aliphatic alcohols to aldehydes. Furthermore, photoluminescence spectroscopy validated the electron quenching effect of zinc oxide's defect sites after surface sensitising the metal-oxide with alizarin red. Powder diffuse reflectance UV/Vis data further substantiated the visible-light attenuated properties of alizarin red sensitised zinc oxide, and hence justification for its visible light reactivity towards alcohol oxidations. Lastly, density functional theory calculations supported the intermolecular photo-electronic transfer between alizarin red organic and zinc oxide.
- Underwood, Timothy M.,Robinson, Ross S.
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p. 24259 - 24266
(2019/08/15)
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- Method for performing aldol condensation reaction in micro-channel reactor
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The invention relates to a method for performing an aldol condensation reaction in a micro-channel reactor. The aldol condensation reaction is performed in the micro-channel reactor under the action of a catalyst at 60 to 170 DEG C and 0 to 5 MPa in the situation that alpha-H aldehyde ketone and other aldoketones in molecules are in the molar ratio of 0.8-1.2:1. According to the aldol condensationreaction involved in a process provided by the invention, the reaction time is shortened by thousands of times; the raw material conversion rate and the product selectivity are improved by 15 percentat least. The process provided by the invention can realize instantaneous uniform mixing; the equivalence ratio of materials in a reaction process is reduced; the using amount of a catalyst in a reaction process is reduced; Cannizzaro side reactions and polymerization reactions are reduced. The process provided by the invention also reduces the use of some additional solvents so as to reduce theproduction cost; the process provided by the invention also improves the safety of a reaction process, so that the types of reactions are safer and more environment-friendly; meanwhile, the micro-channel reactor used by the process provided by the invention is small in occupied area and high in capacity, so that the production efficiency and the production capacity are greatly improved.
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Paragraph 0042; 0043; 0044; 0045; 0046; 0047; 0048-0053
(2018/07/15)
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- Preparation method of spiroglycol
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The invention relates to a chemical industry field and particularly relates to a preparation method of spiroglycol. The preparation method includes steps of compounding 2, 2-dimethyl-3-hydroxy-propionaldehyde; adding formaldehyde solution in a four-opening bottle; controlling temperature at 20 DEG C below; adding potassium carbonate in batches, dissolving the system transparently, and rising temperature to 45 DEG C; starting to drop isobutyraldehyde; after reaction, neutralizing and filtering, drying to obtain 2, 2- dimethyl-3-hydroxy-propionaldehyde; compounding volution ethylene glycol; adding 1, 2- dichloroethane in a four-opening flask with a mixer and a thermometer; then adding 2-methyl-2-hydroxymethyl propionaldehyde and pentaerythritol; when temperature is risen to 75 DEG C, completely dissolving the system and adding catalyst. The preparation method is simple in technical flow, safe in reaction and avoids the generation of a lot of waste water; besides, the reaction is carriedout in a homogeneous phase, the product purity and yield are improved, the production cost is reduced, and the production efficiency and product quality are improved.
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Paragraph 0013
(2018/07/30)
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- Method for preparing hydroxypivalic acid by catalytic oxidation of phosphotungstic acid
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The invention discloses a method for preparing hydroxypivalic acid by catalytic oxidation of phosphotungstic acid and belongs to the technical field of chemical industry.The method comprises: subjecting isobutyraldehyde and formaldehyde to aldol condensation under the catalytic action of triethylamine; in an existing production method of hydroxypivalic acid, the shortest oxidation time takes 9 hours; the process used herein takes only 4 hours to produce a product; in the existing production method of hydroxypivalic acid, highest product yield is about 75%, and the yield of the product of the invention is up to 80-85%.The defects that an original process produces many byproducts and the byproducts are difficult to separate are overcome, product purity is effectively improved, and the technical process is simplified; a catalyst used herein is reusable, the activity of the catalyst decreases at low speed, energy consumption of the oxidation process is low, and production cost is thus reduced.
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Paragraph 0041
(2016/12/01)
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- Preparation method of hydroxypivalic acid
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The invention provides a preparation method of hydroxypivalic acid. The preparation method comprises the following steps: (1) adding a sodium carbonate water solution into a sodium polystyrenesulfonate water solution, stirring, regulating the pH value, adding a barium chloride water solution, stirring, standing, taking out, filtering, washing, and drying to obtain barium carbonate microspheres; (2) adding the barium carbonate microspheres into absolute ethyl alcohol, carrying out ultrasonic dispersion, adding CTAB, continuing to carry out ultrasonic dispersion to obtain a barium carbonate microsphere solution, dropwise adding a hydrated silica solution, carrying out magnetic stirring, standing, carrying out centrifuging, washing, drying, and calcining so as to obtain a BaO/SiO2 core-shell microsphere catalyst; (3) adding a formaldehyde water solution and triethylamine into a four-mouth flask, heating in a water bath, dropwise adding isobutyraldehyde, and carrying out reduced pressure distillation on a reaction liquid, so as to obtain hydroxyl pivaldehyde; and (4) adding hydroxyl pivaldehyde and a sodium hydroxide solution into the four-mouth flask, carrying out heating reflux, adding water and a catalyst, heating while stirring, carrying out suction filtration on the reaction liquid, concentrating a filtrate, regulating the pH value, carrying out extraction, and standing until crystals are separated. The preparation method has the beneficial effects of relatively high benefit, relatively low cost and mild condition.
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Paragraph 0056
(2017/01/02)
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- Perovskites and metal nitrides as catalysts in the base-catalysed aldol addition of isobutyraldehyde to formaldehyde
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Hydroxypivaldehyde represents an important intermediate in the production of neopentyl glycol, which in turn is widely applied in the production of e.g. polyesters, plasticizers, synthetic resin paints and lubricants. It is industrially produced via aldol addition of isobutyraldehyde to formaldehyde catalysed by homogeneous bases. However, the major disadvantages include the difficult separation of the base from the product stream, the formation of salts upon neutralisation and side reactions as well as the catalyst's hazard potential due to corrosion, toxicity and inflammability. A set of perovskites and metal nitrides were investigated as solid catalysts for aldol reactions establishing structure-performance correlations. For perovskites, a correlation of the catalytic activity and the degree of distortion as well as the presence of other phases is found but the most promising catalyst, BaZrO3, shows deactivation in recycling experiments. Amongst the metal nitrides, AlN exhibits high activity and stability in batch recycling experiments. Transferring the system into a continuous fixed bed reactor reveals high stability over 150 h time on stream at 423 K. XRD and SEM/EDX confirm the formation of boehmite caused by the hydrolysis of AlN in an aqueous reaction medium. This transformation is associated with a significant increase in the basicity and acidity of the material, which is proposed to account for its high catalytic activity.
- Kleineberg, Henrike,Eisenacher, Matthias,Lange, Horst,Strutz, Heinz,Palkovits, Regina
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p. 6057 - 6065
(2016/08/05)
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- Npg condensation hydrogenation apparatus and process for producing
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The invention discloses a neopentyl glycol condensation hydrogenation production process which comprises the following steps of: 1) condensation, that is, performing a condensation reaction of isobutyraldehyde with a methanol aqueous solution of formaldehyde, delivering the mixed condensation products into a condensation circulation tower for separation, allowing hydroxypivalaldehyde to enter a hydrogenation reactor from the condensation circulation tower, allowing a gas-phase component to flow back to a raw material mixing zone for mixing, and to enter a condensation reactor; 2) hydrogenation, that is, performing a hydrogenation reaction of the hydroxypivalaldehyde with hydrogen, delivering the products into a gas-liquid separation tank, allowing a gas-phase component to flow back to the hydrogenation reactor, allowing the liquid-phase neopentyl glycol crude product to enter a saponification reactor; 3) refining, that is, performing a saponification reaction of the neopentyl glycol crude product, allowing the product to enter a low-boiling-point substance fractionating tower, allowing a liquid-phase component at the tower bottom to enter a flash tank, allowing a liquid-phase component at the flash tank bottom to enter a pH adjusting tank, adjusting the pH to 6.5-7, allowing the product to enter a falling film evaporator, allowing a gas-phase component at the top of the falling film evaporator to enter a drying tower, then to enter a rectifying tower for refining so as to obtain neopentyl glycol. The process of the invention is high in neopentyl glycol yield, and simple and effective in separation purification process.
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Paragraph 0056-0060
(2017/03/17)
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- Method for preparing Neophentylglycol
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The present invention relates to a method for preparing neophentylglycol(2,2,-dimethyl-1,3-dihydroxypropane). The present invention doesn′t use high-pressure hydrogen gas like an existing technology when hydrogenation reaction to prepare neophentylglycol, but uses a secondary alcohol generating hydrogen ions in reaction as a reaction solvent, thereby progressing the hydrogenation reaction effectively. The present invention suggests plans to solve problems of increase in risk caused by using high-pressure hydrogen gas and cost increasing factors to prepare and manage all related manufacturing devices for high pressure.
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Paragraph 0026-0032
(2017/06/19)
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- Preparation method of hydroxypivaldehyde
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The present invention relates to a method for manufacturing hydroxypivaldehyde using a paraformaldehyde aqueous solution of a specific concentration. Specifically, the present invention provides a method for manufacturing hydroxypivaldehyde, which can recycle paraformaldehyde and contribute to reduction of waste water by dissolving the paraformaldehyde in an aqueous solution of a specific concentration to use in an aldol reaction.(AA) Conversion rate, selectivity (%)(BB) Conversion rate / i-BAL(CC) Selectivity / HPA(DD) Reaction time (min)COPYRIGHT KIPO 2016
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Paragraph 0037-0041
(2016/10/10)
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- Method for the Production of Neopentyl Glycol
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A method for preparing neopentyl glycol by addition of isobutyraldehyde and formaldehyde in the presence of a tertiary alkylamine as catalyst to give hydroxypivalaldehyde with subsequent hydrogenation at a temperature of 80 to 140° C. and at a pressure of 2 to 18 MPa in the liquid phase, is characterized in that the hydrogenation is carried out in the presence of a copper chromite catalyst comprising the activators barium and manganese.
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Paragraph 0044; 0045; 0046
(2015/09/23)
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- Continuous Method for the Production of Neopentyl Glycol
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A continuous method for preparing neopentyl glycol by addition of isobutyraldehyde and formaldehyde in the presence of a tertiary alkylamine as catalyst to give hydroxypivalaldehyde with subsequent hydrogenation in the gas phase at a temperature of 125 to 180° C., is characterised in that the hydrogenation is carried out in the presence of a copper chromite catalyst comprising the activators barium and manganese and at a superatmospheric pressure of 30 to 120 kPa.
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Paragraph 0041-0062
(2015/09/22)
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- Process for producing polyols
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A process for producing polyols (such as neopentyl glycol) is disclosed which comprises reacting formaldehyde and another aldehyde in the presence of a trialkylamine catalyst and a base promoter to form an Aldol condensation reaction product. The base promoter improves removal of nitrogen containing salts prior to hydrogenation of the hydroxy aldehyde to produce the polyol. The improved process also reduces trialkylamine catalyst usage, improves trialkylamine catalyst recovery, and reduces nitrogen-containing salts prior to hydrogenation.
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Page/Page column 6
(2014/05/08)
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- PREPARATION OF HYDROXY ALDEHYDES
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An improved process for preparing hydroxy aldehydes, such as hydroxypivaldehyde, is provided. Specifically, the process employs an alkaline additive for separating by-product amine salts from a hydroxy aldehyde and other reaction products formed in the process of preparing a hydroxy aldehyde using an amine catalyst.
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Paragraph 0031
(2014/08/07)
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- The 2-cyano-2,2-dimethylethanimine-N-oxymethyl group for the 2′-hydroxyl protection of ribonucleosides in the solid-phase synthesis of RNA sequences
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The reaction of 2-cyano-2-methyl propanal with 2′-O- aminooxymethylribonucleosides leads to stable and yet reversible 2′-O-(2-cyano-2,2-dimethylethanimine-N-oxymethyl)ribonucleosides. Following N-protection of the nucleobases, 5′-dimethoxytritylation and 3′-phosphitylation, the resulting 2′-protected ribonucleoside phosphoramidite monomers are employed in the solid-phase synthesis of three chimeric RNA sequences, each differing in their ratios of purine/pyrimidine. When the activation of phosphoramidite monomers is performed in the presence of 5-benzylthio-1H-tetrazole, coupling efficiencies averaging 99 % are obtained within 180 s. Upon completion of the RNA-chain assemblies, removal of the nucleobase and phosphate protecting groups and release of the sequences from the solid support are carried out under standard basic conditions, whereas the cleavage of 2′-O-(2-cyano-2,2-dimethylethanimine-N-oxymethyl) protective groups is effected (without releasing RNA alkylating side-products) by treatment with tetra-n-butylammonium fluoride (0.5 m) in dry DMSO over a period of 24-48 h at 55 °C. Characterization of the fully deprotected RNA sequences by polyacrylamide gel electrophoresis (PAGE), enzymatic hydrolysis, and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry confirmed the identity and quality of these sequences. Thus, the use of 2′-O-aminooxymethylribonucleosides in the design of new 2′-hydroxyl protecting groups is a powerful approach to the development of a straightforward, efficient, and cost-effective method for the chemical synthesis of high-quality RNA sequences in the framework of RNA interference applications. Copyright
- Cie?lak, Jacek,Ausín, Cristina,Grajkowski, Andrzej,Beaucage, Serge L.
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p. 4623 - 4632
(2013/04/24)
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- PROCESS FOR PREPARING NEOPENTYL GLYCOL
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A process for distilling an aqueous NPG mixture comprising NPG, a tertiary amine, water and the adduct of tertiary amine and formic acid (amine formate), said distillation being performed in a distillation column, which comprises drawing off a gaseous stream in the upper region of the column and feeding it to two condensers connected in series, the first condenser being operated in such a way that a portion of the gaseous stream is condensed in the first condenser and the second condenser being operated in such a way that the uncondensed portion of the gaseous stream is essentially fully condensed in the second condenser, the condensed stream from the first condenser being recycled fully or partly as reflux into the column.
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Paragraph 0181; 0182; 0183; 0184; 0185; 0186
(2013/03/26)
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- Aldehydes containing hydroxl groups
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The present invention relates to aldehydes of the formula (I) which contain tertiary amino groups and at least one hydroxyl group. Aldehydes of this kind can be utilized broadly. Aldehydes of particular advantage can be incorporated into a polymer, and find use as curing agents and/or catalysts. Preferably they find use in adhesives and sealants.
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Page/Page column 19
(2013/03/26)
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- Thionium ion initiated medium-sized ring formation: The total synthesis of asteriscunolide D
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The first synthesis of the biologically active humulene natural product asteriscunolide D has been accomplished in nine steps without the use of protecting groups. The challenging 11-membered ring was forged via a diastereoselective thionium ion initiated cyclization, which constitutes a formal aldol disconnection to form a strained macrocycle. A stereospecific thioether activation-elimination protocol was developed for selective E-olefin formation, thus providing access to the most biologically active asteriscunolide. The absolute stereochemical configuration was established by the Zn-ProPhenol catalyzed enantioselective addition of methyl propiolate to an aliphatic aldehyde to afford a γ-hydroxy propiolate as a handle for butenolide formation via Ru-catalyzed alkene-alkyne coupling.
- Trost, Barry M.,Burns, Aaron C.,Bartlett, Mark J.,Tautz, Thomas,Weiss, Andrew H.
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supporting information; experimental part
p. 1474 - 1477
(2012/03/12)
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- METHOD FOR PREPARING POLYMETHYLOLS
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The present invention relates to a process for distilling an aqueous polymethylol mixture which comprises a polymethylol of the formula (I) [in-line-formulae](HOCH2)2—C—R2??(I)[/in-line-formulae] in which each R is independently a further methylol group or an alkyl group having 1 to 22 carbon atoms or an aryl or aralkyl group having 6 to 22 carbon atoms, a tertiary amine, water and the adduct of tertiary amine and formic acid (amine formate), which comprises performing the distillation in a distillation column which is connected at the bottom to an evaporator, the bottom temperature being above the evaporation temperature of the monoester of formic acid and polymethylol (polymethylol formate) which forms during distillation. The present invention further relates to a composition comprising polymethylol and 1 to 10 000 ppm by weight of polymethylol formate, and to the use thereof.
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Page/Page column 8
(2012/01/14)
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- Oxidative esterification of homologous 1,3-propanediols
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The oxidative esterification of a homologous series of diols (1,3-propanediol,2-methyl-propanediol and 2,2-dimethyl-1,3-propanediol) with methanol has been investigated using titania-supported gold, palladium and gold-palladium catalysts using molecular oxygen. The gold-palladium catalysts showed the highest activity and 1,3-propanediol was the most reactive while the additional methyl groups decreased the reactivity. However, it is possible to achieve high selectivity to methyl 3-hydroxypropionate and 2-methyl-3- hydroxyisobutyrate by mono-oxidations. Graphical Abstract: [Figure not available: see fulltext.]
- Kotionova, Tatyana,Lee, Christopher,Miedziak, Peter J.,Dummer, Nicholas F.,Willock, David J.,Carley, Albert F.,Morgan, David J.,Knight, David W.,Taylor, Stuart H.,Hutchings, Graham J.
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p. 1114 - 1120
(2012/10/29)
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- PROCESS FOR PREPARING NEOPENTYL GLYCOL
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The present invention relates to a process for preparing neopentyl glycol (NPG) by continuously hydrogenating hydroxypivalaldehyde (HPA) with hydrogen, in the liquid phase, in the presence of a hydrogenation catalyst, in a hydrogenation reactor (5), by combining an HPA-comprising stream (1) with an NPG-comprising stream (2) to give a hydrogenation feed (4) and introducing the hydrogenation feed (4) into the hydrogenation reactor (5) and additionally supplying at least one pH regulator (3) selected from the group consisting of tertiary amine, an inorganic base, an inorganic acid and an organic acid to the HPA-comprising stream (1) or the NPG-comprising stream (2) or the hydrogenation feed (4), in order to establish a pH of 7.0 to 9.0 at the outlet of the hydrogenation reactor, wherein the weight ratio of HPA to NPG in the hydrogenation feed (4) is in the range from 1:100 to 50:100 and the proportion of HPA and NPG in the hydrogenation feed (4) is at least 50% by weight, based on the hydrogenation feed, and, in the case that the pH regulator (3) is supplied to the HPA-comprising stream (1), the HPA-comprising stream (1) comprises less than 50% by weight of HPA or the residence time between the supply of the pH regulator (3) and the combining of the NPG-comprising stream (2) with the HPA-comprising stream (1) is less than 5 minutes or the temperature of the HPA-comprising stream (1) is less than 75° C.
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Page/Page column 6
(2011/11/30)
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- Synthesis and deprotection of 1,3-Dithianes and 1,3-Dithiolanes by polyphosphoric acid
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A simply, mild and efficient method for the deprotection of 1,3-dithianes and 1,3-dithiolanes to their corresponding carbonyl compounds using a mixture of polyphosphoric acid and acetic acid at 20-45 °C is reported.
- Jin, Yong-Sheng,Zhang, Wei,Zhang, Da-Zhi,Qiao, Li-Ming,Wu, Qiu-Ye,Chen, Hai-Sheng
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experimental part
p. 1117 - 1119
(2011/12/16)
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- METHOD FOR PRODUCING HYDROXY PIVALIN ALDEHYDE AND NEOPENTYL GLYCOL
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The preparation of hydroxypivalaldehyde is effected by aldolizing isobutyraldehyde with formaldehyde and subsequently working up the resulting reaction effluent by distillation, wherein the reaction effluent is fed to a distillation column which is operated at a top pressure in the range from 0.5 to 1.5 bar and in which a two-stage condensation is provided in the top region, in which the vapors are first conducted into a partial condenser operated at a temperature in the range from 50 to 80° C., whose condensate is recycled at least partly into the distillation column, and in which the vapors uncondensed in the partial condenser are fed to a downstream condenser operated at a temperature in the range from ?40 to +30° C., whose condensate is at least partly discharged.
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Page/Page column 2
(2010/05/13)
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- Macroporous hydrogels upregulate osteogenic signal expression and promote bone regeneration
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The objective of this work was to investigate the effects of macroporous hydrogel architecture on the osteogenic signal expression and differentiation of human mesenchymal stem cells (hMSCs). In particular, we have proposed a tissue engineering approach for orbital bone repair based on a cyclic acetal biomaterial formed from 5-ethyl-5-(hydroxymethyl)-β,β-dimethyl-1,3- dioxane-2-ethanol diacrylate (EHD) and poly(ethylene glycol) diacrylate (PEGDA). The EHD monomer and PEGDA polymer may be fabricated into macroporous EH-PEG hydrogels by radical polymerization and subsequent porogen leaching, a novel technique for hydrophilic gels. We hypothesized that EH-PEG hydrogel macroporosity facilitates intercellular signaling among hMSCs. To investigate this phenomenon, hMSCs were loaded into EH-PEG hydrogels with varying pore size and porosity. The viability of hMSCs, the expression of bone morphogenetic protein-2 (BMP-2), BMP receptor type 1A, and BMP receptor type 2 by hMSCs, and the differentiation of hMSCs were then assessed. Results demonstrate that macroporous EH-PEG hydrogels support hMSCs and that this macroporous environment promotes a dramatic increase in BMP-2 expression by hMSCs. This upregulation of BMP-2 expression is associated by a more rapid hMSC differentiation, as measured by alkaline phosphatase expression. Altering hMSC interactions with the EH-PEG hydrogel surface, by the addition of fibronectin, did not appear to augment BMP-2 expression. We therefore speculate that EH-PEG hydrogel macroporosity facilitates autocrine and paracrine signaling by localizing endogenously expressed factors within the hydrogel's pores and thus promotes hMSC osteoblastic differentiation and bone regeneration.
- Betz, Martha W.,Yeatts, Andrew B.,Richbourg, William J.,Caccamese, John F.,Coletti, Domenick P.,Falco, Erin E.,Fisher, John P.
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experimental part
p. 1160 - 1168
(2011/02/23)
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- PROCESS FOR HYDROGENATING METHYLOLALKANALS
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A process for catalytically hydrogenating methylolalkanals of the general formula in which R1 and R2 are each independently a further methylol group or an alkyl group having from 1 to 22 carbon atoms or an aryl or aralkyl group having from 6 to 33 carbon atoms, in the liquid phase over a hydrogenation catalyst, which comprises setting a pH of from 7.0 to 9.0 in the hydrogenation effluent by adding at least one tertiary amine, an inorganic base or an inorganic or organic acid to the hydrogenation feed.
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Page/Page column 3
(2009/04/24)
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- 3-Aminoxypropionate-based linker system for cyclization activation in prodrug design
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A novel linker system based on 3-aminoxypropionate was designed and evaluated for drug release using proteolysis as an activation trigger followed by intramolecular cyclization. The hydroxylamine moiety present in the linker system enabled faster release of the parent drug from the linker-drug conjugate at lower pH as compared to an aliphatic amine moiety. Introduction of two methyl groups strategically at the α position to the carboxylate in the linker further improved the rate of cyclization by nearly 2-fold. The 3-aminoxypropionate linker was successfully applied to a model prodrug for protease activation using α-chymotrypsin as the activating enzyme; the activation of the model prodrug bearing the 3-aminoxypropionate linker was 136 times faster than the corresponding model prodrug bearing an amine linker.
- Ge, Yiyu,Wu, Xinghua,Zhang, Dazhi,Hu, Longqin
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scheme or table
p. 941 - 944
(2009/08/15)
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- PROCESS FOR PRODUCTION OF FLAKE-LIKE DRIED 2-(5-ETHYL-5-HYDROXYMETHYL-1,3-DIOXAN-2-YL)-2-METHYLPROPAN-1-OL
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A method for producing flake-like dried DOG by making DOG containing from 10 to 50 % by mass of a liquid go through a continuous melt-drying step of a specified condition and then making it go through, as a next step, a vacuum-drying step of a specified condition or a ventilation-drying step of a specified condition while holding a molten state thereof, to obtain DOG in which the liquid in DOG is reduced to not more than 0.5 % by mass (dried DOG), and flaking the obtained dried DOG in a flake production step.
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Page/Page column 6
(2009/08/15)
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- Efficient biocatalytic synthesis of (R)-pantolactone
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Screening for stereoselective cyanohydrin synthesis in 96-well plates was employed in the development of an efficient, pH-stable hydroxynitrile lyase for the conversion of sterically hindered aliphatic aldehydes. Site-saturation mutagenesis (SSM) resulted in a powerful catalyst for the stereoselective conversion of hydroxypivalaldehyde and pivalaldehyde to their corresponding (R)-cyanohydrins (ee >97%) which are used as chiral building blocks (e.g., for pantothenic acid production). Furthermore, redesigning the PaHNL5 gene and improving its expression by Pichia pastoris with the help of a new P AOX1 promoter variant and the helper protein PDI (protein disulfide isomerase) led to elevated amounts of today's most efficient biocatalyst for vitamin B5 synthesis.
- Pscheidt, Beate,Liu, Zhibin,Gaisberger, Richard,Avi, Manuela,Skranc, Wolfgang,Gruber, Karl,Griengl, Herfried,Gliedera, Anton
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supporting information; experimental part
p. 1943 - 1948
(2009/08/10)
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- PROCESS FOR PREPARING POLYALCOHOLS FROM FORMALDEHYDE HAVING A LOW FORMIC ACID CONTENT
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The invention relates to a process for preparing polymethylol compounds of the formula (I) [in-line-formulae](HOCH2)2—C—R2 ??(I)[/in-line-formulae] where the radicals R are each, independently of one another, a further methylol group or an alkyl group having from 1 to 22 carbon atoms or an aryl or aralkyl group having from 6 to 22 carbon atoms, by condensation of aldehydes having from 2 to 24 carbon atoms with formaldehyde in an aldol reaction using tertiary amines as catalyst to form alkanals of the formula (II) where the radicals R each independently have one of the abovementioned meanings, and subsequent hydrogenation of the latter. The particular inventive feature of this process is that the aldol reaction is carried out using an aqueous formaldehyde solution having a formic acid content of 150 ppm and preferably 100 ppm. In this way of carrying out the process, the formation of by-products can advantageously be prevented in a targeted manner and the yield of the desired polymethylol compound can thereby be increased.
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Page/Page column 3-4
(2008/12/06)
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- PROCESS FOR THE PRODUCTION OF NEOPENTYLGLYCOL USING FORMALDEHYDE WITH A LOW METHANOL CONTENT
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A process is provided for the preparation of polymethylol compounds of formula (I): [in-line-formulae](HOCH2)2—C—(R)2 , ??(I)[/in-line-formulae] in which the radicals R independently of one another are each a further methylol group, an alkyl group having from 1 to 22 C atoms or an aryl or aralkyl group having from 6 to 22 C atoms, by (a) condensing aldehydes having from 2 to 24 C atoms with formaldehyde in an aldol reaction using tertiary amines as a catalyst to give alkanals of formula (II): in which the radicals R independently of one another are each as defined above, (b) then separating, by distillation, the reaction mixture obtained into a bottom product comprising predominantly the compounds of formula II and a low-boiling stream consisting of unconverted or partially converted starting materials, and (c) hydrogenating the distillation bottom, wherein the aldol reaction is carried out with an aqueous formaldehyde solution having a methanol content of 0.35 to 0.5% by weight of methanol, the low-boiling stream is separated off at a pressure of 1 to 3 bar and temperatures of 100 to 135° C. and completely or partially recycled into the aldol reaction. This procedure advantageously makes it possible specifically to prevent the formation of by-products and hence to increase the yield of the desired polymethylol compound. We have found that this object is achieved by a process for the preparation of polymethylol compounds of formula (I): [in-line-formulae](HOCH2)2—C—(R)2 , ??(I)[/in-line-formulae] in which the radicals R independently of one another are each a further methylol group, an alkyl group having from 1 to 22 C atoms or an aryl or aralkyl group having from 6 to 22 C atoms, by (a) condensing aldehydes having from 2 to 24 C atoms with formaldehyde in an aldol reaction using tertiary amines as a catalyst to give alkanals of formula (II): in which the radicals R independently of one another are each as defined above, (b) then separating, by distillation, the reaction mixture obtained (aldolization product) into a bottom product comprising predominantly the compounds of formula II and a low-boiling stream consisting of unconverted or partially converted starting materials, and (c) hydrogenating the distillation bottom, wherein the aldol reaction is carried out with an aqueous formaldehyde solution having a methanol content of 0.35 to 0.5% by weight, the separation of the low-boiling stream is effected at a pressure of 1.1 to 3 bar, preferably 1.5 bar, and a temperature of 100 to 135° C., preferably of 102 to 125° C., and the low-boiling stream is completely or partially recycled into the aldol reaction, preferably the entire low-boiling stream being recycled. In the aldol reaction, a partially converted starting compound of formula (III): can also be formed in which the radicals R independently of one another are each hydrogen or are as defined above. According to the invention, this partially converted starting compound of formula (III), together with the desired alkanal of formula (II), is separated from the other by-products and the unreacted starting compounds and reacted again in an aldol reaction with formaldehyde having a methanol content of 0.35% by weight to 0.5% by weight, using tertiary amines as a catalyst.
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Page/Page column 4
(2008/06/13)
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- Hydrogenation of methylolalkanals
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Process for the catalytic hydrogenation of methylolalkanals of the general formula where R1 and R2 are each, independently of one another, a further methylol group or an alkyl group having from 1 to 22 carbon atoms or an aryl or aralkyl group having from 6 to 33 carbon atoms, in the liquid phase by means of hydrogen over a hydrogenation catalyst, wherein hydrogen is used in a molar ratio to methylolalkanal of greater than 1.
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Page/Page column 3
(2008/06/13)
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- A convenient one-pot synthesis of 2,2-dialkyl-2,3-dihydro-1H-naphtho[2,1-b] pyrans
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This work describes a convenient one-pot procedure for the synthesis of 2,2-disubstituted 2,3-dihydro-177-naphtho[2,1-b]pyrans {i.e. 2,2-disubstituted 1H-benzo[f]chromans} by the reaction of 2-tetralones and α,α- disubstituted β-hydroxy propionaldehydes under acidic conditions. Georg Thieme Verlag Stuttgart.
- Jha, Amitabh,Huang, Po-Jung Jimmy,Mukherjee, Chandrani,Paul, Nawal K.
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p. 3127 - 3130
(2008/09/19)
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- Process of producing dioxane glycol
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A production method of 2-(5-ethyl-5-hydroxymethyl-1,3-dioxane-2-yl)-2-methylpropane-1-ol (DOG) which includes a step of acetalizing hydroxypivalaldehyde with trimethylolpropane in a solvent in the presence of an acid catalyst. After the acetalization, the reaction product liquid is neutralized and then heated to dissolve the deposited DOG crystals. Then, the reaction product liquid is cooled to recrystallize DOG. DOG produced in such manner has an adequately large particle size. Therefore, DOG is easy to handle and involves little danger of dust explosion.
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Page/Page column 4
(2008/06/13)
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- Process of producing dioxane glycol
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A process of producing 2-(5-ethyl-5-hydroxymethyl-1,3-dioxane-2-yl)-2-methylpropane-1-ol (DOG) by the acetalization of hydroxypivalaldehyde with trimethylolpropane in water in the presence of an acid catalyst and optional seed crystals. DOG crystals having an increased particle size and containing the trans isomer in a high content are produced by the process in which the reaction temperature, pH of the reaction system and concentration of DOG to be produced in the reaction system are controlled.
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Page/Page column 5
(2008/06/13)
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- Method of producing high-purity hydroxypivalaldehyde and/or dimer thereof
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The present invention provides a method of producing high-purity hydroxypivalaldehyde and/or dimer thereof, including: reacting isobutyl aldehyde with formaldehyde in a presence of a basic catalyst; distilling a low boiling point component including unreacted isobutyl aldehyde to obtain an aqueous solution; adding a diluent to the aqueous solution; cooling the aqueous solution to crystallize the hydroxypivalaldehyde and/or the dimer thereof; and subjecting the aqueous solution to a solid-liquid separation, followed by washing with an organic solvent and/or water, in which the diluent and a basic compound are added to the aqueous solution containing the hydroxypivalaldehyde and/or the dimer thereof obtained by distilling the low boiling point component off so that a concentration of the hydroxypivalaldehyde and/or the dimer becomes 5 to 23% by mass, the concentration of formaldehyde becomes 0.2 to 2.5% by mass, and a pH value becomes 5.0 or more, the solution is crystallized at a temperature of 20 to 45° C. and subjected to the solid-liquid separation. In this method, handling of a high-viscosity slurry and carrying out any complicated operation such as regeneration of an ion exchange resin are not required, so the high-purity HPA and/or the dimer thereof can be obtained in high yield with an energetically advantageous manner.
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Page/Page column 4; 6; 7
(2008/06/13)
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- Stabilized hydroxypivalaldehyde
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In the method of the invention, hydroxypivalaldehyde (3-hydroxy-2,2-dimethylpropanal) and/or its dimer is stored under solid conditions containing an amount of water. By storing such solid conditions, hydroxypivalaldehyde and/or its dimer is stored for a long period of time without reducing its purity.
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Page/Page column 5
(2008/06/13)
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- Discovery of potent, nonsystemic apical sodium-codependent bile acid transporter inhibitors (part 1)
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Elevated plasma levels of low-density lipoprotein (LDL) cholesterol are a major risk factor for atherosclerosis leading to coronary artery disease (CAD), which remains the main cause of mortality in Western society. We believe that by preventing the reabsorption of bile acids, a minimally absorbed apical sodium-codependent bile acid transporter (ASBT) inhibitor would lower the serum cholesterol without the potential systemic side effects of an absorbed drug. A series of novel benzothiepines (3R,3R′-2,3,4,5-tetrahydro-5-aryl-1- benzothiepin-4-ol 1,1-dioxides) were synthesized and tested for their ability to inhibit the apical sodium dependent bile acid transport (ASBT)-mediated uptake of [14C] taurocholate (TC) in H14 cells. A 3R,4R,5R/3S,4S,5S racemate was found to have greater potency than the other three possible racemates. Addition of electron-donating groups such as a dimethylamino substituent at the 7 position greatly enhanced potency, and incorporation of a long-chain quaternary ammonium substituent on the 5-phenyl ring was useful in minimizing systemic exposure of this locally active ASBT inhibitor while also increasing water solubility and maintaining potency. The reported results describe the synthesis and SAR development of this benzothiepine class of ASBT inhibitors resulting in an 6000-fold improvement in ASBT inhibition with desired minimal systemic exposure of this locally acting drug candidate.
- Tremont, Samuel J.,Lee, Len F.,Huang, Horng-Chih,Keller, Bradley T.,Banerjee, Shyamal C.,Both, Scott R.,Carpenter, Andrew J.,Wang, Ching-Cheng,Garland, Danny J.,Huang, Wei,Jones, Claude,Koeller, Kevin J.,Kolodziej, Steve A.,Li, James,Manning, Robert E.,Mahoney, Matthew W.,Miller, Raymond E.,Mischke, Deborah A.,Rath, Nigam P.,Fletcher, Theresa,Reinhard, Emily J.,Tollefson, Michael B.,Vernier, William F.,Wagner, Grace M.,Rapp, Steve R.,Beaudry, Judy,Glenn, Kevin,Regina, Karen,Schuh, Joe R.,Smith, Mark E.,Trivedi, Jay S.,Reitz, David B.
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p. 5837 - 5852
(2007/10/03)
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- Process for the production of the spiroglycol 3,9-bis(1,1-dimethyl-2-hydroxyethyl)-2,4,8,10-tetraoxaspiro[5.5]undecane
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In the production of spiroglycol by the reaction of pentaerythritol and hydroxypivalaldehyde in water in the presence of an acid catalyst, (A) a total content of amines and amine salts in hydroxypivalaldehyde is reduced to 1.5% by weight or lower; (B) seed crystals are added to the reaction system before initiating the reaction and/or during the reaction in an amount from 1.5 to 30% by weight on the basis of the total feed amount of pentaerythritol, hydroxypivalaldehyde, water, the acid catalyst and the seed crystals, each being fed into the reaction system; (C) the pH of the reaction system is kept from 0.1 to 4.0 from initiation of the reaction to completion of the reaction; and (D) the sum of a maximum theoretical amount of spiroglycol to be synthesized from pentaerythritol and hydroxypivalaldehyde to be fed into the reaction system and an amount of spiroglycol contained in the seed crystals to be added to the reaction system is controlled within a range from 5 to 35% by weight on the basis of the total feed amount. The spiroglycol produced has an increased particle size. By washing the spiroglycol with a basic solution, the heat stability is improved.
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Page/Page column 5
(2008/06/13)
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