- Synthesis process of chloroacetic anhydride
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The invention discloses a synthesis process of chloroacetic anhydride, and relates to the technical field of medicine synthesis. The problems that the existing process can easily generate corrosion onthe equipment, and the high-temperature and high-vacuum conditions are needed are solved. The process comprises the following steps of chloroacetic anhydride solution preparation: dripping sodium chloroacetate and aprotic solvents into a reaction bottle; performing heating to 40 to 50 DEG C; performing stirring; slowly dripping chloroacetyl chloride; completing the dripping in 2 to 3 hours; continuously performing stirring for 1 to 2 hours under the condition of 40 to 50 DEG C; performing filtering; washing filter cake with aprotic solvents; performing filtering; merging filter liquid to obtain a chloroacetic anhydride solution; purifying the chloroacetic anhydride; adding the chloroacetic anhydride solution into a reactor; adding petroleum ether; performing cooling to 35 to 40 DEG C; continuously performing stilling until solid is separated out; lowering the temperature to 0 to 5 DEG C; performing heat insulation stirring for 1 to 2 hours; performing filtering; washing the filter cake with petroleum ether; drying the filter cake to obtain white crystal solid products which are chloroacetic anhydride. The process has the advantages that hydrogen chloride gas is not generated; theanti-corrosion requirement on the equipment is low; the reaction conditions are mild; the energy consumption is reduced.
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Paragraph 0018-0031
(2018/07/30)
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- Efficient and convenient synthesis of symmetrical carboxylic anhydrides from carboxylic acids with sulfated zirconia by phase transfer catalysis
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An efficient and convenient procedure for the synthesis of symmetrical carboxylic anhydrides from carboxylic acids with sulfated zirconia by PEG-1000 phase transfer catalysis has been developed. The reactions proceeded under mild and solvent-free conditions to provide the carboxylic anhydrides in good to excellent yields. The product can be isolated by a simple extraction with organic solvent, and the catalyst system can be recycled or reused without any significant loss of catalytic activity.
- Hu, Yu Lin,Zhao, Xing E.,Lu, Ming
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experimental part
p. 255 - 262
(2012/04/17)
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- GLUCOKINASE ACTIVATORS
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Compounds are provided for use with glucokinase that comprise the formula: wherein the variables are as defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds; methods and intermediates useful for making the compounds; and methods of using said compounds.
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Page/Page column 60
(2009/04/24)
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- Global optimization of conformational constraint on non-phosphorylated cyclic peptide antagonists of the Grb2-SH2 domain
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Following our earlier work on a phage library derived non-phosphorylated thioether-cyclized peptide inhibitor of Grb2 SH2 domain, a series of small peptide analogues with various cyclization linkage or various ring size were designed and synthesized and evaluated to investigate the optimal conformational constraint for this novel Grb2-SH2 blocker. Our previous SAR studies have indicated that constrained conformation as well as all amino acids except Leu2 and Gly7 in this lead peptide, cyclo(CH 2CO-Glu1-Leu-Tyr-Glu-Asn-Val-Gly-Met-Tyr-Cys 10)-amide (termed G1TE), was necessary for sustenance of the biological activity. In this study, in an effort to derive potent and bioavailable Grb2-SH2 inhibitor with minimal sequence, we undertook a systematic conformational study on this non-phosphorylated cyclic ligand by optimizing the ring linkage, ring configuration and ring size. The polarity and configuration of the cyclization linkage were implicated important in assuming the active conformation. Changing the flexible thioether linkage in G1TE into the relatively rigid sulfoxide linkage secured a 4-fold increase in potency (4, IC50=6.5 μM). However, open chain, shortening or expanding the ring size led to a marked loss of inhibitory activity. Significantly, the introduction of ω-amino carboxylic acid linker in place of three C-terminal amino acids in G1TE can remarkably recover the apparently favorable conformation, which is otherwise lost because of the reduced ring size. This modification, combined with favorable substitutions of Gla for Glu1 and Adi for Glu4 in the resulting six-residue cyclic peptide, afforded peptide 19, with an almost equal potency (19, IC50=23.3 μM) relative to G1TE. Moreover, the lipophilic chain in ω-amino carboxylic acid may confer better cell membrane permeability to 19. These newly developed G1TE analogues with smaller ring size and less peptide character but equal potency can serve as templates to derive potent and specific non-phosphorylated Grb2-SH2 antagonists.
- Long, Ya-Qiu,Lung, Feng-Di T.,Roller, Peter P.
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p. 3929 - 3936
(2007/10/03)
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- Detection of Elusive Chloro- and Bromo Substituted Ozonides by Nucleophilic Substitution Reactions
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Ozonolyses of 2,3-dichloro-2-butene (4), 4,5-dichloro-4-octene (9) and 2,3-dibromo-1,4-dichloro-2-butene (12) on polyethylene gave the corresponding ozonides 5,10 and 13a, respectively, which could not be isolated or unequivocally identified. Their identity could be proven, however, via substitution of the chloro- or bromo substituents at the ozonide rings by stabilizing substituents and subsequent isolation of the substituted ozonides 6, 11, 13b and 13c. Ozonolysis of 2,3-diacetoxy-2-butene (14) on polyethylene, in dichloro methane and in pentane gave mixtures of 16 and 17 but not ozonide 6.
- Griesbaum, Karl,Schlindwein, Konrad,Bettinger, Herbert
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p. 307 - 310
(2007/10/03)
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- Nucleophilic Substitution Reactions at Chloro-Substituted Ozonides and at a Chlorinated Dimeric Peroxide
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Reactions of substituted 3-chloro- (2a-4a) and 3,5-dichloro-1,2,4-trioxolanes (9a, 10a) with AgBF4 in the presence of LiF gave the corresponding fluoro-substituted ozonides (2b - 4b and 9b and 10b).Substitutions of some of these chlorinated ozonides by the methoxy and by the acetoxy groups, and of 3,6-dichloro-3,6-dimethyl-1,2,4,5-tetroxane (22a) with the acetoxy group have been achieved too.
- Griesbaum, Karl,Schlindwein, Konrad
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p. 8062 - 8066
(2007/10/03)
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- Quantitative relationships governing the reaction of transacylation of chloroacetic acid by acetic anhydride
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The method of proton magnetic resonance spectroscopy was used in a quantitative study of the relationships governing transacylation of monochloroacetic acid by acetic anhydride.A mathematical description of the process was provided by solution of a system of differential equations and integration by the Runge-Kutta-Fehlberg method.The advantages of the latter method compared with extrapolation were demonstrated.The activation parameters of the process were determined.The associative nature of the process was postulated.
- Utkin, A. Yu.,Chimishkyan, A. L.
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p. 1496 - 1498
(2007/10/02)
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- Hydroxy protection groups
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The present invention concerns a method for preparing unprotected hydroxy compounds or acylated derivatives thereof by conversion of silyl alkyl-protected hydroxy compounds. The invention also relates to novel intermediates useful in the method and for other purposes.
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- REACTION OF DIPHENYLKETENE N-(p-TOLYL)IMINE WITH CARBOXYLIC ACIDS IN THE PRESENCE OF ARYLAMINES
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The reaction of diphenylketene p-tolylimine with carboxylic acids in aprotic organic solvents is accelerated by primary arylamines.The reaction rate is described by overall kinetic equation including calalytic and noncatalytic path.Additions of pyridine greatly retard the reaction.The proposal according to which the catalytic reaction takes place through a cyclic transition state, formed from the ketene imine and the complex of the carboxylic acid with the amine, was substantiated.
- Mironova, D. F.,Loginova, N. A.
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p. 2344 - 2348
(2007/10/02)
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