541-88-8

Basic information

• Product Name: Chloroacetic anhydride
• Synonyms: 2-Chloroacetic anhydride;2-chloroaceticanhydride;Aceticacid,chloro-,anhydride;alpha,alpha’-dichloroaceticanhydride;Chloracetic anhydride;chloraceticanhydride;chloro-aceticacianhydride;Chloroacetyl anhydride
• CAS NO: 541-88-8
• Molecular Formula: C₄H₄Cl₂O₃
• Molecular Weight: 170.98
• EINECS: 208-794-2
• Product Categories: Pharmaceutical Intermediates;Building Blocks;Carbonyl Compounds;Carboxylic Acid Anhydrides;Chemical Synthesis;Organic Building Blocks
• Mol File: 541-88-8.mol
• Article Data: 9

Chemical Properties

• Melting Point: 51 °C
• Boiling Point: 203 °C
• Flash Point: >230 °F
• Appearance: brown/Crystals, Chunks or Low Melting Mass
• Density: 1.449
• Vapor Pressure: <0.75 mm Hg ( 20 °C)
• Refractive Index: 1.4730 (estimate)
• Storage Temp.: Hygroscopic, -20°C Freezer, Under inert atmosphere
• Solubility: Freely soluble in ether, chloroform. Slightly soluble in benzene
• Sensitive: Moisture Sensitive
• Stability: Moisture Sensitive
• Merck: 14,2113
• BRN: 774533
• CAS DataBase Reference: Chloroacetic anhydride(CAS DataBase Reference)
• NIST Chemistry Reference: Chloroacetic anhydride(541-88-8)
• EPA Substance Registry System: Chloroacetic anhydride(541-88-8)

Safety Data

• Hazard Codes: C,T
• Statements: 34-36/37-43-25
• Safety Statements: 26-28-36/37/39-45-27
• RIDADR: UN 3261 8/PG 2
• WGK Germany: 3
• F: 10-19-21
• TSCA: Yes
• HazardClass: 8
• PackingGroup: II
• Hazardous Substances Data: 541-88-8(Hazardous Substances Data)

Usage

Chemical Properties

brownish semi-transparent crystals, chunks or low

Uses

Different sources of media describe the Uses of 541-88-8 differently. You can refer to the following data:
1. In N-acetylation of amino acids in alkaline solution; preparation of cellulose chloroacetates.
2. Chloroacetic anhydride has been used in the synthesis of 3,3-bis(sulfonato)-4,4-bis(chloroacetamido)azobenzene (BSBCA), a water-soluble, thiol-reactive and photo-switchable cross-linker, D,L-7-azatryptophan, 2-methyl-[3,4-di-O-acetyl-6-O-(chloroacetyl)-1,2-dideoxy-α-D-glucopyrano]-[2,1:4,5]-2-oxazoline.

Preparation

chloroacetic anhydride Synthesis: Powdered s odium monochloroacetate(113.3g, 1.138 mol) was added slowly for a period of 15 min at room temperature (which slowly raises to 60°C) to a stirred solution of commercially available chloroaceyl chloride (127.5g, 1mol) in dry benzene (136mL) was refluxed for 9h. Salts were filtered off, the filtrate was cooled to room temperature, diluted with n-hexane and further cooled to 0°C. The solid separated was then filtered, washed with dry hexane and dried to yield chloroacetic anhydride as white crystalline compound in 60% yield (80g); mp=46-49°C [Lit. mp=46°C]. Alternatively, the benzene layer was directly subjected to high vacuum distillation.The product collected at 109-10°C at 10mm vacuum on cooling chloroacetic anhydride in lump form in 70 % yield (93g). It was observed that, the latter method gives anhydride in lump form while the former method gives in crystalline form.

Purification Methods

Crystallise the it from *benzene. [Eglinton et al. J Chem Soc 1860 1954, Beilstein 2 IV 487.]

InChI:InChI=1/C4H4Cl2O3/c5-1-3(7)9-4(8)2-6/h1-2H2

Synthetic route

sodium monochloroacetic acid (3926-62-3) + chloroacetyl chloride (79-04-9) → Chloroacetic anhydride (541-88-8)

Conditions	Yield
In toluene at 40℃; for 3h; Solvent; Temperature;	93%

chloroacetic acid (79-11-8) → Chloroacetic anhydride (541-88-8)

Conditions	Yield
With PEG-1000; sulfated zirconia at 40℃; for 1.5h; neat (no solvent);	91%
With 1,4-dioxane; hydrogenchloride; hydrogen cyanide
With phosphorus pentaoxide bei der Destillation im Vakuum;

4-methyleneoxetan-2-one (674-82-8) + chloroacetic acid (79-11-8) → Chloroacetic anhydride (541-88-8)

Conditions	Yield
at 70 - 80℃;

tetrakis(chloroacetoxy)silane (919-24-4) → Chloroacetic anhydride (541-88-8)

Conditions	Yield
bei der Destillation im Vakuum;

sodium monochloroacetic acid (3926-62-3) → Chloroacetic anhydride (541-88-8)

Conditions	Yield
With oxalyl dichloride; benzene
With sulfuryl dichloride; ethyl acetate at 50℃;
With phosgene; oxalic acid ester unter Kuehlung;

acetic anhydride (108-24-7) + chloroacetic acid (79-11-8) → Chloroacetic anhydride (541-88-8)

Conditions	Yield
With magnesium(II) perchlorate

acetic anhydride (108-24-7) + chloroacetic acid (79-11-8) → monochloroacetic acid anhydride (4015-58-1) + Chloroacetic anhydride (541-88-8)

acetic acid (64-19-7) + chloroacetyl chloride (79-04-9) → acetic anhydride (108-24-7) + acetyl chloride (75-36-5) + chloroacetic acid (79-11-8) + Chloroacetic anhydride (541-88-8)

Conditions	Yield
at 100℃; Fraktionierung des Reaktionsprodukts;
at 100℃; so erhaelt man bei der Fraktionierung des Reaktionsprodukt unter gewoehnlichem Druck;

monochloroacetic acid anhydride (4015-58-1) + chloroacetic acid (79-11-8) → acetic acid (64-19-7) + Chloroacetic anhydride (541-88-8)

chloroacetic acid (79-11-8) + chloroacetyl chloride (79-04-9) → Chloroacetic anhydride (541-88-8)

Conditions	Yield
zeitlicher Verlauf der Reaktion bei Siedetemperatur;
zeitlicher Verlauf bei Siedetemperatur;
With potassium chloride

chloroacetyl chloride (79-04-9) → Chloroacetic anhydride (541-88-8)

Conditions	Yield
With water; sodium carbonate
With potassium nitrate at 25℃; und spaeter auf dem Wasserbad;

oxalyl dichloride (79-37-8) + sodium monochloroacetic acid (3926-62-3) + benzene (71-43-2) → Chloroacetic anhydride (541-88-8)

acetic anhydride (108-24-7) + chloroacetic acid (79-11-8) → monochloroacetic acid anhydride (4015-58-1) + acetic acid (64-19-7) + Chloroacetic anhydride (541-88-8)

Conditions	Yield
In chloroform-d1 Kinetics; Thermodynamic data; ΔE(excit.), ΔH(excit.), ΔS(excit.);

diphenylketene-N-p-tolylimine (5110-45-2) + chloroacetic acid (79-11-8) → N-(p-tolyl)diphenylacetamide (4107-01-1) + N-(Chloracetyl)-N-(p-methylphenyl)-diphenylacetamid (73197-35-0) + Chloroacetic anhydride (541-88-8)

Conditions	Yield
In acetonitrile at 30℃; Rate constant; Product distribution;

trans-3,5-Diacethoxy-3,5-bis(chloromethyl)-1,2,4-trioxolane → Chloroacetic anhydride (541-88-8)

Conditions	Yield
With dimethylsulfide In chloroform-d1 for 1.5h;

trans-2,3-dibromo-1,4-dichloro-2-butene (85415-22-1) → chloroacetic acid (79-11-8) + Chloroacetic anhydride (541-88-8)

Conditions	Yield
With ozone; polyethylene In pentane at -75℃; for 8h; Product distribution; to r.t.;	A 71 % Spectr. B 14 % Spectr.

chloroacetic acid (79-11-8) + phosphorus pentoxide → Chloroacetic anhydride (541-88-8)

Conditions	Yield
bei der Destillation im Vakuum;

chloroacetic acid (79-11-8) + chloroacetyl chloride (79-04-9) + potassium chloride → Chloroacetic anhydride (541-88-8)

Conditions	Yield
zeitlicher Verlauf bei Siedetemperatur;

(R)-3,4-dihydro-2H-pyran-2-methylamine (144069-81-8) + Chloroacetic anhydride (541-88-8) → N-<((2R)-3,4-dihydro-2H-pyran-2-yl)methyl>chloroacetamide (159691-04-0)

Conditions	Yield
With N,N-diethyl-N-isopropylamine In dichloromethane at 0℃; for 0.666667h;	100%

1D-6-O-(4-oxopentanoyl)-3,4-O-(tetraisopropyldisiloxane-1,3-diyl)-5-O-triethylsilyl-myo-inositol 1-<(1,2-di-O-octadecanoyl-sn-glyceryl) methyl phosphate> (171191-33-6) + Chloroacetic anhydride (541-88-8) → 1D-2-chloroacetyl-6-O-(4-oxopentanoyl)-3,4-O-(tetraisopropyldisiloxane-1,3-diyl)-5-O-triethylsilyl-myo-inositol 1-<(1,2-di-O-octadecanoyl-sn-glyceryl) methyl phosphate> (171191-34-7)

Conditions	Yield
	100%
With dmap; N,N,N',N'-tetramethyl-1,8-diaminonaphthalene In pyridine for 2.5h; Ambient temperature; Yield given;

Chloroacetic anhydride (541-88-8) + 5-(3-amino-2,6-dichlorobenzyloxy)isoquinoline (206883-01-4) → 5-{(2,6-dichloro-3-chloroacetylamino)benzyloxy}isoquinoline (258842-80-7)

Conditions	Yield
In 1,2-dichloro-ethane at 20℃; for 1h; Acylation;	100%

Chloroacetic anhydride (541-88-8) + phenyl 3-O-acetyl-2-azido-4,6-O-benzylidene-2-deoxy-1-seleno-α-D-galactopyranoside (167074-40-0) → Chloro-acetic acid (2S,4aR,6R,7R,8aR)-7-azido-2-phenyl-6-phenylselanyl-hexahydro-pyrano[3,2-d][1,3]dioxin-8-yl ester

Conditions	Yield
With sodium hydrogencarbonate In tetrahydrofuran at -30 - 20℃; Acetylation;	100%

Chloroacetic anhydride (541-88-8) + phenyl 3-O-acetyl-2-azido-4,6-O-benzylidene-2-deoxy-1-seleno-α-D-galactopyranoside (167074-40-0) → Phenyl 2-azido-4,6-benzylidene-3-O-chloroacetyl-2-deoxy-1-seleno-α-D-galactopyranoside (282736-08-7)

Conditions	Yield
With sodium hydrogencarbonate In tetrahydrofuran at 20℃;	100%

Chloroacetic anhydride (541-88-8) + (1S,2R)-1-(N'-acetyl-N-carbamylamino)-2-indanol (359760-98-8) → (1S,2R)-1-(N'-acetyl-N-carbamylamino)-2-indanol O-chloroacetate (359760-99-9)

Conditions	Yield
With pyridine at 20℃; for 1h;	100%

Chloroacetic anhydride (541-88-8) + (2E,4E)-(R)-8-(tert-Butyl-dimethyl-silanyloxy)-2,7-dimethyl-octa-2,4-dien-1-ol (208193-37-7) → (R,2E,4E)-8-t-butyldimethylsilyloxy-2,7-dimethyl-2,4-octadien-1-yl chloroacetate (445493-03-8)

Conditions	Yield
With triethylamine In methanol at 20℃; for 0.25h;	100%

Chloroacetic anhydride (541-88-8) + tert-butyldiphenylsilyl 2,3,4,6-tetra-O-benzyl-β-D-galactopyranosyl-(1->4)-2-acetamido-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranosyl-(1->6)-[2,3,4,6-tetra-O-benzyl-β-D-galactopyranosyl-(1->3)]-2-azido-2-deoxy-β-D-galactopyranoside → tert-butyldiphenylsilyl 2,3,4,6-tetra-O-benzyl-β-D-galactopyranosyl-(1->4)-2-acetamido-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranosyl-(1->6)-[2,3,4,6-tetra-O-benzyl-β-D-galactopyranosyl-(1->3)]-2-azido-4-O-chloroacetyl-2-deoxy-β-D-galactopyranoside

Conditions	Yield
With pyridine In dichloromethane at 0℃; for 3h;	100%

Chloroacetic anhydride (541-88-8) + (1R,2R,5S)-2-(3-hydroxypropyl)-2-methyl-8-oxabicyclo[3.2.1]octan-3-one (553635-94-2) → (1R,2R,5S)-2-[3-(chloroacetyloxy)propyl]-2-methyl-8-oxabicyclo[3.2.1]octan-3-one (553635-95-3)

Conditions	Yield
With pyridine; dmap at 0℃; for 1.5h;	100%

taxol (33069-62-4) + Chloroacetic anhydride (541-88-8) → taxol-2'-chloroacetyl (152565-19-0)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;	100%
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃;	100%
	100%
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 3h;	100%
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 24h;	84.33%

benzyl-methyl-amine (103-67-3) + Chloroacetic anhydride (541-88-8) → N-benzyl-N-methyl-α-chloroacetamide (73685-56-0)

Conditions	Yield
With dmap In tetrahydrofuran at 20℃; for 0.166667h;	100%

pent-4-enyl 2,3,4-tri-O-benzyl-β-D-glucopyranoside (155036-27-4) + Chloroacetic anhydride (541-88-8) → n-pent-4-enyl 2,3,4-O-tribenzyl-6-O-chloroacetyl-β-D-glucopyranoside (1268469-66-4)

Conditions	Yield
With pyridine In dichloromethane at 0 - 20℃;	100%

C33H40O8S (1282034-45-0) + Chloroacetic anhydride (541-88-8) → C35H41ClO9S (1282034-28-9)

Conditions	Yield
With dmap In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere;	100%

tert-butyldiphenylsilyl 4-(N-benzyloxycarbonylamino)-2-azido-2,4,6-trideoxy-β-D-galactopyranoside (1271131-90-8) + Chloroacetic anhydride (541-88-8) → tert-butyldiphenylsilyl 4-(N-benzyloxycarbonylamino)-2-azido-3-O-chloroacetyl-2,4,6-trideoxy-β-D-galactopyranoside (1271132-05-8)

Conditions	Yield
With pyridine In dichloromethane for 1h;	100%
With pyridine In dichloromethane for 1h;	100%

C19H32O4 + Chloroacetic anhydride (541-88-8) → C23H34Cl2O6

Conditions	Yield
With pyridine; dmap In dichloromethane at 0℃; for 2.5h;	100%

Chloroacetic anhydride (541-88-8) + phenyl (6-O-benzyl-2-O-benzoyl-1-thio-β-D-galactopyranoside) (258286-51-0) → phenyl 2,6-di-O-benzyl-3,4-di-O-chloroacetyl-1-thio-β-D-galactopyranoside (1400562-30-2)

Conditions	Yield
With pyridine In monoethylene glycol diethyl ether at 0 - 20℃; for 4h;	100%

methyl [2-(trimethylsilyl)ethyl 5-acetamido-4,7,9-tri-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosid]onate + Chloroacetic anhydride (541-88-8) → methyl [2-(trimethylsilyl)ethyl 5-acetamido-4,7,9-tri-O-acetyl-8-O-chloroacetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosid]onate

Conditions	Yield
With dmap In tetrahydrofuran at 0 - 20℃; for 12h; Inert atmosphere;	100%

methyl [phenyl 3,5-dideoxy-9-O-pivaloyl-2-thio-5-(2,2,2-trichloroethoxycarbamoyl)-D-glycero-β-D-galacto-2-nonulopyranosid]onate + Chloroacetic anhydride (541-88-8) → methyl [phenyl 4,7,8-tri-O-chloroacetyl-3,5-dideoxy-9-O-pivaloyl-2-thio-5-(2,2,2-trichloroethoxycarbamoyl)-D-glycero-β-D-galacto-2-nonulopyranosid]onate

Conditions	Yield
With dmap In tetrahydrofuran at 20℃; for 1h; Inert atmosphere;	100%

6''-dihydro-3,5-isopropylidene-6''-O-(4-methoxybenzyl) leuconolide A1 (124781-21-1) + Chloroacetic anhydride (541-88-8) → 9-O-chloroacetyl-6''-dihydro-3,5-isopropylidene-6''-O-(4-methoxybenzyl) leuconolide A1 (139746-45-5)

Conditions	Yield
With dmap In pyridine at 5℃; for 0.333333h;	99%

Methyl-3,6-di-O-allyl-2-O-benzyl-α-D-mannopyranosid (102728-49-4) + Chloroacetic anhydride (541-88-8) → Methyl-3,6-di-O-allyl-2-O-benzyl-4-O-chloracetyl-α-D-mannopyranosid (129750-07-8)

Conditions	Yield
With pyridine at 0℃; for 0.5h;	99%

{(6S,7R,8S,9R)-9-(tert-Butyl-dimethyl-silanyloxy)-7-((S)-1-hydroxy-3-trimethylsilanyl-prop-2-ynyl)-8-[2-(4-methoxy-phenoxymethoxy)-ethyl]-9-trimethylsilanylethynyl-1,4-dioxa-spiro[4.5]dec-6-yl}-carbamic acid allyl ester + Chloroacetic anhydride (541-88-8) → Chloro-acetic acid (S)-1-{(6S,7R,8S,9R)-6-allyloxycarbonylamino-9-(tert-butyl-dimethyl-silanyloxy)-8-[2-(4-methoxy-phenoxymethoxy)-ethyl]-9-trimethylsilanylethynyl-1,4-dioxa-spiro[4.5]dec-7-yl}-3-trimethylsilanyl-prop-2-ynyl ester

Conditions	Yield
With pyridine	99%

Chloroacetic anhydride (541-88-8) + 1-[Dimethyl-(1,1,2-trimethyl-propyl)-silanyloxy]-pent-4-en-2-ol (206348-79-0) → Chloro-acetic acid 1-[dimethyl-(1,1,2-trimethyl-propyl)-silanyloxymethyl]-but-3-enyl ester (206348-77-8)

Conditions	Yield
With pyridine In dichloromethane at 0℃; for 1.5h;	99%

2,2-diaminoethylthioether (871-76-1) + Chloroacetic anhydride (541-88-8) → bis<2-(α-chloroacetamido)ethyl> sulfide (226211-71-8)

Conditions	Yield
In dichloromethane for 1h; Ambient temperature;	99%

5,5-dimethyl-2-(methylthio)-2-cyclopenten-1-ol (186960-95-2) + Chloroacetic anhydride (541-88-8) → 5,5-dimethyl-2-(methylthio)-2-cyclopenten-1-yl chloroacetate (225790-52-3)

Conditions	Yield
With pyridine In dichloromethane at 0℃; for 2h;	99%

Chloroacetic anhydride (541-88-8) + C81H112O25Si2 → C83H113ClO26Si2

Conditions	Yield
With dmap; triethylamine In tetrahydrofuran at 0 - 25℃; for 1h; Esterification;	99%

Chloroacetic anhydride (541-88-8) + bis{3-[2,3,6-tri-O-acetyl-4-O-(2',3',4',6'-tetra-O-acetyl-β-D-galactopyranosyl)-β-D-glucopyranosyl-1-thiomethylcarbonylamino]propyl}-N-tert-butoxycarbonylamine → bis{3-[2,3,6-tri-O-acetyl-4-O-(2',3',4',6'-tetra-O-acetyl-β-D-galactopyranosyl)-β-D-glucopyranosyl-1-thiomethylcarbonylamino]propyl}-N-chloroacetylamine

Conditions	Yield
Stage #1: bis{3-[2,3,6-tri-O-acetyl-4-O-(2',3',4',6'-tetra-O-acetyl-β-D-galactopyranosyl)-β-D-glucopyranosyl-1-thiomethylcarbonylamino]propyl}-N-tert-butoxycarbonylamine With trifluoroacetic acid In dichloromethane at 0℃; Stage #2: Chloroacetic anhydride With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 8h; Further stages.;	99%

Chloroacetic anhydride (541-88-8) + (2R,4aR,6S,7R,8S,8aS)-7-(4-Methoxy-benzyloxy)-6-methylsulfanyl-2-phenyl-hexahydro-pyrano[3,2-d][1,3]dioxin-8-ol (512171-32-3) → methyl 4,6-O-benzylideme-3-O-chloroacetyl-2-O-p-methoxybenzyl-1-thio-β-D-mannopyranoside

Conditions	Yield
With pyridine In dichloromethane at 0 - 20℃; for 1.16667h;	99%

Chloroacetic anhydride (541-88-8) + C54H75NO14 → C56H76ClNO15

Conditions	Yield
With dmap; triethylamine In dichloromethane at 20℃; for 1h;	99%

(Z)-2-fluoro-n-dec-2-en-1-ol (55371-42-1) + Chloroacetic anhydride (541-88-8) → 1-chloroacetoxy-2-fluorodec-2-ene (848138-01-2)

Conditions	Yield
With pyridine; dmap In dichloromethane at 20℃; for 15h;	99%

Acetic acid (2S,3R,4R,5S,6R)-3-azido-6-benzyloxymethyl-5-hydroxy-2-phenylsulfanyl-tetrahydro-pyran-4-yl ester + Chloroacetic anhydride (541-88-8) → phenyl 3-O-acetyl-2-azido-6-O-benzyl-4-O-chloroacetyl-2-deoxy-1-thio-β-D-glucopyranoside

Conditions	Yield
With pyridine In dichloromethane at 0℃; for 0.5h;	99%

Upstream product

• 674-82-8 4-methyleneoxetan-2-one 
• 79-11-8 chloroacetic acid 
• 919-24-4 tetrakis(chloroacetoxy)silane 
• 3926-62-3 sodium monochloroacetic acid 
• 79-04-9 chloroacetyl chloride 
• 85415-22-1 trans-2,3-dibromo-1,4-dichloro-2-butene 
• 5110-45-2 diphenylketene-N-p-tolylimine 
• 108-24-7 acetic anhydride 
• 79-37-8 oxalyl dichloride 
• 71-43-2 benzene 
• 4015-58-1 monochloroacetic acid anhydride 
• 64-19-7 acetic acid 

Downstream Products

• 102889-39-4 3,7-bis-chloroacetyl-1,5-diphenyl-3,7-diaza-bicyclo[3.3.1]nonan-9-one 
• 7500-76-7 4,4'-dimethoxytriphenylmethane 
• 99-40-1 2-chloro-3',4'-dihydroxyacetophenone 
• 132984-58-8 trans-4-chloroacetoxy-1-(4-nitro-benzyloxycarbonyl)-L-proline 
• 100-06-1 1-(4-methoxyphenyl)ethanone 
• 6397-82-6 4'-methoxyhexanophenone 
• 1889-74-3 1-(4-methoxyphenyl)-2,2-diphenylethanone 
• 7402-89-3 (4-methoxyphenyl)triphenylmethane 
• 2196-99-8 2-chloro-1-(4-methoxyphenyl)ethanone 
• 55010-17-8 3,3-diphenyl-indan-1-one 
• 83-33-0 inden-1-one 
• 6141-22-6 2-chloro-N-(2-formylphenyl)acetamide 
• 587-65-5 N-chloroacetyl-aniline 
• 10147-69-0 2-chloro-N-(3-hydroxyphenyl)acetamide 

Relevant articles and documents

Synthesis process of chloroacetic anhydride

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.

GLUCOKINASE ACTIVATORS

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.

Detection of Elusive Chloro- and Bromo Substituted Ozonides by Nucleophilic Substitution Reactions

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.