63648-81-7

Basic information

• Product Name: Sucrose-6-acetic ester
• Synonyms: sucrose-6-acetic ester;Sucrose-6-acetic est;Sucralose-6-acetate
• CAS NO: 63648-81-7
• Molecular Formula: C₁₄H₂₄O₁₂
• Molecular Weight: 384.332
• Mol File: 63648-81-7.mol
• Article Data: 19

Chemical Properties

• Boiling Point: 674.6±55.0 °C(Predicted)
• Appearance: /
• Density: 1.66±0.1 g/cm3(Predicted)
• Storage Temp.: Hygroscopic, -20°C Freezer, Under inert atmosphere
• Solubility: Ethanol (Slightly), Water (Slightly, Heated)
• PKA: 12.79±0.70(Predicted)
• CAS DataBase Reference: Sucrose-6-acetic ester(CAS DataBase Reference)
• NIST Chemistry Reference: Sucrose-6-acetic ester(63648-81-7)
• EPA Substance Registry System: Sucrose-6-acetic ester(63648-81-7)

Safety Data

• Hazardous Substances Data: 63648-81-7(Hazardous Substances Data)

Usage

Uses

Sucralose 6-Acetate is a useful intermediate in the synthesis of Sucralose, an intensive sweetening agent of safety with no calories. A halogenated analogue of sucrose.

Synthetic route

acetic anhydride (108-24-7) + Sucrose (57-50-1) → 6-O-acetyl sucrose (63648-81-7)

Conditions	Yield
Stage #1: Sucrose With di(n-butyl)tin oxide In cyclohexane; N,N-dimethyl-formamide at 60 - 95℃; for 5h; Stage #2: acetic anhydride In cyclohexane; N,N-dimethyl-formamide at 5 - 20℃; for 4.5h;	98.6%
Stage #1: Sucrose With 1,3-diacetoxy-1,1,3,3-tetrabutyldistannoxane In cyclohexane; N,N-dimethyl-formamide for 0.08h; Heating / reflux; Azeotropic water co-distillation; Stage #2: acetic anhydride In cyclohexane; N,N-dimethyl-formamide at 10℃; for 2h;
Stage #1: Sucrose; di(n-butyl)tin oxide In N,N-dimethyl-formamide at 80 - 85℃; for 10 - 13h; Stage #2: acetic anhydride In N,N-dimethyl-formamide at 0 - 20℃; for 3 - 4h; Product distribution / selectivity;

ethyl acetate (141-78-6) + Sucrose (57-50-1) → 6-O-acetyl sucrose (63648-81-7)

Conditions	Yield
SO4(2-)-TiO2/Al2O3 In N,N-dimethyl-formamide at 80℃; for 6h;	79%

acetic anhydride (108-24-7) + Sucrose (57-50-1) → 6-O-acetyl sucrose (63648-81-7) + 4,6-di-O-acetate sucrose

Conditions	Yield
With pyridine; polymer-supported butyltin(IV) species 1.) MeOH, reflux, 12 h, 2.) DMF, RT, 1 d; Yield given. Multistep reaction. Yields of byproduct given;
With pyridine; polymer-supported butyltin(IV) species 1.) MewOH, reflux, 12 h, 2.) DMF, RT, 1 d; Yield given. Multistep reaction. Yields of byproduct given;

C16H29NO11 → 6-O-acetyl sucrose (63648-81-7)

Conditions	Yield
With water; acidic ion exchange resin In N,N-dimethyl-formamide for 0.5h; pH=~ 6; Product distribution / selectivity;
With water; acetic acid In N,N-dimethyl-formamide at 20℃; for 0.5h; pH=6.5; Product distribution / selectivity;

Acetyl cyanide (631-57-2) + Sucrose (57-50-1) → 6-O-acetyl sucrose (63648-81-7)

Conditions	Yield
In N,N-dimethyl-formamide at 40 - 50℃; for 6h; Product distribution / selectivity;
In N,N,N,N,N,N-hexamethylphosphoric triamide at 20℃; for 4h; Product distribution / selectivity;
In acetonitrile at 60℃; for 2h; Product distribution / selectivity;

acetic anhydride (108-24-7) + di(n-butyl)tin oxide (818-08-6) + Sucrose (57-50-1) → sucrose 4-acetate (63648-80-6) + 6-O-acetyl sucrose (63648-81-7)

Conditions	Yield
Stage #1: di(n-butyl)tin oxide; Sucrose With isopropyl alcohol In N,N-dimethyl-formamide at 100℃; for 5h; Stage #2: acetic anhydride In N,N-dimethyl-formamide at 10 - 27℃; for 6h; Product distribution / selectivity;

1,3-di-(6-O-sucrose)-1,1,3,3-tetrabutyl-distannoxane + acetic anhydride (108-24-7) → sucrose 4-acetate (63648-80-6) + 6-O-acetyl sucrose (63648-81-7) + Sucrose (57-50-1)

Conditions	Yield
In N,N-dimethyl-formamide; isopropyl alcohol at 0 - 20℃; for 5.5h; Product distribution / selectivity;

1,3-di-(6-O-sucrose)-1,1,3,3-tetrabutyl-distannoxane + acetic anhydride (108-24-7) → 6-O-acetyl sucrose (63648-81-7)

Conditions	Yield
In N,N-dimethyl-formamide; isopropyl alcohol at 0 - 20℃; Product distribution / selectivity;

1,3(diO-sucrose)dibutyl stannylene (956499-32-4) + acetic anhydride (108-24-7) → 6-O-acetyl sucrose (63648-81-7)

Conditions	Yield
Stage #1: 1,3(diO-sucrose)dibutyl stannylene In N,N-dimethyl-formamide at 40 - 45℃; for 0.5h; Stage #2: acetic anhydride In N,N-dimethyl-formamide at 0 - 20℃; for 3 - 4h; Product distribution / selectivity;

acetic acid (64-19-7) + Sucrose (57-50-1) → 6-O-acetyl sucrose (63648-81-7)

Conditions	Yield
diethylazodicarboxylate In N,N-dimethyl-formamide at 20℃; for 5h; Product distribution / selectivity;

vinyl acetate (108-05-4) + Sucrose (57-50-1) → sucrose-6,6’-acetate (1450725-30-0) + 6-O-acetyl sucrose (63648-81-7)

Conditions	Yield
With lipase B from Candida antarctica In tert-Amyl alcohol at 40℃; Enzymatic reaction;

Trimethyl orthoacetate (1445-45-0) + Sucrose (57-50-1) → 6-O-acetyl sucrose (63648-81-7)

Conditions	Yield
With sulfonated charcoal at 20 - 40℃; for 7h; Temperature;

6-O-acetyl sucrose (63648-81-7) → sucralose-6-acetate (105066-21-5)

Conditions	Yield
With phosgene; N,N-dimethyl-formamide In dodecane at 10 - 100℃; for 11h; Temperature; Solvent; Large scale;	77%
With tetrachloromethane; C40H62CuN2; zinc In N,N-dimethyl-formamide at 50 - 120℃; for 9h; Reagent/catalyst; Autoclave;	71.3%
With bis(trichloromethyl) carbonate; N,N-dimethyl-formamide In toluene at -10 - 110℃; for 7h; Product distribution / selectivity;	62%

6-O-acetyl sucrose (63648-81-7) → Sucralose (56038-13-2)

Conditions	Yield
With N-chloromethylene-N-phenylethylamine hydrochloride at 80 - 115℃; for 9.5h; Reagent/catalyst; Temperature; Inert atmosphere;	77%
Stage #1: 6-O-acetyl sucrose With (chloromethylene)dimethyliminium chloride In ISOPROPYLAMIDE; N,N-dimethyl-formamide at 3 - 105℃; Stage #2: With water; sodium hydroxide In ISOPROPYLAMIDE; N,N-dimethyl-formamide at 20℃; pH=9.75; Product distribution / selectivity;	70%
With bis(trichloromethyl) carbonate In N,N-dimethyl-formamide at -15 - 20℃; for 0.5h;	65.6%
Stage #1: 6-O-acetyl sucrose With phosphorus pentachloride; N,N-dimethyl-formamide at 0 - 115℃; Stage #2: With calcium hydroxide In water; N,N-dimethyl-formamide pH=9.5;
With phosphorus pentachloride; N,N-dimethyl-formamide at 0 - 115℃; Industry scale;	40 %Chromat.

6-O-acetyl sucrose (63648-81-7) → 2,3,6-tri-O-acetyl-4-chloro-4-deoxy-α-D-galactopyranosyl 3-O-acetyl-1,4,6-trichloro-1,4,6-trideoxy-β-D-fructofuranoside (82950-42-3) + 2,3,6-tri-O-acetyl-4-chloro-4-deoxy-α-D-galactopyranosyl 3,4-di-O-acetyl-1,6-dichloro-1,6-dideoxy-β-D-fructofuranoside (55832-20-7) + 2,3,6-tri-O-acetyl-4-chloro-4-deoxy-α-D-galactopyranosyl 3-O-acetyl-1,4,6-trichloro-1,4,6-trideoxy-β-D-tagatofuranoside

Conditions	Yield
With sulfuryl dichloride In pyridine; chloroform at -60℃;	A 35.3% B 11.1% C 12.2%

acetic anhydride (108-24-7) + 6-O-acetyl sucrose (63648-81-7) → 2,3,6-tri-O-acetyl-4-chloro-4-deoxy-α-D-galactopyranosyl 3-O-acetyl-1,4,6-trichloro-1,4,6-trideoxy-β-D-fructofuranoside (82950-42-3) + 2,3,6-tri-O-acetyl-4-chloro-4-deoxy-α-D-galactopyranosyl 3,4-di-O-acetyl-1,6-dichloro-1,6-dideoxy-β-D-fructofuranoside (55832-20-7) + 2,3,6-tri-O-acetyl-4-chloro-4-deoxy-α-D-galactopyranosyl 3-O-acetyl-1,4,6-trichloro-1,4,6-trideoxy-β-D-sorbofuranoside (82919-97-9)

Conditions	Yield
Yield given. Multistep reaction. Yields of byproduct given;

6-O-acetyl sucrose (63648-81-7) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → 6-acetyl-1',6'-dichloro-1',6'-dideoxy-β-fructofuranasyl-4-chloro-4-deoxy-galactopyranoside

Conditions	Yield
Stage #1: N,N-dimethyl-formamide With phosphorus pentachloride at 30 - 35℃; for 0.5h; Stage #2: 6-O-acetyl sucrose In N,N-dimethyl-formamide at 0 - 115℃; for 10h;

6-O-acetyl sucrose (63648-81-7) → 4,1',6'-trichloro-4,1',6'-trideoxysucrose

Conditions	Yield
Stage #1: 6-O-acetyl sucrose With Vilsmeier reagent; N-[(dichlorophosphinoyloxy)methylene]-N-methylmethanammonium chloride In N,N-dimethyl-formamide at 0 - 115℃; for 7h; Stage #2: With calcium hydroxide; water In N,N-dimethyl-formamide pH=7.0 - 7.5; Product distribution / selectivity;
Stage #1: 6-O-acetyl sucrose With Vilsmeier reagent In N,N-dimethyl-formamide at -5 - 115℃; for 7h; Stage #2: With calcium hydroxide; water In N,N-dimethyl-formamide pH=7.0 - 7.5; Product distribution / selectivity;
Stage #1: 6-O-acetyl sucrose With N-[(dichlorophosphinoyloxy)methylene]-N-methylmethanammonium chloride In N,N-dimethyl-formamide at -5 - 115℃; for 7h; Stage #2: With calcium hydroxide; water In N,N-dimethyl-formamide pH=7.0 - 7.5; Product distribution / selectivity;

6-O-acetyl sucrose (63648-81-7) → sucralose-6-acetate (105066-21-5) + Sucralose (56038-13-2)

Conditions	Yield
With phosphorus pentachloride; N,N-dimethyl-formamide at 0 - 115℃;
With Vilsmeier reagent; acetic acid In N,N-dimethyl acetamide; water; N,N-dimethyl-formamide at 0 - 100℃; Inert atmosphere; Overall yield = 68.61 %Chromat.;

6-O-acetyl sucrose (63648-81-7) → 6-acetyl-1',6'-dichloro-1',6'-dideoxy-β-fructofuranasyl-4-chloro-4-deoxy-galactopyranoside

Conditions	Yield
Stage #1: 6-O-acetyl sucrose With Vilsmeier reagent; N,N-dimethyl-formamide at 20 - 100℃; Stage #2: With sodium hydroxide at 20℃; pH=9.75;

6-O-acetyl sucrose (63648-81-7) → sucralose-6-acetate (105066-21-5) + 3',6'-anhydro-4,1'-dichloro-4,1'-dideoxysucralose + Sucralose (56038-13-2)

Conditions	Yield
With Vilsmeier reagent; acetic acid In N,N-dimethyl acetamide; water; N,N-dimethyl-formamide at 15 - 96℃; Solvent; Inert atmosphere; Overall yield = 66.85 %Chromat.;

C24H42N2O4(2+)*2Cl(1-) + 6-O-acetyl sucrose (63648-81-7) → sucralose-6-acetate

Conditions	Yield
at 110℃; for 5h; Temperature; Green chemistry;	19.8 g

Upstream product

• 1445-45-0 Trimethyl orthoacetate 
• 57-50-1 Sucrose 
• 956499-32-4 1,3(diO-sucrose)dibutyl stannylene 
• 108-24-7 acetic anhydride 
• 141-78-6 ethyl acetate 
• 631-57-2 Acetyl cyanide 
• 64-19-7 acetic acid 
• 108-05-4 vinyl acetate 
• 818-08-6 di(n-butyl)tin oxide 

Downstream Products

• 105066-21-5 sucralose-6-acetate 
• 56038-13-2 Sucralose 
• 82950-42-3 2,3,6-tri-O-acetyl-4-chloro-4-deoxy-α-D-galactopyranosyl 3-O-acetyl-1,4,6-trichloro-1,4,6-trideoxy-β-D-fructofuranoside 
• 55832-20-7 2,3,6-tri-O-acetyl-4-chloro-4-deoxy-α-D-galactopyranosyl 3,4-di-O-acetyl-1,6-dichloro-1,6-dideoxy-β-D-fructofuranoside 
• 82919-97-9 2,3,6-tri-O-acetyl-4-chloro-4-deoxy-α-D-galactopyranosyl 3-O-acetyl-1,4,6-trichloro-1,4,6-trideoxy-β-D-sorbofuranoside 

Relevant articles and documents

Tin(IV)-functionalised polymer supports; non-toxic and practical reagents for regioselective acetylation of sucrose

Polymer-supported butyltin(IV) reagents have been surveyed for regioselectivity in acetylation of sucrose. Polymer-supported butyltin(IV) dichloride 8 catalysed the acetylation of sucrose to give a 59% yield of 6-O-acetyl sucrose 3, the precursor of sucralose. The yield is close to that of a previously reported process involving dibutyltin(IV) oxide (Bu2SnO). The spent polymeric resin could readily be regenerated and can be subsequently used in further synthetic reactions.

Sucrose-6-ester production equipment and production method

The invention provides sucrose-6-ester production equipment and a production method. The equipment comprises a shell, a film scraping device and a base, the film scraping device is arranged on the base, and the shell covers the outer sides of the film scraping device and the base; the shell is provided with a reaction liquid feeding hole and a condensed water outlet; the base is provided with a carboxylic ester feeding pipe, a reaction product discharging pipe and a reaction channel connected with the carboxylic ester feeding pipe; the film scraping device comprises a temperature control device, a rotating pipe and a plurality of scraping pieces arranged on the inner wall of the rotating pipe, and the outer edges of the scraping pieces abut against the outer wall of the temperature control device. The rotating pipe can rotate around the temperature control device, so that the scraper blade can scrape reaction liquid which enters from the reaction liquid feeding hole and flows down along the outer wall of the temperature control device into a liquid film on the outer wall of the temperature control device, and the liquid film is separated into evaporation residual liquid and water vapor. According to the invention, the integrated design of a separation device and a reaction device is realized, the volume of production equipment is reduced, the occupied area is saved, the yield of sucrose-6-ester is improved, and the production cost is greatly saved.

Recrystallization method of sucrose-6-acetate and applications thereof

The invention discloses a recrystallization method of sucrose-6-acetate, and applications thereof. The recrystallization method comprise following steps: a solvent is added into a sucrose-6-acetate mixture obtained via sucrose esterification; and stirring, dissolving, filtering, and drying are carried out so as to obtain sucrose-6-acetate, wherein the solvent is a mixture of a nitrile solvent and an ether solvent. The recrystallization method is capable of increasing sucrose-6-acetate purity, and reducing adverse influences on subsequent chlorination.