33665-90-6 Usage
Description
Acesulfame pottasium (also known as acesulfame K or Ace K) is a calorie free sugar substitute (artificial sweetener). It is ~ 200x sweeter than table sugar and approved for use in food as a non-nutritive sweetener. It is sold under the brand names Sunett? and Sweet One?.
FDA approved it as a general purpose sweetener and flavor enhancer in food, except in meat and poultry, under certain conditions of use. It stays sweet even when used at high temperatures during baking, making it suitable as a sugar substitute in baked goods. Acesulfame potassium has been approved for use in a variety of food products including frozen desserts, candies, beverages, baby food, and baked goods. More than 90 studies support its safety.
Acesulfame K contains the carcinogen methylene chloride. Long-term exposure to methylene chloride can cause headaches, depression, nausea, mental confusion, liver effects, kidney effects, visual disturbances, and cancer in humans.
Identification test
Solubility: easily soluble in water. Very slightly soluble in ethanol. Measure it according to the OT-42 method.
Potassium test result (2 g of test residue): positive (IT-27).
UV absorbance: take 10 mg of the sample to dissolve in 1000 ml of water and the solution had a maximum absorption peak at 227 ± 2 nm (see GT-29).
Take 0.2 g of the sample, add 2 ml of the acetic acid test solution (TS-1) and 2 ml of water. Add several drops of 10% sodium hexachlorocyclohexane solution to this solution, after which there should be a yellow precipitate.
Content analysis
Accurately weighed 0.15g of pre-dried sample, dissolve in 50.0ml glacial acetic acid; apply 0.1mol/L perchloric acid for potentiometric titration; or add two drops of crystal violet test solution (TS-74), titrate with 0.1mol/L perchloric acid titration to blue-green end point, and maintain 30s to perform a blank test at the same time and correct the necessary error. Per mL, 0.1 mol/L perchloric acid is equivalent to 20.12 mg of acesulfame potassium (C4H4NO4SK).
Toxicity
ADI 0-15 (FAO/WHO, 2001).
Being safe to be used in food products (FDA, §172.800, 2000).
Usage limit
GB 2760-2001 (g/kg): beverages, ice cream, pastries, confectionery, jam (excluding canned), pickles, candied fruit, jelly candy, canned rice porridge, jelly, bread, 0.3; dining table-purpose sauce(flake like and powder like): 40 mg per tablet and package; Flavorless yogurt, 0.35; flavoring, 0.5; sugarless (low sugar) candy and gum, 2.0; sugarless chewing gum, 4.
Limited to GMP (FDA, § 172.800, 2000).
Chemical properties
It appears as colorless to white crystalline powder, being odorless with a strong sweetness which is about 150 times that of the sucrose; the flavor properties are similar as that of saccharin. It has bitter at high concentrations and has a good mixing property with sugar alcohols and sucrose, etc., being stable as well. It has a melting point of about 225 °C, the maximum absorption spectrum of 227nm and density 1.83g/cm3 (loose density 1.1~1.3kg/dm3). It is non-hygroscopic, being stable at room temperature, easily soluble in water (30g/100ml, 20 ℃), slightly soluble in ethanol and other organic solvents.
Uses
Different sources of media describe the Uses of 33665-90-6 differently. You can refer to the following data:
1. 1. Non-nutritional sweetener, being able to be widely used in various foods, even in drinks of Ph3.0, it can also be used.
2. For beverages, food, health products and so on
3. Food sweeteners
4. Acesulfame belongs to the fourth generation synthetic sweeteners with single administration accompanied with a certain bitter taste. It has a synergistic effect when being used in combination with aspartame or cyclamate and being able to mask the bitter taste. After intake of the human body, it is not absorbed and does not produce heat, being suitable for patients with diabetes and obesity. It can be used as pastry, jam (excluding canned food), pickles, candy, candied fruit, beverage, ice cream and jelly candy with the maximum dosage of 0.3g/kg; it can also be used as table sweetener (flake or powder) with 40 mg per tablet or per packet.
2. Acesulfame-K is a non-nutritive sweetener also termed acesulfame
potassium. it is a white, crystalline product that is 200 times sweeter
than sucrose. it is not metabolized in the body. it has some metallic
off-tastes. it is readily soluble and heat and acid stable. it provides a
synergistic sweetening effect combined with other sweeteners. it is
used in beverages, desserts, confectionery, and bakery products.
Production method
There are many patents on the preparation of acesulfame, here are four methods.
Aminosulfonic acid and diketene method
Take aminosulfonic acid, triethylamine, diketene and potassium hydroxide as raw material for synthesis. 9.7 g (0.1 mol) of sulfamic acid was added to 16 mL (0.12 mol) of triethylamine and stirred until complete dissolution. 8 mL 0.104 mol of diketene was added drop wise at 0 ° C, and the mixture was stirred at room temperature until completion of the reaction. Add hexane for precipitation and further refinement and the solvent was removed under reduced pressure to obtain 27 to 28 g of a syrup in a yield of 95.7 to 99.0%. The slurry and SO3 were simultaneously added to the container containing CH2Cl2 for stirring continuously of 1-5 hours before the removal of solvent under reduced pressure. The residue was treated with methanol-potassium hydroxide solution under controlling Ph value of 8 to 10. The solvent was removed and dried to give acesulfame potassium salt in 69% yield. This method is easy to obtain raw materials with mild conditions but the process is complex and the yield is not high.
Aminosulfonyl fluoride and diketene method.
To a solution of 76 g (0.55 mol) of potassium carbonate powder and 500 mL of acetone, 57.8 mL (1.0 mol) of sulfamic acid fluoride was added, and 84.3 mL (1.1 mol) of diketene was added dropwise over 15 min. Stir for reaction at 0 °C for 30 min. The reaction is exothermic with the temperature be controlled below 30℃ until the CO2 is completely released before stopping the reaction. The reaction mixture was suction filtered and washed with a small amount of acetone to give the potassium salt of the colorless crystalline acetoacetylamino-N-sulfonyl fluoride. The crystal was stirred together with 4 to 6 mol of methanol-potassium hydroxide solution to cyclize to obtain the acesulfame potassium salt in a yield of 93% of the theoretical amount. This method is easier to obtain raw materials with mild process conditions. The operation is also not complicated, being the ideal preparation method.
Acetoacetamide and fluorinated sulfuryl fluoride method.
Take acetoacetamide, potassium carbonate, fluorinated sulfuryl fluoride and potassium hydroxide as raw materials; (0.1 mol) of acetoacetamide and 69 g (0.5 mol) of potassium carbonate were added to 150 mL of acetone and 8 mL of water. After stirring uniformly, 15.3 g (0.15 mol) of fluorinated sulfuryl fluoride gas was introduced at room temperature for reaction at which point the reaction mixture was allowed to warm to 40 ° C and stirred for 2 h before suction filtration. The filter cake was put into an excess of hydrochloric acid solution of ice to dissolve and react. And then extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to obtain acesulfame. It will react with methanol-potassium hydroxide solution to obtain acesulfame potassium salt with drying to get 14.1 g finished product with the yield of 86.5% of the theoretical amount.
This method is not harsh reaction conditions, the yield is high, but some raw materials are not easy to get.
Acetoacetamide and sulfur trioxide method.
In an inert organic or inorganic solvent, send through SO3 into acetoacetamide for recycling condensation, generating acetoacetyl sulfamic acid. After separation, it is reacted with potassium hydroxide to derive the products. Dissolve 5.1 g (50 mmol) acetoacetamide in 50mLCH2Cl2; dissolve 8 mL (200 mmo1) liquid SO3 in 50 mL Mlch2Cl2; then at-60 ℃, then drop the former one to the latter for stirring reaction of 2h. Add 50 mL acetoacetamide and water and the organic phase was separated after extraction and further subject to aqueous phase extraction with ethyl acetate for twice and combined into the organic phase. After drying over anhydrous sodium sulfate, ethyl acetate was recovered by evaporation. The residue was dissolved in methanol and neutralized with methanol-potassium hydroxide solution. Acesulfame potassium salt was then precipitated and dried, yielding 3.1 g of product in a yield of 31% of the theoretical amount. This method needs to be carried out at low temperature, and the yield is not high.
It can be obtained through the addition reaction of fluorosulfonyl isocyanate (or chlorosulfonyl isocyanate) with various active methylene compounds (including α-unsubstituted ketone, β-diketone, β-keto acid and β-ketoester, etc.) addition .
For example, from the addition reaction between tert-butyl acetoacetate and fluorosulfonyl isocyanate.
References
[1] https://www.fda.gov
[2] Wei-na Cong, Rui Wang, Huan Cai, Caitlin M. Daimon, Morten Scheibye-Knudsen, Vilhelm A. Bohr, Rebecca Turkin, William H. Wood III, Kevin G. Becker, Ruin Moaddel, Stuart Maudsley , Bronwen Martin? (2013) Long-Term Artificial Sweetener Acesulfame Potassium Treatment Alters Neurometabolic Functions in C57BL/6J Mice, Plos One, 8, e70257
Definition
ChEBI: A sulfamate ester that is 1,2,3-oxathiazin-4(3H)-one 2,2-dioxide substituted by a methyl group at position 6.
Check Digit Verification of cas no
The CAS Registry Mumber 33665-90-6 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 3,3,6,6 and 5 respectively; the second part has 2 digits, 9 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 33665-90:
(7*3)+(6*3)+(5*6)+(4*6)+(3*5)+(2*9)+(1*0)=126
126 % 10 = 6
So 33665-90-6 is a valid CAS Registry Number.
InChI:InChI=1/C4H5NO4S.K/c1-3-2-4(6)5-10(7,8)9-3;/h2H,1H3,(H,5,6,7,8);/q;+1/p-1
33665-90-6Relevant articles and documents
Structural and IR-spectroscopic characterization of pyridinium acesulfamate, a monoclinic twin
Baran, Enrique J.,Piro, Oscar E.,Echeverría, Gustavo A.,Parajón-Costa, Beatriz S.
, p. 753 - 758 (2018)
The crystal structure of pyridinium 6-methyl-1,2,3,-oxathiazine-4(3H)-one-2,2-dioxide [(C5NH6)(C4H4NO4S)], for short, pyH(ace), was determined by X-ray diffraction methods. It crystallizes as a twin in the monoclinic space group P21/c with a=6.9878(9), b=7.2211(7), c=21.740(2) ?, β=91.67(1)° and Z=4 molecules per unit cell. The structure was determined employing 1599 reflections with I>2 σ(I) from one of the twin domains and refined employing 2092 reflections from both crystal domains to an agreement R1 factor of 0.0466. Besides electrostatic attractions, intermolecular pyH···O=C(ace) hydrogen bonds stabilize the acesulfamate anion and the pyridinium cation into planar discrete units parallel to the (100) crystal plane. The units form stacks of alternating ace- and pyH+ ions along the a axis that favors inter-ring π-π interactions. The Fourier transform-infrared (FT-IR) spectrum of the compound was recorded and is briefly discussed. Some comparisons with related pyridinium saccharinate salts are also made.
Structural and IR-spectroscopic characterization of cadmium and lead(II) acesulfamates
Echeverría, Gustavo A.,Piro, Oscar E.,Parajón-Costa, Beatriz S.,Baran, Enrique J.
, p. 739 - 745 (2017)
Cadmium and lead(II) acesulfamate, Cd(C4H4NO4S)2 2H2O and Pb(C4H4NO4S)2, were prepared by the reaction of acesulfamic acid and the respective metal carbonates in aqueous solution, and characterized by elemental analysis. Their crystal structures were determined by single crystal X-ray diffraction methods. The Cd(II) compound crystallizes in the monoclinic space group P21/c with Z = 4 and the corresponding Pb(II) salt in the triclinic space group P1 with Z = 2. In both salts, acesulfamate acts both as a bi-dentate ligand through its nitrogen and carbonyl oxygen atoms and also as a mono-dentate ligand through this same oxygen atom, giving rise to polymeric structures; in the Pb(II) salt the ligand also binds the cation through its sulfoxido oxygen atoms. The FTIR spectra of the compounds were recorded and are briefly discussed. Some comparisons with other related acesulfamate and saccharinate complexes are made.
Polymorphism in acesulfame sweetener: Structure-property and stability relationships of bending and brittle crystals
Velaga, Sitaram P.,Vangala, Venu R.,Basavoju, Srinivas,Bostr?m, Dan
, p. 3562 - 3564 (2010)
Acesulfame is found to exist in two crystalline forms of which Form I (needles) shows bending upon mechanical stress. Crystal structures explain their mechanical response. This is the first case of aliphatic organic compounds featuring a bending phenomenon. Form I is physically more stable than Form II in ambient conditions.
Adapting decarbonylation chemistry for the development of prodrugs capable ofin vivodelivery of carbon monoxide utilizing sweeteners as carrier molecules
Brewer, Maya,Cachuela, Alyssa,De La Cruz, Ladie Kimberly,Gallo, David,Ji, Xingyue,Lu, Wen,Menshikh, Anna,Otterbein, Leo,Tan, Chalet,Wang, Binghe,Wang, Minjia,Wang, Siming,Yang, Haichun,Yang, Xiaoxiao,de Caestecker, Mark
, p. 10649 - 10654 (2021/08/20)
Carbon monoxide as an endogenous signaling molecule exhibits pharmacological efficacy in various animal models of organ injury. To address the difficulty in using CO gas as a therapeutic agent for widespread applications, we are interested in developing CO prodrugs through bioreversible caging of CO in an organic compound. Specifically, we have explored the decarboxylation-decarbonylation chemistry of 1,2-dicarbonyl compounds. Examination and optimization of factors favorable for maximal CO release under physiological conditions led to organic CO prodrugs using non-calorific sweeteners as leaving groups attached to the 1,2-dicarbonyl core. Attaching a leaving group with appropriate properties promotes the desired hydrolysis-decarboxylation-decarbonylation sequence of reactions that leads to CO generation. One such CO prodrug was selected to recapitulate the anti-inflammatory effects of CO against LPS-induced TNF-α production in cell culture studies. Oral administration in mice elevated COHb levels to the safe and efficacious levels established in various preclinical and clinical studies. Furthermore, its pharmacological efficacy was demonstrated in mouse models of acute kidney injury. These studies demonstrate the potential of these prodrugs with benign carriers as orally active CO-based therapeutics. This represents the very first example of orally active organic CO prodrugs with a benign carrier that is an FDA-approved sweetener with demonstrated safety profilesin vivo.
CARBON MONOXIDE PRODRUGS FOR THE TREATMENT OF MEDICAL DISORDERS
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Page/Page column 128-131, (2020/05/21)
The present invention provides new compounds and compositions thereof that release carbon monoxide for the treatment of medical disorders that are responsive to carbon monoxide, for example, inflammatory, pain, and dermatological disorders.
