69-65-8 Usage
Description
A white, crystalline solid consisting of D-mannitol and a small
quantity of sorbitol. It is odorless and has a sweet taste. It is soluble
in water, very slightly soluble in alcohol, and practically insoluble
in most other common organic solvents. It is prepared commercially by catalytic reduction of glucose. Mannitol occurs in small
amounts in a variety of foods such as olives, beets, and celery, and
in the exudate of certain trees.
Chemical Properties
Different sources of media describe the Chemical Properties of 69-65-8 differently. You can refer to the following data:
1. Mannitol is D-mannitol. It is a hexahydric alcohol related to
mannose and is isomeric with sorbitol.
Mannitol occurs as a white, odorless, crystalline powder, or freeflowing
granules. It has a sweet taste, approximately as sweet as
glucose and half as sweet as sucrose, and imparts a cooling
sensation in the mouth. Microscopically, it appears as orthorhombic
needles when crystallized from alcohol. Mannitol shows
polymorphism.
2. White or almost white, crystalline powder or free-flowing granules.
Originator
Mannitol,MSD,US,1946
Uses
Different sources of media describe the Uses of 69-65-8 differently. You can refer to the following data:
1. inhibitor of norepinephrine and seritonin uptake, treatment of fibromyalgia
2. Labelled D-Mannitol (M165000). D-Mannitol is widespread in plants and plant exudates; obtained from manna and seaweeds. D-Mannitol is used in the food industry as anticaking and free-flow agent, flavo
ring agent, lubricant and release agent, stabilizer and thickener and nutritive sweetener.
3. Used in titrimetric determination of boric acid.
4. Used with boric acid in the manufacture of dry electrolytic condensers for radio applications; in making artificial resins and plasticizers; in pharmacy as excipient and diluent for solids and liqs; in analytical chemistry for boron determinations; in the manufacture of mannitol hexanitrate. Used in the food industry as anticaking and free-flow agent, flavoring agent, lubricant and release agent, stabilizer and thickener and nutritive sweetener.
Definition
ChEBI: The D-enantiomer of mannitol.
Production Methods
Mannitol may be extracted from the dried sap of manna and other
natural sources by means of hot alcohol or other selective solvents.
It is commercially produced by the catalytic or electrolytic reduction
of monosaccharides such as mannose and glucose.
Manufacturing Process
250 g of glucose is dissolved in distilled water to give a solution of 48% concentration. This solution is heated to 65°C and barium hydroxide added in quantity sufficient to make the concentration of the barium hydroxide 0.2 mol/liter. The solution is agitated and maintained at 65°C for 6 hours after the addition of the barium hydroxide. It is then cooled and neutralized to a pH of 6.8 with sulfuric acid. The precipitated barium sulfate is filtered out. A quantity of activated supported nickel catalyst containing 5 g of nickel is added.The slurry is introduced into a 3-liter rocking autoclave, and hydrogen
admitted to a pressure of 1,500 psi. The autoclave is heated to a temperature
of 150°C in one hour and held at this temperature for 2.5 hours more.
Pressure rises to about 1,800 psi and then declines to about 1,600 during the
hydrogenation. The autoclave is then cooled, emptied, and the catalyst filtered
from the product. The filtrate is then concentrated under vacuum on a hot
water bath to remove a part of the water.The concentrate is taken up in warm aqueous methanol so adjusted that the
composition of the solvent is 90% methanol/10% water, and the weight of the
solvent is 3 times the weight of the solids in the concentrate. This solution is
cooled to 20°C and held overnight. The mannitol which crystallizes is filtered
out. The filtrate is concentrated on a water bath under vacuum to remove
methanol and adjusted to a water percentage of 16%. The resulting syrup is
viscous, noncrystallizing and nongelling, and analysis shows a PN (Pyridine
Number) of 32 and essentially no reducing sugar, according to US Patent
2,749,371.
Brand name
Osmitrol (Baxter Healthcare); Resectisol (B Braun).
Therapeutic Function
Diuretic, Diagnostic aid (kidney function)
General Description
Odorless white crystalline powder or free-flowing granules. Sweet taste.
Air & Water Reactions
Water soluble.
Reactivity Profile
A sugar alcohol. More closely related to carbohydrates than to other polyhydric alcohols [Noller]. Flammable and/or toxic gases are generated by the combination with alkali metals, nitrides, strong reducing agents and strong oxidizing agents.
Hazard
Mildly toxic; mutagen.
Fire Hazard
D-Mannitol is probably combustible.
Pharmaceutical Applications
Mannitol is widely used in pharmaceutical formulations and food
products. In pharmaceutical preparations it is primarily used as a
diluent (10–90% w/w) in tablet formulations, where it is of
particular value since it is not hygroscopic and may thus be used
with moisture-sensitive active ingredients.
Mannitol may be used in direct-compression tablet applications,for which the granular and spray-dried forms are
available, or in wet granulations.Granulations containing
mannitol have the advantage of being dried easily. Specific tablet
applications include antacid preparations, glyceryl trinitrate tablets,
and vitamin preparations. Mannitol is commonly used as an
excipient in the manufacture of chewable tablet formulations
because of its negative heat of solution, sweetness, and ‘mouth
feel’.
In lyophilized preparations, mannitol (20–90% w/w) has been
included as a carrier to produce a stiff, homogeneous cake that
improves the appearance of the lyophilized plug in a vial.A
pyrogen-free form is available specifically for this use.
Mannitol has also been used to prevent thickening in aqueous
antacid suspensions of aluminum hydroxide (<7% w/v). It has been
suggested as a plasticizer in soft-gelatin capsules, as a component of
sustained-release tablet formulations,and as a carrier in dry
powder inhalers.It is also used as a diluent in rapidly
dispersing oral dosage forms.It is used in food applications as
a bulking agent.
Therapeutically, mannitol administered parenterally is used as
an osmotic diuretic, as a diagnostic agent for kidney function, as an
adjunct in the treatment of acute renal failure, and as an agent to
reduce intracranial pressure, treat cerebral edema, and reduce
intraocular pressure. Given orally, mannitol is not absorbed
significantly from the gastrointestinal tract, but in large doses it
can cause osmotic diarrhea;
Biochem/physiol Actions
A sugar alcohol sweet tastant. Used in sweetness inhibition studies.
Safety
Mannitol is a naturally occurring sugar alcohol found in animals
and plants; it is present in small quantities in almost all vegetables.
Laxative effects may occur if mannitol is consumed orally in large
quantities.If it is used in foods as a bodying agent and daily
ingestion of over 20g is foreseeable, the product label should bear
the statement ‘excessive consumption may have a laxative effect’.
After intravenous injection, mannitol is not metabolized to any
appreciable extent and is minimally reabsorbed by the renal tubule,
about 80% of a dose being excreted in the urine in 3 hours.
A number of adverse reactions to mannitol have been reported,
primarily following the therapeutic use of 20% w/v aqueous
intravenous infusions.The quantity of mannitol used as an
excipient is considerably less than that used therapeutically and is
consequently associated with a lower incidence of adverse reactions.
However, allergic, hypersensitive-type reactions may occur when
mannitol is used as an excipient.An acceptable daily intake of mannitol has not been specified by
the WHO since the amount consumed as a sweetening agent was
not considered to represent a hazard to health.
LD50 (mouse, IP): 14 g/kg
LD50 (mouse, IV): 7.47 g/kg
LD50 (mouse, oral): 22 g/kg
LD50 (rat, IV): 9.69 g/kg
LD50 (rat, oral): 13.5 g/kg
storage
Mannitol is stable in the dry state and in aqueous solutions.
Solutions may be sterilized by filtration or by autoclaving and if
necessary may be autoclaved repeatedly with no adverse physical or
chemical effects.In solution, mannitol is not attacked by cold,
dilute acids or alkalis, nor by atmospheric oxygen in the absence of
catalysts. Mannitol does not undergo Maillard reactions.
The bulk material should be stored in a well-closed container in a
cool, dry place.
Purification Methods
D-Mannitol is crystallised from EtOH, MeOH or H2O and dried at 100o. [Thomson Acta Chem Scand 6 270, 279, 280 1952, Beilstein 1 IV 2841.]
Incompatibilities
Mannitol solutions, 20% w/v or stronger, may be salted out by
potassium chloride or sodium chloride.Precipitation has been
reported to occur when a 25% w/v mannitol solution was allowed
to contact plastic.Sodium cephapirin at 2 mg/mL and 30 mg/mL
concentration is incompatible with 20% w/v aqueous mannitol
solution. Mannitol is incompatible with xylitol infusion and may
form complexes with some metals such as aluminum, copper, and
iron. Reducing sugar impurities in mannitol have been implicated in
the oxidative degradation of a peptide in a lyophilized formation.Mannitol was found to reduce the oral bioavailability of
cimetidine compared to sucrose.
Regulatory Status
GRAS listed. Accepted for use as a food additive in Europe.
Included in the FDA Inactive Ingredients Database (IP, IM, IV, and
SC injections; infusions; buccal, oral and sublingual tablets,
powders and capsules; ophthalmic preparations; topical solutions).
Included in nonparenteral and parenteral medicines licensed in the
UK. Included in the Canadian List of Acceptable Mon-medicinal
Ingredients.
Check Digit Verification of cas no
The CAS Registry Mumber 69-65-8 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 6 and 9 respectively; the second part has 2 digits, 6 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 69-65:
(4*6)+(3*9)+(2*6)+(1*5)=68
68 % 10 = 8
So 69-65-8 is a valid CAS Registry Number.
InChI:InChI=1/C6H14O6/c7-1-3(9)5(11)6(12)4(10)2-8/h3-12H,1-2H2/t3-,4-,5-,6+/m0/s1
69-65-8Relevant articles and documents
-
Raistrick,Smith
, p. 1814 (1933)
-
Stelliosphaerols A and B, Sesquiterpene-Polyol Conjugates from an Ecuadorian Fungal Endophyte
Forcina, Giovanni C.,Castro, Amaya,Bokesch, Heidi R.,Spakowicz, Daniel J.,Legaspi, Michelle E.,Kucera, Kaury,Villota, Stephany,Narvez-Trujillo, Alexandra,McMahon, James B.,Gustafson, Kirk R.,Strobel, Scott A.
, p. 3005 - 3010 (2015)
Endophytic fungi are plant tissue-associated fungi that represent a rich resource of unexplored biological and chemical diversity. As part of an ongoing effort to characterize Amazon rainforest-derived endophytes, numerous fungi were isolated and cultured from plants collected in the Yasun National Park in Ecuador. Of these samples, phylogenetic and morphological data revealed a previously undescribed fungus in the order Pleosporales that was cultured from the tropical tree Duroia hirsuta. Extracts from this fungal isolate displayed activity against Staphylococcus aureus and were thus subjected to detailed chemical studies. Two compounds with modest antibacterial activity were isolated, and their structures were elucidated using a combination of NMR spectroscopic analysis, LC-MS studies, and chemical degradation. These efforts led to the identification of stelliosphaerols A (1) and B (2), new sesquiterpene-polyol conjugates that are responsible, at least in part, for the S. aureus inhibitory activity of the fungal extract.
Swan,Hayward
, p. 856,857, 859 (1956)
Seven new drimane-type sesquiterpenoids from a marine-derived fungus paraconiothyrium sporulosum YK-03
Zhang, Li-Hua,Chen, Gang,Sun, Yi,Wang, Hai-Feng,Bai, Jiao,Hua, Hui-Ming,Pei, Yue-Hu
, (2019)
Seven new drimane-type sesquiterpenoids, namely the sporulositols A-D (1-4), 6-hydroxydiaporol (5), seco-sporulositol (6) and sporuloside (7) were isolated from the ethyl acetate extract of fermentation broth for a marine-derived fungus Paraconiothyrium sporulosum YK-03. Their structureswere elucidated by analysis of extensive spectroscopic data, and the absolute configurations were established by crystal X-ray diffraction analysis and comparisons of circular dichroism data. Among them, sporulositols A-E (1-4) and seco-sporulositol (6) represent the first five examples of a unique class of drimanic mannitol derivatives, while compounds 6 and 7 may represent two new series of natural drimanes, possessing an aromatic ring with a rare 4,5-secodrimanic skeleton and an unusual CH3-15 rearranged drimanic α-D-glucopyranside, respectively. Furthermore, the origin of mannitol moiety was investigated by reliable HPLC and NMR analyses.
Selective hydrogenation of d-mannose to d-mannitol using NiO-modified TiO2 (NiO-TiO2) supported ruthenium catalyst
Mishra, Dinesh Kumar,Hwang, Jin-Soo
, p. 13 - 19 (2013)
NiO-modified TiO2 (NiO-TiO2) supported ruthenium catalyst Ru/(NiO-TiO2) is prepared by simple impregnation method and characterized by using energy dispersive X-ray analysis (EDX/EDS), temperature- programmed reduction (TPR), inductively coupled plasma (ICP) mass spectrometry, transmission electron microscopy (TEM), X-ray powder diffraction (XRD) and CO chemisorption. The catalyst Ru/(NiO-TiO2) is evaluated in d-mannose hydrogenation and hydrogenation experiments to produce a selective product d-mannitol were carried out batch wise in a three-phase laboratory scale reactor. A tentative mechanism for reduction of d-mannose is presented. The kinetics of d-mannose hydrogenation to d-mannitol using catalyst Ru/(NiO-TiO2) was studied. The kinetic data were modeled by zero, first and second-order reaction equations. A set of four experiments was also carried out to test the deactivation of the catalyst. For affording maximum d-mannose conversion, yield and selectivity to d-mannitol, the reaction conditions are optimized.
Efficient Synthesis of Sugar Alcohols over a Synergistic and Sustainable Catalyst
Lin, Lu,Qiu, Jiarong,Sun, Yong,Tang, Xing,Zeng, Xianhai,Zhang, Liangqing
, p. 2467 - 2476 (2021/07/16)
A series of catalysts were prepared for sugar alcohols production to overcome the deficiencies of the previous reported catalysts, such as low yield of sugar alcohols, single function, instability, and controversial role of active sites. The role of each metal and their synergistic-cooperation was discussed in detail with a combination of conditional experiments and characterizations. The results indicated that bifunctional Ni6.66Fe1Al1.55 catalyst has unique structure with superparamagnetism and excellent activity. The (111) and (200) planes of metallic Ni are the hydrogenation active phases and preferentially exposed on Ni-Al-Ox spinel. The desired arabitol or mannitol was obtained by tuning the ratio of Br?nsted and Lewis acid sites. The recycling tests indicated that the unique structure of the prepared Ni-based catalyst can suppress leaching and poisoning, which has high textural stability and activity.
Product Control and Insight into Conversion of C6 Aldose Toward C2, C4 and C6 Alditols in One-Pot Retro-Aldol Condensation and Hydrogenation Processes
Gao, Lou,Hou, Wenrong,Hui, Yingshuang,Tang, Yi,Zhan, Yulu,Zhang, Yahong
, p. 560 - 566 (2021/06/25)
Alcohols have a wide range of applicability, and their functions vary with the carbon numbers. C6 and C4 alditols are alternative of sweetener, as well as significant pharmaceutical and chemical intermediates, which are mainly obtained through the fermentation of microorganism currently. Similarly, as a bulk chemical, C2 alditol plays a decisive role in chemical synthesis. However, among them, few works have been focused on the chemical production of C4 alditol yet due to its difficult accumulation. In this paper, under a static and semi-flowing procedure, we have achieved the product control during the conversion of C6 aldose toward C6 alditol, C4 alditol and C2 alditol, respectively. About C4 alditol yield of 20 % and C4 plus C6 alditols yield of 60 % are acquired in the one-pot conversion via a cascade retro-aldol condensation and hydrogenation process. Furthermore, in the semi-flowing condition, the yield of ethylene glycol is up to 73 % thanks to its low instantaneous concentration.
