98-92-0 Usage
description
Nicotinamide aka Vitamin B3 (niacinamide, nicotinic acid amide) is the pyridine 3 carboxylic acid amide form of niacin. It is a water?soluble vitamin that is not stored in the body. The main source of vitamin in diet is in the form of nicotinamide, nicotinic acid, and tryptophan. The main source of niacin include meat, liver, green leafy vegetables, wheat, oat, palm kernel oil, legumes, yeast, mushrooms, nuts, milk, fish, tea, and coffee.The recommended daily dose of vitamin B3 in niacin equivalent is given in Table 1.Nicotinamide is a component of coenzyme I (nicotinamide adenine dinucleotide, NADP) and coenzyme II (nicotinamide adenine dinucleotide phosphate, NADP). The nicotinamide part of these two coenzyme structures in human body has reversible hydrogenation and dehydrogenation characteristics, It plays a hydrogen transfer role in biological oxidation, can promote tissue respiration, biological oxidation process and metabolism, and is of great significance to maintain the integrity of normal tissues, especially skin, digestive tract and nervous system. When lacking, pellagra is caused by the influence of cell respiration and metabolism.
Chemical Properties
Different sources of media describe the Chemical Properties of 98-92-0 differently. You can refer to the following data:
1. It is white needle crystal or crystalline powder, no smell or odor slightly, slightly bitter taste. The relative density is 1.4, melting point is 131-132 ℃.1 g of the above the product is soluble in 1 ml of water, 1.5 ml ethanol or 10 ml glycerin, insoluble in ether. The pH of 10% aqueous solution is 6.5-7.5. in dry air to light and heat stability, in alkaline or acidic solution, heating generation to nicotinic acid. Rats by oral LD502.5-3.5g/kg ADI value does not make special provisions (ECC, 1990)
2. Niacinamide is a white crystalline powder
or forms colorless needle-like crystals.
Uses
Different sources of media describe the Uses of 98-92-0 differently. You can refer to the following data:
1. Nicotinamide is a water-soluble B complex vitamin which is naturally present in animal products, whole cereals and legumes. Together with nicotinic acid (niacin), it belongs to vitamin B3 or vitamin PP, and is required as a nutrient to prevent the niacin deficiency disorder pellagra. It functions as a coenzyme or cosubstrate in many biological reduction and oxidation reactions required for energy metabolism in mammalian systems. It is used as a nutritional supplement, therapeutic agent, skin and hair conditioning agent in cosmetics, and a constituent of consumer household solvent and cleaning products and paints. Nicotinamide is approved for use by the FDA as a food additive to enrich corn meal, farina, rice, and macaroni and noodle products. It is also affirmed as GRAS (Generally Recognized as Safe) by the FDA as a direct human food ingredient which includes its use in infant formula. It is approved for use in pesticide products applied to growing crops only as a synergist with a maximum limitation of 0.5% of formulation.
2. niacinamide is used as a skin stimulant and skin smoother. It is a derivative of niacin, and part of the vitamin B family.
3. Niacinamide is a nutrient and dietary supplement that is an available form of niacin. Nicotinic acid is pyridine beta-carboxylic acid and nicotinamide, which is another term for niacinamide, is the corresponding amide. It is a powder of good water solubility, having a solubility of 1 g in 1 ml of water. Unlike niacin, it has a bitter taste; the taste is masked in the encapsulated form. Used in fortification of cereals, snack foods, and powdered beverages.
4. Niacinamide USP is used as food additive, for multivitamin preparations and as intermediate for pharmaceuticals and cosmetics.
Toxicity
LD50 2.5~3.5 g/kg (rats, through the mouth).
GRAS(FDA，§182.5535，2000).
ADI is no special regulation (EEC, 1990).
Synthesis
1.β-methyl pyridine is oxidized to nicotinic acid by air, and the latter is produced by the action of ammonium hydroxide, and then heating and dehydration.
2.Nicotinic acid, boric acid and ammonia into reaction pot, stirring at the condition of ammonia gas, heating dissolution; then distilled ammonia recovery, to 120℃ after the immigration dewatering pot continues to enrich; when the temperature reached 145 ℃, start adding liquid ammonia, and in 185 to 190℃ to ammonia reaction 20～30h. And then cooled to 130℃, diluted with distilled water, activated carbon was added, and in 70~80℃through ammonia decolorization 2h; reaction after filtered, , filtrate in 24 hours after analysis of cold water, fractional crystallization and washing with ethanol, and drying to obtain the finished product. The yield was 89%.
3. From the nicotinic acid and ammonia react into salt and then dehydrated.
Originator
Niacinamide,Twinlab
Definition
ChEBI: A pyridinecarboxamide that is pyridine in which the hydrogen at position 3 is replaced by a carboxamide group.
Manufacturing Process
Gaseous ammonia was passed into nicotinic acid at a temperature between
200-235°C until the conversion to nicotinamide was 85%. The reaction
mixture was colored light brown. The reaction mass was cooled and grounds
to a fine powder. Fifty grams of this crude nicotinamide were boiled with 500
ml of anhydrous ethyl acetate until a dark solution was. obtained. A little solid remained in suspension. Gaseous ammonia was passed in below the surface
of the ethyl acetate at a temperature between 60-70°C. After a short time
ammonium nicotinate started to precipitate out of solution as a brown solid.
Sufficient gaseous ammonia, was passed into the ethyl acetate solution to
insure complete precipitation of the nicotinic acids as ammonium nicotinate.
The solution was filtered at about 60-70°C. The filter cake consisted of
ammonium nicotinate, which, upon drying, weighed 12.4 grams. The filtrate
was stirred arid boiled for 20 minutes with one-half gram of activated carbon
and two grams of activated adsorbent clay. The mixture was filtered hot. The
filtrate was boiled twenty minutes with one-half gram of activated carbon and
two grams of activated adsorbent clay and then filtered hot. The carbon and
clay treatment was repeated once more. The final filtrate was cooled slowly
with stirring to room temperature to precipitate white crystalline nieocinamide
which, upon drying, weighed 26.7 grams and had a melting point of 129.5°C,
and was over 99 percent pure. The mother liquor from the above filtration
was boiled down to one-third of its volume and cooled to room temperature. A
second crop of nicotinamide of three grams was obtained.
Synthesis Reference(s)
Journal of the American Chemical Society, 76, p. 5774, 1954 DOI: 10.1021/ja01651a043Tetrahedron Letters, 36, p. 8657, 1995 DOI: 10.1016/0040-4039(95)01785-G
General Description
Different sources of media describe the General Description of 98-92-0 differently. You can refer to the following data:
1. Vitamin B3 was formerly called nicotinic acid; however, the term niacin is now preferred to avoid any confusion with the alkaloid, nicotine. Niacinamide, also known as nicotinamide, refers to the amide derivative of niacin that is equivalent in vitamin activity. Some texts use niacin to refer to nicotinic acid, niacinamide, and any derivatives with vitamin activity comparable to niacin. Furthermore, research and chemistry-based resources use the terms nicotinic acid and nicotinamide; whereas pharmacy resources use niacin and niacinamide.
2. White powder.
Air & Water Reactions
Water soluble.
Reactivity Profile
An amine and amide. Acts as a weak base in solution. Amines are chemical bases. They neutralize acids to form salts plus water. These acid-base reactions are exothermic. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides. Organic amides/imides react with azo and diazo compounds to generate toxic gases. Flammable gases are formed by the reaction of organic amides/imides with strong reducing agents. Amides are very weak bases (weaker than water). Imides are less basic yet and in fact react with strong bases to form salts. That is, they can react as acids. Mixing amides with dehydrating agents such as P2O5 or SOCl2 generates the corresponding nitrile. The combustion of these compounds generates mixed oxides of nitrogen (NOx).
Flammability and Explosibility
Nonflammable
Biochem/physiol Actions
Nicotinamide is an amide derivative of vitamin B3 and a PARP inhibitor
Clinical Use
Niacin is used in the treatment of niacin deficiency, which is referred to as pellagra (from the Italian, pelle for “skin” and agra for “dry”). The major systems affected are the gastrointestinal tract (diarrhea, enteritis and stomatitis), the skin (dermatitis), and the CNS (generalized neurological deficits including dementia). Pellagra has become a rare condition in the United States and other countries that require or encourage enrichment of wheat flour or fortification of cereals with niacin. Because the nucleotide form can be synthesized in vivo from tryptophan, pellagra is most often seen in areas where the diet is deficient in both niacin and tryptophan. Typically, maize (corn)-based diets meet this criteria. Niacin deficiency can also result from diarrhea, cirrhosis, alcoholism, or Hartnup disease. It is interesting that niacin deficiency can also, rarely, result from vitamin B6 deficiency (see Vitamin B6 section). Niacin, but not niacinamide, is also one of the few vitamins that are useful in the treatment of diseases unrelated to deficiencies.
Safety Profile
Nicotinamide is a safe and inexpensive compound with negligible side effects. It is well tolerated even in doses of 1g/day to 3g/day.There are no reports of teratogenicity with nicotinamide. Minor side effects include nausea, vomiting, headache, fatigue. It does not cause vasodilatory side effects like flushing, alteration in blood pressure, body temperature or pulse as seen with niacin.In topical formulation, it does not cause skin irritation, photosensitization in concentrations of 0.0001% to 4%.
Potential Exposure
Used as a dietary supplement and
food additive.
Metabolism
Nicotinamide is ingested in food as part of pyridine nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) in plant and animal tissues. After the co?enzymes have separated, nicotinamide is absorbed almost completely in the small intestine. After absorption, nicotinamide is stored as NAD in the liver and excretion occurs via kidneys. Tryptophan is converted to nicotinamide through kynurenine?anthranilate pathway in the liver. Tryptophan can thus satisfy the requirement for dietary nicotinic acid.
Purification Methods
Crystallise niacin from *benzene. It has solubility in g/ml: H2O (1), EtOH (0.7) and glycerol (0.1). [Methods in Enzymology 66 23 1980, UV: Armarego Physical Methods in Heterocyclic Chemistry (Ed Katritzky, Academic Press) Vol III 83 1971, Beilstein 22 III/IV 389, 22/2 V 80.]
Incompatibilities
Combustible solid; dust may form explosive
mixture with air. Amides are incompatible with oxidizers
(chlorates, nitrates, peroxides, permanganates,
perchlorates, chlorine, bromine, fluorine, etc.); contact may
cause fires or explosions. Keep away from alkaline materials,
strong bases, strong acids, oxoacids, epoxides.
References
Zapata-Pérez et al. (2021), NAD+ homeostasis in human health and disease; EMBO Mol. Med., 13 e13943
Guan et al. (2014), Mechanism of inhibition of the human sirtuin enzyme SIRT3 by nicotinamide: computational and experimental studies; PLoS One, 9 e107729
Hwang and Song (2017), Nicotinamide is an inhibitor of SIRT1 in vitro, but can be a stimulator in cells; Mol. Life Sci., 74 3347
Meng et al. (2018), Nicotinamide Promotes Cell Survival and Differentiation as Kinase Inhibitor in Human Pluripotent Stem Cells; Stem Cell Reports, 11 1347
Horwitz et al. (2014), Umbilical cord blood expansion with nicotinamide provides long-term multilineage engraftment; Clin. Invest., 124 3121
Check Digit Verification of cas no
The CAS Registry Mumber 98-92-0 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 9 and 8 respectively; the second part has 2 digits, 9 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 98-92:
(4*9)+(3*8)+(2*9)+(1*2)=80
80 % 10 = 0
So 98-92-0 is a valid CAS Registry Number.
InChI:InChI=1/C6H6N2O/c7-6(9)5-2-1-3-8-4-5/h1-4H,(H2,7,9)
98-92-0Relevant articles and documents
Nitrogen Atom Transfer Catalysis by Metallonitrene C?H Insertion: Photocatalytic Amidation of Aldehydes
Schmidt-R?ntsch, Till,Verplancke, Hendrik,Lienert, Jonas N.,Demeshko, Serhiy,Otte, Matthias,Van Trieste, Gerard P.,Reid, Kaleb A.,Reibenspies, Joseph H.,Powers, David C.,Holthausen, Max C.,Schneider, Sven
, (2022/01/20)
C?H amination and amidation by catalytic nitrene transfer are well-established and typically proceed via electrophilic attack of nitrenoid intermediates. In contrast, the insertion of (formal) terminal nitride ligands into C?H bonds is much less developed and catalytic nitrogen atom transfer remains unknown. We here report the synthesis of a formal terminal nitride complex of palladium. Photocrystallographic, magnetic, and computational characterization support the assignment as an authentic metallonitrene (Pd?N) with a diradical nitrogen ligand that is singly bonded to PdII. Despite the subvalent nitrene character, selective C?H insertion with aldehydes follows nucleophilic selectivity. Transamidation of the benzamide product is enabled by reaction with N3SiMe3. Based on these results, a photocatalytic protocol for aldehyde C?H trimethylsilylamidation was developed that exhibits inverted, nucleophilic selectivity as compared to typical nitrene transfer catalysis. This first example of catalytic C?H nitrogen atom transfer offers facile access to primary amides after deprotection.
Mechanochemical Synthesis of Primary Amides
Gómez-Carpintero, Jorge,Sánchez, J. Domingo,González, J. Francisco,Menéndez, J. Carlos
, p. 14232 - 14237 (2021/10/20)
Ball milling of aromatic, heteroaromatic, vinylic, and aliphatic esters with ethanol and calcium nitride afforded the corresponding primary amides in a transformation that was compatible with a variety of functional groups and maintained the integrity of a stereocenter α to carbonyl. This methodology was applied to α-amino esters and N-BOC dipeptide esters and also to the synthesis of rufinamide, an antiepileptic drug.
Activated Mont K10-Carbon supported Fe2O3: A versatile catalyst for hydration of nitriles to amides and reduction of nitro compounds to amines in aqueous media
Rahman, Taskia,Borah, Geetika,Gogoi, Pradip K
, (2021/03/14)
The iron oxide was successfully supported on activated clay/carbon through an experimentally viable protocol for both hydrations of nitrile to amide and reduction of nitro compounds to amines. The as-prepared catalyst has been extensively characterised by XPS, SEM-EDX, TEM, TGA, BET surface area measurements and powdered X-ray diffraction (PXRD). A wide variety of substrates could be converted to the desired products with good to excellent yields by using water as a green solvent for both the reactions. The catalyst was recyclable and reusable up to six consecutive cycles without compromising its catalytic proficiency. Graphical abstract: Activated Mont K10 carbon-supported Fe2O3 is a very efficient and versatile heterogeneous catalytic system for hydration of nitriles to amides and reduction of nitro compounds to amines and can be reused up to six consecutive cycles without significant loss in catalytic activity.[Figure not available: see fulltext.].
Amide bond formation in aqueous solution: Direct coupling of metal carboxylate salts with ammonium salts at room temperature
Nielsen, John,Tung, Truong Thanh
supporting information, p. 10073 - 10080 (2021/12/10)
Herein, we report a green, expeditious, and practically simple protocol for direct coupling of carboxylate salts and ammonium salts under ACN/H2O conditions at room temperature without the addition of tertiary amine bases. The water-soluble coupling reagent EDC·HCl is a key component in the reaction. The reaction runs smoothly with unsubstituted/substituted ammonium salts and provides a clean product without column chromatography. Our reaction tolerates both carboxylate (which are unstable in other forms) and amine salts (which are unstable/volatile when present in free form). We believe that the reported method could be used as an alternative and suitable method at the laboratory and industrial scales. This journal is
Dihydronicotinamide riboside: synthesis from nicotinamide riboside chloride, purification and stability studies
Abbaspourrad, Alireza,Enayati, Mojtaba,Khazdooz, Leila,Madarshahian, Sara,Ufheil, Gerhard,Wooster, Timothy J.,Zarei, Amin
, p. 21036 - 21047 (2021/07/01)
In the present work, we describe an efficient method for scalable synthesis and purification of 1,4-dihydronicotinamide riboside (NRH) from commercially available nicotinamide riboside chloride (NRCl) and in the presence of sodium dithionate as a reducing agent. NRH is industrially relevant as the most effective, synthetic NAD+precursor. We demonstrated that solid phase synthesis cannot be used for the reduction of NRCl to NRH in high yield, whereas a reduction reaction in water at room temperature under anaerobic conditions is shown to be very effective, reaching a 55% isolation yield. For the first time, by using common column chromatography, we were able to highly purify this sensitive bio-compound with good yield. A series of identifications and analyses including HPLC, NMR, LC-MS, FTIR, and UV-vis spectroscopy were performed on the purified sample, confirming the structure of NRH as well as its purity to be 96%. Thermal analysis of NRH showed higher thermal stability compared to NRCl, and with two major weight losses, one at 218 °C and another at 805 °C. We also investigated the long term stability effects of temperature, pH, light, and oxygen (as air) on the NRH in aqueous solutions. Our results show that NRH can be oxidized in the presence of oxygen, and it hydrolyzed quickly in acidic conditions. It was also found that the degradation rate is lower under a N2atmosphere, at lower temperatures, and under basic pH conditions.
Ring Opening/Site Selective Cleavage in N-Acyl Glutarimide to Synthesize Primary Amides
Govindan, Karthick,Lin, Wei-Yu
supporting information, p. 1600 - 1605 (2021/03/03)
A LiOH-promoted hydrolysis selective C-N cleavage of twisted N-acyl glutarimide for the synthesis of primary amides under mild conditions has been developed. The reaction is triggered by a ring opening of glutarimide followed by C-N cleavage to afford primary amides using 2 equiv of LiOH as the base at room temperature. The efficacy of the reactions was considered and administrated for various aryl and alkyl substituents in good yield with high selectivity. Moreover, gram-scale synthesis of primary amides using a continuous flow method was achieved. It is noted that our new methodology can apply under both batch and flow conditions for synthetic and industrial applications.
Direct Oxidative Amination of the Methyl C-H Bond in N-Heterocycles over Metal-Free Mesoporous Carbon
Long, Xiangdong,Wang, Jia,Gao, Guang,Nie, Chao,Sun, Peng,Xi, Yongjie,Li, Fuwei
, p. 10902 - 10912 (2021/09/08)
Direct oxidative amination of the sp3C-H bond is an attractive synthesis route to obtain amides. Conventional catalytic systems for this transformation are based on transition metals and complicated synthesis processes. Herein, direct and efficient oxidative amination of the methyl C-H bond in a wide range of N-heterocycles to access the corresponding amides over metal-free porous carbon is successfully developed. To understand the fundamental structure-activity relationships of carbon catalysts, the surface functional groups and the graphitization degree of porous carbon have been purposefully tailored through doping with nitrogen or phosphorus. The results of characterization, kinetic studies, liquid-phase adsorption experiments, and theoretical calculations indicate that the high activity of the carbon catalyst is attributed to the synergistic effect of surface acidic functional groups (hydroxyl/carboxylic acid/phosphate) and more graphene edge structures exposed on the surface of carbon materials with a high graphitization degree, in which the role of acidic functional groups is to adsorb the substrate molecule and the role of the graphene edge structure is to activate O2
Aerobic oxidation of primary amines to amides catalyzed by an annulated mesoionic carbene (MIC) stabilized Ru complex
Yadav, Suman,Reshi, Noor U Din,Pal, Saikat,Bera, Jitendra K.
, p. 7018 - 7028 (2021/11/17)
Catalytic aerobic oxidation of primary amines to the amides, using the precatalyst [Ru(COD)(L1)Br2] (1) bearing an annulated π-conjugated imidazo[1,2-a][1,8]naphthyridine-based mesoionic carbene ligand L1, is disclosed. This catalytic protocol is distinguished by its high activity and selectivity, wide substrate scope and modest reaction conditions. A variety of primary amines, RCH2NH2 (R = aliphatic, aromatic and heteroaromatic), are converted to the corresponding amides using ambient air as an oxidant in the presence of a sub-stoichiometric amount of KOtBu in tBuOH. A set of control experiments, Hammett relationships, kinetic studies and DFT calculations are undertaken to divulge mechanistic details of the amine oxidation using 1. The catalytic reaction involves abstraction of two amine protons and two benzylic hydrogen atoms of the metal-bound primary amine by the oxo and hydroxo ligands, respectively. A β-hydride transfer step for the benzylic C-H bond cleavage is not supported by Hammett studies. The nitrile generated by the catalytic oxidation undergoes hydration to afford the amide as the final product. This journal is
Product selectivity controlled by manganese oxide crystals in catalytic ammoxidation
Hui, Yu,Luo, Qingsong,Qin, Yucai,Song, Lijuan,Wang, Hai,Wang, Liang,Xiao, Feng-Shou
, p. 2164 - 2172 (2021/09/20)
The performances of heterogeneous catalysts can be effectively tuned by changing the catalyst structures. Here we report a controllable nitrile synthesis from alcohol ammoxidation, where the nitrile hydration side reaction could be efficiently prevented by changing the manganese oxide catalysts. α-Mn2O3 based catalysts are highly selective for nitrile synthesis, but MnO2-based catalysts including α, β, γ, and δ phases favour the amide production from tandem ammoxidation and hydration steps. Multiple structural, kinetic, and spectroscopic investigations reveal that water decomposition is hindered on α-Mn2O3, thus to switch off the nitrile hydration. In addition, the selectivity-control feature of manganese oxide catalysts is mainly related to their crystalline nature rather than oxide morphology, although the morphological issue is usually regarded as a crucial factor in many reactions.
Catalyst-Free N-Deoxygenation by Photoexcitation of Hantzsch Ester
Cardinale, Luana,Jacobi Von Wangelin, Axel,Konev, Mikhail O.
supporting information, (2020/02/15)
A mild and operationally simple protocol for the deoxygenation of a variety of heteroaryl N-oxides and nitroarenes has been developed. A mixture of substrate and Hantzsch ester is proposed to result in an electron donor-acceptor complex, which upon blue-light irradiation undergoes photoinduced electron transfer between the two reactants to afford the products. N-oxide deoxygenation is demonstrated with 22 examples of functionally diverse substrates, and the chemoselective reduction of nitroarenes to the corresponding hydroxylamines is also shown.
