54-11-5 Usage
Uses
1. Agricultural Uses:
Used in Insecticides:
Nicotine is used as an insecticide and fumigant, classified for restricted use and limited to use by or under the direct supervision of a certified applicator. It is not listed for use in EU countries but is registered for use in the U.S. and Canada as a U.S. EPA restricted Use Pesticide (RUP).
2. Medical Uses:
Used in Smoking Cessation Aids:
Nicotine is used in the treatment of smoking withdrawal syndrome and as a smoking cessation aid in the form of alternate delivery systems such as gums and dermal patches.
Used in Pharmaceutical Applications:
Nicotine is used medically for numerous conditions, and its use is being explored in additional areas, including pain relievers, attention deficit disorder medications, and medications associated with Alzheimer's disease, Parkinson's disease, colitis, herpes, and tuberculosis.
3. Recreational Use:
Used as a Stimulant:
Nicotine is the second most widely used recreational drug after caffeine. At low doses, it acts as a stimulant to the central nervous system by activating acetylcholine receptors in the postsynaptic neurons during nerve transmission.
4. Chemical Properties:
Used as a Prototype Nicotinic Acetylcholine Receptor Agonist:
(S)-(-)-Nicotine is a prototype nicotinic acetylcholine receptor agonist and the naturally occurring isomer. It can be absorbed through the alimentary canal, respiratory tract, and intact skin.
5. Tanning Industry:
Used in Tanning:
Nicotine and its salts are used in the tanning industry, although the specific application reason is not provided in the materials.
6. Pesticide Applications:
Used as a Pesticide:
Nicotine solutions made from soaking tobacco leaves in water have been used as pesticides for several hundred years.
Brand Names:
Habitrol (Novartis), Nicoderm (Sanofi Aventis), Nicotrol (Pharmacia & Upjohn), Prostep (Aveva).
alkaloid
Nicotine is the substance in tobacco, nicotine content of tobacco because there are different species and origin, alkali content of tobacco each part is different. Cigarette factory scraps (tobacco powder) containing about 1% to 2% of the nicotine, tobacco stems and ribs smoke nicotine containing about 1% or so, people smoked cigarette contains nicotine amounted to about 3%. Pure nicotine is a colorless, oily liquid, miscible with water below 60 ℃, hydrate, more than 210 ℃ also miscible with water. Unstable nature, likely to be volatile, soluble in water and organic solvents. Nicotine is an alkaloid, so all properties of a base, to a compound made of salts and acids. In case of light and air turn brown and sticky, there is the odd smell and strong irritant.
Toxicity
Pure nicotine for people, livestock highly toxic rat oral LD50 of 50~60mg/kg, rabbit acute percutaneous LD5050mg/kg.
Rabbit acute percutaneous LD50 for 50~60mg/kg, rabbit acute oral LD50 of 50mg/kg. Based on China's pesticide toxicity
grading standards, is a highly toxic pesticides. However, because of volatile and rapidly decompose in air and light, and
therefore can still be used to control pests on crops. Rapidly absorbed through the skin, inhalation and dermal exposure to
toxic people. Toxic to birds. Young steelhead LC504mg/L, toxic to bees, but there insecticide effect. D. Pulex LC50 of
0.24mg/L. Fish and shellfish toxicity, mild injury to crops.
Originator
Nicotinell TTS,Novartis
Production Methods
The nicotine molecule consists of a pyrrolidine ring attached to a pyridine ring by a bondbetween carbon atoms in the two-ring systems. Nicotine was isolated in impure form fromtobacco in 1809 by Louis Nicholas-Vauquelin (1763–1829). Vauquelin called the substancenicotianine. In 1826, Wilhelm Posselt (1806–1877) and Karl Ludwig Reimann (1804–1872),medical students at Heidelberg University, isolated pure nicotine and published dissertationson its pharmacology in 1828. Louis Henri Melsens (1814–1886) determined nicotine’sempirical formula. Amé Pictet (1857–1937) and P. Crépieux reported the synthesis of nicotine in 1903.
Manufacturing Process
The water extract from Nicotiana tabacum was prepared by distillation of
nicotine contained liquor from tobacco leaves, as described in D.R. Patent No.
319,846; September 12, 1913.5 kg this water extract or the same quantity of tobacco powder in water was
mixed with 1.5 kg of grinded calcium hydroxide and 1.5 kg calcium sulfate.
The mixture stood for 24 hours. The obtained mixture looked like a dry
powder. It was extracted with ether. The ether was distilled and the residue
contented 98% of clear nicotine - liquid with odor of pyridine; BP: 246C/735
mm; d4
20 =1.0097; [α]d
20=- 166.5.
Therapeutic Function
Ganglion depressant, Smoking deterrent
Air & Water Reactions
Flammable. Slightly soluble in water.
Reactivity Profile
An alkaloid produced from tobacco. Colorless, oily liquid, combustible, highly toxic. When heated to decomposition L-Nicotine emits very toxic fumes of carbon monoxide and oxides of nitrogen [Lewis, 3rd ed., 1993, p. 919].
Hazard
Toxic by ingestion, inhalation, and skin
absorption. Gastrointestinal damage, central nervous system impairment, and cardiac impairment
Health Hazard
Nicotine is a highly toxic compound. It stimulatesneuromuscular junctions and nicotinicreceptors, causing depression and paralysisof autonomic ganglia. Exposure routesare ingestion, absorption through skin, orinhalation (smoking or inhaling tobacco).The acute toxic symptoms in humansinclude nausea, vomiting, salivation, muscularweakness, twitching, and convulsions.The symptoms of confusion, hallucinations,and distorted perceptions have also beennoted in humans. Death may occur from respiratoryfailure. The lethal dose is approximately40 mg/kg. Chronic poisoning fromoccupational exposure may exhibit symptomsof vomiting and diarrhea. Fatal casesdue to occupational poisoning are unusual.Nicotine administered in animals producedtoxic symptoms that include somnolence,change in motor activity, ataxia, dyspnea,tremor, and convulsions.LD50 values, intraperitoneal (rats): 14.5 mg/kgLD50 values, oral (rats): 50 mg/kgKramer and coworkers (1989) investigatedthe effect of nicotine on the accumulation ofdopamine in synaptic vesicles prepared frommouse cerebral cortex or bovine striatum. Itwas found to be a weak inhibitor of dopamineaccumulation.The role of nicotine in tobacco carcinogenesisis not yet fully understood. Nicotine is a precursor of N0-nitrosonornicotine , which is asuspected lung carcinogen (Hoffmann et al.1985). Nicotine-derived N-nitrosoaminescontribute significantly to carcinogenesiscaused by tobacco. However, there is noevidence in animals or humans of cancerscaused by nicotine itself. Berger and coworkers(1987) have found a beneficial effect ofperinatal nicotine administration in decreasingthe tumors of the neuorogenic systeminduced by N-methylnitrosourea in Sprague-Dawley rats. Although nicotineis noncarcinogenic, it acts as a cofactorin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene in male Syrian goldenhamsters (Chen and Squier 1990).Nicotine produced teratogenic effects intest animals, causing postimplantation mortality,fetal death, and developmental abnormalities.Nicotine and its primary metabolitecotinine exhibited teratogenic potential withXenopus frog embryo teratogenesis assay(Dowson et al. 1988).Nicotine tested negative in the Neurosporacrassa –aneuploidy and histidinereversion–Ames tests for mutagenicity.
Health Hazard
L-Nicotine is classified as super toxic. Probable oral lethal dose in humans is less than 5 mg/kg or a taste (less than 7 drops) for a 70 kg (150 lbs.) person. It may be assumed that ingestion of 40-60 mg of nicotine is lethal to humans. There is fundamental difference between acute toxicity from use of nicotine as insecticide or from ingestion, and chronic toxicity that may be caused by prolonged exposure to small doses as occurs in smoking. Maternal smoking during pregnancy is associated with increased risk of spontaneous abortion, low birth weight and still-birth. Nicotine was found as a co-carcinogen in animals.
Fire Hazard
There is a moderate explosion hazard when exposed to heat or flame. When heated to decomposition, L-Nicotine emits nitrogen oxides, carbon monoxide and other highly toxic fumes. Avoid oxidizing materials. Stable under normal conditions. Avoid heat or flames.
Trade name
BLACK LEAF?; CAMPBELL'S NICOSOAP
?; DESTRUXOL ORCHARD SPRAY?; EMONIB
?; FLUX MAAG?; FUMETO-TENDUST?; BAC?;
MACH-NIC?; NIAGARA P. A. DUST?; NICODUST?;
NICOFUME?; NICOCIDE?; ORTHO N-4 DUST?; XL
ALL INSECTICIDE?
Potential Exposure
An alkaloid produced from tobacco.
Nicotine is used in some drugs; and in tanning. At one
time, nicotine was used in the United States as an insecticide
and fumigant; however, it is no longer produced or
used in the United States for this purpose.
Carcinogenicity
Nicotine has low carcinogenic
potential. One study found that diets containing
60 ppm nicotine and administered to rats for 300 days
reduced the growth rate. The authors concluded that reduced
body weight gains were only partially attributable to reduced
food intake. No pathology on the rats and no evidence of
carcinogenicity were reported. Rats were injected subcutaneously
(5 days/week) for 26 weeks followed by an approximate
2-month observation period. Similarly, dogs were
injected subcutaneously (5 days/week) for the same period.
No tumors were observed in the test animals, although
hyaline thickening and fibrosis of the vasculature of the
kidney, lung, brain, and heart were evident.
Metabolic pathway
Nicotine has been used as an insecticide for at least 200 years but this
naturally occurring compound lacks persistence and can be hazardous in
use (Corbett et al., 1984). It has been replaced with more effective synthetic
insecticides such as those in the neonicotinoid class. Most of the mformation
on metabolism derives from research into the fate of nicotine after
tobacco smoking as well as from the use of nicotine in agriculture and
horticulture or through the biosynthesis of the alkaloid by plants and
vegetables used as normal foodstuffs. Up to eight metabolites have been
isolated and identified in man with six primary pathways. The main
pathway is N-carbon oxidation of the pyrrolidine ring to form cotinine,
others being N-oxidation of the pyrrolidine ring to form nicotine N-oxide,
N-methylation of the pyridine ring to form an N-methylnicotinium ion
and N-demethylation of the pyrrolidine ring to form nornicotine. Two
other pathways are formation of a nicotine enamhe and of a nicotine
glucuronide (Gabrielsson and Gumbleton, 1993). There is little information
on the fate of nicotine in soil.
Metabolism
Nicotine is well absorbed from the mucous membranes
in the oral cavity, gastrointestinal tract, and respiratory
system. If tobacco smoke is held in the mouth for 2 seconds,
66 to 77% of the nicotine in the smoke will be absorbed
across the oral mucosa. If tobacco smoke is inhaled,
approximately 90 to 98% of the nicotine will be
absorbed. Nicotine is distributed throughout the body,
readily crossing the blood-brain and placental barriers.
The liver, kidney, and lung metabolize approximately 80
to 90% of the alkaloid. The kidney rapidly eliminates
nicotine and its metabolites.
Shipping
UN1654 Nicotine, Hazard Class: 6.1; Labels:
6.1-Poisonous materials.
Purification Methods
(-)-Nicotine is a very pale yellow hygroscopic oil with a characteristic odour (tobacco extract) which turns brown in air on exposure to light. It is purifed by fractional distillation under reduced pressure in an inert atmosphere. A freshly distilled sample should be stored in dark sealed containers under N2. It is a strong base; a 0.05 M aqueous solution has a pH of 10.2. It is very soluble in organic solvents. It is soluble in H2O and readily forms salts. [UV: Parvis J Chem Soc 97 1035 1910, Dobbie & Fox J Chem Soc 103 1194 1913.] The hydrochlorides (mono-and di-) form deliquescent crystals soluble in H2O and EtOH but insoluble in Et2O. It has also been purified via the ZnCl2 double salt. [Ratz Monatsh Chem 26 1241 1905, Biosynthesis: Nakan & Hitchinson J Org Chem 43 3922 1978.] The picrate has m 218o (from EtOH). [Beilstein 23/6 V 64.] POISONOUS.
Degradation
Nicotine is volatile and decomposes relatively quickly under the influence
of light and air. The pyrrolidine nitrogen (pka 8.2) is more basic than the
pyridine moiety (pka 3.1) (PM). Nicotine has a chiral centre, and exists
naturally as the more potent (S) enantiomer.
Incompatibilities
Incompatible with strong 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. Incompatible with
strong acids. Attacks some forms of plastics, rubber, and
coatings.
Waste Disposal
Dissolve or mix the material
with a combustible solvent and burn in a chemical incinerator
equipped with an afterburner and scrubber. All federal,
state, and local environmental regulations must be
observed. In accordance with 40CFR165, follow
recommendations for the disposal of pesticides and pesticide
containers. Must be disposed properly by following
package label directions or by contacting your local or
federal environmental control agency, or by contacting
your regional EPA office. Consult with environmental
regulatory agencies for guidance on acceptable disposal
practices. Generators of waste containing this contaminant
(≥100 kg/mo) must conform with EPA regulations
governing storage, transportation, treatment, and waste
disposal.
References
Pictet, Rotschy., Ber., 33, 2533 (1900)Tschitschibabin, Buchholz.,J. Russ. Phys. Chern. Soc., 50, 548 (1920)Spath, Biniecki., Ber., 72, 1809 (1939)Shmuk, Borozdina., CampI. rend. Acad. Sci., USSR, 12,1582 (1939)Shmuk, Borozdina., J. Appl. Chern. Russ., 14,864 (1941)Smith, Smith., J. Agric. Res., 65, 347 (1942)Pal, Narasinham.,!. Ind. Chern. Soc., 20, 181 (1943)Marion., Can. J. Res., 23B, 165 (1945)Bottomley, Nottle, White., Austral. J. Sci., 8, 18 (1945)Biosynthesis:
Leete.,!. Amer. Chern. Soc., 89,7081 (1967)14C-NMR spectrum:
Ganz, Kelsey, Geiling., Bot. Gaz., 113, 195 (1951)13C-NMR spectrum:
Crain, Wilderman, Roberts., J. Amer. Chern. Soc., 93,990 (1971)Pharmacology :
Rolleston., Lancet., 210,961 (1926)Laessing., Med. Welt., 12, 1485 (1938)Coon, Rothman., Proc. Soc. Exp. Bioi. Med., 42, 231 (1939)Straub, Amann., Klin. Woch., 19,169 (1940)Coon, Rothman., J. Pharm. Exp. Ther. Froc., 72, 9 (1941)Perlman, Dannesborg, Sokoloff., J. Amer. Med. Assoc., 120, 1003 (1942)Roth, McDonald, Sheard., ibid, 125,761 (1944)Burn, Truelove, Burn., Brit. Med. J., i, 403 (1945)
Check Digit Verification of cas no
The CAS Registry Mumber 54-11-5 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 5 and 4 respectively; the second part has 2 digits, 1 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 54-11:
(4*5)+(3*4)+(2*1)+(1*1)=35
35 % 10 = 5
So 54-11-5 is a valid CAS Registry Number.
InChI:InChI=1/C10H14N2/c1-12-7-3-5-10(12)9-4-2-6-11-8-9/h2,4,6,8,10H,3,5,7H2,1H3/p+1/t10-/m1/s1
54-11-5Relevant articles and documents
Synthesis method of nicotine
-
, (2021/07/10)
The invention belongs to the technical field of nicotine synthesis, and particularly relates to a synthesis method of nicotine. The invention discloses a synthesis method of nicotine. The synthesis method comprises the following steps: S1, synthesizing 1-(1-butenyl)-3-nicotyl-2-pyrrolidone, namely reacting 1-(1-butenyl)-pyrrolidone with nicotine ethyl ester under the condition of NaH catalysis by using an N,N-dimethyl formamide solution carrier to obtain the 1-(1-butenyl)-3-nicotyl-2-pyrrolidone; S2, synthesizing 3-cyclopentenyl amino-pyridine, namely concentrating the 1-(1-butenyl) 3-nicotinyl-2-pyrrolidone obtained in the step S1 under a certain condition, so as to obtain the 3-cyclopentenyl amino-pyridine, S3, synthesis of a nicotine precursor: introducing hydrogen into 3-cyclopentenyl amino-pyridine under the action of a Pd/C catalyst to obtain the nicotine precursor; and S4, synthesizing nicotine, namely obtaining nicotine from the nicotine precursor obtained in S3 under the action of formaldehyde and formic acid, wherein the chemical formulas are shown in specification.
Asymmetric preparation method of nicotine
-
, (2021/10/27)
The invention relates to a preparation method of nicotine, in particular to a preparation method of nicotine from nicotinic acid ester as a starting material through five-step reaction. The method comprises the following specific steps: (1) a condensation reaction of the nicotinate with N - methylpyrrolidinone in a suitable reaction vessel, and adding a strong acid to react to obtain 4 - methylamino -1 - (3 - pyridine) - butanone hydrochloride after the reaction is finished. (2) The amino group is protected with a suitable amino protecting reagent to give an intermediate (4). (3) The chiral alcohol intermediate (5) is obtained by asymmetric reduction. (4) The chiral alcohol intermediate can be converted into nicotine through two-step conversion. The asymmetric reduction reaction of metal catalysis is a key step of the method, so that the chiral alcohol intermediate with high optical activity can be obtained, and nicotine can be prepared through two-step conversion. The nicotine preparation method provided by the invention is simple to operate, low in cost, mild in reaction condition and suitable for industrial production.
Method for preparing bioactive (S)-(-)-nicotine
-
, (2021/07/17)
The invention relates to the field of organic synthesis, and discloses a method for preparing bioactive (S)-(-)-nicotine. The method comprises the steps of carrying out first reaction on methyl nicotinate and tert-butyl succinic acid diester, and then carrying out second reaction; and carrying out contact reaction on the system after the second reaction and an acidic material to obtain 4-oxo-4-(3-pyridyl) butyric acid; carrying out asymmetric reduction reaction on 4-oxo-4-(3-pyridyl) butyric acid and (R)-(+)-2-methyl-CBS-oxazoborane to obtain 5-(3-pyridyl) dihydrofuran-2 (3H)-ketone; carrying out third reaction on the 5-(3-pyridyl) dihydrofuran-2 (3H)-ketone and methylamine hydrobromide to obtain 1-methyl-5-(3-pyridyl)-2-pyrrolidone; and carrying out fourth reaction on the 1-methyl-5-(3-pyridyl)-2-pyrrolidone and a reducing agent to obtain the bioactive (S)-(-)-nicotine. According to the method, the bioactive body (S)-(-)-nicotine can be obtained with high yield and high purity.
Method for synthesizing chiral nicotine from butyrolactone
-
, (2021/11/03)
The invention discloses a method for synthesizing chiral nicotine from butyrolactone. The fumarates and γ - butyrolactone are condensed under the action of a basic catalyst to yield 4 - chloro -1 - (3 - pyridine) -1 -butanone by reaction with hydrochloric acid and reacted with a chlorination reagent to produce (- B -) S (-4 -1 -dichlorobutyl) pyridine which is reacted with an amine reagent under basic conditions to give (-3 -) -1 -methyl nicotine and (S)-3 - nicotinic acetylbutanolamines obtained by the reaction with the aminating reagent under an alkaline condition to produce a chiral hydroxy S S group - (1) S- methylnicotine or a (4 -) S nicotinic acid. The application can determine whether a methylation reaction is needed according to the type of amination reagent. The yield of (S)- nicotine was high.
Preparation method of chiral nicotine synthesized by chiral tert-butyl sulfinamide
-
, (2021/09/29)
The preparation method comprises the following steps: 3 - pyridine formaldehyde and chiral tert-butyl sulfinamide are subjected to condensation reaction under the action of titanate. Further, magnesium bromide reacts with (1, 3 - dioxan -2 -ethyl) magnesium bromide. Cyclization is carried out under acidic conditions. Finally, by reduction and amine methylation, chiral nicotine is obtained. The method has the advantages of short reaction route, easily available and cheap raw materials, high yield of chiral nicotine generated by reaction, high ee-value and reduced production cost of chiral nicotine.
Preparation process of high-purity nicotine
-
Paragraph 0014-0015, (2021/04/03)
The invention discloses a novel process for preparing high-purity nicotine from nicotine sulfate, and the process specifically comprises the following steps: neutralizing a 35-55% nicotine sulfate aqueous solution with a 25-35% sodium hydroxide aqueous solution, cooling the system after neutralization, keeping the temperature of the solution at 5-10 DEG C, and performing standing; performing filtering after the sodium sulfate decahydrate precipitates completely; heating the filtrate to 75-85 DEG C, standing for layering, collecting upper-layer nicotine after layering, performing drying to remove water, performing filtering to obtain coarse nicotine, and rectifying the coarse nicotine to obtain high-purity nicotine. The method can greatly reduce the consumption of the extraction agent and the energy consumption of evaporation and concentration of the extraction liquid, saves energy, reduces emission, and shortens the process time.
PROCESS FOR THE PREPARATION OF (S)-NICOTIN FROM MYOSMINE
-
, (2020/06/05)
A process for synthetically producing (S)-nicotine ([(S)-3-(1 -methylpyrrolidin-2-yl)pyridine]) is provided.
Photorelease of Pyridines Using a Metal-Free Photoremovable Protecting Group
Dong, Zaizai,Fang, Xiaohong,Kou, Xiaolong,Tan, Weihong,Tang, Xiao-Jun,Wu, Yayun,Zhang, Zhen,Zhao, Rong,Zhou, Wei
supporting information, p. 18386 - 18389 (2020/08/24)
The photorelease of bioactive molecules has emerged as a valuable tool in biochemistry. Nevertheless, many important bioactive molecules, such as pyridine derivatives, cannot benefit from currently available organic photoremovable protecting groups (PPGs). We found that the inefficient photorelease of pyridines is attributed to intramolecular photoinduced electron transfer (PET) from PPGs to pyridinium ions. To alleviate PET, we rationally designed a strategy to drive the excited state of PPG from S1 to T1 with a heavy atom, and synthesized a new PPG by substitution of the H atom at the 3-position of 7-dietheylamino-coumarin-4-methyl (DEACM) with Br or I. This resulted in an improved photolytic efficiency of the pyridinium ion by hundreds-fold in aqueous solution. The PPG can be applied to various pyridine derivatives. The successful photorelease of a microtubule inhibitor, indibulin, in living cells was demonstrated for the potential application of this strategy in biochemical research.
Method for preparing nicotine
-
, (2020/04/22)
The invention relates to a method for preparing nicotine. The method comprises the following steps: (1) adding N-Cbz pyrrolidone, nicotinate, an alkaline catalyst and a reaction solvent into a reaction container, carrying out a reaction, quenching until the system is neutral, and removing the reaction solvent to obtain a first solid mixture; (2) adding the first solid mixture into an acidic solution, and carrying out a reflux reaction to obtain a second reaction mixture; and (3) adding formic acid or formate solid and a formaldehyde solution into the second reaction mixture, reacting, and purifying the product to obtain racemic nicotine. The preparation method disclosed by the invention has high yield, and the prepared racemic nicotine and the S-nicotine have high purity.
Preparation method of nicotine with optical activity
-
Paragraph 0061-0063; 0095-0097, (2020/06/20)
The invention discloses a preparation method of nicotine with optical activity, which comprises the following steps: adding a nitrogen-containing or phosphorus-containing chiral ligand and a metal catalyst into an organic solvent, preparing a catalyst, sequentially adding an imine salt and a reducing agent to carry out a reduction reaction, and adding an extracting agent to extract the nicotine compound. According to the preparation method disclosed by the invention, the imine salt derivative is used as a precursor, the initial raw material cost is low, the reaction conditions are mild (for example, catalysis and reduction reactions occur in a temperature range near normal temperature), the catalyst and the reducing agent are common chemical substances, the synthesis yield and the chemicalpurity of the final product nicotine are high, and large-scale industrial production is convenient to realize.
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