1-Phenyl-2-nitropropene, or simply phenyl-2-nitropropene, or P2NP, as it is commonly referred to, is a
chemical compound
A chemical compound is a chemical substance composed of many identical molecules (or molecular entities) containing atoms from more than one chemical element held together by chemical bonds. A molecule consisting of atoms of only one element ...
from the
aromatic
In chemistry, aromaticity is a chemical property of cyclic ( ring-shaped), ''typically'' planar (flat) molecular structures with pi bonds in resonance (those containing delocalized electrons) that gives increased stability compared to satur ...
group of compounds, with the formula C
9H
9NO
2. It is a light-yellow crystalline solid with a distinct smell.
Phenyl-2-nitropropene is used in the pharmaceutical industry to manufacture the drug
Adderall
Adderall and Mydayis are trade names for a combination drug called mixed amphetamine salts containing four salts of amphetamine. The mixture is composed of equal parts racemic amphetamine and dextroamphetamine, which produces a (3:1) ratio bet ...
, an
amphetamine
Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...
mixture used to treat
ADHD
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inapp ...
and
narcolepsy
Narcolepsy is a long-term neurological disorder that involves a decreased ability to regulate sleep–wake cycles. Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. About 70% of those affec ...
. P2NP and other similar nitrostyrenes are also employed in the
clandestine manufacture of drugs of the amphetamine class, and are listed as drug precursors in many countries.
Uses
In the pharmaceutical industry, P2NP is used to produce a
racemic
In chemistry, a racemic mixture, or racemate (), is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as racemates. ...
amphetamine
Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...
mixture, branded under the trade names
Adderall
Adderall and Mydayis are trade names for a combination drug called mixed amphetamine salts containing four salts of amphetamine. The mixture is composed of equal parts racemic amphetamine and dextroamphetamine, which produces a (3:1) ratio bet ...
and
Mydayis, amongst others. In this case, the double bond is hydrogenated and the nitro group is reduced,
thus 1-phenyl-2-nitropropene becomes 1-phenyl-2-aminopropane, which is another name for amphetamine. Different reducing agents and solvents are used for this reaction, and various protocols exist. Often
lithium aluminium hydride
Lithium aluminium hydride, commonly abbreviated to LAH, is an inorganic compound with the chemical formula Li Al H4. It is a white solid, discovered by Finholt, Bond and Schlesinger in 1947. This compound is used as a reducing agent in organic ...
(LAH),
aluminum amalgam or
Raney nickel are used as a reducing agent, and the reaction is carried in a solvent like
isopropyl alcohol
Isopropyl alcohol (IUPAC name propan-2-ol and also called isopropanol or 2-propanol) is a colorless, flammable organic compound with a pungent alcoholic odor. As an isopropyl group linked to a hydroxyl group (chemical formula ) it is the simple ...
or
THF
Tetrahydrofuran (THF), or oxolane, is an organic compound with the formula (CH2)4O. The compound is classified as heterocyclic compound, specifically a cyclic ether. It is a colorless, water- miscible organic liquid with low viscosity. It is ...
![Рeduction of P2NP to Amphetamine](https://upload.wikimedia.org/wikipedia/commons/8/86/%D0%A0eduction_of_P2NP_to_Amphetamine.png)
The above diagram depicts P2NP reduction to amphetamine by using either
LAH,
sodium amalgam
Sodium amalgam, commonly denoted Na(Hg), is an alloy of mercury and sodium. The term amalgam is used for alloys, intermetallic compounds, and solutions (both solid solutions and liquid solutions) involving mercury as a major component. Sodium amal ...
,
Raney nickel, or
palladium
Palladium is a chemical element with the symbol Pd and atomic number 46. It is a rare and lustrous silvery-white metal discovered in 1803 by the English chemist William Hyde Wollaston. He named it after the asteroid Pallas, which was itself na ...
as a catalyst in the reduction. Platinum, in the form of
Adams' catalyst
Adams' catalyst, also known as platinum dioxide, is usually represented as platinum(IV) oxide hydrate, PtO2•H2O. It is a catalyst for hydrogenation and hydrogenolysis in organic synthesis. This dark brown powder is commercially available. The ox ...
, can also be used.
P2NP can also be reduced to
phenylacetone
Phenylacetone is an organic compound with the chemical formula C6H5CH2COCH3. It is a colorless oil that is soluble in organic solvents. This substance is used in the manufacture of methamphetamine and amphetamine, where it is commonly known as ...
, which is a precursor in the synthesis of
methamphetamine
Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug and less commonly as a second-line treatment for attention deficit hyperactivity disorder and obesity. Methamph ...
.
In this preparation, phenyl-2-nitropropene is reduced to phenyl-2-nitropropane using
sodium borohydride
Sodium borohydride, also known as sodium tetrahydridoborate and sodium tetrahydroborate, is an inorganic compound with the formula Na BH4. This white solid, usually encountered as an aqueous basic solution, is a reducing agent that finds appli ...
, followed by hydrolysis of the nitro group with
hydrogen peroxide
Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscous than water. It is used as an oxidizer, bleaching agent, and antiseptic, usually as a dilute solution (3% ...
and
potassium carbonate
Potassium carbonate is the inorganic compound with the formula K2 CO3. It is a white salt, which is soluble in water. It is deliquescent, often appearing as a damp or wet solid. Potassium carbonate is mainly used in the production of soap and gl ...
to produce phenylacetone (1-phenyl-2-propan-2-one).
Phenyl-2-nitropropene can also be reduced by hydrochloric acid and iron, forming an intermediate that will hydrolyze, which will form phenylacetone as well.
Synthesis
In the lab, phenyl-2-nitropropene is produced by the reaction of
benzaldehyde
Benzaldehyde (C6H5CHO) is an organic compound consisting of a benzene ring with a formyl substituent. It is the simplest aromatic aldehyde and one of the most industrially useful.
It is a colorless liquid with a characteristic almond-like odor. ...
and
nitroethane
Nitroethane is an organic compound having the chemical formula C2H5NO2. Similar in many regards to nitromethane, nitroethane is an oily liquid at standard temperature and pressure. Pure nitroethane is colorless and has a fruity odor.
Preparati ...
in the presence of a basic
catalyst
Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
like
n-butylamine
''n''-Butylamine is an organic compound (specifically, an amine) with the formula CH3(CH2)3NH2. This colourless liquid is one of the four isomeric amines of butane, the others being ''sec''-butylamine, ''tert''-butylamine, and isobutylamine. It ...
. The reaction is a nitroaldol reaction, and is a variant of a
Knoevenagel condensation reaction, which is one of a broader class of reactions called
Henry condensations, or simply Henry reactions. These are named after the German chemist
Emil Knoevenagel
Heinrich Emil Albert Knoevenagel (18 June 1865 – 11 August 1921) was the German chemist who established the Knoevenagel condensation reaction. The Knoevenagel condensation reaction of benzaldehydes with nitroalkanes is a classic general met ...
, and the Belgian chemist Louis Henry, respectively.
In this type of reaction, the basic catalyst deprotonates the nitroethane to form a
resonance stabilized anion. This anion nucleophilically adds to the
aldehyde
In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl grou ...
forming a β-nitro alcohol, which is subsequently dehydrated to yield the
nitroalkene A nitroalkene, or nitro olefin, is a functional group combining the functionality of its constituent parts, an alkene and nitro group, while displaying its own chemical properties through alkene activation, making the functional group useful in spe ...
. Water is produced as a byproduct, and must be actively removed from the reaction mixture.
Often, primary amines like
n-butylamine
''n''-Butylamine is an organic compound (specifically, an amine) with the formula CH3(CH2)3NH2. This colourless liquid is one of the four isomeric amines of butane, the others being ''sec''-butylamine, ''tert''-butylamine, and isobutylamine. It ...
,
methylamine
Methylamine is an organic compound with a formula of . This colorless gas is a derivative of ammonia, but with one hydrogen atom being replaced by a methyl group. It is the simplest primary amine.
Methylamine is sold as a solution in methanol, ...
, and
ethylamine
Ethylamine, also known as ethanamine, is an organic compound with the formula CH3CH2NH2. This colourless gas has a strong ammonia-like odor. It condenses just below room temperature to a liquid miscible with virtually all solvents. It is a nucleo ...
are used as catalysts, as is anhydrous
ammonium acetate
Ammonium acetate, also known as spirit of Mindererus in aqueous solution, is a chemical compound with the formula NH4CH3CO2. It is a white, hygroscopic solid and can be derived from the reaction of ammonia and acetic acid. It is available commerci ...
at times.
Many other drugs of the amphetamine class are produced in a similar fashion, where substituted benzaldehyde derivatives are used to produce a different nitrostyrene, which is later reduced to the desired amine. One such reaction is the Knoevenagel condensation of
piperonal
Piperonal, also known as heliotropin, is an organic compound which is commonly found in fragrances and flavors.Karl-Georg Fahlbusch, Franz-Josef Hammerschmidt, Johannes Panten, Wilhelm Pickenhagen, Dietmar Schatkowski, Kurt Bauer, Dorothea Garbe a ...
with nitroethane, yielding 3,4-methylenedioxy-1-phenyl-2-nitropropene, or MDP2NP. This is reduced to
3,4-methylenedioxyamphetamine
3,4-Methylenedioxyamphetamine (also known as MDA and sass) is an empathogen-entactogen, psychostimulant, and psychedelic drug of the amphetamine family that is encountered mainly as a recreational drug. In terms of pharmacology, MDA acts mo ...
, or MDA, which can be methylated to
3,4-methylenedioxymethamphetamine, or MDMA.
Another uses 2,5-dimethoxybenzaldehyde and nitromethane to yield 2,5-dimethoxy-β-nitrostyrene.
Many of these Knoevenagel condensations were used by
Dr. Alexander Shulgin to yield over 100 amphetamine derivatives, which he detailed in his book, ''
PiHKAL''.
Safety and Storage
P2NP is labeled as harmful by the
GHS, and is a known irritant. Thus, breathing fumes and direct skin and eye contact should be avoided.
The
median lethal dose
In toxicology, the median lethal dose, LD50 (abbreviation for "lethal dose, 50%"), LC50 (lethal concentration, 50%) or LCt50 is a toxic unit that measures the lethal dose of a toxin, radiation, or pathogen. The value of LD50 for a substance is the ...
for oral exposure in rats and mice is greater than 500 mg/kg and 1176 mg/kg, respectively.
Based on available data, the classification criteria are not met to classify P2NP as a
carcinogen
A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive substan ...
. However, the toxicological properties have not been thoroughly investigated.
P2NP should be stored at 2°C to 8°C and away from strong
oxidizing agents
An oxidizing agent (also known as an oxidant, oxidizer, electron recipient, or electron acceptor) is a substance in a redox chemical reaction that gains or " accepts"/"receives" an electron from a (called the , , or ). In other words, an oxid ...
. At higher temperatures, P2NP is not very stable, and degrades with time.
References
{{reflist, refs=
[Alfa Aesar entry on 2-Nitro-1-phenylpropene](_blank)
, accessed on March 20, 2021
["Chemical Book" Website - entry on 1-Phenyl-2-nitropropene](_blank)
accessed on March 21, 2021
[Material Safety Data Sheet P2NP (PDF) from Cayman Chemical, accessed on March 20, 2021]
[Material Safety Data Sheet 1-(Phenyl)2-nitropropene (PDF) from Biosynth Carbosynth, accessed on March 20, 2021]
[Material Safety Data Sheet trans-β-Methyl-β-nitrostyrene (PDF) from Sigma-Aldrich, accessed on March 20, 2021]
/ref>
[ ttps://www.erowid.org/archive/rhodium/chemistry/amph.urushibara.html Urushibara Style Amphetamine/ref>
][3,4-Methylenedioxyphenyl-2-Nitropropene
From Piperonal, Nitroethane & NaOH](_blank)
/ref>
[Erowid, phenyl-2-nitropropene](_blank)
/ref>
/ref>
[ Pihkal: A Chemical Love Story, Alexander Shulgin and Ann Shulgin, 1991]
[Phenyl-2-nitropropene synthesis via Ammonium acetate catalysis](_blank)
2021
[{{cite book, author = Организация Объединённых Наций , chapter = Синтез амфетамина. Восстановительное аминирование (каталическое восстановление с использованием металла), chapter-url = https://books.google.com/books?id=Nf2y_9j9i_kC&pg=PA12, format = , url = , title = Рекомендуемые методы обнаружения и анализа амфетамина, метамфетамина и их замещённых по циклу аналогов в конфискованных материалах , orig-year = , agency = , edition = , location= Нью-Йорк , date = 2007 , publisher= , volume= , pages = 12, series = , isbn = 9789214480303]
[{{cite book, author = Организация Объединённых Наций , chapter = Синтез 1-фенил-2-пропанона, chapter-url = https://books.google.com/books?id=G_OfkRtfz8oC&pg=PA40, format = , url = , title = Бюллетень по наркотическим средствам , orig-year = , agency = , edition = , location= , date = 2008 , publisher= , volume= , pages = 40, series = , isbn = 978-92-1-448027-3]
Nitro compounds
Phenyl compounds