Amyl nitrite

Last updated
Amyl nitrite
Amyl nitrite Formula V.1.svg
Amyl-nitrite-3D-balls.png
Clinical data
Other namesIsoamyl nitrite,
Isopentyl nitrite,
Nitramyl,
3-methyl-1-nitrosooxybutane,
Pentyl alcohol nitrite (ambiguous),
poppers (ambiguous, colloquial, slang)
ATC code
Legal status
Legal status
Identifiers
  • (3-methylbutyl) nitrite
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
CompTox Dashboard (EPA)
Chemical and physical data
Formula C5H11NO2
Molar mass 117.148 g·mol−1
3D model (JSmol)
Density 0.872 g/cm3
Boiling point 99 °C (210 °F)
Solubility in water Slightly soluble mg/mL (20 °C)
  • CC(C)CCON=O
  • InChI=1S/C5H11NO2/c1-5(2)3-4-8-6-7/h5H,3-4H2,1-2H3 Yes check.svgY
  • Key:OWFXIOWLTKNBAP-UHFFFAOYSA-N Yes check.svgY
   (verify)

Amyl nitrite is a chemical compound with the formula C5H11ONO. A variety of isomers are known, but they all feature an amyl group attached to the nitrite functional group. The alkyl group is unreactive and the chemical and biological properties are mainly due to the nitrite group. Like other alkyl nitrites, amyl nitrite is bioactive in mammals, being a vasodilator, which is the basis of its use as a prescription medicine. [1] As an inhalant, it also has a psychoactive effect, which has led to its recreational use, with its smell being described as that of old socks or dirty feet. [2] It was first documented in 1844 and came into medical use in 1867. [3]

Contents

Uses

Nomenclature

The term "amyl nitrite" encompasses several isomers. In older literature, the common non-systematic name amyl was often used for the pentyl group, where the amyl group is a linear or normal (n) alkyl group, and the resulting amyl nitrite would have the structural formula CH3(CH2)3CH2ONO, also referred to as n-amyl nitrite.

A common form of amyl nitrite is the isomer with the formula (CH3)2CHCH2CH2ONO, which may be more specifically referred to as isoamyl nitrite.

The similarly named amyl nitrate has very different properties. At the same time, isopropyl nitrite has a similar structure and similar uses (also called 'poppers') but with worse side-effects. [11]

Amyl nitrite is sometimes referred to colloquially as banapple gas. [12]

Synthesis and reactions

Alkyl nitrites are prepared by the reaction of alcohols with nitrous acid: [13]

ROH + HONO → RONO + H2O, where R = alkyl group

The reaction is called esterification. Synthesis of alkyl nitrites is, in general, straightforward and can be accomplished in home laboratories. A common procedure includes the dropwise addition of concentrated sulfuric acid to a cooled mixture of an aqueous sodium nitrite solution and an alcohol. The intermediately-formed stoichiometric mixture of nitrogen dioxide and nitric oxide then converts the alcohol to the alkyl nitrite, which, due to its low density, will form an upper layer that can be easily decanted from the reaction mixture.

Isoamyl nitrite decomposes in the presence of base to give nitrite salts and the isoamyl alcohol:

C5H11ONO + NaOH → C5H11OH + NaNO2

Amyl nitrite, like other alkyl nitrites, reacts with carbanions to give oximes. [14]

Amyl nitrites are also useful as reagents in a modification of the Sandmeyer reaction. The reaction of the alkyl nitrite with an aromatic amine in a halogenated solvent produces a radical aromatic species, this then frees a halogen atom from the solvent. For the synthesis of aryl iodides diiodomethane is used, [15] [16] whereas bromoform is the solvent of choice for the synthesis of aryl bromides. [17]

Physiological effects

An early container of amyl nitrite, Hunterian Museum, Glasgow An early container of Amyl Nitrite, Hunterian Museum, Glasgow.jpg
An early container of amyl nitrite, Hunterian Museum, Glasgow

Amyl nitrite, in common with other alkyl nitrites, [18] is a potent vasodilator; it expands blood vessels, resulting in lowering of the blood pressure. Amyl nitrite may be used during cardiovascular stress testing in patients with suspected hypertrophic cardiomyopathy to cause vasodilation and thereby reduce afterload and provoke obstruction of blood flow towards the aorta from the ventricle by increasing the pressure gradient, thereby causing left ventricular outflow obstruction. Alkyl nitrites are a source of nitric oxide, which signals for relaxation of the involuntary muscles. Physical effects include decrease in blood pressure, headache, flushing of the face, increased heart rate, dizziness, and relaxation of involuntary muscles, especially the blood vessel walls and the internal and external anal sphincter. There are no withdrawal symptoms. Overdose symptoms include nausea, vomiting, hypotension, hypoventilation, shortness of breath, and fainting. The effects set in very quickly, typically within a few seconds and disappear within a few minutes. Amyl nitrite may also intensify the experience of synesthesia. [19] Amyl nitrite, when given as a medication for patients with angina, can also be administered as an ampule. The ampule is put in a gauze pad and then inhaled by the patient during an angina attack and repeated every fifteen minutes. However, oral dosing of amyl nitrite is ineffective due to poor absorption and extensive hepatic metabolism. Amyl nitrite has been widely replaced by nitroglycerin for the treatment of acute angina.

Toxicity

Although there are case reports of life-threatening toxicity involving unusually large amounts, [20] typical inhaled doses of amyl nitrite are considered relatively safe. [21] [22] However, liquid amyl nitrite is highly toxic when ingested because of the unsafely high concentration it causes in blood. [23] Regardless of the form or route of administration, acute toxicity principally results when the nitrite oxidizes a significant proportion of hemoglobin in the blood without oxygen, forming methemoglobin, which cannot carry oxygen. Severe poisoning cases will progress to methemoglobinemia, characterized by a blue-brown discoloration under the skin which could be mistaken for cyanosis. [20] [23] Treatment with oxygen and intravenous methylene blue frustrates visual confirmation further as methylene blue itself is, as its name suggests, a blue dye; the patient's changes in different shades of blue notwithstanding, it is an effective antidote by way of catalyzing the production of the enzyme responsible for reducing the methemoglobin in the blood back to hemoglobin.

The discoloration does mean that regular near-infrared–based pulse oximetry becomes useless. More fundamentally, blood gas analysis on the whole has limited effectiveness, as the increased methemoglobin level increases the oxygen binding affinity of regular hemoglobin. [20] Therefore, the measurement of actual ratios and levels of methemoglobin and hemoglobin must accompany any blood gas partial pressure sample in these cases.

The Columbo episode titled "Troubled Waters" (1974-1975) features amyl nitrite inhaled by the antagonist Hayden Danziger – played by Robert Vaughn – to help him feign a heart attack for his alibi. However, the episode consistently refers to the substance incorrectly as amyl nitrate. [24]

The 1978 Derek Jarman film Jubilee features a character named Amyl Nitrate (a misspelled reference to amyl nitrite).

The punk band Amyl and the Sniffers reference recreational use of amyl nitrite in their name. [25]

Related Research Articles

<span class="mw-page-title-main">Ether</span> Organic compounds made of alkyl/aryl groups bound to oxygen (R–O–R)

In organic chemistry, ethers are a class of compounds that contain an ether group—an oxygen atom connected to two organyl groups. They have the general formula R−O−R′, where R and R′ represent organyl groups. Ethers can again be classified into two varieties: if the organyl groups are the same on both sides of the oxygen atom, then it is a simple or symmetrical ether, whereas if they are different, the ethers are called mixed or unsymmetrical ethers. A typical example of the first group is the solvent and anaesthetic diethyl ether, commonly referred to simply as "ether". Ethers are common in organic chemistry and even more prevalent in biochemistry, as they are common linkages in carbohydrates and lignin.

<span class="mw-page-title-main">Inhalant</span> Chemical, often household, breathed in to cause intoxication

Inhalants are a broad range of household and industrial chemicals whose volatile vapors or pressurized gases can be concentrated and breathed in via the nose or mouth to produce intoxication, in a manner not intended by the manufacturer. They are inhaled at room temperature through volatilization or from a pressurized container, and do not include drugs that are sniffed after burning or heating. For example, amyl nitrite (poppers), gasoline, nitrous oxide and toluene – a solvent widely used in contact cement, permanent markers, and certain types of glue – are considered inhalants, but smoking tobacco, cannabis, and crack cocaine are not, even though these drugs are inhaled as smoke or vapor.

<span class="mw-page-title-main">Methylene blue</span> Blue dye also used as a medication

Methylthioninium chloride, commonly called methylene blue, is a salt used as a dye and as a medication. As a medication, it is mainly used to treat methemoglobinemia by chemically reducing the ferric iron in hemoglobin to ferrous iron. Specifically, it is used to treat methemoglobin levels that are greater than 30% or in which there are symptoms despite oxygen therapy. It has previously been used for treating cyanide poisoning and urinary tract infections, but this use is no longer recommended.

<span class="mw-page-title-main">Methemoglobinemia</span> Condition of elevated methemoglobin in the blood

Methemoglobinemia, or methaemoglobinaemia, is a condition of elevated methemoglobin in the blood. Symptoms may include headache, dizziness, shortness of breath, nausea, poor muscle coordination, and blue-colored skin (cyanosis). Complications may include seizures and heart arrhythmias.

The nitrite ion has the chemical formula NO-2. Nitrite is widely used throughout chemical and pharmaceutical industries. The nitrite anion is a pervasive intermediate in the nitrogen cycle in nature. The name nitrite also refers to organic compounds having the –ONO group, which are esters of nitrous acid.

<span class="mw-page-title-main">Amyl nitrate</span> Chemical compound

Amyl nitrate is the chemical compound with the formula CH3(CH2)4ONO2. This molecule consists of the 5-carbon amyl group attached to a nitrate functional group. It is the ester of amyl alcohol and nitric acid.

<span class="mw-page-title-main">Sodium nitrite</span> Chemical compound

Sodium nitrite is an inorganic compound with the chemical formula NaNO2. It is a white to slightly yellowish crystalline powder that is very soluble in water and is hygroscopic. From an industrial perspective, it is the most important nitrite salt. It is a precursor to a variety of organic compounds, such as pharmaceuticals, dyes, and pesticides, but it is probably best known as a food additive used in processed meats and (in some countries) in fish products.

<span class="mw-page-title-main">Methemoglobin</span> Type of hemoglobin

Methemoglobin (British: methaemoglobin, shortened MetHb) (pronounced "met-hemoglobin") is a hemoglobin in the form of metalloprotein, in which the iron in the heme group is in the Fe3+ (ferric) state, not the Fe2+ (ferrous) of normal hemoglobin. Sometimes, it is also referred to as ferrihemoglobin. Methemoglobin cannot bind oxygen, which means it cannot carry oxygen to tissues. It is bluish chocolate-brown in color. In human blood a trace amount of methemoglobin is normally produced spontaneously, but when present in excess the blood becomes abnormally dark bluish brown. The NADH-dependent enzyme methemoglobin reductase (a type of diaphorase) is responsible for converting methemoglobin back to hemoglobin.

Amyl may refer to:

<span class="mw-page-title-main">Cyclohexyl nitrite</span> Chemical compound

Cyclohexyl nitrite is an organic compound, with formula C6H11NO2. It is the ester of cyclohexanol and nitrous acid, i.e. it is an alkyl nitrite. Like amyl nitrite and butyl nitrite, it acts as an antianginal due to vasodilation. The compound is colorless, volatile liquid.

Poppers is a slang term referring to recreational drugs belonging to the alkyl nitrite family of chemical compounds. When fumes from these substances are inhaled, they act as potent vasodilators, producing mild euphoria, warmth, and dizziness. Most effects have a rapid onset and are short-acting. Its recreational use is believed to be potentially dangerous for people with heart problems, anaemia and glaucoma. Reported adverse effects include fainting, retinal toxicity and vision loss.

The Sandmeyer reaction is a chemical reaction used to synthesize aryl halides from aryl diazonium salts using copper salts as reagents or catalysts. It is an example of a radical-nucleophilic aromatic substitution. The Sandmeyer reaction provides a method through which one can perform unique transformations on benzene, such as halogenation, cyanation, trifluoromethylation, and hydroxylation.

Histotoxic hypoxia is the inability of cells to take up or use oxygen from the bloodstream, despite physiologically normal delivery of oxygen to such cells and tissues. Histotoxic hypoxia results from tissue poisoning, such as that caused by cyanide and certain other poisons like hydrogen sulfide.

<span class="mw-page-title-main">Potassium nitrite</span> Chemical compound

Potassium nitrite (distinct from potassium nitrate) is the inorganic compound with the chemical formula KNO2. It is an ionic salt of potassium ions K+ and nitrite ions NO2, which forms a white or slightly yellow, hygroscopic crystalline powder that is soluble in water.

<span class="mw-page-title-main">Pentyl group</span> Chemical compound

Pentyl is a five-carbon alkyl group or substituent with chemical formula -C5H11. It is the substituent form of the alkane pentane.

<span class="mw-page-title-main">Alkyl nitrite</span> Organic compounds of the form R–O–N=O

In organic chemistry, alkyl nitrites are a group of organic compounds based upon the molecular structure R−O−N=O, where R represents an alkyl group. Formally they are alkyl esters of nitrous acid. They are distinct from nitro compounds.

<span class="mw-page-title-main">Cytochrome b5 reductase</span> Class of enzymes

Cytochrome-b5 reductase is a NADH-dependent enzyme that converts ferricytochrome from a Fe3+ form to a Fe2+ form. It contains FAD and catalyzes the reaction:

<span class="mw-page-title-main">Cyanide poisoning</span> Broad-spectrum poisoning

Cyanide poisoning is poisoning that results from exposure to any of a number of forms of cyanide. Early symptoms include headache, dizziness, fast heart rate, shortness of breath, and vomiting. This phase may then be followed by seizures, slow heart rate, low blood pressure, loss of consciousness, and cardiac arrest. Onset of symptoms usually occurs within a few minutes. Some survivors have long-term neurological problems.

<span class="mw-page-title-main">Cyanocobalamin</span> Form of vitamin B-12

Cyanocobalamin is a form of vitamin B
12
used to treat and prevent vitamin B
12
deficiency
except in the presence of cyanide toxicity. The deficiency may occur in pernicious anemia, following surgical removal of the stomach, with fish tapeworm, or due to bowel cancer. It is used by mouth, by injection into a muscle, or as a nasal spray.

Hexyl nitrite has the formula C6H13NO2 and is a nitrite and more specifically, an alkyl nitrite. It is an ester of hexanol and nitrous acid. It has the structural formula of: CH3(CH2)5ONO The CAS Registry Number is 638-51-7 and the European Community number 680-102-5. It is REACH and TSCA registered. It is also known as nitrous acid, hexyl ester. It is the aliphatic analogue of cyclohexyl nitrite.

References

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  24. "Episode review: Columbo Troubled Waters". Columbophile blog. 29 September 2018. Retrieved 8 April 2023.
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Further reading