Acetamide

Acetamide (systematic name: ethanamide) is an organic compound with the formula CH3CONH2. It is the simplest amide derived from acetic acid. It finds some use as a plasticizer and as an industrial solvent.[4] The related compound N,N-dimethylacetamide (DMA) is more widely used, but it is not prepared from acetamide. Acetamide can be considered an intermediate between acetone, which has two methyl (CH3) groups either side of the carbonyl (CO), and urea which has two amide (NH2) groups in those locations.

Acetamide
Acetamide skeletal
Acetamide-3D-balls
Names
Preferred IUPAC name
Acetamide[1]
Systematic IUPAC name
Ethanamide
Other names
Acetic acid amide
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.000.430
EC Number 200-473-5
KEGG
RTECS number AB4025000
UNII
Properties
C2H5NO
Molar mass 59.068 g·mol−1
Appearance colorless, hygroscopic solid
Odor odorless
mouse-like with impurities
Density 1.159 g cm−3
Melting point 79 to 81 °C (174 to 178 °F; 352 to 354 K)
Boiling point 221.2 °C (430.2 °F; 494.3 K) (decomposes)
2000 g L−1[2]
Solubility ethanol 500 g L−1[2]
pyridine 166.67 g L−1[2]
soluble in chloroform, glycerol, benzene[2]
log P −1.26
Vapor pressure 1.3 Pa
Acidity (pKa) 15.1 (25 °C, H2O)[3]
−0.577 × 10−6 cm3 g−1
1.4274
Viscosity 2.052 cP (91 °C)
Structure
trigonal
Hazards
Safety data sheet External MSDS
GHS pictograms The health hazard pictogram in the Globally Harmonized System of Classification and Labelling of Chemicals (GHS)
GHS signal word Warning
H351
P201, P202, P281, P308+313, P405, P501
NFPA 704
Flammability code 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g., canola oilHealth code 3: Short exposure could cause serious temporary or residual injury. E.g., chlorine gasReactivity code 1: Normally stable, but can become unstable at elevated temperatures and pressures. E.g., calciumSpecial hazards (white): no codeNFPA 704 four-colored diamond
1
3
1
Flash point 126 °C (259 °F; 399 K)
Lethal dose or concentration (LD, LC):
7000 mg kg−1 (rat, oral)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Production

Laboratory scale

Acetamide can be produced in the laboratory from ammonium acetate by dehydration:[5]

[NH4][CH3CO2] → CH3C(O)NH2 + H2O

Alternatively acetamide can be obtained in excellent yield via ammonolysis of acetylacetone under conditions commonly used in reductive amination.[6]

It can also be made from anhydrous acetic acid, acetonitrile and very well dried hydrogen chloride gas, using an ice bath, alongside more valuable reagent acetyl chloride. Yield is typically low (up to 35%), and the acetamide made this way is generated as a salt with HCl.

Industrial scale

In a similar fashion to some laboratory methods, acetamide is produced by dehydrating ammonium acetate or via the hydrolysis of acetonitrile, a byproduct of the production of acrylonitrile:[4]

CH3CN + H2O → CH3C(O)NH2

Use

Occurrence

Acetamide has been detected near the center of the Milky Way galaxy.[7] This finding is potentially significant because acetamide has an amide bond, similar to the essential bond between amino acids in proteins. This finding lends support to the theory that organic molecules that can lead to life (as we know it on Earth) can form in space.

On 30 July 2015, scientists reported that upon the first touchdown of the Philae lander on comet 67/P's surface, measurements by the COSAC and Ptolemy instruments revealed sixteen organic compounds, four of which – acetamide, acetone, methyl isocyanate, and propionaldehyde[8][9][10] – were seen for the first time on a comet.

In addition, acetamide is found infrequently on burning coal dumps, as a mineral of the same name.[11][12]

Acetamide crystal structure
Acetamide crystal structure

References

  1. ^ "Front Matter". Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge: The Royal Society of Chemistry. 2014. p. 841. doi:10.1039/9781849733069-FP001. ISBN 978-0-85404-182-4.
  2. ^ a b c d The Merck Index, 14th Edition, 36
  3. ^ Haynes, William M., ed. (2016). CRC Handbook of Chemistry and Physics (97th ed.). CRC Press. pp. 5–88. ISBN 9781498754293.
  4. ^ a b "Acetic Acid", Ullmann's Encyclopedia of Industrial Chemistry, Weinheim: Wiley-VCH, doi:10.1002/14356007.a01_045.pub2
  5. ^ Coleman, G. H.; Alvarado, A. M. (1923). "Acetamide". Organic Syntheses. 3: 3. doi:10.15227/orgsyn.003.0003.; Collective Volume, 1, p. 3
  6. ^ Schwoegler, Edward J.; Adkins, Homer (1939). "Preparation of Certain Amines". J. Am. Chem. Soc. 61 (12): 3499–3502. doi:10.1021/ja01267a081.
  7. ^ Hollis, J. M.; Lovas, F. J.; Remijan, A. J.; Jewell, P. R.; Ilyushin, V. V.; Kleiner, I. (2006). "Detection of Acetamide (CH3CONH2): The Largest Interstellar Molecule with a Peptide Bond" (PDF). Astrophys. J. 643 (1): L25–L28. Bibcode:2006ApJ...643L..25H. doi:10.1086/505110.
  8. ^ Jordans, Frank (30 July 2015). "Philae probe finds evidence that comets can be cosmic labs". The Washington Post. Associated Press. Retrieved 30 July 2015.
  9. ^ "Science on the Surface of a Comet". European Space Agency. 30 July 2015. Retrieved 30 July 2015.
  10. ^ Bibring, J.-P.; Taylor, M.G.G.T.; Alexander, C.; Auster, U.; Biele, J.; Finzi, A. Ercoli; Goesmann, F.; Klingehoefer, G.; Kofman, W.; Mottola, S.; Seidenstiker, K.J.; Spohn, T.; Wright, I. (31 July 2015). "Philae's First Days on the Comet - Introduction to Special Issue". Science. 349 (6247): 493. Bibcode:2015Sci...349..493B. doi:10.1126/science.aac5116. PMID 26228139. Retrieved 30 July 2015.
  11. ^ "Acetamide". Mindat.org.
  12. ^ "Acetamide" (PDF). Handbook of Mineralogy. RRUFF Project.

External links

Amide

An amide ( or or ), also known as an acid amide, is a compound with the functional group RnE(O)xNR′2 (R and R′ refer to H or organic groups). Most common are carboxamides (organic amides) (n = 1, E = C, x = 1), but many other important types of amides are known, including phosphoramides (n = 2, E = P, x = 1 and many related formulas) and sulfonamides (E = S, x = 2). The term amide refers both to classes of compounds and to the functional group (RnE(O)xNR′2) within those compounds.

Amide can also refer to the conjugate base of ammonia (the anion H2N−) or of an organic amine (an anion R2N−). For discussion of these "anionic amides", see Alkali metal amides.

Due to the dual use of the word 'amide', there is debate as to how to properly and unambiguously name the derived anions of amides in the first sense (i.e., deprotonated acylated amines), a few of which are commonly used as nonreactive counterions.The remainder of this article is about the carbonyl–nitrogen sense of amide.

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 commercially.

Bis(trimethylsilyl)acetamide

Bis(trimethylsilyl)acetamide (BSA) is an organosilicon compound with the formula Me3SiNC(OSiMe3)Me (Me = CH3). It is a colorless liquid that is soluble in diverse organic solvents, but reacts rapidly with compounds, including solvents and moisture, containing OH and NH functional groups. It is used in analytical chemistry for the derivatisation of compounds in analysis to increase their volatility, e.g. for gas chromatography. It is also used to introduce the trimethylsilyl protecting group in organic synthesis. A related reagent is N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA).

Carboxamide

In organic chemistry carboxamides (or amino carbonyls) are functional groups with the general structure R-CO-NR'R′′ with R, R', and R′′ as organic substituents, or hydrogen.Two amino acids, asparagine and glutamine, have a carboxamide group in them. The properties and reactivity of the carboxamide group arise from the hydrogen bonding capabilities of the -NH2 group as well as the carbonyl oxygen. Furthermore, the carbon atom in a carboxamide has a low-lying LUMO that is capable of accepting electron density from the nonbonding lone pair on the nitrogen, weakening the carbon-oxygen bond.

Examples of simple carboxamides include:

Acetamide

Benzamide

Comet nucleus

The nucleus is the solid, central part of a comet, popularly termed a dirty snowball or an icy dirtball. A cometary nucleus is composed of rock, dust, and frozen gases. When heated by the Sun, the gases sublimate and produce an atmosphere surrounding the nucleus known as the coma. The force exerted on the coma by the Sun's radiation pressure and solar wind cause an enormous tail to form, which points away from the Sun. A typical comet nucleus has an albedo of 0.04. This is blacker than coal, and may be caused by a covering of dust.Results from the Rosetta and Philae spacecraft show that the nucleus of 67P/Churyumov–Gerasimenko has no magnetic field, which suggests that magnetism may not have played a role in the early formation of planetesimals. Further, the ALICE spectrograph on Rosetta determined that electrons (within 1 km (0.62 mi) above the comet nucleus) produced from photoionization of water molecules by solar radiation, and not photons from the Sun as thought earlier, are responsible for the degradation of water and carbon dioxide molecules released from the comet nucleus into its coma. On 30 July 2015, scientists reported that the Philae spacecraft, that landed on comet 67P/Churyumov-Gerasimenko in November 2014, detected at least 16 organic compounds, of which four (including acetamide, acetone, methyl isocyanate and propionaldehyde) were detected for the first time on a comet.

DPA-714

DPA-714 or N,N-diethyl-2-[4-(2-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide is a selective ligand for the translocator protein (TSPO) currently under evaluation for several clinical applications. For this reason, a practical, multigram synthetic route for its preparation has been described.The binding affinity of DPA-714 for TSPO is reported as Ki = 7.0 ± 0.4 nM.[18F]DPA-714 is currently under investigation as a potential radiopharmaceutical for imaging TSPO in living systems using positron emission tomography (PET). DPA-714, along with other members of the DPA class of TSPO ligands, has been shown to decrease microglial activation and increase neuronal survival in a quinolinic acid rat model of excitotoxic neurodegeneration, suggesting potential neuroprotective effects.

Dichloroacetamide

Dichloroacetamide is a chlorinated derivative of acetamide.

Dimethylacetamide

Dimethylacetamide (DMAc or DMA) is the organic compound with the formula CH3C(O)N(CH3)2. This colorless, water-miscible, high boiling liquid is commonly used as a polar solvent in organic synthesis. DMA is miscible with most other solvents, although it is poorly soluble in aliphatic hydrocarbons.

Fluoroacetamide

Fluoroacetamide is an organic compound based on acetamide with one fluorine atom replacing hydrogen on the methyl group. it is a metabolic poison which disrupts the citric acid cycle and was used as a rodenticide.

Methyl isocyanide

Methyl isocyanide or isocyanomethane is an organic compound and a member of the isocyanide family. This colorless liquid is isomeric to methyl cyanide (acetonitrile), but its reactivity is very different. Methyl isocyanide is mainly used for making 5-membered heterocyclic rings. The C-N distance in methyl isocyanide is very short, 1.158 Å as is characteristic of isocyanides.

Methylphenylpiracetam

Methylphenylpiracetam is a derivative of piracetam and a positive allosteric modulator of the sigma-1 receptor. It differs from phenylpiracetam by having a methyl group.E1R is the (4R,5S) stereoisomer of methylphenylpiracetam.

N-Vinylacetamide

N-Vinylacetamide (NVA) is a non-ionic monomer. Copolymers made of NVA and other monomers can exhibit practical characteristics in addition to those common with the existing hydrophilic polymers.

Pilsicainide

Pilsicainide (INN) is an antiarrhythmic agent.

It is marketed in Japan as サンリズム (Sunrythm). The JAN applies to the hydrochloride salt, pilsicainide hydrochloride.

Pilsicainide is a drug used clinically in Japan to treat cardiac arrhythmias. It functions by blocking the fast inward movement of sodium ions through the Nav1.5 sodium channel that contributes to the rapid depolarization characteristic of phase 0 in the cardiac action potential. Pilsicainide is a pure sodium channel blocker, meaning it does not significantly affect any other cardiac channels including potassium and calcium channels. Pilsicainide binds to a common site on the sodium channel through either intracellular or extracellular application(3). The affinity of pilsicainide for the sodium channel receptor and its rate of binding are dependent on the state of the channel. It has been proven to have a greater affinity for the receptor in its inactivated state as opposed to resting or open(4), thereby following the modulated receptor hypothesis(5). Binding of pilsicainide selectively inhibits the channel(6), preventing the movement of sodium ions into the cardiac cell. This decreases the rate of depolarization of the cell membrane as well as the action potential amplitude, but has no effect on the overall duration of the action potential(6). Suppression of the depolarization rate is use-dependent(7), and therefore inhibition increases with increased stimulation. Pilsicainide also causes delayed impulse conduction through the myocardium in a dose-dependent manner(8). The effects of pilsicainide have a slow rate of onset and offset resulting in a prolonged recovery time(9). This contributes to its potent blocking activity and its classification as a class 1c antiarrhythmic agent(10).

A cardiac arrhythmia includes any abnormal heartbeat and can be manifested as tachycardia, bradycardia, or other irregular rhythms. Pilsicainide has been proven successful in treating both ventricular(11) and supraventricular arrhythmias with few adverse effects(12). It is especially effective in the treatment of atrial fibrillation. Atrial fibrillation is the most common type of arrhythmia(14). It may result from various heart abnormalities or may occur spontaneously in a seemingly healthy individual(15). Atrial fibrillation is characterized by rapid, disorganized electrical impulses in the atria resulting in depolarization of only a small group of myocardial cells. This prevents the atria from undergoing coordinated contraction, instead resulting in small fibrillations of the heart muscle. Re-entry occurs when an impulse does not die after activating the heart but instead returns to the atria and causes re-excitation(16). Simultaneous re-entry of multiple impulses with short wavelengths results in atrial fibrillation(17). Impulse wavelength is the product of the conduction velocity and the effective refractory period. Pilsicainide suppresses atrial conduction velocity but also increases the effective refractory period(18). Its effects on the refractory period are significantly more substantial, and therefore pilsicainide treatment results in an increased wavelength and termination of atrial fibrillation. A single oral dose of pilsicainide effectively restores normal sinus rhythm in patients with recent-onset atrial fibrillation and a healthy left ventricle. Long-term therapy with pilsicainide is successful in treating chronic atrial fibrillation).3. Hattori Y, and Inomata N. Modes of the Na channel blocking action of pilsicainide, a new antiarrhythmic agent, in cardiac cells. Jpn J Pharmacol. 1992;58(4):365-73.

4. Desaphy JF, Dipalma A, Costanza T, Bruno C, Lentini G, Franchini C, George A, and Conte Camerino D. Molecular determinants of state-dependent block of voltage-gated sodium channels by pilsicainide. Br J Pharmacol. 2010;160(6):1521-33.

5. Hille B. Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptor reaction. J Gen Physiol. 1977;69:497-515.

6. Hattori Y, Inomata N, Aisaka K, Ishihara T. Electrophysiological actions of N-(2,6-dimethylphenyl)-8-pyrrolizidine-acetamide hydrochloride hemihydrate (SUN 1165), a new antiarrhythmic agent. J Cardiovasc Pharmacol. 1986;8(5):998-1002.

7. Courtney KR. Interval-dependent effects of small antiarrhythmic drugs on excitability of guinea-pig myocardium. J Mol Cell Cardiol. 1980;12(11):1273-86.

8. Hidaka T, Hamasaki S, Aisaka K, Ishihara T, Morita M, Toyama J, and Yamada K. N-(2,6-dimethylphenyl)-8-pyrrolizidineacetamide hydrochloride hemihydrate (SUN 1165), a new antiarrhythmic agent: effects on cardiac conduction. Arzneimittelforschung. 1985;35(9):1381-6.

9. Hattori Y, Hidaka T, Aisaka K, Satoh F, and Ishihara T. Effect of SUN 1165, a new potent antiarrhythmic agent, on the kinetics of rate-dependent block of Na channels and ventricular conduction of extrasystoles. J Cardiovasc Pharmacol. 1988;11(4):407-12.

10. Campbell TJ. Kinetics of onset of rate-dependent effects of class I antiarrhythmic drugs are important in determining their effects on refractoriness in guinea-pig ventricle, and provide a theoretical basis for their subclassification. Cardiovasc Res. 1983;17(6):344-52.

11. Hashimoto H, Satoh N, and Nakashima M. Effects of SUN-1165, N-(2,6-dimethylphenyl)-8-pyrrolizidine acetamide hydrochloride hemihydrate, a new class I antiarrhythmic drug, on ventricular arrhythmias, intraventricular conduction, and the refractory period in canine myocardial infarction. J Cardiovasc Pharmacol. 1992;19(3):417-24.

12. Ino T, Atarashi H, Kuruma A, Onodera T, Saitoh H, and Hayakawa H. Electrophysiologic and hemodynamic effects of a single oral dose of pilsicainide hydrochloride, a new class 1c antiarrhythmic agent. J Cardiovasc Pharmacol. 1998;31(1):157-64.

14. Feinberg WM, Blackshear JL, Laupacis A, Kronmal R, and Hart RG. Prevalence, age distribution, and gender of patients with atrial fibrillation. Analysis and implications. Arch Intern Med. 1995;155(5):469-73.

15. Dang D, Arimie R, and Haywood LJ. A review of atrial fibrillation. J Natl Med Assoc. 2002;94(12):1036-48.

16. Veenhuyzen GD, Simpson CS, and Abdollah H. Atrial Fibrillation. Can Med Assoc J. 2004;171(7):755-60.

17. Rensma PL, Allessie MA, Lammers WJ, Bonke FI, and Schalij MJ. Length of excitation wave and susceptibility to reentrant atrial arrhythmias in normal conscious dogs. Circ Res. 1988;62(2):395-410.

18. Kanki H, Mitamura H, Takatsuki S, Sueyoshi K, Shinagawa K, Sato T, and Ogawa S. Postrepolarization refractoriness as a potential anti-atrial fibrillation mechanism of pilsicainide, a pure sodium channel blocker with slow recovery kinetics. Cardiovasc Drugs Ther. 1998;12(5):475-82.

Piracetam

Piracetam (sold under many brand names) is a medication in the racetams group, with chemical name 2-oxo-1-pyrrolidine acetamide. It is approved in the United Kingdom but is not approved in the United States. In the UK, piracetam is prescribed mainly for myoclonus, but is used off-label for other conditions. Evidence to support its use for many conditions is unclear, although it is marketed as a nootropic (cognitive enhancer). Studies of piracetam's cognitive effects have had equivocal results, sometimes showing modest benefits in specific populations and sometimes showing minimal or no benefit.It shares the same 2-oxo-pyrrolidone base structure with pyroglutamic acid. Piracetam is a cyclic derivative of GABA (gamma-Aminobutyric acid). Related drugs include the anticonvulsants levetiracetam and brivaracetam, and the putative nootropics aniracetam and phenylpiracetam.

Poly(N-vinylacetamide)

Poly(N-vinylacetamide) (PNVA) is a polymer having affinity for both water and alcohol made primarily from N-vinylacetamide (NVA) monomer. The homopolymer of NVA is called GE191 grade. Copolymer of NVA and sodium acrylate called GE167 grade.

Propionaldehyde

Propionaldehyde or propanal is the organic compound with the formula CH3CH2CHO. It is a saturated 3-carbon aldehyde and is a structural isomer of acetone. It is a colorless liquid with a slightly irritating, fruity odor.

Silylation

Silylation is the introduction of a (usually) substituted silyl group (R3Si) to a molecule. The process is the basis of organosilicon chemistry.

Trimethylsilyl

For tetramethylsilane, which is also abbreviated as TMS, see tetramethylsilane.

A trimethylsilyl group (abbreviated TMS) is a functional group in organic chemistry. This group consists of three methyl groups bonded to a silicon atom [−Si(CH3)3], which is in turn bonded to the rest of a molecule. This structural group is characterized by chemical inertness and a large molecular volume, which makes it useful in a number of applications.

A trimethylsilyl group bonded to a methyl group forms tetramethylsilane, which is abbreviated as TMS as well.

Compounds with trimethylsilyl groups are not normally found in nature. Chemists sometimes use a trimethylsilylating reagent to derivatize rather non-volatile compounds such as certain alcohols, phenols, or carboxylic acids by substituting a trimethylsilyl group for a hydrogen in the hydroxyl groups on the compounds. This way trimethylsiloxy groups [−O-Si(CH3)3] are formed on the molecule. A couple of examples of trimethylsilylating agents include trimethylsilyl chloride and bis(trimethylsilyl)acetamide. Trimethylsilyl groups on a molecule have a tendency to make it more volatile, often making the compounds more amenable to analysis by gas chromatography or mass spectrometry. An example of such trimethylsilylation is mentioned in the Brassicasterol article. Such derivatizations are often done on a small scale in special vials.

When attached to certain functional groups in a reactant molecule, trimethylsilyl groups may also be used as temporary protecting groups during chemical synthesis or some other chemical reactions.

In chromatography, derivitization of accessible silanol groups in a bonded stationary phase with trimethylsilyl groups is referred to as endcapping.

In an NMR spectrum, signals from atoms in trimethylsilyl groups in compounds will commonly have chemical shifts close to the tetramethylsilane reference peak at 0 ppm. Also compounds, such as high temperature silicone "stopcock" grease, which have polysiloxanes (often called silicones) in them will commonly show peaks from their methyl groups (attached to the silicon atoms) having NMR chemical shifts close to the tetramethylsilane standard peak, such as at 0.07 ppm in CDCl3.Otherwise very reactive molecules can be isolated when enveloped by bulky trimethylsilyl groups. This effect can be observed in tetrahedranes.

Tryptophan 2-monooxygenase

In enzymology, a tryptophan 2-monooxygenase (EC 1.13.12.3) is an enzyme that catalyzes the chemical reaction

L-tryptophan + O2 (indol-3-yl)acetamide + CO2 + H2O

Thus, the two substrates of this enzyme are L-tryptophan and O2, and its 3 products are (indol-3-yl)acetamide, CO2, and H2O.

This enzyme belongs to the family of oxidoreductases, specifically those acting on single donors with O2 as oxidant and incorporation of two atoms of oxygen into the substrate (oxygenases). The oxygen incorporated need not be derived from O with incorporation of one atom of oxygen (internal monooxygenases o internal mixed-function oxidases). The systematic name of this enzyme class is L-tryptophan:oxygen 2-oxidoreductase (decarboxylating). This enzyme participates in tryptophan metabolism.

Molecules
Deuterated
molecules
Unconfirmed
Related

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