Acetanilide (c8h9no): Structure, Properties, Synthesis

The acetanilide (C8H9NO) is an aromatic amide receives several additional names: N-acetilarilamina, N-phenylacetamide and acetanilo. It occurs as an odorless solid in the form of flakes, its chemical nature is amide, and as such it can form flammable gases when reacting with strong reducing agents.

Furthermore, it is a weak base, being able to react with dehydrating agents such as P 2 O 5 to produce a nitrile. Acetanilide was found to have analgesic and antipyretic action, and was used in 1886 under the name Antifebrina by A. Cahn and P. Hepp.

acetanilide

In 1899, acetylsalicylic acid (aspirin) was introduced on the market, which had the same therapeutic actions as acetanilide. As the use of acetanilide was associated with the appearance of cyanosis in patients — a consequence of acetanilide-induced methemoglobinemia — its use was ruled out.

Subsequently, it was established that the analgesic and antipyretic action of acetanilide resided in a metabolite of this called paracetamol (acetoaminophen), which did not have its toxic effects, as suggested by Axelrod and Brodie.

Chemical structure

acetanilide

The upper image represents the chemical structure of acetanilide. On the right is the hexagonal aromatic ring of benzene (with dotted lines), and on the left is the reason why the compound consists of an aromatic amide: the acetamido group (HNCOCH 3 ).

The acetamido group gives the benzene ring a greater polar character; that is, it creates a dipole moment in the acetanilide molecule.

Why? Because nitrogen is more electronegative than any of the carbon atoms in the ring, and it is also bonded to the acyl group, whose O atom also attracts electron density.

On the other hand, almost the entire molecular structure of acetanilide rests on the same plane due to sp 2 hybridization  of the atoms that compose it.

There is an exception linked to those of the –CH 3 group , whose hydrogen atoms make up the vertices of a tetrahedron (the white spheres on the far left come out of the plane).

Resonance structures and intermolecular interactions

The solitary pair without sharing in the N atom circulates through the π system of the aromatic ring, originating several resonance structures. However, one of these structures ends up with a negative charge on the O atom (more electronegative) and a positive charge on the N atom.

Thus, there are resonance structures where a negative charge moves in the ring, and another where it resides in the O atom. As a consequence of this “electronic asymmetry” —which comes from the hand of molecular asymmetry—, acetanilide it interacts intermolecularly by dipole-dipole forces.

However, the hydrogen bonding interactions (NH — O-…) between two acetanilide molecules are, in fact, the predominant force in their crystal structure. 

Thus, acetanilide crystals consist of orthorhombic unit cells of eight molecules oriented in “flat ribbon” shapes by their hydrogen bonds.

This can be visualized by placing one acetanilide molecule on top of the other, in parallel. So, as the HNCOCH 3 groups spatially overlap, they form hydrogen bonds.

In addition, between these two molecules a third can also “slip”, but with its aromatic ring pointing to the opposite side.

Chemical properties

Molecular weight

135.166 g / mol.

Chemical description

White or off-white solid. It forms bright white flakes or a crystalline white powder.

Odor

Toilet.

Taste

Slightly spicy.

Boiling point

304 ° C to 760 mmHg (579 ° F to 760 mmHg).

Melting point

114.3 ° C (237.7 ° F).

Flash point or flash point

169 ° C (337 ° F). Measurement made in an open glass.

Density

1,219 mg / mL at 15 ° C (1,219 mg / mL at 59 ° F)

Vapor density

4.65 relative to air.

Vapor pressure

1 mmHg at 237 ° F, 1.22 × 10-3 mmHg at 25 ° C, 2Pa at 20 ° C.

Stability

It undergoes a chemical rearrangement when exposed to ultraviolet light. How does the structure change? The acetyl group forms new bonds on the ring at the ortho and para positions. In addition, it is stable in air and incompatible with strong oxidizing agents, caustics and alkalis.

Volatility

Appreciably volatile at 95ºC.

Autoignition

1004ºF.

Decomposition

It decomposes when heated, emitting a highly toxic smoke.

pH

5-7 (10 g / L H 2 O at 25 ° C)

Solubility

– In water: 6.93 × 103 mg / mL at 25 ºC.

– Solubility of 1 g of acetanilide in different liquids: in 3.4 ml of alcohol, 20 ml of boiling water, 3 ml of methanol, 4 ml of acetone, 0.6 ml of boiling alcohol, 3.7 ml of chloroform, 5 ml of gliecerol, 8 ml of dioxane, 47 ml of benzene and 18 ml of ether. Chloral hydrate increases the solubility of acetanilide in water.

Synthesis

It is synthesized by reacting acetic anhydride with acetanilide. This reaction appears in many texts of Organic Chemistry (Vogel, 1959):

C 6 H 5 NH 2  + (CH 3 CO) 2 O => C 6 H 5 NHCOCH 3  + CH 3 COOH

Applications

-It is an inhibitor agent of the decomposition process of hydrogen peroxide (hydrogen peroxide).

-Stabilizes cellulose ester varnishes.

-It takes part as an intermediary in the acceleration of rubber production. Likewise, it is an intermediary in the synthesis of some colorants and camphor.

-Acts as a precursor in the synthesis of penicillin.

-It is used in the production of 4-acetamidosulfonylbenzene chloride. Acetanilide reacts with chlorosulfonic acid (HSO 3 Cl), thus producing 4-aminosulfonylbenzene chloride. This reacts with ammonium or a primary organic amine to form sulfonamides.

-It was used experimentally in the 19th century in the development of photography.

-Acetanilide is used as a marker of electroosmotic fluxes (EOF) in capillary electrophoresis for the study of the link between drugs and proteins.

-Recently (2016) acetanilide has been linked to 1- (ω-phenoxyalkyluracil) in experiments to inhibit hepatitis C virus replication. Acetanilide binds to position 3 of the pyrimidine ring.

-The experimental results indicate a reduction in the replication of the viral genome, regardless of the viral genotype.

-Before identifying the toxicity of acetanilide, it was used as an analgesic and antipyretic from 1886. Later (1891), it was used in the treatment of chronic and acute bronchitis by Grün.

References

  1. J. Brown & DEC Corbridge. (1948). Crystal Structure of Acetanilide: Use of Polarized Infra-Red Radiation. Nature volume 162, page 72. doi: 10.1038 / 162072a0.
  2. Grün, EF (1891) The use of acetanilide in the treatment of acute and chronic bronchitis. Lancet 137 (3539): 1424-1426.
  3. Magri, A. et al. (2016). Exploration of acetanilide derivatives of 1- (ω-phenoxyalkyl) uracils as novel inhibitors of Hepatitis C Virus replication. Sci. Rep. 6, 29487; doi: 10.1038 / srep29487.
  4. Merck KGaA. (2018). Acetanilide. Retrieved on June 5, 2018, from: sigmaaldrich.com
  5. SIDS Initial Assessment Report for 13th SIAM. Acetanilide. [PDF]. Retrieved on June 5, 2018, from: inchem.org
  6. Wikipedia. (2018). Acetanilide. Retrieved on June 05, 2018, from: en.wikipedia.org
  7. PubChem. (2018). Acetanilide. Retrieved on June 5, 2018, from: pubchem.ncbi.nlm.nih.gov

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