Phthalimide – Preparation, Chemical Reactions & Uses with Example

Phthalimides are the natural aromatic molecule with the chemical formula C₆H₄(CO)₂NH, consisting of nitrogen hetero-atom. It possesses a resonance-stabilized covalent bond and an acidic pH. Resonance increases the structure’s resistance. A powerful base may easily remove the H atom connected to the nucleophile. The resulting ion can then react with bromine to create N-bromophthalimide. The Gabriel Phthalimide Synthesis is a crucial stage in this process since it produces aliphatic amines. The article discusses phthalimides, chemical reactions, uses, and their physical and chemical properties.

What is Phthalimide?

Phthalimide is made from using phthalic anhydride. The substance formed is phthalic anhydride’s amide derivative, phthalic anhydride imide. Water solubility can vapourise this solid white precipitate. And more after adding the base. It serves as a precursor in other organic molecules and as an underground ammonia source. It belongs to a family of nitrogen compounds. Phthalimide is produced from phthalic anhydride.

Interesting Facts Chemically, potassium phthalimide has the formula C8H4KNO2. The phthalimide potassium salt often appears as fluffy, extremely pale yellow crystals. The desired product precipitates when a heated solution of phthalimide in ethanol is added to a mixture of potassium hydroxide in ethanol. Potassium phthalimide is a reagent that can be purchased for the Gabriel synthesis of amines.

 

Informative Details Since phthalimides possess analgesic, anti-inflammatory, and anticonvulsant characteristics, it is extensively employed in manufacturing pharmaceuticals and chemical compounds. It is widely used in dye industries. It serves as a concealed ammonia source. Therefore, it is helpful in the production of molecules containing nitrogen.

Phthalimide Composition

The chemical formula of phthalimide is C₆H₄(CO)₂NH. This chemical compound comprises benzene rings, a hydrogen atom, two carbonyl compounds, and a nucleophile. (A nitrogen heteroatom is present in another five-membered circle.) The increased stability of the compound is due to resonance structures. The table below provides a breakdown of phthalimide’s chemical composition:

Composition	Information
Structural Composition	C 58.53%, H 4.91%, N 17.06%, O 19.49%
Chemically Safe	Corrosive, Irritating Substance
Molecular (Molar) Formula	C8H8NO2
Molecular (Molar) Weight	147.13

Preparation of Phthalimides 

Phthalimides can be created by heating the binary compound ammonia and anhydride. 

 

Phthalimide can also be synthesized by heating a mixture of the chemical and carbonate. Potassium phthalimide is created when it is combined with ethanolic caustic potash, which turns it into mildly acidic, phthalimide.

The acid molecule could be a key intermediate in the chemical industry. Additionally, it is made commercially by oxidising hydrocarbons. The hydrocarbons are oxidized to create the end product using flaring sulfuric acid and mercury catalysts. The vapour stage of combustion can also lead to the oxidation of hydrocarbons. Although it is simple to create anhydrides from acids, no such anhydrides are present in equilibrium radical acids.

Informative Details The most crucial step in synthesizing phthalimides is the dehydrative confluence of phthalic anhydride at high temperatures when primary amines are accessible. When the amine is not easily accessible, the direct N-alkylation of phthalimides using alcohols at Mitsunobu conditions and potassium phthalimide using alkyl halides (Gabriel Synthesis) are the common alternatives to Ph-protected amines.

Phthalimide Properties

Physical Properties

• Phthalimides are both solid and white.
• The molecule weighs 147.33 g per mole.
• Phthalimide has melting and boiling temperatures of 238°C and 336°C, respectively.
• It has great thermal and electrical conductivity.

Chemical Properties

• It is acidic and has a pH level of 8.3.
• Stability of resonance is ensured.
• Phthalimide, which is an imide variant, contains heteroatoms.
• When it comes into contact with a base, salts are created.
• The low pH level is due to the presence of two electrophilic carboxyl.

Phthalimide Reaction

Phthalic acid derivatives are created by the reaction of phthalic anhydride or the acid with alcohol and are used in diffusion pumps and to substitute mercury in manometer tubes. Esters such as di-ethyl and di-hexyl are frequently used in this application. Effective insect repellents include dimethyl phthalate. Alkyd resins are frequently made using the substance phthalic anhydride. These resins are made of polyhydroxy alcohols and acids featuring two hydroxyl groups. Phthalimide reaction produces metallic salts due to the acidic imidazole hydrogen atom located in the middle of the two hydroxyl groups.

You may be aware that Gabriel manufactures amines and amino acids using the salt of potassium phthalimide. As already mentioned, phthalimide can be broken down by the Hofmann reaction to produce anthranilic acid. When phthalic anhydride is processed with alkaline peroxide in a cool environment, acidified mono-per phthalic acid is created.

       Phthalimide Uses 

• It is frequently used in the medical industry to synthesize various chemical molecules with nitrogen. It serves as a secretive source of ammonia. It is therefore preferred to free ammonia.
• It is employed in producing anthranilic acid, which is extensively used in the dye business.
• It is the molecular predecessor in the chemical synthesis of peptides.
• Due to its antibacterial, analgesic, antifungal, antitumor, anxiolytic, and anti-HIV-1 properties, phthalimides have drawn attention. Drug development benefits from its anti-inflammatory, analgesic, and anticonvulsant properties.
• The focus of the current review reveals that a significant class of heterocyclic phthalimide derivatives holds its promise as effective treatments for various illnesses, including AIDS, tumours, diabetes, pain, multiple myeloma, convulsions, inflammation, and bacterial infections. The development of phthalimide scaffolds with an excellent therapeutic feature would be a crucial first step in the potential development of drugs for the treatment of various ailments. These extensive efforts will provide new options for researchers to produce priceless medicinal agents.

Thalidomide, cetrimide, amphotalide, and trimethoprim are a few phthalimide medication examples. Folpet is a phthalimide-derived fungicide with a trichloromethylthio group.

 

Informative Details Studies employing phthalimides and their derivatives have revealed that these compounds have only mildly harmful effects when used at an acute dose. A therapeutic safety test was conducted in a study involving aryl phthalimides and their hypolipidemic and anti-inflammatory activities to ascertain their acute toxicity.  Even at the highest tested dose of 2 g / kg, there was no destructive potential. The animals also did not exhibit any signs of potential complications, such as behavioral changes like twitching, respiration, breathlessness, irregular heartbeats, and decreased breathing function. This test showed that the prescribed dosages for the biological functions tested [250 mg/kg] were safe.

Phthalimide Reaction: Limitations

The composition of the solution differs with the ratio of the component. However, if a significant amount of ammonia is employed, the primary amine takes precedence. The procedure is not particularly important in terms of application because it is challenging to separate the solution. One of the common illustrations of this reaction is the nucleophilic substitution reaction. Because the related haloarenes are far less reactive than alkyl halides, thus, cannot use the process to prepare aniline or other aromatic amines. The nucleophilic group of NH₃ does not cause the breakage of the C-X bond.

Things to Remember

• Anhydrous ammonia can be used to produce 95% to 99% of phthalimide by heating the anhydrous anhydride with ammonia.
• Phthalimide is an anthranilic acid precursor used to create azo colours and aspartame.
• A naturally occurring homologue of phthalimide is the mineral kladnoite. It can only be found in a few charcoal furnaces around the world.
• At lethal dosage, phthalimides are comparatively mildly toxic.
• Phthalimide salts are produced when it is handled with bases, such as sodium hydroxide.

Conclusion

Phthalimides are an intriguing class of chemicals with many applications amongst bicyclic non-aromatic nitrogen heterocycles. Many different alkaloids and pharmacophores have been synthesized using phthalimides as precursor materials and intermediates. As a result of recent findings, the biological activity of phthalimide and some of its derivatives have significant biological effects comparable to or even greater than those of well-known pharmaceutical compounds.

Frequently Asked Questions Phthalimide

Q1.What function does phthalimide serve?

A:Phthalimide is an organic compound with the chemical formula C₆H₄(CO)₂NH. It is a phthalic anhydride’s amide derivative. It is a white solid that can be sublimated and is mildly soluble in water but becomes more so when the base is added. It serves as a covert ammonia source and is a predecessor to other chemical molecules. In chemical synthesis, alkyl phthalimides are helpful building blocks for amines, especially in synthesizing peptides, where they are employed to “block both hydrogens and avoid substrates from becoming racemized.

Q2.Define “amide group”

A:An amide is a chemical functional group of amides consisting of a collection of carbonyls linked to a nitrogen atom. Amides can be synthesized from an amine and a carboxylic acid. Additionally, an amide is also known as the NH2 inorganic anion.

Q3.How is phthalimide produced?

A:When phthalic anhydride and alcoholic ammonia are heated, 95–97% phthalimide is produced. As an alternative, it can be made by treating the anhydride with ammonium carbonate or urea. Additionally, it can also be caused by o-xylene ammoxidation.

Q4.What components make phthalimide? 

A:Phthalimide is an imido chemical compound of phthalic acid. Here, phthalic acid is the main compound. The word “amide” describes a substituent that can be seen in organic synthesis and comprises two nitrogen-bonded carbonyl groups. Because they’re hydrophobic and inert, they can pass through the cellular membranes found in vivo. These compounds have structural traits with acid anhydrides. The bulk of imides are created through carboxyl group synthesis, and their names are derived from the acids with which they were synthesized.