Key Reactions and Applications of Phthalimide Explained
It is an organic aromatic compound with the chemical formula C6H4(CO2)NH. It has a heteroatom Nitrogen present in it. It belongs to the nitrogen-containing compound. It is prepared from Phthalic anhydride. It is acidic in nature and its conjugate base is resonance stabilized. Resonance provides extra stability to the structure. It has one H atom attached to the nitrogen atom, which can be easily removed using any strong base. Then the resulting ion can be made to react with bromine, which will result in the formation of N-bromophthalimide. This process is known as Gabriel Phthalimide Synthesis, which is very important in the synthesis of aliphatic amines. In this article, we will discuss the phthalimide, preparation of phthalimide, the use of phthalimide, and reactions of phthalic anhydride.
Structure
The molecular formula of Phthalimide is C6H4(CO2)NH. It contains one benzene ring, two electrophilic carbonyl groups, a Nitrogen atom, and a Hydrogen atom. Another five-membered ring is also [present with a heteroatom N. The extra stability of this compound is due to the resonance structures. The structure of Phthalimide is shown below:
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Preparation of Phthalimide
Now, as we already know what is phthalimide, our next motive is to know about the preparation methods. It is derived from Phthalic anhydride. When Phthalic anhydride is heated in the presence of aqueous ammonia, Phthalimide is obtained as the product. The reaction is shown below:
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The second method involves the use of ammonium carbonate along with phthalic anhydride. Ammonium carbonate is slightly acidic in nature. When it is made to react with KOH, it results in the formation of Potassium phthalimide.
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Properties
Physical Properties
It is solid in nature and white in colour.
The molar mass of the compound is 147.33 g/mol.
Phthalimide melting point is 238℃ and the boiling point is 336℃.
Chemical Properties
It is acidic in nature with a pKa value of 8.3.
It is resonance stabilized.
It is an imide derivative and has a heteroatom present in it.
When it is reacted with base, it results in the formation of salts.
The reason for high acidity is the presence of two electrophilic carbonyl groups.
Reactions of Phthalic Anhydride
The main use of phthalimide is in the formation of aliphatic amines. The process is known as Gabriel Phthalimide synthesis. Phthalic anhydride is used here to synthesize phthalimide. Ammonium carbonate is made to react with phthalic anhydride in the presence of base KOH. It results in the formation of the potassium salt of phthalimide. Typically, this reaction uses the potassium salt of phthalimide.
When this salt is made to react with an alkyl halide, it gives N-alkylphthalimde as the product. When this product is reacted with hydrazine in the presence of the base, the desired product is obtained.
The complete synthesis is shown below:
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Various alternatives to this reagent have been developed. In Gabriel synthesis, the Sodium salt of saccharin is also being used in place of salts of phthalimide. The alternate Gabriel Synthesis hydrolyzes and gives secondary amines easily.
Phthalimide Uses
It is widely used in the pharmaceutical industry for the synthesis of various chemical compounds containing nitrogen. It acts as a masked source of ammonia. So, it is more beneficial than free ammonia.
It is used in the synthesis of anthranilic acid which is extensively used in dye industries.
It is the chemical precursor in the chemical synthesis of peptides.
It is used in the synthesis of medicines because of its anti-inflammatory, analgesic, anticonvulsant properties.
The number of anti-inflammatory phthalimide derivatives has been synthesized as tumour necrosis inhibitors.
FAQs on Phthalimide: Structure, Properties, Preparation, and Uses
1. What is phthalimide and what is its chemical formula?
Phthalimide is an organic chemical compound that is the imide derivative of phthalic anhydride. It appears as a white solid at room temperature and is only slightly soluble in water. Structurally, it consists of a benzene ring fused to a five-membered ring containing two carbonyl groups attached to a central nitrogen atom. Its chemical formula is C₈H₅NO₂.
2. What is the IUPAC name for phthalimide?
The preferred IUPAC name for phthalimide is 1H-Isoindole-1,3(2H)-dione. This name precisely describes its heterocyclic structure, indicating an isoindole ring system with two ketone (oxo) groups at positions 1 and 3.
3. Why is phthalimide considered acidic despite having an amine-like group?
The hydrogen atom attached to the nitrogen in phthalimide is significantly acidic due to the powerful electron-withdrawing effect of the two adjacent carbonyl groups. This effect delocalises the nitrogen's lone pair of electrons across the O=C-N-C=O system. When the proton (H⁺) is lost, the resulting anion (the phthalimide ion) is highly stabilised by resonance, which makes the parent molecule act as a notable acid, readily forming salts with strong bases like KOH.
4. What are the most important applications of phthalimide in organic chemistry?
Phthalimide is primarily used for the following applications:
- Gabriel Synthesis: It is a key reagent in the Gabriel synthesis, a reliable method for preparing pure primary aliphatic amines.
- Precursor for Dyes: It serves as a precursor in the synthesis of various dyes, such as anthranilic acid, which is used to produce indigo dye.
- Masked Source of Ammonia: Due to its structure, it acts as a stable and manageable source of an amino group for various chemical transformations where direct use of ammonia would be problematic.
5. How does the structure of phthalimide contribute to its role in the Gabriel synthesis?
The structure of phthalimide is ideal for Gabriel synthesis for two reasons:
1. The acidic N-H bond allows for easy deprotonation by a base (like KOH) to form a stable, nucleophilic phthalimide anion.
2. This anion can then perform a nucleophilic attack on an alkyl halide. Because the nitrogen is bonded to two carbonyl groups, it is sterically hindered and less prone to over-alkylation, ensuring that predominantly primary amines are formed upon subsequent hydrolysis.
6. What are the main limitations of using phthalimide in the Gabriel synthesis reaction?
The Gabriel phthalimide synthesis has two significant limitations:
- It cannot be used to prepare aromatic primary amines (like aniline). This is because aryl halides are generally unreactive towards nucleophilic substitution by the phthalimide anion due to the partial double-bond character of the C-X bond in the aryl halide.
- It is not suitable for synthesizing secondary or tertiary amines, as the bulky phthalimide group prevents further alkylation at the nitrogen atom.
7. What is the fundamental difference between Phthalimide and Phthalamide?
The key difference lies in their structure. Phthalimide is a cyclic imide, where a single nitrogen atom is part of a five-membered ring and is bonded to two carbonyl groups. In contrast, phthalamide is a diamide and is an acyclic compound. It features two separate amide groups (–CONH₂) attached to the benzene ring at adjacent positions (ortho positions).
8. How is phthalimide typically prepared in a laboratory setting?
Phthalimide is commonly prepared by heating phthalic anhydride with a source of ammonia. The reaction is typically carried out by heating phthalic anhydride with either aqueous ammonia or ammonium carbonate. This process involves an initial formation of the half-amide (phthalamic acid), which upon further heating, undergoes dehydration to close the ring and form the stable phthalimide molecule.
