Phthalimide

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Phthalimide
Phthalimide.svg
Phthalimide-3D-balls.png
Names
Preferred IUPAC name
1H-Isoindole-1,3(2H)-dione
Other names
1,3-dioxoisoindoline
Phthalimidoyl (deprotonated)
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.001.458 OOjs UI icon edit-ltr-progressive.svg
PubChem CID
UNII
  • InChI=1S/C8H5NO2/c10-7-5-3-1-2-4-6(5)8(11)9-7/h1-4H,(H,9,10,11) Yes check.svgY
    Key: XKJCHHZQLQNZHY-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/C8H5NO2/c10-7-5-3-1-2-4-6(5)8(11)9-7/h1-4H,(H,9,10,11)
    Key: XKJCHHZQLQNZHY-UHFFFAOYAS
  • O=C2c1ccccc1C(=O)N2
Properties [1]
C8H5NO2
Molar mass 147.133 g·mol−1
AppearanceWhite solid
Melting point 238 °C (460 °F; 511 K)
Boiling point 336 °C (637 °F; 609 K) sublimes
<0.1 g/100 ml (19.5 °C)
Acidity (pKa)8.3
Basicity (pKb)5.7
−78.4×10−6 cm3/mol
Related compounds
Related Amides
Maleimide
Related compounds
Phthalic anhydride
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

Phthalimide is the organic compound with the formula C6H4(CO)2NH. It is the imide derivative of phthalic anhydride. It is a sublimable white solid that is slightly soluble in water but more so upon addition of base. It is used as a precursor to other organic compounds as a masked source of ammonia. [2]

Contents

Preparation

Phthalimide can be prepared by heating phthalic anhydride with alcoholic ammonia giving 95–97% yield. Alternatively, it may be prepared by treating the anhydride with ammonium carbonate or urea. It can also be produced by ammoxidation of o-xylene. [2]

Uses

Folpet, a phthalimide, is a commercial fungicide. Folpet.png
Folpet, a phthalimide, is a commercial fungicide.

Phthalimide is used as a precursor to anthranilic acid, a precursor to azo dyes and saccharin. [2]

Alkyl phthalimides are useful precursors to amines in chemical synthesis, especially in peptide synthesis where they are used "to block both hydrogens and avoid racemization of the substrates". [4] Alkyl halides can be converted to the N-alkylphthalimide:

C6H4(CO)2NH + RX + NaOH → C6H4(CO)2NR + NaX + H2O

The amine is commonly liberated using hydrazine:

C6H4(CO)2NR + N2H4 → C6H4(CO)2N2H2 + RNH2

Dimethylamine can also be used. [5]

Some examples of phthalimide drugs include thalidomide, amphotalide, taltrimide, talmetoprim, and apremilast. With a trichloromethylthio substituent, a phthalimide-derived fungicide is Folpet.

Reactivity

It forms salts upon treatment with bases such as sodium hydroxide. The high acidity of the imido N-H is the result of the pair of flanking electrophilic carbonyl groups. Potassium phthalimide, made by reacting phthalimide with potassium carbonate in water at 100 °C or with potassium hydroxide in absolute ethanol, [6] is used in the Gabriel synthesis of primary amines, such as glycine.

Natural occurrence

Kladnoite is a natural mineral analog of phthalimide. [7] It is very rarely found among a few burning coal fire sites.

Safety

Phthalimide has low acute toxicity with LD50 (rat, oral) of greater than 5,000 mg/kg. [2]

Related Research Articles

<span class="mw-page-title-main">Amine</span> Chemical compounds and groups containing nitrogen with a lone pair (:N)

In chemistry, amines are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Formally, amines are derivatives of ammonia (NH3, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines, trimethylamine, and aniline. Inorganic derivatives of ammonia are also called amines, such as monochloramine.

<span class="mw-page-title-main">Carboxylic acid</span> Organic compound containing a –C(=O)OH group

In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group attached to an R-group. The general formula of a carboxylic acid is often written as R−COOH or R−CO2H, sometimes as R−C(O)OH with R referring to an organyl group, or hydrogen, or other groups. Carboxylic acids occur widely. Important examples include the amino acids and fatty acids. Deprotonation of a carboxylic acid gives a carboxylate anion.

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

Acridine is an organic compound and a nitrogen heterocycle with the formula C13H9N. Acridines are substituted derivatives of the parent ring. It is a planar molecule that is structurally related to anthracene with one of the central CH groups replaced by nitrogen. Like the related molecules pyridine and quinoline, acridine is mildly basic. It is an almost colorless solid, which crystallizes in needles. There are few commercial applications of acridines; at one time acridine dyes were popular, but they are now relegated to niche applications, such as with acridine orange. The name is a reference to the acrid odour and acrid skin-irritating effect of the compound.

<span class="mw-page-title-main">Haloalkane</span> Group of chemical compounds derived from alkanes containing one or more halogens

The haloalkanes are alkanes containing one or more halogen substituents. They are a subset of the general class of halocarbons, although the distinction is not often made. Haloalkanes are widely used commercially. They are used as flame retardants, fire extinguishants, refrigerants, propellants, solvents, and pharmaceuticals. Subsequent to the widespread use in commerce, many halocarbons have also been shown to be serious pollutants and toxins. For example, the chlorofluorocarbons have been shown to lead to ozone depletion. Methyl bromide is a controversial fumigant. Only haloalkanes that contain chlorine, bromine, and iodine are a threat to the ozone layer, but fluorinated volatile haloalkanes in theory may have activity as greenhouse gases. Methyl iodide, a naturally occurring substance, however, does not have ozone-depleting properties and the United States Environmental Protection Agency has designated the compound a non-ozone layer depleter. For more information, see Halomethane. Haloalkane or alkyl halides are the compounds which have the general formula "RX" where R is an alkyl or substituted alkyl group and X is a halogen.

<span class="mw-page-title-main">Phthalic acid</span> Aromatic organic compound with formula C6H4(COOH)2

In organic chemistry, phthalic acid is an aromatic dicarboxylic acid, with formula C6H4(CO2H)2 and structure HO(O)C−C6H4−C(O)OH. Although phthalic acid is of modest commercial importance, the closely related derivative phthalic anhydride is a commodity chemical produced on a large scale. Phthalic acid is one of three isomers of benzenedicarboxylic acid, the others being isophthalic acid and terephthalic acid.

<span class="mw-page-title-main">Phthalic anhydride</span> Chemical compound

Phthalic anhydride is the organic compound with the formula C6H4(CO)2O. It is the anhydride of phthalic acid. Phthalic anhydride is a principal commercial form of phthalic acid. It was the first anhydride of a dicarboxylic acid to be used commercially. This white solid is an important industrial chemical, especially for the large-scale production of plasticizers for plastics. In 2000, the worldwide production volume was estimated to be about 3 million tonnes per year.

<span class="mw-page-title-main">Imide</span> Class of chemical compounds

In organic chemistry, an imide is a functional group consisting of two acyl groups bound to nitrogen. The compounds are structurally related to acid anhydrides, although imides are more resistant to hydrolysis. In terms of commercial applications, imides are best known as components of high-strength polymers, called polyimides. Inorganic imides are also known as solid state or gaseous compounds, and the imido group (=NH) can also act as a ligand.

The Hofmann rearrangement is the organic reaction of a primary amide to a primary amine with one less carbon atom. The reaction involves oxidation of the nitrogen followed by rearrangement of the carbonyl and nitrogen to give an isocyanate intermediate. The reaction can form a wide range of products, including alkyl and aryl amines.

The Gabriel synthesis is a chemical reaction that transforms primary alkyl halides into primary amines. Traditionally, the reaction uses potassium phthalimide. The reaction is named after the German chemist Siegmund Gabriel.

<span class="mw-page-title-main">Xanthate</span> Salt that is a metal-thioate/O-esters of dithiocarbonate

A xanthate is a salt or ester of a xanthic acid. The formula of the salt of xanthic acid is [R−O−CS2]M+. Xanthate also refers to the anion [R−O−CS2]. The formula of a xanthic acid is R−O−C(=S)−S−H, such as ethyl xanthic acid, while the formula of an ester of a xanthic acid is R−O−C(=S)−S−R', where R and R' are organyl groups. The salts of xanthates are also called O-organyl dithioates. The esters of xanthic acid are also called O,S-diorganyl esters of dithiocarbonic acid. The name xanthate is derived from Ancient Greek ξανθός (xanthos) meaning 'yellowish' or 'golden', and indeed most xanthate salts are yellow. They were discovered and named in 1823 by Danish chemist William Christopher Zeise. These organosulfur compounds are important in two areas: the production of cellophane and related polymers from cellulose and for extraction of certain sulphide bearing ores. They are also versatile intermediates in organic synthesis.

<span class="mw-page-title-main">Copper(II) hydroxide</span> Hydroxide of copper

Copper(II) hydroxide is the hydroxide of copper with the chemical formula of Cu(OH)2. It is a pale greenish blue or bluish green solid. Some forms of copper(II) hydroxide are sold as "stabilized" copper(II) hydroxide, although they likely consist of a mixture of copper(II) carbonate and hydroxide. Cupric hydroxide is a strong base, although its low solubility in water makes this hard to observe directly.

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

Ethylenediamine (abbreviated as en when a ligand) is the organic compound with the formula C2H4(NH2)2. This colorless liquid with an ammonia-like odor is a basic amine. It is a widely used building block in chemical synthesis, with approximately 500,000 tonnes produced in 1998. Ethylenediamine is the first member of the so-called polyethylene amines.

In chemistry, aminolysis (/am·i·nol·y·sis/) is any chemical reaction in which a molecule is lysed by reacting with ammonia or an amine. The case where the reaction involves ammonia may be more specifically referred to as ammonolysis.

<span class="mw-page-title-main">Anthranilic acid</span> Chemical compound

Anthranilic acid is an aromatic acid with the formula C6H4(NH2)(CO2H) and has a sweetish taste. The molecule consists of a benzene ring, ortho-substituted with a carboxylic acid and an amine. As a result of containing both acidic and basic functional groups, the compound is amphoteric. Anthranilic acid is a white solid when pure, although commercial samples may appear yellow. The anion [C6H4(NH2)(CO2)], obtained by the deprotonation of anthranilic acid, is called anthranilate. Anthranilic acid was once thought to be a vitamin and was referred to as vitamin L1 in that context, but it is now known to be non-essential in human nutrition.

Bis(trimethylsilyl)amine (also known as hexamethyldisilazane and HMDS) is an organosilicon compound with the molecular formula [(CH3)3Si]2NH. The molecule is a derivative of ammonia with trimethylsilyl groups in place of two hydrogen atoms. An electron diffraction study shows that silicon-nitrogen bond length (173.5 pm) and Si-N-Si bond angle (125.5°) to be similar to disilazane (in which methyl groups are replaced by hydrogen atoms) suggesting that steric factors are not a factor in regulating angles in this case. This colorless liquid is a reagent and a precursor to bases that are popular in organic synthesis and organometallic chemistry. Additionally, HMDS is also increasingly used as molecular precursor in chemical vapor deposition techniques to deposit silicon carbonitride thin films or coatings.

<span class="mw-page-title-main">2-Ethylanthraquinone</span> Intermediate Chemical in H2O2 Synthesis

2-Ethylanthraquinone is an organic compound that is a derivative of anthraquinone. This pale yellow solid is used in the industrial production of hydrogen peroxide (H2O2).

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

Phthalonitrile is an organic compound with the formula C6H4(CN)2, which is an off-white crystal solid at room temperature. It is a derivative of benzene, containing two adjacent nitrile groups. The compound has low solubility in water but is soluble in common organic solvents. The compound is used as a precursor to phthalocyanine and other pigments, fluorescent brighteners, and photographic sensitizers.

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

Trichloroacetonitrile is an organic compound with the formula CCl3CN. It is a colourless liquid, although commercial samples often are brownish. It is used commercially as a precursor to the fungicide etridiazole. It is prepared by dehydration of trichloroacetamide. As a bifunctional compound, trichloroacetonitrile can react at both the trichloromethyl and the nitrile group. The electron-withdrawing effect of the trichloromethyl group activates the nitrile group for nucleophilic additions. The high reactivity makes trichloroacetonitrile a versatile reagent, but also causes its susceptibility towards hydrolysis.

In chemistry, a fatty amine is loosely defined as any amine possessing a mostly linear hydrocarbon chain of eight or more carbon atoms. They are typically prepared from the more abundant fatty acids, with vegetable or seed-oils being the ultimate starting material. As such they are often mixtures of chain lengths, ranging up to about C22. They can be classified as oleochemicals. Commercially important members include coco amine, oleylamine, tallow amine, and soya amine. These compounds and their derivatives are used as fabric softeners, froth flotation agents, corrosion inhibitors, lubricants and friction modifiers. They are also the basis for a variety of cosmetic formulations.

<i>N</i>-Hydroxyphthalimide Chemical compound

N-Hydroxyphthalimide is the organic compound with the formula C6H4(CO)2NOH. A white or yellow solid, it is a derivative of phthalimide. The compound is as a catalyst in the synthesis of other organic compounds. It is soluble in water and organic solvents such as acetic acid, ethyl acetate and acetonitrile.

References

  1. "Phthalimide". Chemicalland21. Retrieved 15 November 2011.
  2. 1 2 3 4 Lorz, Peter M.; Towae, Friedrich K.; Enke, Walter; Jäckh, Rudolf; Bhargava, Naresh; Hillesheim, Wolfgang. "Phthalic Acid and Derivatives". Ullmann's Encyclopedia of Industrial Chemistry . Weinheim: Wiley-VCH. doi:10.1002/14356007.a20_181.pub2. ISBN   978-3527306732.
  3. Dreikorn, Barry A.; Owen, W. John (2000). "Fungicides, Agricultural". Kirk-Othmer Encyclopedia of Chemical Technology. doi:10.1002/0471238961.0621140704180509.a01. ISBN   978-0-471-48494-3.
  4. "Phthalimides" . Retrieved 2013-02-07.
  5. "Deprotection – removal of amine protecting groups (phthalimide and dimethylaminosulphonyl)". Archived from the original on 2014-12-03. Retrieved 2013-02-07.
  6. Salzberg, P. L.; Supniewski, J. V. "β-Bromoethylphthalimide". Organic Syntheses . 7: 8. doi:10.15227/orgsyn.007.0008 ; Collected Volumes, vol. 1, p. 119.
  7. "Kladnoite". mindat.org. Retrieved 15 November 2011.

General reading