Phthalimide

Not to be confused with Thalidomide.
Phthalimide
skeletal formula of the phthalimide molecule
ball-and-stick model of the phthalimide molecule
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 Edit this at Wikidata
UNII
  • InChI=1S/C8H5NO2/c10-7-5-3-1-2-4-6(5)8(11)9-7/h1-4H,(H,9,10,11) checkY
    Key: XKJCHHZQLQNZHY-UHFFFAOYSA-N checkY
  • 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
Appearance White 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).
checkY verify (what is checkY☒N ?)

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]

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.[3]

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]

References

  1. ^ "Phthalimide". Chemicalland21. Retrieved 15 November 2011.
  2. ^ a b c d 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