Phthalimide

Not to be confused with Thalidomide.

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]

Phthalimide

Names
Preferred IUPAC name 1H-Isoindole-1,3(2H)-dione
Other names 1,3-dioxoisoindoline Phthalimidoyl (deprotonated)
Identifiers
CAS Number	85-41-6 Y
3D model (JSmol)	Interactive image
ChEBI	CHEBI:38817 Y
ChEMBL	ChEMBL277294 Y
ChemSpider	6550 Y
ECHA InfoCard	100.001.458
PubChem CID	6809
UNII	1J6PQ7YI80 Y
CompTox Dashboard (EPA)	DTXSID3026514
InChI InChI=1S/C8H5NO2/c10-7-5-3-1-2-4-6(5)8(11)9-7/h1-4H,(H,9,10,11) Y Key: XKJCHHZQLQNZHY-UHFFFAOYSA-N Y 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
SMILES O=C2c1ccccc1C(=O)N2
Properties[1]
Chemical formula	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
Solubility in water	<0.1 g/100 ml (19.5 °C)
Acidity (pKa)	8.3
Basicity (pKb)	5.7
Magnetic susceptibility (χ)	−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). Y verify (what is YN ?) Infobox references

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. 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

• Vollhardt, K. Peter C.; Schore, Neil Eric (2002). Organic Chemistry: Structure and Function (4th ed.). New York: W. H. Freeman. ISBN 978-0-7167-4374-3.
• Finar, Ivor Lionel (1973). Organic Chemistry. Vol. 1 (6th ed.). London: Longman. ISBN 0-582-44221-4.