Phthalimide

{{Chembox

| Watchedfields = changed

| verifiedrevid = 464205909

| Name = Phthalimide

| ImageFile1_Ref = {{chemboximage|correct|??}}

| ImageFile1 = Phthalimide.svg

| ImageSize1 = 150

| ImageName1 = skeletal formula of the phthalimide molecule

| ImageFile2 = Phthalimide-3D-balls.png

| ImageSize2 = 170

| ImageName2 = ball-and-stick model of the phthalimide molecule

| PIN = 1H-Isoindole-1,3(2H)-dione

| OtherNames = 1,3-dioxoisoindoline
Phthalimidoyl (deprotonated)

|Section1={{Chembox Identifiers

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 38817

| SMILES = O=C2c1ccccc1C(=O)N2

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 6550

| PubChem = 6809

| InChI = 1/C8H5NO2/c10-7-5-3-1-2-4-6(5)8(11)9-7/h1-4H,(H,9,10,11)

| InChIKey = XKJCHHZQLQNZHY-UHFFFAOYAS

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 277294

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C8H5NO2/c10-7-5-3-1-2-4-6(5)8(11)9-7/h1-4H,(H,9,10,11)

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = XKJCHHZQLQNZHY-UHFFFAOYSA-N

| CASNo_Ref = {{cascite|correct|CAS}}

| CASNo = 85-41-6

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 1J6PQ7YI80

| RTECS =

}}

|Section2={{Chembox Properties

| Properties_ref = {{cite web |url= http://www.chemicalland21.com/specialtychem/finechem/PHTHALIMIDE.htm|title= Phthalimide|publisher= Chemicalland21|accessdate= 15 November 2011}}

| C=8 | H=5 | O=2 | N=1

| Appearance = White solid

| Density =

| Solubility = <0.1 g/100 ml (19.5 °C)

| MeltingPtC = 238

| BoilingPtC = 336

| BoilingPt_notes = sublimes

| pKa = 8.3

| pKb = 5.7

| Viscosity =

| MagSus = {{val|-78.4|e=-6|u=cm³/mol}}

}}

|Section3={{Chembox Structure

| MolShape =

| Coordination =

| CrystalStruct =

| Dipole =

}}

|Section7={{Chembox Hazards

| ExternalSDS =

| MainHazards =

| FlashPt =

| HPhrases =

| PPhrases =

| GHS_ref =

}}

|Section8={{Chembox Related

| OtherFunction_label = Amides

| OtherFunction = Maleimide

| OtherCompounds = Phthalic anhydride

}}

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.{{Ullmann | first1 = Peter M. | last1 = Lorz | first2 = Friedrich K. | last2 = Towae | first3 = Walter | last3 = Enke | first4 = Rudolf | last4 = Jäckh | first5 = Naresh | last5 = Bhargava | first6 = Wolfgang | last6 = Hillesheim | title = Phthalic Acid and Derivatives | doi = 10.1002/14356007.a20_181.pub2}}

Uses

:image:Folpet.png, a phthalimide, is a commercial fungicide.{{cite book |doi=10.1002/0471238961.0621140704180509.a01 |chapter=Fungicides, Agricultural |title=Kirk-Othmer Encyclopedia of Chemical Technology |date=2000 |last1=Dreikorn |first1=Barry A. |last2=Owen |first2=W. John |isbn=978-0-471-48494-3 }}|left]]

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

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".{{cite web | url = https://www.organic-chemistry.org/protectivegroups/amino/phthalimides.htm | title = Phthalimides | accessdate = 2013-02-07}} 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.{{cite web | url = http://scientificupdate.co.uk/process-chemistry-information/item/deprotection-removal-of-amine-protecting-groups-phthalimide-and-dimethylaminosulphonyl.html | title = Deprotection – removal of amine protecting groups (phthalimide and dimethylaminosulphonyl) | accessdate = 2013-02-07 | url-status = dead | archiveurl = https://archive.today/20141203032450/http://scientificupdate.co.uk/process-chemistry-information/item/deprotection-removal-of-amine-protecting-groups-phthalimide-and-dimethylaminosulphonyl.html | archivedate = 2014-12-03 }}

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,{{OrgSynth|id=cv1p0119|title=β-Bromoethylphthalimide|first1=P. L.|last1=Salzberg|first2=J. V.|last2=Supniewski|date=1927|volume=7|page=8|collvol=1|collvolpages=119|doi=10.15227/orgsyn.007.0008}} is used in the Gabriel synthesis of primary amines, such as glycine.

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.

:File:Phthalimide from phthalic anhydride.svg{{clear-left}}

Phthalimide can also be prepared from phthalic acid by the following process:

:File:Phthalimide synthesis.svg{{clear-left}}

Carboxylic acids when reacted with ammonia give ammonium salts, which in turn give amides when strongly heated.

Natural occurrence

Kladnoite is a natural mineral analog of phthalimide.{{cite web |url= http://www.mindat.org/min-2222.html|title= Kladnoite|publisher= mindat.org|accessdate= 15 November 2011}} 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.

References

=General reading=

{{cite book|last1= Vollhardt|first1= K. Peter C.|last2= Schore|first2= Neil Eric|authorlink2= Neil E. Schore|title= Organic Chemistry: Structure and Function|edition= 4th|year= 2002|publisher= W. H. Freeman|location= New York|isbn= 978-0-7167-4374-3|url-access= registration|url= https://archive.org/details/organicchemistry00voll_0}}
{{cite book |last1= Finar|first1= Ivor Lionel|title= Organic Chemistry|edition= 6th|volume= 1|year= 1973|publisher= Longman|location= London|isbn= 0-582-44221-4}}