N-Hydroxyphthalimide

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N-Hydroxyphthalimide
N-Hydroxyphthalimid Struktur.svg
Names
Preferred IUPAC name
2-Hydroxy-1H-isoindole-1,3(2H)-dione
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
ECHA InfoCard 100.007.600 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 208-358-1
PubChem CID
UNII
  • InChI=1S/C8H5NO3/c10-7-5-3-1-2-4-6(5)8(11)9(7)12/h1-4,12H
    Key: CFMZSMGAMPBRBE-UHFFFAOYSA-N
  • O=C2N(O)C(C1=CC=CC=C12)=O
Properties
C8H5NO3
Molar mass 163.132 g·mol−1
Appearancewhite to pale yellow crystalline solid
Density 1.64 g/mL
Melting point 233°C
Boiling point 370°C
water, polar organic solvents
Hazards
GHS labelling:
GHS-pictogram-exclam.svg
Warning
H315, H319, H335
P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, P501
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

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 used as a catalyst in the synthesis of other organic compounds. [1] [2] It is soluble in water and organic solvents such as acetic acid, ethyl acetate and acetonitrile. [3]

Contents

Occurrence and production

As described by Lassar Cohn in 1880, N-hydroxyphthalimide was produced from phthaloyl chloride and hydroxylamine hydrochloride in the presence of sodium carbonate. [4]

Synthesis of N-hydroxyphthalimide from phthaloyl chloride using hydroxylamine hydrochloride N-Hydroxyphthalimid aus Phthalsauredichlorid.svg
Synthesis of N-hydroxyphthalimide from phthaloyl chloride using hydroxylamine hydrochloride

The product forms as a red sodium salt under basic conditions, while white N-hydroxyphthalimide precipitates in 55% yield as the solution is acidified. N-hydroxyphthalimide is also produced by reacting hydroxylamine hydrochloride with diethyl phthalate in the presence of sodium acetate, [5] or with phthalic anhydride in the presence of sodium carbonate with heating. In the last case, an overall yield of 76% is produced following purification by recrystallization. [6]

Microwave irradiation of phthalic anhydride and hydroxylamine hydrochloride in pyridine produces N-hydroxyphthalimide in 81% yield. [7] Even in the absence of a base, phthalic anhydride and hydroxylamine phosphate react to produce N-hydroxyphthalimide in 86% yield when heated to 130 °C. [8]

Preparation of N-hydroxyphthalimide from phthalic anhydride N-Hydroxyphthalimid aus Phthalsaureanhydrid.svg
Preparation of N-hydroxyphthalimide from phthalic anhydride

Properties

N-Hydroxyphthalimide exists in two polymorphs, colorless and yellow, In the colorless white form, the NOH group is rotated about 1.19° from the plane of the molecule, while in the yellow form it is much closer to planarity (0.06° rotation). [9]

The color of the synthesized N-hydroxyphthalimide is determined by the solvent used; the color transition from white to yellow is irreversible. [10] N-Hydroxyphthalimide forms strongly colored, mostly yellow or red salts with alkali and heavy metals, ammonia and amines. [11] Hydrolysis of N-hydroxyphthalimide by the addition of strong bases produces phthalic acid monohydroxamic acid by adding water across one of the carbon–nitrogen bonds. [5] N-Hydroxyphthalimide ethers, on the other hand, are colorless and provide O-alkylhydroxylamines by alkaline hydrolysis or cleavage through hydrazine hydrate.

The "phthalylhydroxylamine" reported by Cohn was known to have a molecular formula of C
8H
5NO
3, but the exact structure was not known. [4] Three possibilities were discussed and are shown in the Figure below: a mono-oxime of phthalic anhydride ("phthaloxime", I), an expanded ring with two heteroatoms, (2,3-benzoxazine-1,4-dione, II), and N-hydroxyphthalimide (III). [10] [12] It was not until the 1950s that Cohn's product was definitely shown to be N-hydroxyphthalimide (III). [13]

Three structural isomers of C 8H 5NO 3 considered as Cohn's "phthalylhydroxylamine" Isomere Strukturen von C8H5NO3.svg
Three structural isomers of C
8H
5NO
3 considered as Cohn's "phthalylhydroxylamine"

Applications and reactions

Nefkens and Tesser developed a technique for generating active esters from N-hydroxyphthalimide [14] for use in peptide synthesis, [15] an approach later extended to using N-hydroxysuccinimide. [16] The ester linkage is formed between the N-hydroxyphthalimide and a carboxylic acid by elimination of water, the coupling achieved with N,N′-dicyclohexylcarbodiimide (DCC). For peptide synthesis, the N-terminus of the growing peptide is protected with tert-butyloxycarbonyl while its C-terminus (Z–NH–CH(R)–COOH) is coupled to N-hydroxyphthalimide. An ester of the next amino acid in the desired peptide sequence is shaken with activated ester, adding to the chain and displacing the N-hydroxyphthalimide. This reaction is quantitative and nearly instantaneous at 0 °C. [15] [17] The resulting ester needs to be hydrolysed before the cycle can be repeated.

Conversion of the C-terminus of a peptide to an active ester of N-hydroxyphthalimide N-Hydroxyphthalimid-Aktivester.svg
Conversion of the C-terminus of a peptide to an active ester of N-hydroxyphthalimide

The N-hydroxyphthalimide can be removed by shaking with sodium bicarbonate, [15] but the N-hydroxysuccinimide approach shows greater reactivity and convenience, and is generally preferred. [16] [17]

Esters of N-hydroxyphthalimide and activated sulfonic acids such as trifluoromethanesulfonic anhydride or p-toluenesulfonyl chloride are used as so-called photoacids, which split off protons during UV irradiation.

UV reaction with NHPI triflate UV-Reaktion mit NHPI-triflat.svg
UV reaction with NHPI triflate

The protons generated serve for the targeted local degradation of acid-sensitive photoresists. [18]

N-Hydroxyphthalimide can be converted with vinyl acetate in the presence of palladium(II)acetate to the N-vinyloxyphthalimide, which is quantitatively hydrogenated to N-ethoxyphthalimide and subsequently O-ethylhydroxylamine. [19]

Synthesis of O-alkoxyamines via N-hydroxyphthalimides O-Alkoxyamine via N-Hydroxyphthalimid.svg
Synthesis of O-alkoxyamines via N-hydroxyphthalimides

A variety of functional groups can be oxidized with the aminoxyl radical (phthalimide-N-oxyl, PINO) [20] formed by the abstraction of a hydrogen atom from N-hydroxyphthalimide under gentle conditions (similar to TEMPO): [1]

Formation of the PINO radical Bildung des PINO-Radikals.svg
Formation of the PINO radical

Using molecular oxygen alkanes can be oxidized to form alcohols, secondary alcohols to ketones, acetals to esters and alkenes to epoxides. [21] [22] [23] Amides can be converted into carbonyl compounds with N-hydroxyphthalimide and cobalt(II)salts under mild conditions. [24]

Oxidation of amides with N-hydroxyphthalimide Oxidation von Amiden mit N-Hydroxyphthalimid.svg
Oxidation of amides with N-hydroxyphthalimide

Efficient oxidation reactions of precursors of important basic chemicals are of particular technical interest. For example, ε-caprolactam can be prepared using NHPI from the so-called KA oil ("ketone-alcohol" oil, a mixture of cyclohexanol and cyclohexanone) which is obtained during the oxidation of cyclohexane. The reaction proceeds via cyclohexanol hydroperoxide, which reacts with ammonia to give peroxydicyclohexylamine followed by a rearrangement in the presence of catalytic amounts of lithium chloride. [22] [25]

Oxidation of KA oil to caprolactam Oxidation von KA-Ol zu Caprolactam.svg
Oxidation of KA oil to caprolactam

The use of N-hydroxyphthalimide as a catalyst in the oxidation of KA oil avoids the formation of the undesirable by-product ammonium sulfate which is produced by the conventional ε-caprolactam synthesis (Beckmann rearrangement of cyclohexanone oxime with sulfuric acid).

Alkanes are converted into nitroalkanes in the presence of nitrogen dioxide. [26]

Nitrogenation/oxidation of cyclohexane by means of NHPI Nitrierung von Cyclohexan mittels NHPI.svg
Nitrogenation/oxidation of cyclohexane by means of NHPI

Cyclohexane is converted at 70 °C with nitrogen dioxide/air into a mixture of nitrocyclohexane (70%), cyclohexyl nitrate (7%) and cyclohexanol (5%).

N-hydroxyphthalimide serves as an oxidizing agent in photographic developers [27] and as charge control agents in toners [28] have been described in the patent literature.

Phthalimido-N-oxyl (PINO)

The radical derived by removal of a hydrogen atom from N-hydroxyphthalimide is called N-phthalimido-N-oxyl, acronym being PINO. It is a powerful H-atom abstracting agent. [1] The bond dissociation energy of NHPI (i.e., PINO–H) is 88–90 kcal/mol (370–380 kJ/mol), depending on the solvent. [29]

References

  1. 1 2 3 Recupero, Francesco; Punta, Carlo (2007). "Free Radical Functionalization of Organic Compounds Catalyzed by N-Hydroxyphthalimide". Chem. Rev. 107 (9): 3800–3842. doi:10.1021/cr040170k. PMID   17848093.
  2. ↑ Melone, Lucio; Punta, Carlo (2013). "Metal-free aerobic oxidations mediated by N-hydroxyphthalimide. A concise review". Beilstein J. Org. Chem. 9: 1296–1310. doi: 10.3762/bjoc.9.146 . PMC   3701383 . PMID   23843925.
  3. ↑ Gambarotti, Cristian; Punta, Carlo; Recupero, Francesco; Zlotorzynska, Maria; Sammis, Glenn (2013). "N-Hydroxyphthalimide". N-Hydrophthalimide. Encyclopedia of Reagents for Organic Synthesis . doi:10.1002/047084289X.rn00598.pub2. ISBN   978-0471936237.
  4. 1 2 Cohn, Lassar (1880). "Phthalylhydroxylamin: Ueberführung der Phthalsäure in Salicylsäure" [N-hydroxyphthalimide: Conversion of phthalic acid into salicylic acid]. Justus Liebigs Ann. Chem. (in German). 205 (3): 295–314. doi:10.1002/jlac.18802050304.
  5. 1 2 Bauer, Ludwig; Miarka, Stanley V. (1957). "The Chemistry of N-Hydroxyphthalimide". J. Am. Chem. Soc. 79 (8): 1983–1985. doi:10.1021/ja01565a061.
  6. ↑ Gross, H.; Keitel, I. (1969). "Zur Darstellung von N-Hydroxyphthalimid und N-Hydroxysuccinimid" [On the preparation of N-hydroxyphthalimide and N-hydroxysuccinimide]. J. Prakt. Chem. (in German). 311 (4): 692–693. doi:10.1002/prac.19693110424.
  7. ↑ Sugamoto, Kazuhiro; Matsushita, Yoh‐ichi; Kameda, Yu‐hei; Suzuki, Masahiko; Matsui, Takanao (2005). "Microwave‐assisted Synthesis of N‐Hydroxyphthalimide Derivatives". Synth. Commun. 35 (1): 67–70. doi:10.1081/SCC-200046498. S2CID   96623891.
  8. ↑ EPapplication 1085013,Elke Fritz-Langhals,"Verfahren zur Herstellung cyclischer N-Hydroxy-dicarboximide [Process for the preparation of cyclic N-hydroxydicarboximides]",published 2001-03-21, assigned to Consortium für elektrochemische Industrie GmbH
  9. ↑ Reichelt, Hendrik; Faunce, Chester A.; Paradies, Henrich H. (2007). "Elusive forms and structures of N-hydroxyphthalimide: The colorless and yellow crystal forms of N-hydroxyphthalimide". J. Phys. Chem. A . 111 (13): 2587–2601. Bibcode:2007JPCA..111.2587R. doi:10.1021/jp068599y. PMID   17388355.
  10. 1 2 Ames, D. E.; Grey, T. F. (1955). "N-Hydroxy-imides. Part II. Derivatives of homophthalic and phthalic acid". J. Chem. Soc. : 3518–3521. doi:10.1039/JR9550003518.
  11. ↑ Porcheddu, Andrea; Giacomelli, Giampaolo (2009). "Synthesis of oximes and hydroxamic acids". In Rappaport, Zvi; Lieberman, Joel F. (eds.). The Chemistry of Hydroxylamines, Oximes, and Hydroxamic Acids, Part 1. Chichester: Wiley. pp. 224–226. ISBN   978-0-470-51261-6.
  12. ↑ Bradly, Oscar L.; Baker, Leslie C.; Goldstein, Richard F.; Harris, Samuel (1928). "LXVIII.—The isomerism of the oximes. Part XXXIII. The oximes of opianic acid and of phthalic anhydride". J. Chem. Soc. : 529–539. doi:10.1039/JR9280000529.
  13. ↑ Hurd, Charles D.; Buess, Charles M.; Bauer, Ludwig (1954). "Succino- and phthalo-hydroxamic acids". J. Org. Chem. 19 (7): 1140–1149. doi:10.1021/jo01372a021.
  14. ↑ Nefkens, G. H. L.; Tesser, G. I.; Nivard, R. J. F. (1962). "Synthesis and reactions of esters of N-hydroxyphthalimide and N-protected amino acids". Recl. Trav. Chim. Pays-Bas . 81 (8): 683–690. doi:10.1002/recl.19620810807.
  15. 1 2 3 Nefkens, G. H. L.; Tesser, G. I. (1961). "A Novel Activated Ester in Peptide Synthesis". J. Am. Chem. Soc. 83 (5): 1263. doi:10.1021/ja01466a068.
  16. 1 2 Anderson, George W.; Zimmerman, Joan E.; Callahan, Francis M. (1964). "The Use of Esters of N-Hydroxysuccinimide in Peptide Synthesis". J. Am. Chem. Soc. 86 (9): 1839–1842. doi:10.1021/ja01063a037.
  17. 1 2 Bodanszky, Miklos (1993). "Activation and Coupling". Principles of Peptide Synthesis (2nd ed.). Springer-Verlag. pp. 9–61. doi:10.1007/978-3-642-78056-1_2. ISBN   9783642780561.
  18. ↑ EP 0919867,K. Elian, E. Günther, R. Leuschner,"Chemisch verstärkter Resist für die Elektronenstrahllithografie",published 2003-05-21, assigned to Infineon Technologies AG
  19. ↑ WO 1995025090,D.M.C. Callant, A.M.C.F. Castelijns, J.G. De Vries,"Cyclic N-alkenyloxyimides and a method for the preparation of cyclic N-alkenyloxyimides, the corresponding cyclic N-alkoxyimides and O-alkoxyamines",published 1995-09-21, assigned to DSM N.V.
  20. ↑ S. Coseri (2009), "Phthalimide‐N‐oxyl (PINO) Radical, a Powerful Catalytic Agent: Its Generation and Versatility Towards Various Organic Substrates", Catal. Rev. Sci. Eng., vol. 51, no. 2, pp. 218–292, doi:10.1080/01614940902743841, S2CID   97018136
  21. ↑ Y. Ishii, K. Nakayama, M. Takeno, S. Sakaguchi, T. Iwahama, Y. Nishiyama (1995), "Novel Catalysis by N-Hydroxyphthalimide in the Oxidation of Organic Substrates by Molecular Oxygen", J. Org. Chem. , vol. 60, no. 13, pp. 3934–3935, doi:10.1021/jo00118a002 {{citation}}: CS1 maint: multiple names: authors list (link)
  22. 1 2 "Discovery of a carbon radical producing catalyst and its application to organic synthesis" (PDF). TCIMAIL, Number 116. Tokyo Chemical Industry Co. Ltd. April 2003. Retrieved 2016-08-11.
  23. ↑ B.B. Wentzel, M.P.J. Donners, P.L. Alsters, M.C. Feiters, R.J.M. Nolte (2000), "N-Hydroxyphthalimide/cobalt(II) catalyzed low temperature benzylic oxidation using molecular oxygen", Tetrahedron , vol. 56, no. 39, pp. 7797–7803, doi:10.1016/S0040-4020(00)00679-7 {{citation}}: CS1 maint: multiple names: authors list (link)
  24. ↑ F. Minisci, C. Punta, F. Recupero, F. Fontana, G.F. Pedulli (2002), "Aerobic Oxidation of N-Alkylamides Catalyzed by N-Hydroxyphthalimide under Mild Conditions. Polar and Enthalpic Effects", J. Org. Chem. , vol. 67, no. 8, pp. 2671–2676, doi:10.1021/jo016398e, PMID   11950315 {{citation}}: CS1 maint: multiple names: authors list (link)
  25. ↑ O. Fukuda, S. Sakaguchi, Y. Ishii (2001), "A new strategy for catalytic Baeyer-Villiger oxidation of KA-oil with molecular oxygen using N-hydroxyphthalimide", Tetrahedron Lett. , vol. 42, no. 20, pp. 3479–3481, doi:10.1016/S0040-4039(01)00469-5 {{citation}}: CS1 maint: multiple names: authors list (link)
  26. ↑ S. Sakaguchi, Y. Nishiwaki, T. Kitamura, Y. Ishii (2001), "Efficient catalytic alkane nitration with NO2 under air assisted by N-hydroxyphthalmide", Angew. Chem., Int. Edit. , vol. 40, no. 1, pp. 222–224, doi:10.1002/1521-3773(20010105)40:1<222::AID-ANIE222>3.0.CO;2-W {{citation}}: CS1 maint: multiple names: authors list (link)
  27. ↑ EPapplication 0664479,W. Ishikawa&T. Sampei,"Method of processing silver halide photographic lightsensitive material",published 1994-07-26, assigned to Konica Corp.
  28. ↑ US 5332637,J.C. Wilson; S.M. Bonser& H.W. Osterhoudt,"Electrostatographic dry toner and developer compositions with hydroxyphthalimide",issued 1994-07-26, assigned to Eastman Kodak Co.
  29. ↑ Coseri, Sergiu (2009). "Phthalimide‐N‐oxyl (PINO) Radical, a Powerful Catalytic Agent: Its Generation and Versatility Towards Various Organic Substrates". Catalysis Reviews. 51 (2): 218–292. doi:10.1080/01614940902743841. S2CID   97018136.
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