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Utente:Grasso Luigi/sanbox1/Anione nitrile

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La struttura dell'anione nitrile in (blu)

Gli anioni nitrili o nitriluri [1] sono ioni mancanti di un protone nell'atomo C in posizione α al gruppo nitrile ed hanno forma generale R2C-C≡N. Subiscono addizione nucleofila e reazioni di sostituzione con vari elettrofili.[2]

Anche se questi ioni sono simili funzionalmente agli enolati, l'extra legame multiplo negli anioni nitrili fornisce loro una geometria simile al chetene. Inoltre, le cianidrine deprotonate possono agire come anioni acilici mascherati, dando prodotti impossibili da ottenere solo con enolati. I meccanismi di aggiunta e sostituzione del nitrile sono ben conosciuti; tuttavia, di solito sono richieste condizioni fortemente basiche, limitando l'utilità sintetica della reazione.

Sintesi modifica

I nitriluri sono spesso generati attraverso l'azione di una base appropriata. Inoltre, il pKa dei nitrili si estende in un campo di almeno 20 unità. Pertanto, la scelta corretta della base dipende solitamente dal substrato. Gli acetonitrili contenenti un gruppo di stabilità extra per prelievo elettronico (ad esempio un anello aromatico) di solito vengono deprotonati usando come basi idrossidi o alcossidi. I nitrili instabili, invece, richiedono o basi ammidiche di metalli alcalini (come NaNH2) o basi alchilmetalliche (come butillitio) per ottenere una sicura deprotonazione. In quest'ultimo caso avviene l'addizione competitiva del gruppo alchilico al nitrile.

 
Deprotonazione acetonitrile generico
 
Tautomeria dell'anione acetonitrile

Studi di spettroscopia IR hanno dimostrato l'esistenza di almeno due forme tautomere dell'anione nitrile.

I polianioni dei nitrili si possono generare per deprotonazioni multiple e queste specie producono prodotti polialchilati in presenza di elettrofili alchilici.[3] Metodi alternativi per produrre nitriluri includono l'addizione nucleofila coniugata a nitrili α,β-insaturi,[4] reazioni di riduzione,[5] e il processo di transmetallazione. [6]

Meccanismo di reazione modifica

I meccanismi delle reazioni che coinvolgono l'anione nitrile dipendono principalmente dalla natura dell'elettrofilo coinvolto. Le alchilazioni semplici avvengono per spostamento SN2 (una sostituzione nucleofila bimolecolare)[7] and are subject to the usual stereoelectronic requirements of the process. Phase-transfer catalysis has been employed in alkylations of arylacetonitriles.[8][9] Nitrile anions can also be involved in Michael-type additions to activated double bonds and vinylation reactions with a limited number of polarized, unhindered acetylene derivatives.[10]

 

Arylation of nitrile anions is also possible, and can take place through different mechanisms depending on the substrates and reaction conditions. Aryl halides lacking electron-withdrawing groups react through an addition-elimination mechanism involving benzyne intermediates. Aryl phosphates and ammoniums react through the SRN1 pathway, which involves the generation of an aryl radical anion, fragmentation, and bond formation with a nucleophile. Electron transfer to a second molecule of arene carries on the radical chain.

 

Electron-poor aromatic compounds undergo nucleophilic aromatic substitution in the presence of nitrile anions.

Reazioni e limitazioni modifica

The primary difficulty for alkylation reactions employing nitrile anions is over-alkylation. In the alkylation of acetonitrile, for instance, yields of monoalkylated product are low in most cases. Two exceptions are alkylations with epoxides (the nearby negative charge of the opened epoxide wards off further alkylation) and alkylations with cyanomethylcopper(I) species. Side reactions may also present a problem; concentrations of the nitrile anion must be high in order to mitigate processes involving self-condensation, such as the Thorpe–Ziegler reaction. Other important side reactions include elimination of the alkyl cyanide product or alkyl halide starting material and amidine formation.

The cyclization of ω-epoxy-1-nitriles provides an interesting example of how stereoelectronic factors may override steric factors in intramolecular substitution reactions. In the cyclization of 1, for instance, only the cyclopropane isomer 2 is observed. This is attributed to better orbital overlap in the SN2 transition state for cyclization. 1,1-disubstituted and tetrasubstituted epoxides also follow this principle.

 

Conjugated nitriles containing γ hydrogens may be deprotonated at the γ position to give resonance-stabilized anions. These intermediates almost always react with α selectitivity in alkylation reactions, the exception to the rule being anions of ortho-tolyl nitriles.

 

Formation of cyanohydrins from carbonyl compounds renders the former carbonyl carbon acidic. After protection of the hydroxyl group with an acyl or silyl group, cyanohydrins can function essentially as masked acyl anions. Because ester protecting groups are base labile, mild bases must be employed with ester-protected cyanohydrins. α-(Dialkylamino)nitriles can also be used in this context.[11]

Examples of arylation and acylation reactions are shown below. Although intermolecular arylations using nitrile anions result in modest yields, the intramolecular procedure efficiently gives four-, five-, and six-membered benzo-fused rings. Acylation can be accomplished using a wide variety of acyl electrophiles, including carbonates, chloroformates, esters, anyhdrides, and acid chlorides.[12] In these reactions, two equivalents of base are used to drive the reaction towards acylated product—the acylated product is more acidic than the starting material.

 

Reazioni di laboratorio modifica

Condizioni tipiche

The most common bases used to deprotonate nitriles are the alkali metal amides, substituted amides, and hydrides. These reagents require inert, anhydrous conditions and careful handling. Polyalkylation is a significant problem for primary or secondary nitriles; however, a number of solutions to this problem exist. Alkylation of cyanoacetates followed by decarboxylation provides one solution.[13] Acylation of primary or secondary nitriles provides a convenient entry to the starting materials for this sequence. Distillation and chromatography are only practical for the separation of mono- and di-alkylated material when the molecular weight difference between the two is large.

Acylation is much more straightforward, as the resulting α-cyanocarbonyl compounds are much more acidic (and less nucleophilic) than corresponding starting materials. Monoacylated products can be obtained easily.

Esempio di processo[14]

To a suspension of 24.4 g (1.017 mol) of sodium hydride in 200 mL of anhydrous toluene was added a mixture of 122 g (1.043 mol) of phenylacetonitrile and 150 g (1.095 mol) of isobutyl bromide. The mixture was heated at 65 °C, at which temperature the reaction commenced. The heating mantle was removed, and the flask was cooled in order to keep the reaction from becoming too vigorous during the initial 0.5-hour reaction period. The reaction mixture was refluxed for an additional 5 hours and permitted to stand overnight. Ethanol (40 mL) was cautiously added dropwise, followed by the dropwise addition of 200 mL of water. The organic layer was separated, and the aqueous layer was extracted with benzene. The combined organic layers were washed successively with dilute acid, water, sodium carbonate solution, and water. After filtration through a layer of sodium sulfate, the benzene was evaporated and the product was fractionally distilled to afford 115 g (66%) of 2-phenyl-4-methylvaleronitrile, bp 130–134 °C (10 mm) [lit. (540) bp 136–138 °C (15 mm)].

 

Applicazioni sintetiche modifica

L'alchilazione di un anione nitrile seguita da decianazione riduttiva è stata impiegata nella nuova sintesi del (2)-9-dotlecen-1-il acetato, il feromone sessuale della falena detta Paralobesia viteana.[15]

 

Note modifica

  1. ^ (EN) Favre Henri A. e Powell Warren H. (a cura di), Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013, IUPAC Chemical Nomenclature and Structure Representation Division, Londra, IUPAC/RSC, 2013, ISBN 978-0-85404-182-4.
  2. ^ (EN) Arseniyadis S.; Kyler K. S.; Watt D. S., Addition and Substitution Reactions of Nitrile-Stabilized Carbanions, in Org. React., vol. 31, 1984, pp. 1-71, DOI:10.1002/0471264180.or031.01, ISBN 0471264180.
  3. ^ (EN) G. Marr; J. Ronayne, Organometallic derivatives. V. The lithiation of ferrocenylmethyl cyanide, in J. Organomet. Chem., vol. 47, 1973, pp. 417, DOI:10.1016/S0022-328X(00)81753-2.
  4. ^ (EN) G. C. Barrett; T. J. Grattan, Organic electrosynthesis ambident substitution reactivity of cyano-alkanes: electrochemically-directed αC-alkylation by bromo-alkanes, in Tetrahedron Lett., vol. 1979, n. 43, 1979, pp. 4237, DOI:10.1016/S0040-4039(01)86554-0.
  5. ^ (EN) T. Saegusa; Y. Ito; H. Kinoshita; S. Tomita, ynthetic Reactions by Complex Catalysts. XVI. The Dimerization of Acrylonitrile and Acrylate by Means of the Metal-Isocyanide Complex, in Bull. Chem. Soc. Jpn., vol. 43, n. 3, 1970, pp. 877, DOI:10.1246/bcsj.43.877.
  6. ^ (EN) M. Pereyre; Y. Odic, Alkylations en α de fonctions organiques par l'intermédiaire de compostés organostanniques, in Tetrahedron Lett., vol. 1969, n. 2, 1969, pp. 505, DOI:10.1016/S0022-328X(00)82070-7.
  7. ^ (EN) A. C. Cope; H. L. Holmes; H. O. House, The Alkylation of Esters and Nitriles, in Org. React., vol. 9, 1957, pp. 107, DOI:10.1002/0471264180.or009.04, ISBN 0471264180.
  8. ^ Heterogeneous ethylation of phenylacetonitrile, in J. Org. Chem., vol. 45, n. 21, 1980, DOI:10.1021/jo01309a023.
  9. ^ Phase-Transfer Alkylation of Nitriles: 2-Phenylbutyronitrile, in Organic Syntheses, vol. 55, 1976, DOI:10.15227/orgsyn.055.0091.
  10. ^ M. Makosza, Reactions of organic anions. XII. Vinylation of phenylacetonitrile derivatives, in Tetrahedron Lett., vol. 1966, n. 45, 1966, DOI:10.1016/S0040-4039(00)70128-6.
  11. ^ N,N-diethylaminoacetonitrile: a generally useful latent acyl carbanion, in Tetrahedron Lett., vol. 1978, n. 52, 1978, DOI:10.1016/S0040-4039(01)85842-1.
  12. ^ Isolation of primary decomposition products of azides. II. Azidopyrazoles, in J. Org. Chem., vol. 35, n. 7, 1970, DOI:10.1021/jo00832a024.
  13. ^ Indirect Methods of Preparation of Pure Monoalkylphenylacetonitriles, in J. Org. Chem., vol. 31, n. 11, 1966, DOI:10.1021/jo01349a525.
  14. ^ Notes. Selected Phenyl-2-methylhexanes, in J. Org. Chem., vol. 24, n. 10, 1959, DOI:10.1021/jo01092a044.
  15. ^ (EN) D. Savoia; E. Tagliavini; C. Trombini; A. Umani-Ronchi, Potassium on Alumina as a Reagent for Reductive Decyanation of Alkylnitriles., in J. Org. Chem., vol. 45, n. 16, 1980, pp. 3227, DOI:10.1021/jo01304a016.

Voci correlate modifica

  Portale Chimica: il portale della scienza della composizione, delle proprietà e delle trasformazioni della materia
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