Categories: C=N Bond Formation >
Synthesis of imines
A mild three-component reaction of aromatic aldehydes, alkyl bromides, and aqueous ammonia as the nitrogen source gives imines in very good yields. The reaction conditions are compatible with a range of functional groups. The reaction of aldehydes and aqueous ammonia with epoxides leads to imines bearing a vicinal hydroxyl group regioselectively.
J.-M. Huang, J.-F. Zhang, Y. Dong, W. Gong, J. Org. Chem., 2011, 76, 3511-3514.
Neat non-volatile amines react efficiently with various aromatic aldehydes in the absence of any catalyst or solvent, to give imines after a reaction time of eight minutes under microwave irradiation. 1,3-dimethylurea dispersed on montmorillonite K10 is used as an methylamine precursor.
L. Paquin, J. Hamelin, F. Texier-Boullet, Synthesis, 2006, 1652-1656.
Pyrrolidine as an organocatalyst enables a general and efficient biomimetic method for the synthesis of aldimines from aldehydes and compounds bearing an amino group. This nucleophilic catalysis proceeds via iminium activation with outstanding yields in the absence of acids and metals under simple conditions. The method has been applied to the synthesis of N-sulfinyl, N-sulfonyl imines, N-phosphinoyl, N-alkyl, and N-aryl imines.
S. Morales, F. G. Guijarro, J. L. G. Ruano, M. B. Cid, J. Am. Chem. Soc., 2014, 136, 1082-1089.
Tris(2,2,2-trifluoroethyl)borate [B(OCH2CF3)3] is a mild and general reagent for condensation of amides or amines with carbonyl compounds providing N-Sulfinyl, N-toluenesulfonyl, N-(dimethylamino)sulfamoyl, N-diphenylphosphinoyl, N-(α-methylbenzyl), and N-(4-methoxyphenyl) aldimines at room temperature. The reactions are operationally simple, and the products are obtained without special workup or isolation procedures.
J. T. Reeves, M. D. Visco, M. A. Marsini, N. Grinberg, C. A. Busacca, A. E. Mattson, C. H. Senanayake, Org. Lett., 2015, 17, 2442-2445.
The use of low loadings of a silver NHC catalysts enables a mild, selective oxidation of alcohols to aldehydes or carboxylic acids in the presence of BnMe3NOH or KOH under dry air in excellent yield. The catalytic system can also be used for a one-pot synthesis of imines in excellent yield.
L. Han, P. Xing, B. Jiang, Org. Lett., 2014, 16, 3428-3431.
Manganese dioxide is employed as an in situ oxidant for the one-pot conversion of alcohols into imines. In combination with polymer-supported cyanoborohydride (PSCBH), a one-pot oxidation-imine formation-reduction sequence enables alcohols to be converted directly into both secondary and tertiary amines.
L. Blackburn, R. J. K. Taylor, Org. Lett., 2001, 3, 1637-1639.
Imines and secondary amines were synthesized selectively by a Pd-catalyzed one-pot reaction of benzyl alcohols with primary amines. The reactions did not require any additives and were effective for a wide range of alcohols and amines.
M. S. Kwon, S. Kim, S. Park, W. Bosco, R. K. Chidrala, J. Park, J. Org. Chem., 2009, 74, 2877-2879.
A modular aerobic oxidation of amines to imines has been achieved using an ortho-naphthoquinone (o-NQ) catalyst. Whereas the cooperative catalyst system of o-NQ and Cu(OAc)2 provided homocoupled imines from benzylamines, the presence of TFA helped the formation of cross-coupled imines in excellent yields. The oxidation of secondary amines to imines or ketimines is facilitated with the help of Ag2CO3 as cocatalyst.
Y. Goriya, H. Y. Kim, K. Oh, Org. Lett., 2016, 18, 5174-5177.
Iron-catalyzed aerobic oxidative reactions of primary amines, secondary amines, benzylamines with anilines, and alcohols with amines in the presence of air as the economic and safe oxidant, provide several direct, practical, and greener approaches for the preparation of useful imines.
E. Zhang, H. Tian, S. Xu, X. Yu, Q. Xu, Org. Lett., 2013, 15, 2704-2707.
A base-mediated protocol enables the synthesis of imines and amines from N-phenylureas and alcohols in good yields under air. This protocol is as an efficient alternative to conventional methods for the synthesis of imines and amines.
D. K. T. Yadav, B. M. Bhanage, Synlett, 2014, 25, 1611-1615.
An intermolecular reductive Schiff base formation from nitroarenes and benzaldehydes to yield diarylimines is carried out in the presence of iron powder and dilute acid. This process tolerates various functional groups and often proceeds quantitatively with no need for purification.
A. L. Korich, T. S. Hughes, Synlett, 2007, 2602-2604.
The use of photosensitive C70 for the catalytic oxidation of benzylamines to the corresponding imines enables faster reaction rates, lower catalyst loadings, and clean reactions with simple workup without chromatography, compared to C60 or other commonly used photosensitizers such as tetraphenylporphyrin (TPP). Singlet oxygen (1O2) and the superoxide radical anion (O2•–) act as important reactive species in this oxidation.
R. Kumar, E. H. Gleißner, E. G. V. Tiu, Y. Yamakoshi, Org. Lett., 2016, 18, 184-187.
By employing Pd(OAc)2 and (t-Bu)2PNP(i-BuNCH2CH2)3N as ligand, a broad range of aryl bromides and chlorides possessing base-sensitive substituents provide coupling products with bulky aryl amines in good to excellent yields. An efficient coupling of vinyl bromides with a variety of amines produces imines and enamines at room temperature.
Ch. V. Reddy, J. V. Kingston, J. G. Verkade, J. Org. Chem., 2008, 73, 3047-3062.
A Michael addition of amines and hydrazines to nitrostyrenes provides N-alkyl/aryl substituted benzyl imines and N-methyl/phenyl substituted benzyl hydrazones via a retro-aza-Henry-type process under mild, noncatalytic conditions. The method can be used for the synthesis of biologically important N-methyl pyrazoles in a one-pot manner, simple starting with the corresponding nitrostyrenes and the methylhydrazine.
M. G. Kallitsakis, P. D. Tancini, M. Dixit, G. Mpourmpakis, I. N. Lykakis, J. Org. Chem., 2018, 83, 1176-1184.
Scandium(III) triflate catalyzes a direct synthesis of N-unprotected ketimines from ketones in high yields with broad functional group tolerance, even in multigram scales. The reactions were readily applicable for one-pot synthesis of important compounds without isolation of the N-unprotected ketimine intermediates.
Y. Kondo, T. Kadota, Y. Hirazawa, K. Morisaki, H. Morimoto, T. Ohshima, Org. Lett., 2020, 22, 120-123.
Heat-drying methods of molecular sieves can be crucial for reproducibility. Molecular sieve 5Å dried at 160 °C for 5 h under vacuum efficiently promoted the condensation of various ketones and amines to afford even relatively bulky ketimines. A continuous-flow acetalization reaction of alcohols using the activated molecular sieve 5Å was also demonstrated.
T. Yasukawa, H. Nakajima, R. Masuda, Y. Yamashita, S. Kobayashi, J. Org. Chem., 2022, 87, 13750-13756.
A novel Au(I)-precatalyst is applied to intermolecular alkyne hydroamination. DFT calculations revealed the cyclopropenium counterion of this Au(I)-precatalyst imparts stability through H-bonding and other noncovalent interactions.
R. Mir, T. Dudding, J. Org. Chem., 2016, 81, 2675-2679.
Readily available and stable titanocene-alkyne complexes can be used for the hydroamination of internal and terminal alkynes. The reactions of terminal alkynes with aliphatic amines proceed highly selectively to give the corresponding primary anti-Markovnikov functionalized imines in good to excellent yields.
A. Tillack, I. G. Castro, C. G. Hartung, M. Beller, Angew. Chem. Int. Ed., 2002, 41, 2541-2543.
Terminal alkynes react efficiently with anilines in the presence of a cationic rhodium(I) catalyst under very mild, neutral reaction conditions at room temperature to provide the corresponding imines in very good yields. An easy one-pot protocol for the synthesis of secondary amines was developed by combining this alkyne amination reaction with in situ addition of organolithium reagents.
C. G. Hartung, A. Tillack, H. Trauthwein, M. Beller, J. Org. Chem., 2001, 66, 6339-6343.
A number of new reactions of IBX with heteroatom-containing substrates were discovered and their utility was demonstrated. IBX was used for the generation of imines from secondary amines in notably high yields, for the oxidative aromatization of nitrogen heterocycles and for the cleavage of dithianes.
K. C. Nicolaou, C. J. N. Mathison, T. Montagnon, Angew. Chem., 2003, 115, 4211-4216.
[RuCl2(CO)3]2/dppp is a highly effective catalyst system for the intramolecular oxidative amination of various aminoalkenes in presence of K2CO3 and allyl acetate in N-methylpiperidine to give the corresponding cyclic imines and indoles in excellent yields.
T. Kondo, T. Okada, T.-A. Mitsudo, J. Am. Chem. Soc., 2002, 124, 186-187.
A transition-metal-free oxidative C-C bond cleavage process for a broad range of ester and dicarbonyl compounds involves carbanion addition to nitrosobenzene and proceeds via fragmentation of a previously unobserved oxazetidin-4-one heterocycle.
J. N. Payette, H. Yamamoto, J. Am. Chem. Soc., 2008, 130, 12276-12278.
A rhodium-catalyzed reaction of N-hydroxyanilines with diazo compounds provides α-imino esters. Furthermore, a three-component reaction enables the synthesis of highly functionalized β-lactams in good yields and diastereoselectivities.
L. Chen, L. Zhang, Y. Shao, G. Xu, X. Zhang, S. Tang, J. Sun, Org. Lett., 2019, 21, 4124-4127.
A metathesis of azobenzene derivatives in the presence of α-diazo esters and [Cp*RhI2]2 as catalyst provides α-imino esters that would be difficult to make otherwise. Rather than involving metal nitrenes, the reaction proceeds via aza-ylides that evolve into diaziridines
D. J. Tindall, C. Werlé, R. Goddard, P. Philipps, C. Farès, A. Fürstner, J. Am. Chem. Soc., 2018, 140, 1884-1893.
The reaction of aldehydes, amines, and TMSCN in the presence of 2-iodoxybenzoic acid (IBX) and tetrabutylammonium bromide (TBAB) afforded α-iminonitriles in good to excellent yields under mild conditions. The presence of TBAB is essential for this transformation.
P. Fontaine, A. Chiaroni, G. Masson, J. Zhu, Org. Lett., 2008, 10, 1509-1512.
A highly regioselective hydroamination of unsymmetrical electron-poor and electron-rich alkynes with anilines is catalyzed by Au(I) under mild conditions. In addition, applications toward indole syntheses are presented including an example of a one-pot synthesis from a nonfunctionalized aniline.
S. Kramer, K. Dooleweerdt, A. T. Lindhardt, M. Rottländer, T. Skrydstrup, Org. Lett., 2009, 11, 4208-4211.
A high-yielding, asymmetric synthesis of novel 4-formyl-1-(2- and 3-haloalkyl)azetidin-2-ones was developed as valuable starting materials for the synthesis of different enantiomerically enriched bicyclic azetidin-2-ones, such as piperazine, morpholine, and 1,4-diazepane annulated β-lactam derivatives.
W. Van Brabandt, M. Vanwalleghem, M. D'hooghe, N. De Kimpe, J. Org. Chem., 2006, 71, 7083-7086.