Reductive Aminolysis Research Articles

Hf4+-exchanged montmorillonite-boosted Pd-catalyzed reductive aminolysis of aryl ethers to efficiently synthesize cyclohexylamines

A robust and completely heterogeneous catalyst, Pd/Hf-MMT, was highly efficient for reductive aminolysis of aryl ethers to producce N-cyclohexyl-substituted amines at a low H2 pressure of 0.3 MPa without using any homogeneous acidic additives.

Bis-Boric Acid-Mediated Regioselective Reductive Aminolysis of 3,4-Epoxy Alcohols.

Herein we report a bis-boric acid-mediated regioselective reductive aminolysis of 3,4-epoxy alcohols, providing new access to prepare amino diols in high diastereofidelity directly starting from nitroarenes. Notably, this step-economical process is enabled by the essential dual function of bis-boric acid, which is engaged initially in the 4,4'-bipyridine-catalyzed reduction of nitro compounds as the reductant and subsequently promotes the ring opening reaction of 3,4-epoxy alcohols with the in situ-generated anilines.

Comparison of jet loop and trickle-bed reactor performance in large-scale exploitation of glucose reductive aminolysis

Commercial scale jet-loop and trickle bed reactor simulations have been performed for the reductive aminolysis of glucose with dimethylamine (DMA) in combination with an experimental assessment in a (large) lab-scale fed-batch and trickle bed reactor. Based on the intrinsic kinetics of the sequence of homogeneous and heterogeneously catalyzed reaction steps in the reductive aminolysis reaction network, coupled with a different flow pattern and catalyst-to-liquid ratio, significant differences in the yield of N,N,N’,N’-tetramethylethylenediamine (TMEDA) and N,N-dimethylaminoethanol (DMAE) can be expected for both reactor types. Yet, TMEDA is obtained in the highest yields irrespective of the reactor type. In the jet-loop reactor, which is operated overall as a batch reactor, an optimized TMEDA yield up to 57 % is simulated, while a non-negligible yield of DMAE, up to 12 %, is also achieved. The optimized operating conditions are such that they correspond to the high DMA to glucose ratio used during lab-scale fed-batch experimentations, also explaining why the jet-loop product spectrum is almost identical to the latter. This is ensured by the efficient heat-exchange in the jet-loop reactor, which is, in contrast, one of the main bottlenecks for exploitation of the reductive aminolysis in a trickle bed reactor. The second challenge to address in the trickle bed reactor is the limited extent of hydrogen transfer from gas to liquid, which can only be partially overcome by increasing the feed flow rates. While isothermal operation indicates TMEDA yields of about 60 %, non-isothermally simulated TMEDA yields only amount to 40 %. The latter yield loss was also validated experimentally in the trickle bed reactor and confirmed that avoiding degradation reactions remains challenging as it is critical in the reductive aminolysis of glucose.

Catalytic Reductive Aminolysis of Reducing Sugars: Elucidation of Reaction Mechanism

A catalytic reductive aminolysis of reducing monosaccharides into short ethylene diamines (or C2 diamines) was recently communicated by our group (Pelckmans et al. Angew. Chem. Int. Ed. 2017, 56, 14540–14544). Here, a general mechanism for this novel reaction is proposed based on the results of a combined experimental and theoretical study. The mechanism involves hemiaminal formation and subsequent dehydration to produce a zwitterionic iminium intermediate, which undergoes fast C–C cleavage as a result of intramolecular deprotonation, followed by hydrogenation of the formed unsaturated amine intermediate. The role of the amine in facilitating the C–C scission is explained in detail and supported by DFT calculations. Different catalysts, carbohydrate substrates, and reaction conditions were tested to validate the proposed reaction mechanism. Reductive aminolysis of sugars is preferably carried out in the presence of a passivated silica(-alumina) supported Ni catalyst and an alkyl amine using 75–85 bar H2 a...

Kinetics of homogeneous and heterogeneous reactions in the reductive aminolysis of glucose with dimethylamine

The reductive aminolysis of glucose with dimethylamine (DMA) as aminating agent has been investigated experimentally as well as via kinetic model construction. A fed-batch reactor configuration was used at following conditions: temperatures ranging between 383 K–398 K, total pressures from 6.0 MPa to 7.5 MPa, an overall catalyst to glucose ratio of 9–31 gcat mol−1, an overall DMA to glucose ratio of 12–24 mol mol−1 and an overall hydrogen to glucose ratio of 5–10 mol mol−1. Such a reactor configuration, combined with a controlled feeding rate of the sugar, allowed to significantly avoid degradation reactions. The main desired products, i.e., dimethylaminoethanol (DMAE) and tetramethylethylenediamine (TMEDA), were obtained after amination followed by retro-aldol cleavage with maximum selectivity, amounting up to 15% and 60% respectively. Retro-aldol cleavage after amination proceeds at lower temperatures, evidenced by an activation energy of 60 kJ mol−1, than without amination, where activation energies amounting to 140 kJ mol−1 have been reported. A higher catalyst to glucose ratio leads to more parallel side products such as N,N-dimethylglucamine and 4‐dimethylamino-1,2,3-butanetriol. The effects of temperature and catalyst to glucose ratio were much more pronounced than that of the total pressure or the ratio of the aminating agent to glucose. The developed kinetic model is based on the most prominent homogeneous bulk phase and heterogeneously catalyzed reactions and accounts quantitatively for degradation reactions. A statistically and physically significant model which could satisfactorily reproduce the experimental observations, was thus obtained.

Low‐Temperature Reductive Aminolysis of Carbohydrates to Diamines and Aminoalcohols by Heterogeneous Catalysis

AbstractShort amines, such as ethanolamines and ethylenediamines, are important compounds in today's bulk and fine chemicals industry. Unfortunately, current industrial manufacture of these chemicals relies on fossil resources and requires rigorous safety measures when handling explosive or toxic intermediates. Inspired by the elegant working mechanism of aldolase enzymes, a novel heterogeneously catalyzed process—reductive aminolysis—was developed for the efficient production of short amines from carbohydrates at low temperature. High‐value bio‐based amines containing a bio‐derived C2 carbon backbone were synthesized in one step with yields up to 87 C%, in the absence of a solvent and at a temperature below 405 K. A wide variety of available primary and secondary alkyl‐ and alkanolamines can be reacted with the carbohydrate to form the corresponding C2‐diamine. The presented reductive aminolysis is therefore a promising strategy for sustainable synthesis of short, acyclic, bio‐based amines.

Low-Temperature Reductive Aminolysis of Carbohydrates to Diamines and Aminoalcohols by Heterogeneous Catalysis.

Short amines, such as ethanolamines and ethylenediamines, are important compounds in today's bulk and fine chemicals industry. Unfortunately, current industrial manufacture of these chemicals relies on fossil resources and requires rigorous safety measures when handling explosive or toxic intermediates. Inspired by the elegant working mechanism of aldolase enzymes, a novel heterogeneously catalyzed process-reductive aminolysis-was developed for the efficient production of short amines from carbohydrates at low temperature. High-value bio-based amines containing a bio-derived C2 carbon backbone were synthesized in one step with yields up to 87 C%, in the absence of a solvent and at a temperature below 405 K. A wide variety of available primary and secondary alkyl- and alkanolamines can be reacted with the carbohydrate to form the corresponding C2-diamine. The presented reductive aminolysis is therefore a promising strategy for sustainable synthesis of short, acyclic, bio-based amines.

ChemInform Abstract: Asymmetric Synthesis of Amino Acids by Catalytic Reduction of Azlactones of Substituted Acylaminoacrylic Acids. Part 25. Study of Reductive Aminolysis of 2-Phenyl- and 2-Methyl-δ2-oxazolin-5- ones (I) with the Chiral Catalytic System

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Asymmetric Synthesis of Amino Acids by Catalytic Reduction of Azlactones of Acylaminoacrylic Acids. Part 24. Reductive Aminolysis of 2-Methyl-4-benzylidene-δ2-oxazolin-5-one (I) with a Catalytic System Based on (S)-Phenylalanine Deriv

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Polymeric Pd catalysts for the reduction of acetamidocinnamic acid azlactone and its solvolysis products

Pd complexes have been obtained from linear and cross-linked copolymers ofR,S-, R-, andS-1-(4-vinylphenyl)ethylamine (1) with styrene and divinylbenzene. Reduction of these compounds gave catalysts which were active in the reductive solvolysis of α-acetaminocinnamic acid azlactone (2) and hydrogenation of the solvolysis products α-acetamidocinnamic acid (ACA), its esters, and its 1-phenylethylamide. The catalysts showed no enantioselective properties in the reductive hydrolysis, but were more active than the catalyst obtained in the absence of the polymer (the “monomeric” analog). The use of polymeric catalysts has shown that, in reductive aminolysis, the chiral nucleophile plays the dominant part in determining the stereoselectivity of the reaction, rather than the chiral ligand of the catalytic complex. The polymer matrix stabilizes the low-valent state of the palladium in the complex. In the hydrogenation of ACA and its esters, the catalyst on the cross-linked polymer is much more active than its “monomeric” analog, but showed no enantioselectivity. Hydrogenation of acetamidocinnamic acidR-andS-1-phenylethylamides on a chiral Pd-polymer catalyst occurred with double asymmetric induction.

Asymmetric synthesis of amino acids via the catalytic reduction of substituted acylaminoacrylic acid azlactone derivatives

We have studied the reaction of Δ2-oxazolin-5-ones with R-phenylglycine methyl ester in the presence of PdCl2; the reaction gives phenylalanine or valine dipeptide derivatives with the RS-configuration. The presence of triethylamine during the reductive aminolysis of oxazolinones in dimethoxyethane solvent significantly increases the stereoselectivity of the reaction process. The stepwise mechanism of the reaction has also been explored.

ChemInform Abstract: Asymmetric Synthesis of Amino Acids by Catalytic Reduction of Azlactones of Substituted Acylaminoacrylic Acids. Part 23. Reductive Aminolysis of 2‐Methyl‐4‐benzylidene‐δ2‐oxazolin‐5‐one (I) with the Chiral Catalytic System Pd/(S)‐Amino Alcohol, e.g. PdCl2/(S)‐(II).

ChemInform Abstract: Asymmetric Synthesis of Amino Acids by Catalytic Reduction of Azlactones of Substituted Acylaminoacrylic Acids. Part 23. Reductive Aminolysis of 2‐Methyl‐4‐benzylidene‐δ2‐oxazolin‐5‐one (I) with the Chiral Catalytic System Pd/(S)‐Amino Alcohol, e.g. PdCl2/(S)‐(II).

Asymmetric synthesis of amino acids by catalytic reduction of azlactones of substituted acylaminoacrylic acids. 23. Study of the reductive aminolysis of 2-methyl-4-benzyllidene-?2-oxazolin-5-one with the chiral catalytic system pd-s-aminoalcohol

1. Reductive aminolysis of 2-methyl-4-benzylidene-Δ2-oxazolin-5-one in the chiral catalytic system PdCl2-S-phenylglycinol results in the formation of phenylalanine amides with an excess of the SS-diastereomer. 2. Reductive aminolysis in the catalytic system PdCl2-S-phenylalaninol mainly gives phenylalanine amides with an excess of the RS-diasteromer.

Asymmetric synthesis of amino acids via catalytic reduction of azalactone-substituted acylaminoacrylic acids. 21. Catalytic asymmetric synthesis of the phenylethylamide of N-acyl-p-difluoromethoxyphenylalanine

1. Catalytic reductive aminolysis of the azalactones of N-acyl-p-difluoromethoxy-α-aminocinnamic acid in dimethoxyethane, isopropanol, and tert-butanol proceeds stereoselectively, leading to the α-phenylethylamides of N-acyl-p-difluoromethoxyphenylalanine with a 3–55% excess of the S,S-diastereomer. 2. Replacement of dimethoxyethane by isopropanol or tert-butanol leads to an increase in the stereoselectivity of the process. 3. Hydrogenation of the S-(+)-α-phenylethylamide of N-acyl-p-difluoromethoxy-α-aminocinnamic acid proceeds stereoselectively, and leads to production of the α-phenylethylamide of N-acyl-p-difluoromethoxyphenylalanine with a 9–18% excess of the R,S-diastereomer.

ChemInform Abstract: Asymmetric Synthesis by Catalytic Reductive Aminolysis of p‐Fluoro‐α‐ acetylaminocinnamic Acid Azlactone. Part 18. Preparation of (S)‐(‐)‐p‐ Fluorophenylalanine.

ChemInformVolume 19, Issue 4 Natural Products ChemInform Abstract: Asymmetric Synthesis by Catalytic Reductive Aminolysis of p-Fluoro-α- acetylaminocinnamic Acid Azlactone. Part 18. Preparation of (S)-(-)-p- Fluorophenylalanine. L. F. GODUNOVA, L. F. GODUNOVA Inst. org. khim. im. Zelinskogo AN SSSR, MoskvaSearch for more papers by this authorE. I. KARPEISKAYA, E. I. KARPEISKAYA Inst. org. khim. im. Zelinskogo AN SSSR, MoskvaSearch for more papers by this authorE. S. LEVITINA, E. S. LEVITINA Inst. org. khim. im. Zelinskogo AN SSSR, MoskvaSearch for more papers by this authorE. I. KLABUNOVSKII, E. I. KLABUNOVSKII Inst. org. khim. im. Zelinskogo AN SSSR, MoskvaSearch for more papers by this authorYU. L. YAGUPOL'SKII, YU. L. YAGUPOL'SKII Inst. org. khim. im. Zelinskogo AN SSSR, MoskvaSearch for more papers by this authorM. T. KOLYCHEVA, M. T. KOLYCHEVA Inst. org. khim. im. Zelinskogo AN SSSR, MoskvaSearch for more papers by this author L. F. GODUNOVA, L. F. GODUNOVA Inst. org. khim. im. Zelinskogo AN SSSR, MoskvaSearch for more papers by this authorE. I. KARPEISKAYA, E. I. KARPEISKAYA Inst. org. khim. im. Zelinskogo AN SSSR, MoskvaSearch for more papers by this authorE. S. LEVITINA, E. S. LEVITINA Inst. org. khim. im. Zelinskogo AN SSSR, MoskvaSearch for more papers by this authorE. I. KLABUNOVSKII, E. I. KLABUNOVSKII Inst. org. khim. im. Zelinskogo AN SSSR, MoskvaSearch for more papers by this authorYU. L. YAGUPOL'SKII, YU. L. YAGUPOL'SKII Inst. org. khim. im. Zelinskogo AN SSSR, MoskvaSearch for more papers by this authorM. T. KOLYCHEVA, M. T. KOLYCHEVA Inst. org. khim. im. Zelinskogo AN SSSR, MoskvaSearch for more papers by this author First published: January 26, 1988 https://doi.org/10.1002/chin.198804349Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume19, Issue4January 26, 1988 RelatedInformation

Asymmetric synthesis of aminoacids by catalytic reduction of azlactones by substituted acylaminoacrylic acids. 19. Reaction of catalyst with substrate

Reaction of 2-methyl-4-benzylideneoxazol-5-one with a zerovalent palladium complex containing S-(-)-α-phenylethylamine as ligand, in chloroform or dichloromethane as solvent, gives a heteroligand complex which is a reactive intermediate in reductive aminolysis,

Asymmetric synthesis of aminoacids by catalytic reduction of azlactones by substituted aminoacrylic acids. 20. Steric control in the reductive aminolysis of ?2-oxazolin-5-ones

1. PMR examination of deuterated acetylphenylalanine α-phenylethylatnide and the methyl esters of acetyl- and benzoylphenylalanine, obtained by the reductive solvolysis of 2-methyl- and 2-phenyl-4-benzylideneoxazolin-5-ones, has shown that in the reduction of oxazolinones the hydrogen undergoes cis- and trans-addition in a ratio of 1∶1. 2. Asymmetric induction in the reductive solvolysis of oxazolin-5-ones arises as a result of the fact that the proportions of cis- and trans-addition of hydrogen are different, and are strictly observed for the diastereoisomeric catalyst-substrate adducts, 3. The enantioselectivity of the reaction is determined at the stage of protonation of the semi-hydrogenated intermediate, and is independent of differentiation between the sides of the plane of the double bond at the step in which the substrate is bound.

ChemInform Abstract: Catalytic Asymmetric Synthesis of Dipeptides Using 2‐Trifluoromethylδ2‐ and 2‐Trifluoromethyl‐δ3‐oxazolin‐5‐ones.

AbstractThe reductive aminolysis of the Δ2‐oxazoline (I) with the amino acids (S)‐(II) gives the dipeptides (III) with an excess of the (RS)‐diastereomer.

Asymmetric synthesis by catalytic reductive aminolysis of p-fluoro-?-acetaminocinnamic acid azalactone. Communication 18. Preparation of S-(-)-p-fluorophenylalanine

1. In reductive aminolysis of p-fluoroacetaminocinnamic acid azalactone by S-(-)-a-phenylethylamine in the presence of PdCl2 and H2 in dimethoxyethane or isopropyl alcohol, N-acetyl-p-fluorophenylalanine phenylethylamide was formed with 28 and 46% excesses of the SS diastereomer, respectively, the hydrolysis of which, after crystallization, afforded optically pure S-(-)-p-fluorophenylalanine. 2. Hydrogenation of p-fluoroacetaminocinnamic acid S-(+)-phenylethylamide in isopropyl alcohol and dimethoxyethane occurred stereoselectively and afforded N-acetyl-p-fluorophenyl-alanine phenylethylamide with 10% excess of the RS diastereomer.

Catalytic asymmetric synthesis of dipeptides from 2-trifluoromethyl-?2- and 2-trifluoromethyl-?3-oxazolin-5-ones

1. Reductive aminolysis of 2-trifluoromethyl-4-benzylidene-Δ2-oxazolin-5-one in the presence of S-amino acid esters, PdCl2 and H2 proceeds via the intermediate formation of RS-peptides. 2. Aminolysis of 2-trifluoromethyl-Δ3-oxazolin-5-ones with S-AlaOMe, S-ValOMe, S-PheOMe proceeds with a high stereoselectivity, with the formation of SS-diastereomer, so that optically pure SS-PheAla and SS-PhePhe dipeptides could be obtained. 3. Aminolysis of 2-trifluoromethyl-Δ3-oxazolin-5-ones with S-ProOMe preferentially gives RS-peptides.