264 research outputs found
Catalizzatori idrosolubili contenenti il sale sodico dell’acido diidrotiottico come legante
No full textL’uso di specie catalitiche a base di metalli di transizione modificate con opportuni leganti idrosolubili consente di condurre reazioni in sistemi bifasici (acqua/solvente organico) così da permettere una semplice separazione e riciclo del catalizzatore. La nostra ricerca, improntata all’uso di leganti idrosolubili semplici e a basso costo, si è indirizzata da tempo verso l’utilizzo del sale sodico dell’acido diidrotiottico (DHTANa), forma ridotta dell’acido tiottico (TA) o acido α-lipoico, un composto facilmente reperibile ed economico. In uno studio preliminare erano state preparate soluzioni del precursore catalitico ottenute per reazione di [Rh(COD)Cl]2 con DHTANa in H2O in presenza di Na2CO3 in eccesso. Queste soluzioni, utilizzate tal quali, avevano mostrato alta attività e selettività in reazioni di idrogenazione e di idroformilazione. 1,2
Sulla base di questi risultati promettenti ci siamo riproposti di indagare meglio sia la struttura che l’attività del catalizzatore, estendendo la ricerca anche a derivati dell’iridio. Sono stati pertanto preparati complessi a base di Rh e di Ir partendo da [Rh(COD)Cl]2 e [Ir(COD)Cl]2, rispettivamente. In entrambi i casi si forma una specie idrosolubile, presumibilmente di struttura [M(DHTANa)Cl]2 (M = Rh o Ir) ed una specie, probabilmente di natura polimerica, solubile in acqua ma solo a pH alcalino. Tutte queste specie hanno mostrato una buona attività catalitica in ambiente bifasico acquoso sia nella riduzione di doppi legami carbonio-carbonio che di nitroderivati aromatici. Infine, nell’ottica di migliorare la sostenibilità del processo, stiamo valutando la possibilità di studiare la riduzione di TA a DHTA per via elettrochimica, evitando così l’uso del NaBH4, e di usare precursori metallici più economici.
Riferimenti
1. S. Paganelli, O. Piccolo, P. Pontini, R. Tassini, V.D. Rathod, Catal. Today, 247 (2015) 64-69.
2. V.D. Rathod, S. Paganelli, O. Piccolo, Catal. Commun., 84 (2016) 52-55
Riduzioni biocatalizzate di composti carbonilici
No full textIl progetto di tesi ha riguardato la riduzione biocatalizzata di alcuni composti contenenti un gruppo carbonilico, per ottenere prodotti enantiomericamente arricchiti di possibile interesse applicativo.
La presente ricerca si è inserita in un filone d’indagine già iniziato presso il gruppo di ricerca dove si è svolto il lavoro di tesi e ha utilizzato un materiale vegetale di scarto, o enzimi chetoriduttasi commerciali di origine microbica.
Ulteriore obiettivo è stato quello di valutare e cercare di ottimizzare il processo di liofilizzazione utilizzato per preservare l’attività catalitica riducente delle cellule vegetali derivanti dal fusto del broccolo e l’effetto di co-solventi che permettessero la solubilizzazione, almeno parziale, dei composti carbonilici utilizzati nell’ambiente acquoso di reazione.
I composti ottenuti sono stati caratterizzati mediante tecniche cromatografiche, incluso HPLC su fase stazionaria chirale, e spettroscopiche
La tesi sperimentale si è svolta sotto la guida della Dottoressa Antonella Petri e, come relatore esterno, del Dottor Oreste Piccolo, consulente industriale nel settore della Chimica Fine e Farmaceutica
)‐1‐[3,5‐bis(trifluoromethyl)phenyl]ethanol by an Immobilized KRED in Batch and Flow Conditions
No full textBoth enantiomers of 1-(3,5-bis(trifluoromethyl)phenyl)-ethanol (BTPE) constitute important building-blocks for the synthesis of active pharmaceuticals ingredients (APIs). The reduction of 3',5'-bis(trifluoromethyl)acetophenone (BTAP) performed with soluble and immobilized ketoreductases (KREDs) can be considered as one of the most efficient routes to produce enantiopure BTPE. In the present work, a commercial KRED was employed as biocatalyst after undergoing immobilization processes and it proved to be extremely efficient in the asymmetric synthesis of (S)-BTPE. The immobilization was studied on a set of different commercially available supports. The best results were obtained with samples immobilized via covalent interaction on short chain amino-functionalized support. Two reaction parameters, temperature, and solvent were optimized in the biocatalytic reduction of BTAP in batch conditions. A 90 : 10 (v/v) 2-propanol (IPA): water solvent system and 30 & DEG;C proved to be the best reaction conditions in terms of substrate conversion and easy recovery of the product by simple solvent evaporation. Biotransformations were then performed in a flow system under optimized reaction conditions obtaining with most samples complete conversion after 24 hours and excellent enantiomeric excess (>99.9 %). Finally, the reusability of the immobilized biocatalyst was successfully tested in five consecutive reaction cycles, demonstrating the potential of this approach
Immobilization of Alcohol Dehydrogenases on Silica-Based Supports and Their Application in Enantioselective Ketone Reductions
No full textThe use of immobilized alcohol dehydrogenases (ADHs) offers numerous advantages,
especially in the reaction conditions required by industrial applications. Looking for more efficient
and cost-effective methods of ADH immobilization, in this study we explored silica-based supports as
an alternative to the use of functionalized polymeric resins. Three commercially available ADHs were
immobilized by adsorption and covalent bond formation. The obtained supported biocatalysts were
applied for the bioreduction of acetophenone and some derivatives with good yields and excellent
enantioselectivity. The important intermediate (S)-1-[3,5-bis(trifluoromethyl)phenyl]ethanol was
obtained with a high enantiomeric excess (>99%) by using the highest performing immobilized ADH
sample. The reusability of this biocatalyst was investigated in a flow system for five consecutive
runs; the experiments showed that the biocatalyst could be recycled without a loss of activity and
enantioselectivity. Finally, cross-linking with the glutaraldehyde of the supported biocatalyst was
also carried out to prevent the leaching of the enzyme during the catalytic reactions
Asymmetric synthesis of a high added value chiral amine using immobilized ω-transaminases
No full textChiral N-heterocyclic molecules and in particular compounds with an amino functional group such as 3-aminopiperidine are valuable intermediates for the production of a large number of bioactive compounds with pharmacological properties. In this paper, the
synthesis of both enantiomers of 3-amino-1-Boc-piperidine by amination of the prochiral precursor 1-Boc-3-piperidone using
immobilized ω-transaminases (TAs-IMB), isopropylamine as amine donor and pyridoxal-5’-phosphate (PLP) as cofactor is described. Compared to other methods, the present approach affords the target compound in just one step with high yield and high
enantiomeric excess starting from a commercial substrate. The reaction was carried out by using different commercially available
immobilized enzymes, evaluating the catalytic activity and the enantioselectivity under different experimental conditions. Re-use of
the most efficient enzyme was performed both in batch and in a semi-continuous system. The selected biocatalyst showed good
stability under the reaction conditions providing consistent results in terms of conversion and enantiomeric excess after several
cycles. The reported results may be of practical interest in view of the development of this sustainable approach to an industrial
scale
Sustainable Synthesis of Aryl and Heteroaryl Aldehydes
No full textAromatic aldehydes are important intermediates for the synthesis of valuable fine and specialty chemicals and many procedures for their preparation have been developed but, nowadays, most of these synthetic methods require large amounts of reagents and multiple steps, with production of wastes. In this paper, we focused on the synthesis of some (hetero)aromatic aldehydes, used either as industrial flavor/fragrances of commercial interest, such as Heliotropine®, or as key intermediates for the preparation of some APIs and of other fragrances such as Lioral® and Helional®, by reductive carbonylation of halo derivative precursors. In order to carry out an easier and more applicable process, hydrogen donors, instead of gaseous flammable and explosive hydrogen, and recyclable phosphine free low metal content catalysts, were employed
Biocatalytic conversion of 5-hydroxymethylfurfural: Synthesis of 2,5-bis(hydroxymethyl)furan and 5-(hydroxymethyl)furfurylamine
No full textTwo different green biocatalytic methods were investigated for the transformation of 5-hydroxymethylfurfural
(HMF) to valuable disubstituted furan derivatives. 2,5-bis(hydroxymethyl) furan (BHMF) was obtained by
biocatalytic reduction using lyophilized plant tissues. 5-(hydroxymethyl)furfurylamine (HMFA) was synthesized
by amination transfer reaction catalysed by immobilized transaminase enzymes. By choosing suitable reaction
conditions both products were obtained with high yields in water as reaction medium, at room temperature or
50 °C within a reaction time of 48 and 24 h. The studied protocols represent environmentally benign and promising
green catalytic processes, generating less waste than other synthetic approache
Nuovi catalizzatori eterogenei a basso contenuto di metallo
No full textI catalizzatori metallici supportati, in cui piccole quantità di centri metallici cataliticamente attivi sono dispersi sulla superficie di un solido poroso, sono di grande importanza economica in ambito industriale. Recentemente abbiamo preparato nuovi catalizzatori eterogenei a basso contenuto di metallo a base di Pd, Ni e Ru, in particolare [0,3% Pd/Al2O3], [0,3% Ni/Al2O3] e [0,3% Ru/Al2O3]. Questi catalizzatori sono stati preparati partendo da sali metallici quali cloruri o nitrati, impiegando una procedura da noi sviluppata ed ottimizzata. Nel caso del composto a base di Pd, per esempio, il palladio cloruro è stato ridotto con idrogeno in presenza di triottilammina (TOA), in un solvente organico anidro (THF o CPME). Successivamente, l’impregnazione sul supporto solido delle particelle metalliche ottenute è stata possibile aggiungendo la miscela in esame alla -allumina, dispersa nello stesso solvente organico anidro scelto, sotto atmosfera di idrogeno. Il catalizzatore è stato poi filtrato, seccato sotto vuoto a temperatura ambiente e usato tal quale senza alcun trattamento di calcinazione, rappresentando questo un grosso vantaggio rispetto ai metodi tradizionali. Il catalizzatore è stabile e può essere conservato per mesi in assenza di umidità. Le particelle di metallo formate rimangono distanti le une dalle altre grazie alla TOA che, causando un ingombro sterico notevole, non permette il fenomeno della sinterizzazione bensì favorisce la distribuzione e deposizione omogenea di tali nanoparticelle sul supporto solido.
Questi catalizzatori, nonostante il loro basso contenuto di metallo, si sono mostrati molto attivi in reazioni di ossidazione di alcoli alle corrispondenti aldeidi e di idrogenazione di doppi e tripli legami carbonio-carbonio e di nitroderivati aromatici
Optimization of Biocatalysed Kinetic Resolutions in the Synthesis of Some Enantiopure Hydroxy-N-Heterocycles
No full textN-benzyl-3-hydroxypyrrolidine (I) and N-benzyl-3-hydroxypiperidine (II) are valuable intermediates in the synthesis of numerous pharmaceutical active ingredients. Different preparative strategies have been accomplished using stereotechnologies such as for example asymmetric hydrogenation, enantioselective addition of water on suitable unsatured compounds, use of some chiral synthons, kinetic resolution and resolution by diastereoselective crystallization. All these techniques present some advantages, but also one or more drawbacks for a sustainable process; in this communication we want to present our research work (1) finalized to optimize known (2) biocatalysed kinetic resolutions, through the hydrolysis of some acyl derivatives of compounds I and II.
Investigated variables of this process were : nature of solvents, type of commercially available free or immobilized biocatalysts, ratio (w/w) between substrate and catalyst amounts, length of acyl chain. Furthermore, preliminary attempts to invert configuration of the wrong enantiomer were also performed and will be here discussed.Under the best reaction conditions, both target compounds were obtained with a near theoretically yield (50%) and enantiomeric excess up to 99.5%, determined by HPLC, on chiral stationary phases. Also the inversion of configuration of a wrong enantiomer (S, e.e. >99%) was realized in few steps with about 95% yield and the enantiomeric excess of recovered compound (R) was >95%.
Finally preliminary experiments in a semi-continuous process with recycle of used immobilized biocatalyst, at least for five times, seem very encouraging for a sustainable scale up
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