28 research outputs found
Synthesis and derivatization of 2,5-bis(hydroxymethyl)furan (BHMF)
No full textBiomass-derived C6-furanic platform chemicals are regarded as the most promising building blocks in biorefinery exploitation. 5-Hydroxymethylfurfural (HMF) is referred as a “sleeping giant” in consideration of its potential in bridging the gap from a fossil-based chemistry to a more sustainable one. HMF is a versatile substrate with enormous market potential as it can be easily converted into high value chemicals, materials and bio-based polymers.[1] However, there are some limitations in developing an efficient HMF-based chemistry, i.e., its preferred solubility in water rather than in organic solvents, the absence of a cost-efficient scale-up synthesis, and well know HMF stability issue partially solved by the addition of small amount of specific stabilizers.
In our laboratory we have developed a new approach to HMF from D-Fructose using dimethyl carbonate as an extracting solvent in the presence of an acidic heterogenous catalyst. This synthesis is easily scalable up to 20 grams of D-fructose and allows to recover HMF in 70% isolated yield.[2] Quick reduction of HMF to the related 2,5-bis(hydroxymethyl)furan (BHMF) was also carried out using sodium borohydride as reducing agent. This latter approach led to prepare rapidly a rather large amount of BHMF. As a result, BHMF derivatization was also investigated. In particular we have focused on BHMF etherification reaction to achieve 2,5-bis(alkoxymethyl) furans (BAMFs) – well-known biofuel candidates. Several catalysts were investigated; (mild) reaction conditions were optimized and thus employed for the preparation of a library of BAMFs (10 compounds). Products isolation and purification were addressed for each BAMFs.[3] Two examples of etherification reactions were also conducted in gram-scale i.e. for the synthesis of 2,5-bis(methoxymethyl)furan and 2,5-bis(isopropoxymethyl) furan.
Ongoing research on BHMF includes studying its reactivity with dialkyl carbonates. The idea is to develop a library of easy accessible bio-based monomers for polycarbonate, polyurethanes as well as potentially interesting intermediates for surfactants and detergents production.[4
Analoghi carbonati delle ipriti
No full textI gas mostarda o ipriti, bis(2-cloroetil)solfuro e la bis(2-cloroetil)etilammina, sono tristemente conosciuti per il loro impiego come armi chimiche durante la Prima Guerra Mondiale.1 La tossicità delle ipriti è strettamente correlata alla loro elevata reattività. Infatti, questi composti sono in grado di eliminare lo ione cloruro attraverso una sostituzione nucleofila intramolecolare grazie all’effetto anchimerico dello zolfo o dell’azoto vicinale, generando uno ione episolfonico o aziridinico ciclico che è – a sua volta - estremamente reattivo.2 Nonostante la loro ben nota tossicità, questi composti trovano largo impiego nella preparazione di farmaci, nonché come reagenti per la sintesi di intermedi di reazione.3
Nello studio qui presentato, i dialchil carbonati (DAC)4 – noti reagenti e solventi Green – sono stati fatti reagire con alcoli/dioli precursori dei gas mostarda portando ad una nuova classe di composti: le mostarde carbonate. La reattività degli analoghi carbonati delle ipriti è stata successivamente investigata dimostrando che questi composti preservano l’effetto anchimerico dei gas mostarda, ma non presentano alcuna tossicità, nè pericolo per l’operatore o l’ambiente.5 Le reazioni di alchilazione favorite dall’effetto anchimerico delle mostarde carbonate sono state condotte impiegando diversi nucleofili e operando sia in autoclave ad alta temperatura (180 °C) che in neat a temperature inferiori (150 °C) e a pressione atmosferica. Inoltre, recentemente sono state studiate reazioni di alchilazione in one-pot dove la mostarda carbonata è sintetizzata in situ e reagisce immediatamente con il nucleofilo scelto.
Riferimenti
1. a) J. C. Dacre, M. Goldman, Pharmacol. Rev. 1996, 48, 289–326; b) J. Liu, K. L. Powell, H. D. Thames, M. C. MacLeod, Chem. Res. Toxicol. 2010, 23, 488–496.
2. E. Block in Reactions of Organosulfur Compounds, Academic Press, New York, 1978, pp. 141–145.
3. M. C. S. Barnes, H. J. Dennison, S. S. Flack, J. A. Lumley, P. S. Pang, K. C. Spencer, WO2011/27156, 2011.
4. a) P. Tundo, M. Selva, Acc. Chem. Res. 2002, 35, 9, 706; b) Fabio Arico,̀ A. S. Aldoshin, and P. Tundo, ACS Sustainable Chem. Eng.2016, 4, 2843−2851
5. F. Aricò, M. Chiurato, J. Peltier, P. Tundo. Eur. J. Org. Chem. 2012, 3223–322
Dimethyl isosorbide via organocatalyst N-methyl pyrrolidine: scaling up, purification and concurrent reaction pathways
No full textDimethyl isosorbide (DMI) is a green replacement for conventional dipolar solvents as dimethyl sulfoxide (DMSO) and dimethylformamide (DMF) that are toxic and dangerous for human and environmental health. DMI is one of the simplest derivatives well-known bio-based platform chemical isosorbide, an anhydro sugar readily synthesised by D-sorbitol dehydration reaction. [1] The synthesis of DMI is mainly based on the etherification of bio-based platform chemical isosorbide in the presence of basic or acid catalyst employing different alkylating agent. Among them, dimethyl carbonate (DMC) is relevant thanks to its
haracteristics: good biodegradability and low toxicity. [2] In this work, we report an extensive investigation on highly yielding methylation of isosorbide via DMC chemistry promoted by several nitrogen organocatalyst. [3] Reaction conditions were performed and then applied for the methylation of isosorbide epimers - isomannide and isoidide - and for preliminary scale-up test (10 g of isosorbide). Pure DMI, starting from mixture reaction, was obtained by both column chromatography and distillation at reduced pressure. Between all nitrogen used, N-methyl pyrrolidine (NMPy) demonstrated excellent behaviour as catalyst also for the one-pot conversion of D-sorbitol into DMI. Furthermore, for the first time, all seven methyl and carboxymethyl intermediates - observed during the etherification of isosorbide - were synthetized, isolated and characterised. This study allowed us to know more deeply the concurrent reaction pathways (methylation, methyl carbonylation and decarboxylation) leading to DMI and on the role played by NMPy in the methylation of isosorbide and in this way to propose a mechanism of conversion into isosorbide into DMI via DMC chemistry
Turning mustard gas chemistry into green chemistry: a new tool for pharmaceutical synthesis
No full textN,N
-dialkyl ethylamine moiety can be found in numerous scaffolds of macromolecules, catalysts and especiallypharmaceuticals such as Tamoxifen, Raloxifene, Amiodarone, Phenyltoloxamine, Trifenagrel and Trimethobenzamide.Common synthetic procedures for its incorporation in a substrate rely on the use of a nitrogen mustard gas or onmultistep syntheses featuring chlorine hazardous/toxic chemistry. Herein are reported our latest results on the one-potsynthetic approach for the introduction of the
N,N
-dialkyl ethylamine moiety in different phenolic substrates via dialkylcarbonate chemistry. In a typical reaction, 2-dimethylaminoethanol was reacted with a nucleophile (a phenolic scaffold)and dialkyl carbonate (DAC), i.e., diethyl carbonate (DEC), in the presence of a base. In particular, DEC was used for thein-situ formation of ß-aminocarbonate (mustard carbonate) that in turn acts as an alkylating agent via nitrogen nitrogenanchimeric assistance. Different substrates were investigated including precursors of commercially available drugsgiving the related alkylated compound in good to quantitative yields.
This one-pot alkylation approach is a striking example of chlorine-free direct substitution of an alcohol, indicated as oneof the key Green Chemistry research areas for pharmaceuticals manufacturers. Furthermore, an in vitro toxicity studyhas been conducted on ß-aminocarbonate and its alcohol precursor, giving an insight into the cytotoxicity values of thereagents for the synthetic procedure proposed
5,5'(Oxy-bis(methylene)bis-2-furfural (OBMF) da 5-hydroxymethyl-2-furfural (HMF): studio sistematico per la sintesi di una nuova molecola piattaforma da sostanze rinnovabili
No full textIl continuo sfruttamento e il progressivo esaurimento dei combustibili fossili, ha spinto la comunità scientifica a ricercare alternative più sostenibili e rispettose dell’ambiente. Negli ultimi dieci anni, la sintesi di prodotti chimici derivati dalla biomassa è diventata una priorità per incentivare la transizione da raffineria a bioraffineria. Gli zuccheri sono una biorisorsa estremamente abbondante in natura; ancora oggi, una delle reazioni più studiate è la sintesi del 5-hydroxymethyl-2-furfural (HMF). Questo composto è considerato estremamente importante per la bioraffineria per la sua vasta gamma di possibili applicazioni (farmaceutiche, biocarburanti, precursori polimerici, tensioattivi). Tuttavia è stata osservata, durante il processo spontaneo degenerativo del HMF, la formazione di un composto che potrebbe avere altrettanta rilevanza importante il 5,5’-[oxybis(methylene)]bis-2-furfural (OBMF). La sintesi del OBMF è scarsamente riportata in letteratura, soltanto negli ultimi anni l’interesse verso questo dimero del HMF è emerso per le sue possibili applicazioni in ambito industriale. Buoni valori di resa del OBMF vengono riportati in letteratura a partire dal HMF (Figura 1) in presenza di un catalizzatore acido; tuttavia, i solventi utilizzati sono i più comuni solventi alogenati e/o aromatici, noti per essere tossici. Obiettivo di questo lavoro è stato quello di trovare una valida via sintetica per poter accedere al OBMF senza dover ricorrere all’utilizzo di tali solventi e, in aggiunta, utilizzare catalizzatori acidi già disponibili commercialmente ed economici. Tramite le ottimizzazioni in piccola scala, il miglior solvente è risultato essere il dimetil carbonato; inoltre, due catalizzatori acidi eterogenei - Purolite 269 e solfato ferrico (Fe2(SO4)3) - hanno mostrato una ottima efficienza nel promuovere la reazione di eterificazione del HMF con rese quantitative (> 90%). Successivamente è stato effettuato uno scale-up della reazione, ottenendo l’OBMF con una resa isolata del 73%. Visti gli ottimi risultati ottenuti, questo lavoro può essere di spunto per intraprendere lo studio di nuove metodologie sintetiche per questa molecola come ad esempio reazioni in flusso continuo di cui la letteratura risulta essere assent
5,5'(Oxy-bis(methylene)bis-2-furfural (OBMF) from 5-hydroxymethyl-2-furfural (HMF): a systematic study for the synthesis of a new platform molecule from renewable substances
No full textThe continued exploitation and depletion of fossil fuels has prompted the scientific community to search for more sustainable and environmentally friendly alternatives. In the last decade, the synthesis of biomass-derived chemicals has become a priority to boost the transition from refinery to biorefinery. Sugars are an extremely abundant bio-resource in nature; even today, one of the most studied reactions is the synthesis of 5-hydroxymethyl-2-furfural (HMF). This compound is considered extremely important for biorefinery because of its wide range of possible applications (pharmaceutical, biofuels, polymer precursors, surfactants). However, it has been observed, during the spontaneous degenerative process of HMF, the formation of a compound that could be equally important 5,5'-[oxybis(methylene)]bis-2-furfural (OBMF). The synthesis of OBMF is scarcely reported in the literature, only in recent years interest in this dimer of HMF has emerged for its possible applications in industry. Good yield values of OBMF are reported in the literature from HMF (Figure 1) in the presence of an acid catalyst; however, the solvents used are the most common halogenated and/or aromatic solvents, known to be toxic. The objective of this work was to find a viable synthetic route to access OBMF without having to resort to the use of such solvents and, in addition, utilize already commercially available and inexpensive acid catalysts. Through smallscale optimizations, the best solvent was found to be dimethyl carbonate;4 In addition, two heterogeneous acid catalysts - Purolite 269 and ferric sulfate (Fe2(SO4)3) - showed excellent efficiency in promoting the HMF etherification reaction with quantitative yields (> 90%). Subsequently, a scale-up of the reaction was carried out, obtaining OBMF with an isolated yield of 81%. Given the excellent results obtained, this work can be a starting point to undertake the study of new synthetic methodologies for this molecule such as continuous flow reactions of which the literature is lacking
Alkyl Levulinates from Furfuryl Alcohol Using CT151 Purolite as Heterogenous Catalyst: Optimization, Purification, and Recycling
No full textCommercially available Purolite CT151 demonstrated to be an efficient acid catalyst for the synthesis of alkyl levulinates via alcoholysis of furfuryl alcohol (FA) at mild temperatures (80–120 °C) and short reaction time (5 h). Reaction conditions were first optimized for the synthesis of ethyl levulinate and then tested for the preparation of methyl-, propyl-, isopropyl-, butyl, sec-butyl- and allyl levulinate. Preliminary scale-up tests were carried out for most of the alkyl levulinates (starting from 5.0 g of FA) and the resulting products were isolated as pure by distillation in good yields (up to 63%). Furthermore, recycling experiments, conducted for the preparation of ethyl levulinate, showed that both the Purolite CT151 and the exceeding ethanol can be recovered and reused for four consecutive runs without any noticeable loss in the catalyst activity
Metrics for green syntheses: two case studies in biorefinery
No full textGreen metrics is a relatively new concept in Green Chemistry. The application of rigorous green metrics must go along with the experimental validation of synthetic procedures; this is necessary to give precise guidelines so to define a green synthetic approach and avoid misunderstanding and pretentious claims originating from subjective rather than objective evaluations.
5-(hydroxymethyl)furfural (HMF) has been labelled as the “sleeping giant” of the bio-based platform-chemicals realm, due to its versatility and being the starting point for endless chemical transformations into novel monomers for producing bio-based polymers. Among HMF derivatives, 2,5-Furandicarboxylic acid (FDCA) has been extensively studied as monomer for the production of polyesters such as polyethylene furanoate (PEF), considered as one of the most valuable bio-based substitute of the petroleum-derived polyethylene terephthalate (PET). However, the sustainability of the synthetic procedures leading to HMF and its derivatives represent a key aspect that must be addressed in order to foster their entrance into the bio-based plastic market. In this scenario, green metrics such as the environmental factor (E-factor) and the process mass intensity (PMI) represent an useful tool towards this goal.1
From these premises, the present study reports an alternative synthetic procedure for the production of 2,5-furandicarboxylic acid dimethyl ester (FDME) starting from galactaric acid via dimethyl carbonate (DMC) chemistry. Both sulfonic resins and an iron-based Lewis acid showed to promote the one-pot formation of FDME. The pure product was retrieved as a white crystalline solid with an isolated yield of up to 70%. Based on the different intermediates identified, a possible reaction mechanism was proposed, which highlights the essential contribute of DMC in the product formation.2 This presentation is also focussing on some key points inherent to the IUPAC project 2017-030-2-041: Metrics for Green synthesis. Thus, the greenness of the herein discussed synthetic procedure was evaluated using the most common green metrics and compared with other available synthetic pathways
Synthesis of 2,5-furandicarboxylic acid esters from galactaric acid
No full text2,5-Furandicarboxylic acid (FDCA) has been extensively studied as monomer for the production of polyesters[1] such as polyethylene furanoate (PEF), considered as one of the most valuable bio-based substitute of the petroleum-derived polyethylene terephthalate (PET). [2] Most of the synthetic processes to FDCA employ glucose and fructose as substrates, with the formation of 5-hydroxymethyl furfural (HMF) as an intermediate.[1] The main disadvantage of this process regards the intrinsic instability of HMF, together with its high market price and its difficult separation and purification, which ultimately lead to the production of humins, drastically lowering the overall reaction yield.[3] Few studies focused instead on the production of FDCA from different substrates. In fact, FDCA can be synthetized starting from aldaric acids, which can be obtained either via oxidation of sugars or directly extracted from citruses peel.[4] From these premises, the present study reports an alternative synthetic procedure for the production of 2,5-furandicarboxylic acid dimethyl ester (FDME) starting from galactaric acid through dimethyl carbonate (DMC) chemistry. Both sulfonic resins and an iron-based Lewis acid showed to promote the one-pot formation of FDME. The pure product was isolated as a white crystalline solid without the aid of any chromatographic techniques with an isolated yield up to 70 %. Finally, on the basis of the different intermediates identified, a possible reaction mechanism was proposed, which highlights the essential contribute of DMC in the product formation
Nitrile Furanics via Copper‐Catalyzed Dehydration of Aldoximes and Knoevenagel Condensation
No full textIn this work two synthetic approaches to introduce nitrile moieties into bio-based derived furanic compounds were
investigated, i. e., dehydration of aldoximes and Knoevenagel condensation. Both methodologies have been first tested and optimized on furfural and thus exploited on 5-hydroxymethyl-2-furfural (HMF) and 5,5’-oxy(bismethylene)-2-furaldehyde (OBMF). The syntheses of furfural, HMF and OBMF aldoximes were efficiently conducted (also in large scale) under mild reaction conditions and short reaction time. The subsequent dehydration to nitrile furanic compounds was carried out in the presence of catalytic amount of copper acetate monohydrate. Furthermore, Knoevenagel condensations were performed on furfural, HMF and OBMF with different Activated Methylene Group compounds, using for the first-time dimethyl carbonate as the reaction media. Most of the resulting products were isolated as pure via simple liquid-liquid extraction in good to
excellent yields. Future applications of these compounds might include aldoxime reduction into amine furanics - herein also preliminary investigated - and hydrolysis of the nitrile derivatives in the related carboxylic acid (or ester) furanics. All these products are interesting monomers for the preparation of biobased polymers
