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Deep Eutectic Solvents (DESs) have been widely used in many fields to exploit their ecofriendly characteristics, from green synthetic procedures to environmentally benign industrial methods. In contrast, their application in emerging solar technologies, where the abundant and clean solar energy is used to properly respond to most important societal needs, is still relatively scarce. This represents a strong limitation since many solar devices make use of polluting or toxic components, thus seriously hampering their eco-friendly nature. Herein, we review the literature, mainly published in the last few years, on the use of DESs in representative solar technologies, from solar plants to last generation photovoltaics, featuring not only their passive role as green solvents, but also their active behavior arising from their peculiar chemical nature. This collection highlights the increasing and valuable role played by DESs in solar technologies, in the fulfillment of green chemistry requirements and for performance enhancement, in particular in terms of long-term temporal stability.

Dimethindene is a selective histamine H1 antagonist and is commercially available as a racemate. Upon analyzing the synthetic pathways currently available for the industrial preparation of dimethindene, we set up a sustainable approach for the synthesis of this drug, switching from petroleum-based volatile organic compounds (VOCs) to eco-friendly solvents, such as 2-methyltetrahydrofuran (2-MeTHF) and cyclopentyl methyl ether (CPME) belonging to classes 3 and 2, respectively. Beyond decreasing the environmental impact of the synthesis (E-factor: 24.1–54.9 with VOCs; 12.2–22.1 with 2-MeTHF or CPME), this switch also improved the overall yield of the process (from 10% with VOCs to 21–22% with 2-MeTHF or CPME) and remarkably simplified the manual operations, working under milder conditions. Typical metrics applied at the first and second pass, according to the CHEM21 metrics toolkit, were also calculated for the whole synthetic procedure of dimethindene, and the results were compared with those of the classical procedure.

A new series of multifunctional hybrids, based on the structure of the donepezil (DNP) drug, have been developed and evaluated as potential anti Alzheimer’s disease (AD) agents. The rationale of this study was the conjugation of a benzylpiperidine/benzylpiperazine moiety with derivatives of bioactive heterocyclics (benzimidazole or benzofuran), to mimic the main structure of DNP and to endow the hybrids with additional relevant properties such as inhibition of amyloid beta (Aβ) peptide aggregation, antioxidant activity and metal chelation. Overall, they showed good activity for AChE inhibition (IC50=4.0–30.0 μΜ) and moderate ability for inhibition of Aβ1–42 self-mediated aggregation. The hybrids containing chelating groups showed improvement in the inhibition of Cu-induced Aβ42 aggregation and the antioxidant capacity. Moreover, neuroprotective effects of these compounds were evidenced in neuroblastoma cells after Aβ1–42 induced toxicity. Structure–activity relationship allowed the identification of some promising compounds and the main determinant structural features for the targeted properties., Graphical Abstract

A series of multi-target-directed ligands (MTDLs), obtained by attachment of a hydroxyphenylbenzimidazole (BIM) unit to donepezil (DNP) active mimetic moiety (benzyl-piperidine/-piperazine) was designed, synthesized, and evaluated as potential anti-Alzheimer&rsquo, s disease (AD) drugs in terms of biological activity (inhibition of acetylcholinesterase (AChE) and &beta, &ndash, amyloid (A&beta, ) aggregation), metal chelation, and neuroprotection capacity. Among the DNP-BIM hybrids studied herein, the structural isomerization did not significantly improve the biological properties, while some substitutions, namely fluorine atom in each moiety or the methoxy group in the benzyl ring, evidenced higher cholinergic AChE activity. All the compounds are able to chelate Cu and Zn metal ions through their bidentate BIM moieties, but compound 5, containing a three-dentate chelating unit, is the strongest Cu(II) chelator. Concerning the viability on neuroblastoma cells, compounds 9 and 10 displayed the highest reduction of A&beta, induced cell toxicity. In silico calculations of some pharmacokinetic descriptors indicate that all the compounds but the nitro derivatives have good potential oral-bioavailability. Overall, it can be concluded that most of the studied DNP-BIM conjugates showed quite good anti-AD properties, therefore deserving to be considered in further studies with the aim of understanding and treating AD.

An unsubstituted 2-hydroxyphenylbenzimidazole has recently been included as a scaffold in a series of hybrids (including the hit compound PZ1) based on the framework of the acetylcholinesterase (AChE) inhibitor Donepezil, which is a new promising multi-target ligand in Alzheimer&rsquo, s disease (AD) treatment. Building upon these findings, we have now designed and completed the whole synthesis of PZ1 in the so-called deep eutectic solvents (DESs), which have emerged as an unconventional class of bio-renewable reaction media in green synthesis. Under optimized reaction conditions, the preparation of a series of 2-hydroxyphenylbenzimidazole-based nuclei has also been perfected in DESs, and comparison with other routes which employ toxic and volatile organic solvents (VOCs) provided. The functionalization of the aromatic ring can have implications on some important biological properties of the described derivatives and will be the subject of future studies of structure-activity relationships (SARs).

An efficient protocol was developed for the synthesis of tertiary alcohols via nucleophilic addition of organometallic compounds of s-block elements (Grignard and organolithium reagents) to esters performed in the biodegradable choline chloride/urea eutectic mixture or in water. This approach displays a broad substrate scope, with the addition reaction proceeding quickly (20 s reaction time) and cleanly, at ambient temperature and under air, straightforwardly furnishing the expected tertiary alcohols in yields of up to 98%. The practicability of the method is exemplified by the sustainable synthesis of some representative S-trityl- l -cysteine derivatives, which are a potent class of Eg5 inhibitors, also via telescoped one-pot processes.

A few symptomatic drugs are currently available for Alzheimer&rsquo, s Disease (AD) therapy, but these molecules are only able to temporary improve the cognitive capacity of the patients if administered in the first stages of the pathology. Recently, important advances have been achieved about the knowledge of this complex condition, which is now considered a multi-factorial disease. Researchers are, thus, more oriented toward the preparation of molecules being able to contemporaneously act on different pathological features. To date, the inhibition of acetylcholinesterase (AChE) and of &beta, amyloid (A&beta, ) aggregation as well as the antioxidant activity and the removal and/or redistribution of metal ions at the level of the nervous system are the most common investigated targets for the treatment of AD. Since many natural compounds show multiple biological properties, a series of secondary metabolites of plants or fungi with suitable structural characteristics have been selected and assayed in order to evaluate their potential role in the preparation of multi-target agents. Out of six compounds evaluated, 1 showed the best activity as an antioxidant (EC50 = 2.6 &plusmn, 0.2 &mu, mol/&micro, mol of DPPH) while compound 2 proved to be effective in the inhibition of AChE (IC50 = 6.86 &plusmn, 0.67 &mu, M) and A&beta, 1&ndash, 40 aggregation (IC50 = 74 &plusmn, 1 &mu, M). Furthermore, compound 6 inhibited BChE (IC50 = 1.75 &plusmn, 0.59 &mu, M) with a good selectivity toward AChE (IC50 = 86.0 &plusmn, 15.0 &mu, M). Moreover, preliminary tests on metal chelation suggested a possible interaction between compounds 1, 3 and 4 and copper (II). Molecules with the best multi-target profiles will be used as starting hit compounds to appropriately address future studies of Structure-Activity Relationships (SARs).

An unprecedented, environmentally friendly, and faster method for the determination of Ochratoxin A (OTA) (a mycotoxin produced by several species of Aspergillus and Penicillium and largely widespread in nature, in wheat and derived products) has, for the first time, been set up and validated using choline chloride (ChCl)-based deep eutectic solvents (DESs) (e.g., ChCl/glycerol (1:2) and ChCl/ urea (1:2) up to 40% (w/w) water) as privileged, green, and biodegradable extraction solvents. This also reduces worker exposure to toxic chemicals. Results are comparable to those obtained using conventional, hazardous and volatile organic solvents (VOCs) typical of the standard and official methods. OTA recovery from spiked durum wheat samples, in particular, was to up to 89% versus 93% using the traditional acetonitrile-water mixture with a repeatability of the results (RSDr) of 7%. Compatibility of the DES mixture with the antibodies of the immunoaffinity column was excellent as it was able to retain up to 96% of the OTA. Recovery and repeatability for durum wheat, bread crumbs, and biscuits proved to be within the specifications required by the current European Commission (EC) regulation. Good results in terms of accuracy and precision were achieved with mean recoveries between 70% (durum wheat) and 88% (bread crumbs) and an RSDr between 2% (biscuits) and 7% (bread).

The influence of the sulfinyl group as a chiral auxiliary in the stereoselective addition of oxiranyllithiums to (S)-2-p-tolylsulfinylbenzaldehyde has been studied. All reactions evolve with retention of configuration at the starting lithiated carbon. Completely stereoselective additions have been observed when configurations at sulfur and the lithiated carbon are different (matched pair), whereas variable dr's values (ranging between 52:48 and >99

The influence of the p-tolylsulfinyl group, located at ortho-, meta-, and para-position, on the regio- and stereoselectivity of the deuteration reactions of substituted styrene oxides has been investigated. The sulfinyl group at an ortho-position reduces the configurational stability of α-lithiated styrene oxides, whereas meta- and para-sulfinyl derivatives completely control the regioselectivity only yielding deuterated products at the aromatic ring due to its strong ortho-director effect.

The reaction of α-lithiated-2-alkyl-2-oxazolines 1 - Li with aliphatic, aromatic and heteroaromatic N -cumyl nitrones results in the stereoselective formation of N -cumyl-1,6-dioxa-2,9-diazaspiro[4,4]nonanes 3 which equilibrate with the hydroxylamino derivatives 4 . Such equilibrating mixtures can be easily transformed into β-amino alkanamides 5 under reductive conditions, whereas acidic hydrolysis with trifluoroacetic acid (TFA) furnishes high yields of β-phenylamino alkanamides 6 via a cumene hydroperoxide-type rearrangement. Derivatives 5 and 6 provide a backbone of potentially useful unnatural β 2,2,3 -amino acids.

The α-lithiation reaction of optically active oxazolinyloxiranes has been investigated. The trapping reaction with D2O, MeI and acetone affording substituted oxazolinyloxiranes proved that the corresponding lithiated species are configurationally unstable. A stereoconvergency was observed in the case of lithiation–deuteration sequence of two oxazolinyloxiranes.

Lithiated N -sulfonyloxazolinylaziridines 6a and 7a , generated by deprotonation of the corresponding aziridines 6 and 7 with sec -BuLi/TMEDA at −98°C in THF, were found to be chemically and configurationally stable to be stereospecifically captured by electrophiles, while warming up to rt resulted in the formation of oxazolinylazirine 15 . In contrast, lithiation of N -phenyloxazolinylaziridines 8 and 9 led to oxazolinylenamine 18 . Tricyclic aziridines 10 and 11 resulted from an intramolecular addition of the aziridinyllithium 6a to the phenyl ring of the benzenesulfonyl group.

4,4-Dimethyl-2-(3-chloro-2-methyl-1-propenyl)-2-oxazoline has been synthesized and deprotonated with LDA in THF to give the corresponding lithiated species, which has been found to react α-regioselectively with NH4Cl and alkyl halides, and γ-regioselectively with carbonyl compounds to afford α-protonated (or α-alkyl-substituted) regioisomers and vinyl epoxides, respectively. The Z diastereoselectivity of both the protonation and the alkylation reactions was usually found to increase with the temperature. Ab initio calculations, performed on both the naked lithium salt and the corresponding solvated form, support the observed regioselectivity.

— Aryl substituted oxazolinyloxiranes 1a – g have been found to undergo smooth isomerization into oxazolinyl substitutedaryl alkanones 2a – g upon treatment with LDA in Et 2 Oat−98°C, warming to room temperature and quenching with satd aq.NH 4 Cl. A mechanism involving an oxazoline-assisted ortho lithiation of the aryl group ( cis to the oxazoline system) of oxiranes 1 is proposed. © 2002 Published by Elsevier Science Ltd. Oxiranes are versatile synthetic intermediates. 1 Theirreactions generally involve cleavage of the strainedoxirane ring and include a wide range of nucleophilicring openings and acid- and base-induced isomeriza-tions. 2 The chemistry of oxiranes under basic condi-tions has been extensively investigated, including: (a) -deprotonation to give an oxiranyl anion, which, inturn, can be captured by an electrophile, dimerize togenerate alkenediols, ring open to give an enolate or acarbene, or undergo a C H insertion reaction; 3 and (b) -elimination to furnish an allylic alcohol.

Lithiated 2,4,4-trimethyl-2-oxazoline 2a and 2-chloromethyl-4,4-dimethyl-2-oxazoline 2b react smoothly with a number of nitrones 3 to produce α,β-unsaturated oxazolines 6 and 7 highly stereoselectively.

Optically pure chloromethyloxazolines have been prepared, lithiated and then reacted with benzophenone to famish stereoselectively oxazolinyl oxiranes and formyl oxiranes. The stereoselection observed has been related to the geometry of the intermediate lithium azaenolates. Calculations have been carried out in order to evaluate the relative stability of the E and Z forms of the lithium azaenolates. The reaction of a lithium azaenolate with other ketones leading to oxazolinyl epoxides is also reported. (C) 2001 Elsevier Science Ltd. All rights reserved

Boron azaenolates 2 and 8 from the optically active chloromethyloxazolines 1 and 7 have been found to couple with ketones in a highly diastereoselective fashion, which depends markedly upon the geometry (Z) of the azaenolates and the nature of the ligands which are present on the boron atom, in good accordance with semiempirical calculations (AM1).

Lithiated chloromethyl derivatives 2a-d , available by deprotonation of 2-(chloromethyl)-1,3-benzothiazole 1a , -1,3-oxazoline 1b , -pyridine 1c and -quinoline 1d , react with carbonyl compounds to give chlorohydrins 3a-g and then epoxides 4a-g upon treatment with NaOH/ i PrOH. The same chlorohydrins 3a-g could be converted into heterosubstituted chloroalkenes 5a-g with very high E stereoselection upon reaction with MeSO/ 2 ClEt 3 N Download full-size image

2-Oxiranyl and 2-aziridinyl thiazoles 3 and 7 have been prepared by lithiation of thiazoles 1a and 1b and reaction with α-halogenocarbonyl compounds [1a, 1c-d] and α-halogenoimines [1b], respectively.

Deprotonation of oxazolinyl oxirane 1a with sec-BuLi/TMEDA at −100 °C in Et2O furnished oxazolinyl oxiranyllithium 1b, which could be trapped with electrophiles to give oxiranes 1c-g. The reaction of 1b with aldehydes produced diastereomers syn (2a-d) and anti (3a-d). Oxiranyllithium 1i from trans-1-oxazolinyl-2-p-tolyl epoxy ethane 1h was found to be configurationally stable while oxiranyllithium 11, generated from the cis isomer 1k, was not. Oxazolinyl epoxides 1d, 1j and 1m could be deblocked to acyl oxiranes 5a-e through oxazolidines 4a-e.

Lithiation of 2-(chloroethyl)benzothiazole 1a gives (benzothiazolylchloroethyl)lithium 1b . The reaction of 1b with ketones in the presence of (−)-sparteine leads to chlorohydrins 2a-c that cyclize to epoxides 3a-c , enantioselectively, the enantiomeric enrichment being dependent upon the solvent, the lithiating agent, the reaction time. The reaction with aldehydes furnishes chlorohydrins 2d-g and then epoxides 3d-g diastereo- and enantioselectively.

2-chloroalkylbenzothiazoles 1a-c react with alkoxides to give substitution and ring-expanded products 3 and 4. The substitution ring-enlargement competition much depends upon the solvent, the substitution reaction being preferred in alcohols and the ring-enlargement in DMF.

α,β-epoxy aldehydes have been prepared by deblocking of oxazolinyl oxiranes, which in turn have been synthesized on treatment of 4,4-dimethyloxazolinylchloromethyllithium with aldehydes.

Reductive ring cleavage of thiochromane and benzodihydrothiophene by the radicalanion 4,4′-di- tert -butylbiphenylide (LDBB) leads to organolithium compounds bearing a lithium arylthiolate group. The adducts of the latter with aldehydes and ketones undergo ring closure when treated under appropriate acidic conditions. The result is a two-pot one-carbon subsititutive ring expansion of the original sulfur heterocycle.

Trimethylbenzothiazoline 1 has been reductively lithiated by lithium 4,4′- di-t-butylbiphenylide (LDBB) leading to dianion 3, that has been trapped with electrophiles to give aminodisulfides 4, aminosulfide 8 and aminoalcohols 9.

A high-yield one-pot two-step synthesis of 2-aminoimidazoles (2-AI), exploiting an under-air heterocyclodehydration process between α-chloroketones and guanidine derivatives, and using deep eutectic solvents (DESs) as nonconventional, "green" and "innocent" reaction media, has been accomplished successfully. The combination of either glycerol or urea with choline chloride (ChCl) proved to be effective for decreasing the reaction time to about 4-6 h in contrast to the 10-12 h usually required for the same reaction run in toxic and volatile organic solvents and under an argon atmosphere. In addition, the use of the ChCl-urea as a DES also enables the direct isolation of triaryl-substituted 2-AI derivatives by means of a simple work-up procedure consisting in filtration and crystallization, and allows the recycle of the DES mixture. A plausible mechanism highlighting the potential role played by hydrogen bonding catalysis has also been illustrated.

the title heteroarylalkylidene dihydro-1,4-ben/othiazines 7 have been prepared from heteroarylalkyllithiums 4 and 2-chloromethylbenzothiazole 1.

Benzothiazolylchloromethyllithium 1c and benzothiazolyldichloromethyllithium 1e, easily available by lithiation of 1b and 1d (or 1f) respectively, undergo a different type of self-condensation reaction giving 5 and 7a respectively. The possibility that 1c and 1e behave as halocarbenoids is discussed.

The synthesis of terminal oxazolinyloxiranes, even in enantioenriched form, has been performed by Darzens-type reaction of lithiated chloroalkyloxazolines with benzotriazolylmethanol (BtCH(2)OH) or by chloromethylation of 2-acyl-2-oxazolines. The synthetic utility of such oxiranes based on their ability to act either as electrophiles, undergoing ring-opening reactions with nucleophiles, or as nucleophiles in form of the oxiranyl anions, generated by stereoselective beta-deprotonation, has been investigated. (C) 2009 Elsevier Ltd. All rights reserved

Highly enantiomerically enriched beta-aminoalkanamides 12 and beta-phenylaminoalkanamides 13 have been prepared by the addition reaction of alpha-lithiated 2-alkyl-2-oxazolines 9-Li, derived from optically active oxazolines 9, to N-cumyl nitrones 2. The relative stereochemistry of alkanamides 5 and 6 has been established by 1D-NOESY experiments carried out on the related pyrimidinones 7, whereas the absolute configuration of alkanamides 12 and 13 has been confirmed by an X-ray analysis. (C) 2007 Elsevier Ltd. All rights reserved.

The synthesis of α-oxazolinylalkanamides 2 , based on the reaction of α-chloroalkyloxazolines 1 with hexacarbonyltungsten [W(CO) 6 ] and lithium amides, has been developed. A plausible mechanism involving the ketene 5 as the intermediate is also proposed.

The preparation of N-substituted oxazolinylaziridines and their deprotonation to afford the corresponding aziridinyllithiums is described. The chemical and configurational stability of the lithiated species depends on the N-substituent on the aziridine ring. The trapping with carbonyl compounds of (R*,S*) configurated oxazolinylaziridines is an interesting route for the preparation of functionalised α,β-aziridino-γ-lactones.

The addition reaction of α-lithiated oxazolinyloxiranes to nitrones has been investigated. 1,5,9-Trioxa-8,10-diazadispiro[2.0.4.3]undecanes formed in a completely diastereoselective manner upon treatment of α-lithiated oxiranes with nitrones. The lithiation of optically active trans and cis-oxazolinyloxiranes followed by the addition of a nitrone resulted in the formation of the same dispirocyclic compound. An explanation for the observed stereoselectivity is provided.

Lithiated (α-chloroalkyl)heterocycles, generated by deprotonation with LDA at −78 °C in THF, add to various enantiopure imines affording ‘one pot’ chiral heterosubstituted aziridines in a diastereoselective manner. Lithiated heterosubstituted aziridines, obtained by deprotonation of the corresponding aziridines with n-BuLi at −78 °C in THF, were trapped by electrophiles (D2O or CH3I) with high stereoselectivity.

Oxazolinyl allylic alcohols 2 convert smoothly into 3-alkylidene-2-iminooxetanes 3 and dienic carboxylic acids 7 simply upon treatment with aqueous HCl.

Palladium acetate and 1,4-bis(diphenylphosphino)butane (dppb) catalyze regioselective cyclocarbonylation of 4-allylsteroids forming exclusively 7-membered ring lactones with excellent yields (96–98 %). The stereoselective addition of an epoxide ring on the side-chain of steroids is realized by coupling the carbonyl group of the cyclopentanone ring of the steroid with 2-benzothiazolylchloromethyllithium 1 or 4,4-dimethyl-2-oxazolinylchloroalkylithiums 2 and 3 .

Aziridinyllithiums 4a and 4b , which are stable at low temperature, can be generated by deprotonation of 3a and 3b . Oxazolinyl aziridines 5a-j and 6a-b have been prepared by the reaction of oxazolinyl aziridinyllithiums 4a and 4b with electrophiles. Aziridines 6c and 6d were, instead, synthesized by a Darzens-like reaction from 2-(1-chloroethyl)-2-oxazoline 1b .

α-Keto-2-oxazolines 5a–j have been efficiently prepared by lithiation [sec-(or n-)BuLi/TMEDA, Et2O, −100°C] and rearrangement of oxiranyl oxazolines 2a–j.

Boron and titanium azaenolates 2 and 4 , generated at 0°C and −100°C, respectively, from the optically active chloromethyloxazoline 1 , have been found to couple with aliphatic ketones in a highly diastereoselective fashion ending up with the formation of optically active oxazolinyl oxiranes 3 . Less stereoselective was the reaction with aromatic ketones.