Thiophene/selenophene-based S-shaped double helicenes: regioselective synthesis and structures

• Mengjie Wang,
• Lanping Dang,
• Wan Xu,
• Zhiying Ma,
• Liuliu Shao,
• Guangxia Wang,
• Chunli Li and
• Hua Wang

Beilstein J. Org. Chem. 2022, 18, 809–817, doi:10.3762/bjoc.18.81

• (5 mL) was added at −78 °C, the mixture kept for 1 h, and then the reaction mixture was warmed up slowly to ambient temperature overnight. The reaction mixture was quenched with CH3OH and extracted with CH2Cl2 (3 × 10 mL). The organic layer was washed with saturated NaCl (20 mL) and water (2 × 20 mL

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• odor”. Alternatively, the reaction mixture is pumped to an oxidation module in which the pinacol boronates are mixed with a solution of sodium perborate in water/tetrahydrofuran to perform oxidation to the corresponding alcohols 20 at 40 °C in 60 s. In order to quench remaining oxidants, the reaction

• quite clean top note that is mostly employed in men’s fragrances, both in classical (Davidoff: Cool Water at approx. 0.2%) and modern fragrances (Chanel: Allure Homme Sport, Jean-Paul Gaultier: Le Mâle at approx. 0.01%). However, small doses of mint notes give a desirable sparkle even to female

• formation of hydrazone 28. As one equivalent of water is formed in this condensation process, which is detrimental for the subsequent Shapiro reaction, water is continuously removed by in-line separation of the reaction mixture using a PTFE-membrane separator. The organic layer is then mixed with a solution

An isoxazole strategy for the synthesis of 4-oxo-1,4-dihydropyridine-3-carboxylates

• Timur O. Zanakhov,
• Ekaterina E. Galenko,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2022, 18, 738–745, doi:10.3762/bjoc.18.74

• due to their specific characteristics such as basicity, hydrogen bond forming ability, water solubility, and especially because of pyridine rings are bioisosteres of amines, amides, N-heterocyclic rings and benzene rings [1][2][3][4][5]. A special type of pyridine, the 4-pyridones, is also fairly well

A trustworthy mechanochemical route to isocyanides

• Francesco Basoccu,
• Federico Cuccu,
• Federico Casti,
• Rita Mocci,
• Claudia Fattuoni and
• Andrea Porcheddu

Beilstein J. Org. Chem. 2022, 18, 732–737, doi:10.3762/bjoc.18.73

• are high for EDGs (2d,e), while from good to high for the EWGs (2b,c). To confirm what has been previously stated, isonitrile 2a was recovered in lower yields than compound 2e (Scheme 3). At the end of the reaction, adding 0.5 equivalents of water for a 15 minute grinding step was necessary to

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• enzymatically incorporated into fumigatonoid A, in which the oxygen atoms of the endoperoxide are derived from the O2 molecule and the C3' hydroxy group most likely originates from the solvent water. Although the oxygen atom in the hydroxylation reaction is usually from molecular oxygen, the oxygen atom in the

• Fe(III)-OH species can be exchanged with the solvent water [76]. Therefore, the fact that almost all of the oxygen atoms in the Fe(III)-OH species exchanged with the solvent in the enzyme reaction of NvfI suggested the presence of a long-lived C3' radical and the hydroxy ligand during the reaction

• the water addition occurs on the C3' carbocation, which is generated by one electron transfer to the ferric iron from the C3' radical intermediate (carbocation mechanism in Scheme 9). Notably, in this last step, the stereochemistry of the hydroxylation reaction is regulated by the enzyme to be the R

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• second variant is the steam methane reforming process. Since complex solids such as wood, sewage sludge or municipal waste cannot be evaporated, they are reformed using supercritical water on a heterogeneous catalyst at 250–300 bar, 400–550 °C, and a large excess of water [28]. The former process is the

• this reaction, CO2 and H2 are converted to CH4 (Scheme 4). This process can be used as a catalytic cycle in combination with electrolysis of water to produce the hydrogen exactly when the demand requires it. The reactions are very powerful and can represent an important access to synthetic fuels. This

• amounts of lignin as a byproduct. The authors compared the fast pyrolysis of poplar wood and switchgrass by RF heating. The highest yield of bio-oil was obtained for switchgrass at a pyrolysis temperature as low as 450 °C. 2.8 Water electrolysis Electrolysis of water as a power-to-hydrogen (PtH) concept

Rapid gas–liquid reaction in flow. Continuous synthesis and production of cyclohexene oxide

• Kyoko Mandai,
• Tetsuya Yamamoto,
• Hiroki Mandai and
• Aiichiro Nagaki

Beilstein J. Org. Chem. 2022, 18, 660–668, doi:10.3762/bjoc.18.67

• pressure regulator (BPR). The reaction solution was cooled to ambient temperature in a water bath at the position right before BPR and collected in a sample vial. The solution was then immediately diluted with deuterated chloroform for 1H NMR analysis. Investigation of the temperature effect Initially, we

• condenser. The reaction temperature was controlled either in a water bath or an oil bath. At a certain reaction time, 50 μL of the reaction solution was taken out using a gastight syringe and immediately diluted with deuterated chloroform for 1H NMR analysis. General procedure for epoxidation of cyclohexene

• . The reaction mixture was then passed through the microtube ((ϕ = 2.17 mm, L = 1 m) immersed in a water bath. The resulting solution was collected in a vessel for 1 min, then a small amount of it was immediately diluted with deuterated chloroform and analyzed by 1H NMR to obtain yield and conversion

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• interactions with appropriate guest molecules through H-bonding. Different organic molecules, such as nitroolefins, capable of forming H-bonding with the urea moieties inside the cavity were investigated in water for their ability to encapsulate in the cavity under heterogeneous conditions. Successful binding

• of the guest molecule was proven by UV–vis and IR spectroscopy. The multicomponent prism (Figure 3) was finally utilized as a heterogeneous catalyst for Michael and Diels–Alder (DA) reactions in water, representing an uncommon hydrogen-bond donating heterogeneous catalyst [59]. Intrigued by the

• into the Pt8 cage 25a = (22)4(19)2(NO3)8 [65]. Counter anion exchange from NO3− to PF6− made the cages soluble in acetonitrile. All three cages formed spherical supramolecular nano-aggregates in a water/acetonitrile (9:1) mixture and showed increased emission in the aggregated state [66]. Rhodamine B

A study of the photochemical behavior of terarylenes containing allomaltol and pyrazole fragments

• Constantine V. Milyutin,
• Andrey N. Komogortsev,
• Boris V. Lichitsky and
• Valeriya G. Melekhina

Beilstein J. Org. Chem. 2022, 18, 588–596, doi:10.3762/bjoc.18.61

• solvents excluding acetic acid, DMSO and DMF. Initially, UV irradiation of compound 12a was carried out at a wavelength of 365 nm in a solution of DMSO in common glassware for 24 h. However, subsequent water treatment did not allow the isolation of the target product 14a. Due to the fact that aqueous

Syntheses of novel pyridine-based low-molecular-weight luminogens possessing aggregation-induced emission enhancement (AIEE) properties

• Masayori Hagimori,
• Tatsusada Yoshida,
• Yasuhisa Nishimura,
• Yukiko Ogawa and
• Keitaro Tanaka

Beilstein J. Org. Chem. 2022, 18, 580–587, doi:10.3762/bjoc.18.60

• S20 in Supporting Information File 1). The UV–vis spectra of all compounds in H2O are shown in Figure S17 (Supporting Information File 1). The fluorescence intensities of the ring-fused compounds 3a,b gradually decreased with increasing water fractions, and the ratio of water to ethanol Φ values (ΦH2O

• of compounds 4a–e increased in 100% water, and the ΦH2O/ΦEtOH value was higher than 1.0, indicating that AIEE occurred. In particular, the fluorescence of compounds 4a and 4e, bearing Br and CF3 groups, respectively, largely increased with the addition of H2O to an ethanolic solution (Figure 2) with

• , are listed in Table 4. The experimentally observed Exmax values for the S0→S1 transition are somewhat different from the calculated ones, but the order of Exmaxcalc corresponds to Exmaxobs other than in water, i.e. Exmax (4a) > Exmax (3a) > Exmax (4e) in dichloromethane and ethanol. As anticipated

Shift of the reaction equilibrium at high pressure in the continuous synthesis of neuraminic acid

• Jannis A. Reich,
• Miriam Aßmann,
• Kristin Hölting,
• Paul Bubenheim,
• Jürgen Kuballa and
• Andreas Liese

Beilstein J. Org. Chem. 2022, 18, 567–579, doi:10.3762/bjoc.18.59

• . Chemicals All compounds were ordered from Biosynth Carbosynth (United Kingdom) and used without further purification. Buffer preparation: potassium phosphate buffer: 5.3 mL of 0.2 M potassium dihydrogenphosphate (KH2PO4) with 94.7 mL of 0.2 M potassium hydrogenphosphate (K2HPO4) in 100 mL water resulting in

• with buffer solution. Then, a slurry of particles was prepared in buffer solution (10 or 100 mM KPi buffer at pH 7.5) and taken up using a syringe. The syringe was then placed on top of the reactor forming a water bridge and allowing the particles to sediment. Once the reactor was filled, it was shaken

Terpenoids from Glechoma hederacea var. longituba and their biological activities

• Dong Hyun Kim,
• Song Lim Ham,
• Zahra Khan,
• Sun Yeou Kim,
• Sang Un Choi,
• Chung Sub Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2022, 18, 555–566, doi:10.3762/bjoc.18.58

• 13C NMR data, see Table 3; HRESIMS (Supporting Information File 1, Figure S36) m/z: 549.3031 [M + Na]+ (calcd for C28H46O9Na, 549.3040). Enzyme hydrolysis of compounds 1–3. Compounds 1 (0.8 mg), 2 (0.7 mg), and 3 (0.8 mg) were dissolved in water (2 mL) and then hydrolyzed with β-glucosidase (20 mg

Synthesis of a new water-soluble hexacarboxylated tribenzotriquinacene derivative and its competitive host–guest interaction for drug delivery

• Man-Ping Li,
• Nan Yang and
• Wen-Rong Xu

Beilstein J. Org. Chem. 2022, 18, 539–548, doi:10.3762/bjoc.18.56

• water-soluble hexacarboxylated tribenzotriquinacene derivative (TBTQ-CB6) was synthesized and used as a supramolecular drug carrier to load the model anticancer drugs dimethyl viologen (MV) and doxorubicin (DOX) via host–guest interactions. The drugs could be effectively released by spermine (SM), a

• novel TBTQ-based host–guest drug delivery system may have potential use in supramolecular chemotherapy. Keywords: competitive substitution; drug delivery; host–guest chemistry; tribenzotriquinacene; water soluble; Introduction Chemotherapy is considered to be one of the most effective strategies in

• cancer treatment [1][2]. Many types of chemotherapeutic drugs have been commonly used in clinical practice, including doxorubicin (DOX) [3], chlorambucil [4], oxaliplatin [5], etc. However, the use of most chemotherapeutic agents is often challenged by their poor water solubility and non-selective

Substituent effect on TADF properties of 2-modified 4,6-bis(3,6-di-tert-butyl-9-carbazolyl)-5-methylpyrimidines

• Irina Fiodorova,
• Tomas Serevičius,
• Rokas Skaisgiris,
• Saulius Juršėnas and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 497–507, doi:10.3762/bjoc.18.52

• pressure, water (40 mL) was added to the residue, and the mixture was extracted with chloroform (3 × 25 mL). The combined extracts were washed with brine, dried with anhydrous Na2SO4, filtered, and chloroform was removed by distillation under reduced pressure. The residue was purified by column

• equiv by active component), and DMF (3 mL) were stirred at 80 °C for 3 h. After completion of the reaction, water (40 mL) was added to reaction mixture and the aqueous solution was extracted with chloroform (3 × 25 mL). The combined extract was washed with brine twice, dried with anhydrous Na2SO4

• distillation under reduced pressure, water (30 mL) was added to the residue, and the aqueous solution was extracted with chloroform (3 × 25 mL). The combined extract was washed with brine, dried with anhydrous Na2SO4, filtered, and chloroform was removed by distillation under reduced pressure. The residue was

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• mL round bottomed flask provided with a reflux condenser. Then the reaction mixture was stirred at 60–70 °C for 6 hours. After reaching the completion, the reaction mixture was examined by TLC. Then the reaction mixture was cooled to room temperature, diluted with 10 mL of water and extracted with

Comparative study of thermally activated delayed fluorescent properties of donor–acceptor and donor–acceptor–donor architectures based on phenoxazine and dibenzo[a,j]phenazine

• Saika Izumi,
• Prasannamani Govindharaj,
• Anna Drewniak,
• Paola Zimmermann Crocomo,
• Satoshi Minakata,
• Leonardo Evaristo de Sousa,
• Piotr de Silva,
• Przemyslaw Data and
• Youhei Takeda

Beilstein J. Org. Chem. 2022, 18, 459–468, doi:10.3762/bjoc.18.48

• ). The PL spectrum is similar to that in a CBP host matrix (vide infra). The compound 1 showed an aggregation-induced emission (AIE) behavior in a THF/water system, showing a more red-shifted emission peak at around λem = 600 nm when compared with the as-prepared solid state (Figure S2 in Supporting

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• Agriculture, Agricultural Research Service, University of Mississippi, Mississippi 38677, USA 10.3762/bjoc.18.47 Abstract Herein we report a method for the synthesis of 3,4,5-trisubstituted isoxazoles in water under mild basic conditions at room temperature via a [3 + 2]-cycloaddition of nitrile oxides and

• 1,3-diketones, β-ketoesters, or β-ketoamides. We optimized the reaction conditions to control the selectivity of the production of isoxazoles and circumvent other competing reactions, such as O-imidoylation or hetero [3 + 2]-cycloaddition. The reaction happens fast in water and completes within 1–2

• phosphate buffer under weakly acidic conditions (pH 4.0) at room temperature for 15–24 h and generated 3,5-disubstituted isoxazolines and 3,4,5-trisubstituted isoxazoles in good yields (Figure 1) [28]. Notably, no metal catalysts were used in this method. The development of organic reactions in water not

Tetraphenylethylene-embedded pillar[5]arene-based orthogonal self-assembly for efficient photocatalysis in water

• Zhihang Bai,
• Krishnasamy Velmurugan,
• Xueqi Tian,
• Minzan Zuo,
• Kaiya Wang and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2022, 18, 429–437, doi:10.3762/bjoc.18.45

• supramolecular self-assembled nanosystem based on host–guest interactions between water-soluble tetraphenylethylene-embedded pillar[5]arene (m-TPEWP5) and ammonium benzoyl-ʟ-alaninate (G) in an aqueous medium. The obtained assembly of m-TPEWP5 and G showed aggregation-induced emission (AIE) via the blocking of

• photosynthesis and exhibited a high catalytic efficiency for the photocatalytic dehalogenation reaction of various bromoketone derivatives with good yields in short reaction time in water. Keywords: aggregation-induced emission; Förster resonance energy transfer; host–guest interaction; photocatalysis

• to improve the efficiency of chemical reactions in water [26]. Until now, various macrocyclic host-assisted supramolecular donor–acceptor systems have been developed based on the FRET process and further utilized for different photochemical reactions [27][28]. For instance, Yi et al. [29] developed a

Cs₂CO₃-Promoted reaction of tertiary bromopropargylic alcohols and phenols in DMF: a novel approach to α-phenoxyketones

• Ol'ga G. Volostnykh,
• Olesya A. Shemyakina,
• Anton V. Stepanov and
• Igor' A. Ushakov

Beilstein J. Org. Chem. 2022, 18, 420–428, doi:10.3762/bjoc.18.44

• in 6–9% preparative yield. Hydrocarbonates CsHCO3 and KHCO3 were also tested in the reaction, which gave 5-bromomethylene-1,3-dioxolan-2-one 6a as a major product in 29–36% yield (Table 1, entries 11 and 12). Considering that hydration occurs during the formation of phenoxyketone 4a, we added water

• triple bond is a minor direction for the reaction of bromopropargylic alcohols and phenol in the presence of Cs2CO3/DMF, which was completely suppressed by addition of water. When DMF was replaced by DMSO (Table 1, entry 13), the preparative yield of reaction products decreased possibly due to product

• (2i)). Addition of water to the reaction mixture also reduces the pH of the medium and simultaneously increases the concentration of hydroxide ions, therefore, diphenoxyketones 5 were not produced and dihydroxyketones 8 were formed as side products in these cases. Among the approaches to produce α

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• ]. Moreover, in adult humans, vitamin K1 can be converted into vitamin K2, a process that requires menadione as intermediate [12]. Menadione sodium bisulfite complex (MSB, 13) [13] and menadiol (vitamin K4, 14) [14], in turn, are two water-soluble derivatives converted in the body, to menadione. The MSB

• -triisopropylsilyloxy-1,3-butadiene (48) gave compound 50 in 96% yield and 91% ee (Scheme 14). In 2006, Nishimoto and co-workers described an interesting application of a Diels–Alder reaction conducted, among others, in water and fluorous solvents [109]. Especially, the employment of water as solvent has gained great

• (Scheme 19) [47]. The reaction was carried out in a separatory funnel to which was added menadione (10), sodium hydrosulfite, and water [47]. The mixture was shaken for a few minutes until the solution passed through a brown phase and became yellow. Despite of being an old method, it is very efficient and

Four bioactive new steroids from the soft coral Lobophytum pauciflorum collected in South China Sea

• Di Zhang,
• Zhe Wang,
• Xiao Han,
• Xiao-Lei Li,
• Zhong-Yu Lu,
• Bei-Bei Dou,
• Wen-Ze Zhang,
• Xu-Li Tang,
• Ping-Lin Li and
• Guo-Qiang Li

Beilstein J. Org. Chem. 2022, 18, 374–380, doi:10.3762/bjoc.18.42

• subfractions (F41–F43). Subfraction F41 (2.1 g) was chromatographed over silica gel column (PE/acetone, 50:1 to 2:1) to give seven subfractions (F411–F417), F411 (330 mg) was purified by semi-preparative HPLC (ODS, 5 µm, 250 × 10 mm; methanol/water, 95:5, v/v; 2.0 mL/min) to afford compound 4 (2.3 mg), 5 (4.7

• mg), 6 (15.5 mg) and 7 (10.2 mg). Fr.412 (210 mg) was chromatographed on semi-preparative HPLC (ODS, 5 µm, 250 × 10 mm; methanol/water, 85:15, v/v; 2.0 mL/min) to give compound 1 (2.5 mg), 2 (5.8 mg) and 3 (13.3 mg). Identification of new compounds Compound 1: colorless crystals; [α]D25 −19.28 (c

• -operation and Development (OECD). The zebrafish were maintained under a 14/10 h light/dark cycle at the temperature (28 ± 0.5°C) in a closed flow-through system with charcoal-filtered tap water to ensure normal spawning. CuSO4-induced model of zebrafish In a manner similar to literature reference [11

Borylated norbornadiene derivatives: Synthesis and application in Pd-catalyzed Suzuki–Miyaura coupling reactions

• Robin Schulte and
• Heiko Ihmels

Beilstein J. Org. Chem. 2022, 18, 368–373, doi:10.3762/bjoc.18.41

• THF/water at 60 °C giving 2-phenylbicyclo[2.2.1]heptadiene (5a) in 56% yield. Under these optimized conditions, the Suzuki–Miyaura coupling reaction of 2a was also carried out with other representative haloarenes 5b–j to assess the scope and limits of this synthetic route. Thus, the coupling reaction

Amamistatins isolated from Nocardia altamirensis

• Till Steinmetz,
• Wolf Hiller and
• Markus Nett

Beilstein J. Org. Chem. 2022, 18, 360–367, doi:10.3762/bjoc.18.40

• supernatant by filtration, the adsorbed compounds were eluted from the resin with methanol. The resulting extract was concentrated to dryness and a first preliminary fractionation was accomplished by flash column chromatography on reversed-phase silica gel using increasing concentrations of methanol in water

• added to the culture broth to bind the secreted metabolites. The resin was separated from the culture broth by filtration, washed with distilled water, and exhaustively extracted with methanol. Isolation of metabolites 1–6 The concentrated extract was first fractionated by flash column chromatography

• over Polygoprep 60-50 C18 (Macherey-Nagel) using an increasing concentration of methanol in water. Fractions that gave a color change in the CAS assay were prepurified by reversed-phase HPLC using a Nucleodur C18 ec column (125 × 21 mm, 5 μm, Macherey-Nagel) and a gradient of methanol in water

A resorcin[4]arene hexameric capsule as a supramolecular catalyst in elimination and isomerization reactions

• Tommaso Lorenzetto,
• Fabrizio Fabris and
• Alessandro Scarso

Beilstein J. Org. Chem. 2022, 18, 337–349, doi:10.3762/bjoc.18.38

• series of reactions like the carbonyl–ene cyclization of (S)-citronellal preferentially to isopulegol, the water elimination from 1,1-diphenylethanol, the isomerization of α-pinene and β-pinene preferentially to limonene and minor amounts of camphene. The role of the supramolecular catalyst consists in

• sixty hydrogen bonds between six units of 1 and eight water molecules (Scheme 1). A very recent publication investigated different possible assemblies that are present in solution as function of the water content [22]. The pseudo-spherical host structure is highly dynamic, with a large cavity of about

• reactions involving the formation of cationic intermediate species [41] like water elimination from an alcohol to provide the corresponding alkene, the isomerization of β-pinene and α-pinene and the cyclization of (S)-citronellal to secondary alcohols. The key point to interpret the action of the capsule in

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• , and even emergence of new reaction pathways [19][20][21][22][23][24]. To simulate the aqueous environment of enzyme-catalyzed physiological transformations, researchers seek to design and synthesize supramolecular hosts in a water-soluble way. The ionic and polyol forms of them would provide good

• water solubility, and, on the other hand, these kinds of water-soluble moieties could also be introduced into the structures of other hosts to help them gain some extent of water solubility. In aqueous solution, the molecular containers provide hydrophobic pockets capable of binding a wide range of

• anthracene and phthalimide guests with unusual and controllable site-selectivity mediated by organopalladium-coordinated hosts in water (Figure 1) [34]. The water-solubility of the coordinated host traced from its ionic form, and the aqueous reaction conformed with the concept of green chemistry. In previous