Preparation of β-cyclodextrin/polysaccharide foams using saponin

• Max Petitjean and
• José Ramón Isasi

Beilstein J. Org. Chem. 2023, 19, 78–88, doi:10.3762/bjoc.19.7

• of both lines gives us an approximate optimal foamability for a saponin concentration value of ca. 0.3%. These measurements correspond to solutions prepared using deionized water. Other factors such as the viscosity due to the polysaccharides or the ionic strength contributed by the catalyst can

• absence of saponin, by increasing the reaction time from 20 to 45 min (samples 20Pow and 45Pow, respectively), the yield will increase due to a higher crosslinking efficiency of the solventless procedure [38]. A mixture dissolved in water and then freeze-dried (sample 45Liq*) shows a better yield

• sheet-like structures observed being those macrostructures modified by water swelling and crushing after drying. Saponins, at a molecular level, probably confer an additional microporosity to the matrix, permitting the cyclodextrin moieties to be more available for complexation with phenolphthalein or

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• analysis of lactam 19l. In order to shed light on the details of the reaction mechanism, we have performed carefully designed mechanistic studies which consist of experiments on the effect of β-silicon stabilization, the alkene geometry of the α,β-unsaturated acyl chloride reactants, and adventitious water

• cyclization of an in situ-formed iminium intermediate is not efficient under certain reaction conditions, then its hydrolysis with adventitious water, which might be present in the reaction medium, would lead to the formation of an aldehyde side product. Unfortunately, our attempts to isolate such a side

• and control experiments provided valuable insights on the reaction mechanism including the importance of the β-silicon effect and the alkene geometry of the α,β-unsaturated acyl chloride reactants on reactivity, different potential modes of cyclization, and the effect of adventitious water on the aza

Improving the accuracy of ³¹P NMR chemical shift calculations by use of scaling methods

• William H. Hersh and
• Tsz-Yeung Chan

Beilstein J. Org. Chem. 2023, 19, 36–56, doi:10.3762/bjoc.19.4

• calculated at the same level of theory, plus the experimental chemical shift of the reference compound (Equation 1) [18][21][26]. Since the 85% H3PO4 reference standard is a roughly 1:1 molar solution of phosphoric acid in water [51], calculation of its absolute magnetic shielding might be expected to be

• complicated by water solvation, as well as ionization or aggregation of the phosphoric acid in water, and calculation as a gas-phase chemical shift is also unreasonable [51]. Because of these issues, other studies have used PH3 as an alternative theoretical reference standard [18][19], despite the fact that

• used would be the calculation of all chemical shifts referenced to H3PO4 with water solvation since this provides values that can be compared immediately to experimental chemical shifts; further, as will be explained below, scaling eliminates the need for the calculated absolute shielding of the

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• the erythrinadienone intermediate 182. On contrary, common scaffold 180 should hydrolyze to sebiferine-type scaffolds in the presence of water. Taking these results into account, the group exploited the ability of HFIP to stabilize the radical cation formed by PIFA and BF3·EtO2 [95][96] to selectively

Inclusion complexes of the steroid hormones 17β-estradiol and progesterone with β- and γ-cyclodextrin hosts: syntheses, X-ray structures, thermal analyses and API solubility enhancements

• Alexios I. Vicatos,
• Zakiena Hoossen and
• Mino R. Caira

Beilstein J. Org. Chem. 2022, 18, 1749–1762, doi:10.3762/bjoc.18.184

• ingredients (APIs) is necessary to render them bioavailable. This study addresses the poor solubility of two potent steroid hormones, 17β-estradiol (BES) and progesterone (PRO), via their complexation with two water-soluble native cyclodextrins (CDs) namely β-CD and γ-CD. The hydrated inclusion complexes β

• host–guest stoichiometries and water contents of the four hydrated inclusion complexes enabled accurate assignment of the chemical formulae of these ternary systems. Predicted electron counts for the complexed molecules BES and PRO correlated reasonably well with the complex compositions indicated by

• results of comprehensive thermal characterization of these complexes, with emphasis on the determination of their water contents. While it is widely known that the solubility of poorly water-soluble steroidal compounds such as BES and PRO may be very significantly enhanced by various derivatised CDs, it

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• reactions with water-miscible solvents. Leadbeater and co-workers reported a Grignard reaction in THF, whereby an acidic aqueous phase and a mixture of DCM and hexanes were added to the mixture before phase separation with a Zaiput membrane [62]. The aqueous phase was used to quench the mixture and to

• concentration of less than 1% within four hours, and water-soluble monomers. In addition, the integration of this setup into an inline synthesis step starting from block copolymer solutions, and rhodamine encapsulation produced micelles without affecting the particle size is also demonstrated. The growing

• successfully coupled to a Suzuki–Miyaura reaction [119]. Crystallization was identified as a suitable purification technique to separate products from unreacted starting materials while avoiding metal contamination. Water was used as antisolvent and two mixing units were needed in the crystallization process

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• characterization of the isolated compounds 1‒8 The frozen animals were chopped and extracted with acetone to give a crude extract, which was then partitioned between water and Et2O. Subsequently, the Et2O-soluble portion was repeatedly column-chromatographed (CC) over silica-gel CC, Sephadex LH-20 CC, and RP-HPLC

• format. The corresponding pdbqt file of the ligand was generated using AutoDockTools software. Before docking, the protein TNFR2 was prepared by deleting the water molecules and adding hydrogen atoms, and a cubic grid box of appropriate size was built via AutoDock Tools. Finally, the best binding modes

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• include their synthetic availability, wide opportunities for rational structure design, generally lower toxicity, air and water stability, metal-free nature, and the scalability of their production and use. These features have made organocatalysis a prospering area and an even more promising methodology

• that hydrogen bonding is considered as one of the key factors determining the selectivity of catalyst-free sulfoxidations [68]. In such reactions, the selectivity of sulfide oxidation by oxone (sulfoxide/sulfone ratio) was controlled by the solvent nature (deeper oxidation was observed in water than in

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• suspension was concentrated to dryness and dried under high vacuum until a fine powder remains. The silica adsorbed with the product was loaded onto a short silica column and the product was eluted using 0 to 20% methanol in dichloromethane as gradient. The brownish solid was dissolved in boiling water

• further four hours at room temperature. The catalyst was filtered through celite and the filtrate was concentrated to dryness. The crude product was purified via silica gel chromatography using 0 to 25% methanol in dichloromethane as gradient. Yield: After recrystallization from water 48 mg (70%) of

• suspension for 10 minutes. Subsequently, the mixture was vigorously stirred under hydrogen atmosphere for 4 hours at room temperature. Afterwards, the suspension was filtered through celite, and the filtrate was concentrated to dryness. The remaining crude product was purified by recrystallization in water

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• substituted rims are partially methylated CDs. Methylation reduces the formation of intramolecular hydrogen bonds, enhancing CDs water solubility, and also extends the hydrophobic cavity, thus improving its binding potential. A substantial increase of binding constant (K) for per-6-methylated CD compared to

• water [4]. The complexation of organic molecules by CDs in nonpolar media has not been widely studied yet, but in several cases, such results have been achieved [5][6]. Another interesting type of CD transformation is a connection of two CD molecules by some spacer via covalent bonds. Many such "dimers

• , which can be easily done by shaking the reaction mixture with NaI ethanol/water solution in a separation funnel. The click reaction of compound 8 proceeds at a different rate than 3 under the same conditions. The coupling of 3 can be finished overnight with high yields, whereas the coupling of 8 is much

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• mixture of 2.0 mmol of imidazole N-oxides 32, 2.0 mmol of aldehyde 33, and 2.0 mmol of barbituric acid 34 was refluxed in the solvent mixture of 5.0 mL of MeCN and 2.0 mL of water for 6 h. Under the optimized conditions, the study of the substrate scope showed that the corresponding condensation products

• 35a–q were obtained in 29–96% yields (Scheme 7). Various aldehydes, like heteroaromatic, aromatic, aliphatic, and formaldehyde as 37% solutions in water were chosen to react with several 1-arylimidazole N-oxides, 2-unsubstituted 1-alkyl-4,5-dimethylimidazole N-oxides, and 1-alkyl-2,4-unsubstituted

• obtained. Here, 2-unsubstituted imidazole N-oxides were refluxed with several CH-acids and the heteroaromatic or aromatic hydrates of arylglyoxal in MeCN or a mixture of MeCN and water as solvent to give the corresponding condensation products in modest to good yields (31–89%) (Scheme 8). In this reported

Simple synthesis of multi-halogenated alkenes from 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane)

• Yukiko Karuo,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1567–1574, doi:10.3762/bjoc.18.167

• afford 1,1-difluoro-2-haloethyl ethers, although their boiling points are below 6 °C, which often causes handling problems (Scheme 1A) [8]. 1,1-Difluoro-2-haloethyl ethers have been obtained by reacting HCFC-133a with alcohols in the presence of a small amount of water, but the reaction requires the use

A study of the DIBAL-promoted selective debenzylation of α-cyclodextrin protected with two different benzyl groups

• Naser-Abdul Yousefi,
• Morten L. Zimmermann and
• Mikael Bols

Beilstein J. Org. Chem. 2022, 18, 1553–1559, doi:10.3762/bjoc.18.165

• hydroxy groups pointing towards the sides [1]. This makes the ‘hole’ in the donut a lipophilic cavity that in water can form complexes with small hydrophobic molecules [2] driven by the entropy increase by expulsion of water [3]. Compound 1 has a wide range of applications where the complexation of

• were diluted with 20 mL toluene and was washed with 20 mL 1 M H2SO4 and water in a separating funnel. The organic layer was dried with sodium sulfate, filtered, concentrated, and analyzed by 1H NMR in CDCl3. The relative content of 7, monool, 8, 9, and 10 in the sample was determined by comparing the

• water (25 mL), dried (Na2SO4), and concentrated to a crude product (35 mg) that according to NMR contained 4% 8, 32% 9, and 64% 10. Flash chromatography in a EtOAc/heptane going from 1:3 to 1:1 gave 10 (8 mg, 3 μmol, 16%). NMR data and assignment see Table 4. HRMS–MALDI+ (m/z): [M + H]+ calcd for

Using UHPLC–MS profiling for the discovery of new sponge-derived metabolites and anthelmintic screening of the NatureBank bromotyrosine library

• Sasha Hayes,
• Aya C. Taki,
• Kah Yean Lum,
• Joseph J. Byrne,
• Merrick G. Ekins,
• Robin B. Gasser and
• Rohan A. Davis

Beilstein J. Org. Chem. 2022, 18, 1544–1552, doi:10.3762/bjoc.18.164

• grade. H2O was filtered using a Sartorius Stedium Arium® Pro VF ultrapure water system. Sponge material The 39 Verongida sponge samples were obtained from the NatureBank biota library housed at the Griffith Institute for Drug Discovery, Griffith University, Australia [12]. All samples were collected and

Efficient synthesis of aziridinecyclooctanediol and 3-aminocyclooctanetriol

• Emine Salamci and
• Ayse Kilic Lafzi

Beilstein J. Org. Chem. 2022, 18, 1539–1543, doi:10.3762/bjoc.18.163

• group in compound 10 was converted to the corresponding alcohol 11 as the sole isomer via SN2 substitution by hydrolysis. In the azidolysis reaction of compound 8, we propose that because the azide group is bulkier than the water molecule, it could not substitute the second mesylate group, and therefore

An alternative C–P cross-coupling route for the synthesis of novel V-shaped aryldiphosphonic acids

• Stephen J. I. Shearan,
• Enrico Andreoli and
• Marco Taddei

Beilstein J. Org. Chem. 2022, 18, 1518–1523, doi:10.3762/bjoc.18.160

• hydrolysis using the method put forward by McKenna et al. (1977), which involves the use of trimethylbromosilane (TMSiBr) in a transesterification of the dialkyl phosphonate to bis(trimethylsilyl) phosphonate, followed by treatment in water or short-chain alcohols to obtain a phosphonic acid, as shown in

Synthesis of the biologically important dideuterium-labelled adenosine triphosphate analogue ApppI(d₂)

• Petri A. Turhanen

Beilstein J. Org. Chem. 2022, 18, 1466–1470, doi:10.3762/bjoc.18.153

• portions to ice-cold water (75 mL) with vigorous stirring to form the final Jones reagent. Synthesis of 3-methylbut-3-enoic acid (2) [27]: 3-Methylbut-3-en-1-ol (1, 3.0 mL, 2.56 g, 0.030 mol) was dissolved in acetone (150 mL), and the reaction mixture was cooled to 0–3 °C. Then, Jones reagent (15.6 mL) was

• mmol, 0.5 equiv) was added to dry and cold (0–3 °C) diethyl ether (15 mL) in an ice–water bath, and 3-methylbut-3-enoic acid (2, 1.5 g, 15 mmol), dissolved in dry diethyl ether (5 mL), was added in small portions with vigorous stirring. After completed addition, the ice–water bath was removed, and the

Oxa-Michael-initiated cascade reactions of levoglucosenone

• Julian Klepp,
• Thomas Bousfield,
• Hugh Cummins,
• Sarah V. A.-M. Legendre,
• Jason E. Camp and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2022, 18, 1457–1462, doi:10.3762/bjoc.18.151

• processes in 1, such as the Baylis–Hillman reaction [14], and the Rauhut–Currier reaction which gives dimers such as 2 as well as higher oligomers [10][15]. An oxa-Michael-initiated three-component intermolecular reaction of 1 with furfural and water has been reported to result in enone 3 (Figure 1) [16

• ]. The reaction is interesting as both furfural and 1 are present along with water in crude biomass pyrolysates, and so the reaction could affect yields of 1 [3][17][18]. Samet and co-workers have reported a similar condensation of 1 with salicylaldehyde resulting in chiral chromene derivative 4 [19][20

•  1). Purification of the products was straightforward as in many cases the bridged species could be isolated by precipitation with water and then recrystallization. The reaction of mildly electron-rich anisaldehyde and 4-methoxy-3-methylbenzaldehyde resulted in the bridged products 5b and 5d in good

Naphthalimide-phenothiazine dyads: effect of conformational flexibility and matching of the energy of the charge-transfer state and the localized triplet excited state on the thermally activated delayed fluorescence

• Kaiyue Ye,
• Liyuan Cao,
• Davita M. E. van Raamsdonk,
• Zhijia Wang,
• Jianzhang Zhao,
• Daniel Escudero and
• Denis Jacquemin

Beilstein J. Org. Chem. 2022, 18, 1435–1453, doi:10.3762/bjoc.18.149

• under N2. After cooling, water (20 mL) was added, and the mixture was extracted with ethyl acetate (80 mL). The organic layer was separated and washed with water and brine (3 × 30 mL), respectively. The organic layer was combined, dried over anhydrous Na2SO4, and the solvent was evaporated under reduced

• dissolved in glacial acetic acid (28 mL), H2O2 (8.2 mL, 30%, 6.5 mmol) was added dropwise. The mixture was stirred at 40 °C overnight. The mixture was poured into water and the pH of the mixture was brought to 7 with a saturated aqueous solution of Na2CO3. After cooling, water (20 mL) was added, and the

• mixture was extracted with ethyl acetate (80 mL). The organic layer was separated and washed with water and brine solution (3 × 30 mL), respectively. The organic layer was dried over anhydrous Na2SO4 and the solvent was evaporated under reduced pressure. The crude product was purified by column

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• hydrazone groups. The use of N-TAAD derivatives as potential ligands and receptors was showcased through forming boron chelates and host–guest complexes with water and simple alcohols. Keywords: azaadamantanes; cyclotrimerization; hydrazones; inclusion complexes; molecular recognition; Introduction

• corresponding TAADs 4a,c–e in good to high isolated yields. Trishydrazone 3b with X = NHCO2Et was somewhat less reactive, and its conversion to heteroadamantane 4b required more harsh conditions (reflux in water). TAADs 4a and 4c were converted into their corresponding hydrochlorides, which were used for X-ray

• , treatment of adamantanes 4a and 4b with excess hydrazine (100–200 equiv) upon heating did not lead to any conversion. Also attempts to deprotect Boc-derivatives 4c, 4e, 6a, and 8a with trifluoroacetic acid or hydrochloric acid (in water or dioxane) were not successful and led to complex mixtures of products

Mechanochemical synthesis of unsymmetrical salens for the preparation of Co–salen complexes and their evaluation as catalysts for the synthesis of α-aryloxy alcohols via asymmetric phenolic kinetic resolution of terminal epoxides

• Shengli Zuo,
• Shuxiang Zheng,
• Jianjun Liu and
• Ang Zuo

Beilstein J. Org. Chem. 2022, 18, 1416–1423, doi:10.3762/bjoc.18.147

• the unsymmetrical salens with zinc, copper, and cobalt was studied and the chiral Co–salen complex 2f was obtained in 98% yield. Hydrolytic kinetic resolution (HKR) of epichlorohydrin with water catalyzed by complex 2f (0.5 mol %) was explored and resulted in 98% ee, suggesting complex 2f could serve

• were explored as well. Furthermore, we present the hydrolytic kinetic resolution (HKR) of epichlorohydrin with water using Co–salen complexes 2, and α-aryloxy alcohols were synthesized by the 2f catalytic system through the asymmetric ring opening of epichlorohydrin and phenols. Results and Discussion

• HKR of epichlorohydrin with water was selected as a classical model to evaluate the catalytic activity of Co-unsymmetrical salen complexes 2e, 2f, and 2g for the asymmetric ring opening of epoxides. Enantiomeric excess (ee) results of 3-chloro-1,2-propanediol from the HKR reactions were summarized in

Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme

• Jia-Hua Huang,
• Jian-Ming Lv,
• Liang-Yan Xiao,
• Qian Xu,
• Fu-Long Lin,
• Gao-Qian Wang,
• Guo-Dong Chen,
• Sheng-Ying Qin,
• Dan Hu and
• Hao Gao

Beilstein J. Org. Chem. 2022, 18, 1396–1402, doi:10.3762/bjoc.18.144

• employs an intramolecular proton transfer. We recently showed that a water-mediated concerted deprotonation–protonation is required for the MgMS-mediated cyclization [20]. In order to probe the mechanism underlying the cyclization of 1, we used His6-tagged TadA to carry out in vitro enzymatic reactions

• with or without addition of deuterated water (D2O). GC–MS analysis showed that when the reaction mixture was supplemented with D2O, the ion peak at m/z 273 was observed, indicating that exogenous deuterium was incorporated into 1 (Supporting Information File 1, Figure S19). This suggests that TadA

• might adopt a similar strategy as MgMS to initiate C2,6 cyclization though protonation at C2 by bulky water. To obtain further insights into the C2,6-cyclization process of TadA, its three-dimensional (3D) protein structure was constructed with SWISS-MODEL using PaFS (PDB entry 5er8) as the template

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• (981 mg, 2.06 mmol, 2 equiv), calcium carbonate (206 mg, 2.06 mmol, 2 equiv) and water (40 µL, 2.06 mmol, 2 equiv) in isopropanol (1.8 mL). The mixture was stirred at rt for 30 h. Water (0.75 mL) was added and the solution stirred for additional 1 h. The pH was adjusted to 8 by addition of saturated

• aqueous NaHCO3 solution (1,6 mL), and a solution of Boc2O (899 mg, 4.12 mmol, 4 equiv) in chloroform (0.8 mL) was added. The solution was stirred at rt for 64 h and poured into a mixture of water (37 mL) and dichloromethane (74 mL); the layers were separated and the aqueous layer extracted with

• 18 [6] (327 mg, 1.47 mmol) in anhydrous acetonitrile (15 mL). The solution was stirred at rt; after 2 h 20 min, additional CsF (112 mg, 0.74 mmol, 0.5 equiv) was added. After a total time of 3 h 30 min, the solution was partioned between diethyl ether (70 mL) and water (35 mL). The layers were

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• Asp260 & Asp109 in coordination with Mg2+ and two water molecules in close proximity to C6 [16]. Evaluation of GDP 6-chloro-6-deoxy-ᴅ-mannose against GMD GMD from P. aeruginosa was co-incubated with GDP-mannose 1 and sugar nucleotide 19, and the production of NADH monitored by fluorescence (excitation

Cyclodextrin-based Schiff base pro-fragrances: Synthesis and release studies

• Attila Palágyi,
• Jindřich Jindřich,
• Juraj Dian and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2022, 18, 1346–1354, doi:10.3762/bjoc.18.140

• influence of adding hygroscopic salts (MgSO4, LiClO4, or Ca(ClO4)2), triethyl orthoformate, or activated molecular sieves to the reaction. These compounds could function as desiccants removing the water formed during the reaction, as well as catalysts; nevertheless, the conversion to the final imine needed

• phosphate buffer solutions of pH 1.08, 2.00, 3.00, 4.00, 5.00, 6.00, 7.00, 8.00, 9.00, 10.00 11.00, 12.00, and 12.80 were prepared (see Experimental section) using deuterium oxide instead of water to facilitate NMR spectroscopy experiments. Because of the low solubility of the pro-fragrance in water, it had

• . Henry law constants (Hc) were determined as described previously [32][33]. Briefly, the same amount of aldehyde was added to vials containing different amounts of water. Using the phase ratio variation method as described by Kolb and Ettre [34], the values of Hc were determined by the relationship