2020-01-15 08:55:40
Yuan Cheng, Xiongyu Ou, Jimei Ma, Linhao Sun, and Zhong-Hua Ma
Introduction
Using water as a reaction media offers advantages for cost, safety, and environment, and is therefore considered green and ideal for laboratory and industry processes. Hence many efforts have been devoted to the development of aqueous catalytic reactions.[1] In aqueous suspension, some reactions involving organic substrates are accelerated, which has been defined as “on water” reactions by Sharpless.[1b] Several approaches have been aimed to strengthen the interaction of organic substrates under “on water” conditions, including the use of surfactants as amphiphilic additives,[1d,1e] the use of phase-transfer catalysts,[2] and the specifically functionalized design of the catalyst structure.[1e–1g] Water also brings some benefits for product isolation. Various types of reactions forming C-C and C-heteroatom bond have been carried out in water with enhanced reactivity and selectivity, such as the nucleophilic attack of a carbanion species in conjugate addition reaction, known as Michael-type reactions.[1a,1c] For example, a Michael addition of ß,ß-disubsti- tuted nitroalkenes with malonate derivatives was reported by Song, in which the otherwise unreactive substrate systems were demonstrated as on-water catalytic reaction.[1a]
An effective promotion for nucleophilic addition is via the use of Brønsted or Lewis acids to activate electrophiles.[3] How- ever, the activating ability of Brønsted acids is commonly weak- ened in presence of water. A few studies,[4] initiated by Kobaya- shi's pioneering work,[3e] were developed on Brønsted acid-surfactant-combined catalysts and their applications in aqueous systems. The surfactant segments assemble into micelles as microreactor, whose hydrophobic cores trap the labile sub- strates and exclude water molecules,[3b,5] while the micelle exte- rior remains hydrated, and allows the permeation of protons for substrate activation.[6] This surfactant-combined strategy has also been extended to solid Brønsted acids.
The hydrophobic assembly is probably caused by fluorocar- bon chain except hydrocarbon chain. Perfluoroalkyl chains have a stronger hydrophobic character than hydrocarbon chains due to their greater molecular cross-sectional area.[7] A classic exam- ple is -C8F17, which is applied in fluorous biphasic media for fluorous catalyst recycling.[8] Even relatively short -C4F9 chains exhibit significant hydrophobicity. Our previous research dem- onstrated that -C4F9 hindered access of water molecules to ad- jacent SO2NHSO2 acid sites,[9] and hydrogen was impeded to bind with the negative conjugate base SO2N–SO2.[10] Similarly, in Wang's reports, pyrrolidine perfluorobutyl sulfonamide was used in aqueous catalysis.[11] On the other hand, perfluoroalkyl sulfonylimides, (RFSO2)2NH, known as nitrogen acids, is widely applied in catalytic field instead of SO3H analogues to practice challenging tasks because of their strong acidity.[3c,3d,9] Gener- ally, compounds with high fluorine content (> 60 %) strongly prefer to go into fluorous phase in fluorocarbon–hydrocarbon systems.[12] These distinct properties could provide water- shielded microenvironments for aqueous reactions. However, too long fluorocarbon chain will inevitably lead to low miscibility of organic and fluorous substrates, weaken the interaction of organic substrates, and increas the cost.
Herein, in the structure of designed sulfonimide catalyst 1a/ 1b, fluorine content and acid density are well balanced by split- ting long perfluoroalkyl chain into two relatively short perfluoroalkyl chains, attached to respective imide Brønsted acid sites (Scheme 1). This method adjusts fluorine content at relative low level with elevated acid density per molecule. The acidity is examined by using the Hammett acidity function, the 31P NMR shift of Et3P=O probe, and conductance titration. The binary acid catalyst has been applied in water to promote the nucleo- philic addition (the Friedel–Crafts reactions). The substrates used herein were indoles, a widely distributed core structure in nature, and there is a large number of applications of synthetic indoles as pharmaceuticals and agrochemicals.[3a,13] With the use of 1a, Friedel–Crafts alkylation of indoles in water was easily performed, via 1,4-addition with ß-monosubstituted vinyl ket- ones and condensation with aldehydes, respectively. The prod- ucts are isolated without column chromatography or recrystalli- zation. The aqueous solution containing 1a is recyclable at least three runs. Furthermore, typically poor-reactive ß,ß-disubsti- tuted vinyl ketones were also activated by the strong acidity of the catalyst, giving medium to good product yields.
Results and Discussion
Catalyst Design
Compounds 1a/1b comprise two N-H groups, respectively at- tached to perfluoroalkyl groups (Scheme 1). Perfluoroalkyl groups bring some advantages of stabilizing the anionic charge of the conjugate bases due to its electron-withdrawing effect. Furthermore, there is an extensive delocalization system over N, O and phenyl ring, which conspire to increase the propensity of dissociation of N–H bonds, largely improving the intrinsic acidity and decreases the dependence on external solvation.[14] An example is the analogue (CF3SO2)2NH, whose pKa values were 2.8, 2.7 and 2.1, respectively in H2O, MeOH, and DMSO. The values demonstrate the effect of the two factors on high acidity.[15] Compounds 1a/1b is thus reasoned to serve as strong acid.
1b was given by acidification of 1b·2Na, but decomposed when handled at ca. 55–65 °C to remove the remained solvent; whereas 1a was obtained. The result suggests that a certain linkage in 1b is more susceptible to the intrinsic acidity at higher temperature than that in 1a. The most likely linkage is -CONH-, which is possibly decomposed by the strong acidity, but stabilized by -C4F9 in 1a. It is inferred that the nonpolar segments, including -C4F9 groups and phenyl ring, aggregate to protect -CONH- group. Especially in the presence of water, due to the hydrophobic hydration effect, the aggregation splits each other's H-bond association of the water molecules near hydrophobic segments, and the bulk water thus hardly en- croaches -CONH- group.[6a,16] The similar aggregation much less efficiently happens to the shorter -CF3 of 1b. 1a is thus a stable amphiphile.
A simple Tyndall effect trial was conducted to confirm the formation of the hydrophobic aggregation (Figure 1a). The Tyn- dall effect is often used as a measurement of a colloid, and the intensity of the effect is proportional to the mean volume of the particles. In our trial, obvious Tyndall phenomenon hap- pened to 1a solution, showing the nano-level aggregation ex- isted. As a comparison, no similar phenomenon was observed for CF3SO3H solution. Furthermore, TEM images of 1a aqueous solution is shown in Figure 1(b). A large amount of nano-size aggregates was observed, with a size of 15–20 nm. Their rela- tively small diameters implied a stacked hydrophobic segment among molecules.
The Acidity Analysis
The acidity of 1a was examined by the Hammett acidity func- tion (H0), Gutmann method, and conductance titration. The re- sults are summarized in Table 1. H0 was obtained by UV/Vis spectrophotometry method, which is a semiquantitative meas- ure of acidity used for concentrated solutions of strong acid.[10] As shown, the H0 value of 1a was –0.52, definitely comparable with tested –0.33 of concentrated H2SO4. The acidity was fur- ther determined by the 31P NMR shift of the Et3P=O probe according to the classical Gutmann method.[10,17] The probe formed Et3P=O···H H-bond with acids. The stronger acidity, the stronger hydrogen bond, and the lower electron density at the phosphorus, and the larger 31P chemical shift. The chemical shift difference (Δδ31P) of 1a/Et3P=O adducts to the reference (C6H5)2ClP=O was 46.44, very close to 46.40 of H2SO4/Et3P=O adducts.[10] These results are also supported by the initial con- ductances of 1a and H2SO4 with the same concentrations, which are both 0.136 ms/cm, meaning the close ionization abil- ity of 1a and H2SO4. The values are obviously higher than 0.111 ms/cm of oxalic acid. Also, the acid content of 1a is calculated as 2.49 mmol/g (vs. theoretic 2.62 mmol/g) based on the titration curve, suggesting at least 95 % purity of 1a. These results demonstrate 1a can rival the acidity of concentrated H2SO4.
Catalytic Michael Addition of Indoles with α,ß-Unsaturated Ketones in Water
Acid-catalyzed Michael addition reactions of indoles with α,ß- unsaturated carbonyl compounds construct 3-substituted ind- oles, a type of important precursors in the synthesis of biologi- cally active compounds and natural products.[18] Our initial at- tempt involved the use of differently active substrates to react with indole 2a, such as vinyl aldehyde (3a), 3-methyl-2-butenal (3b), methyl acrylate (3c), 4-methyl-3-penten-2-one (3d), and 3- penten-2-one (3e), in the presence of 1a. The results are shown in Table 2.
Active 3a and 3b were easily consumed, but no purification was conducted for products 4a and 4b, due to the complex product system based on TLC analysis; while the reaction of poor-reactive ester 3c was sluggish using up to 5.0 mol-% 1a (Entries 1–3). The reaction results of ß,ß-disubstituted vinyl ket- one 3d, which lacks reactivity attributed to the steric and elec- tronic nature of ß-carbon, are given in entries 4–8. Solvent screening demonstrated THF and H2O afforded comparable 80 % and 78 % yields, superior to other solvents (48–61 %). Wa- ter was thus preferred from the perspective of green chemis- try.[1a,1d] The relatively reactive vinyl ketone 3e furnished com- plex products under the same conditions, and only 6 % yield of 4e was given (Entry 9); whereas, it went up to 62 % at 30 °C with reduced 2.5 mol-% of 1a (Entry 10). Furthermore, 91 % yield occurred with the equimolar 2a and 3e (Entry 11).
With the optimized reaction conditions in hand, the general- ity of the catalytic system was explored, and the results are listed in Scheme 2. To our delight, the high catalytic perform- ance of 1a was extended to various indoles with high func- tional group tolerance. ß-Monosubstituted vinyl ketones gave 86–98 % yields (4e–4p); while ß, ß-Disubstituted vinyl ketone exhibited 78–85 % yields (4d, 4r–4t) and moderate 42 % yield of 4q.
Various Brønsted acid catalysts were used to catalyze the re- actions to get a mechanistic insight, and the results are summa- rized in Table 3. Keeping loading the same mol of H+ into the system, H2SO4 gave only 8 % and 22 % yields of 4k, in 3 h and 24 h, respectively; while CF3SO3H gave 26 % yield in 3 h (Entries 2–4). Interestingly, the micelle-type acid, o-C12H25C6H4SO3 H, gave 91 % yield in 2 h (Entry 5). The difference was insignifi- cantly relative to acid strength for ß-monosubstituted vinyl ketone. The acid strength, based on the H0 values, has the fol- lowing order: CF3SO3OH (–3.52) > H2SO4 (–0.33) ≈ 1a (–0.52) >o-C12H25C6H4SO3H (ca. 0.44–0.58).[10] It was thus reasoned that the hydrophobic segments -C12H25 of o-C12H25C6H4SO3H formed micelles, locating the organic substrates and facilitating the reaction. Contrarily, H2SO4 and CF3SO3H lacked hydro- phobic segment, giving poor catalytic efficiency. The similar hy- drophobic nano-aggregations were formed in 1a for its amphiphilic structure, leading to 98 % yield of 4k (Entry 1), slightly higher than 91 % by o-C12H25C6H4SO3H. This probably sug- gested less product residual in the nano-aggregations. The nano-aggregations were confirmed by Tyndall effect and TEM image (Figure 1). The fluorine content of 1a comes to 45 %, and the lipophobicity of fluorocarbon chain promoted the separa- tion of the product from the catalyst. Moreover, C4F9- groups are adjacent to N-H sites, and the hydrophobic aggregations can control the local polarity around active sites. The controlling allows modulating the activity of catalysts.[1g,9] A homemade acid, Cl(CH2)3SO2NHSO2C4F9, was used to support the idea.[10] The acid gave slightly reduced yield (91 %), in which ClCH2CH2CH2- instead of C4F9- led to the fluorine content down to 39 %. Moreover, the product isolation is simple. The aqueous system with 1a allowed obvious oily product floated on the face (Figure 2, inset). A simple extraction using EtOAc was enough to offer pure products, without chromatography and recrystallization, which reduced the waste generation.
On the other hand, 1a-catalysed addition of ß,ß-disubsti- tuted vinyl ketone 3d gave 82 % yield, much higher than 36 % by C12H25C6H4SO3H and 61 % by Cl(CH2)3SO2NHSO2C4F9. 1a and Cl(CH2)3SO2NHSO2C4F9, with more excellent acidity, acti- vated 3d more efficiently than C12H25C6H4SO3H. 1a thus exhib- ited the best catalytic performance.
In our experiments, the use of water as medium improved the reaction yield and controlled the product solubility, which simplified the product purification process in the reaction of active ß-monosubstituted substrate. The strong acidity of 1a expanded the substrate scope to the ß,ß-disubstituted ketones, to which o-C12H25C6H4SO3H was not effective due to lower acidity. Furthermore, 1a is a dual Brønsted acid, and the catalyst dosage was less (2.5 mol-% vs. 5 mol-%).
Based on the observations and literatures, a tentative enrich- ment and activation model of α,ß-unsaturated ketone is pro- posed, as depicted in Figure 2. The fluorocarbon chains of 1a tend to regroup and segregate from both the hydrophilic -NH and lipophilic phenyl ring, and aggregate in a separate zone.
Benefiting from its bulkiness, the aggregations stack into a large-size nuclear hydrophobic zone; while the attached -NH sites hang on the outer zone. -NH groups form H-bond with the carbonyl group of enol ketone or competitive bulky water. However, the fluorocarbon chains, along with phenyl ring, help to resist bulk water, and the organic substrates was thus acti- vated. Moreover, the ethylene linkage of enol ketones possibly get accessible to the phenyl rings. The organic substrate is thus enriched around 1a, facilitating the further reaction.
The recycling performance of 1a was investigated using 2a and 3f to give 4k, and the results are in Table 4. CCl4 was used to extract 4k, and the aqueous phase was fed with fresh 2a and 3f for the next run. As shown, the catalyst could be reused at least three runs with > 92 % yields. The extension of reaction time was possibly owed to slight catalyst loss. In the following cycle, the yield was down to 87 % in 12 h.
Catalytic Condensation of Indoles with Aldehyde in Water
Furthermore, the catalytic generality of 1a in water was investi- gated in condensation of indole with aldehyde. The product 3, 3-bis(indolyl)alkanes (BIAs), which were widely isolated from various natural sources, exhibit a range of biological activi- ties.[13b] The investigations started with 4-anisaldehyde (5a) and 2a in water at 30 °C (Table 5). 2a was consumed completely in 15 minutes in the presence of 2.5 mol-% 1a, but with complex products (Entry 1). A reduced amount of 1a (1 mol-%) produced unsolvable sticky product (Entry 2), but contaminated by resid- ual 2a and 5a. Probably, 1a worked highly efficiently, and BIA precipitated quickly so that the reagents were wrapped in. A trace of organic solvents was thus added (Entries 3, 4). As men- tioned above, the hydrophobic aggregations were loose, and thus water remains in contact with the hydrophobic chain to some degree.[6a] The added organic solvents filled the inter- space, and induced the hydrophobic zone becoming denser. A little CHCl3 or EtOAc (5 %, v: v) was as expected, and provided 94 % and 91 % yields, respectively. It suggested most of the remained substrate went into the hydrophobic aggregation. EtOH was also used, only producing sticky product very quickly (Entry 5). Yield of 79 % was obtained by column chromatogra- phy in extended 4 h (Entry 6). This was reasonable considering EtOH dispersed over the system because of the water-solubility.
Less toxic EtOAc was used in the exploration experiments of substrate scope. The results are shown in Scheme 3. Simple filtration for powder products or extraction for sticky products were carried out with > 95 % purity, confirmed by NMR spectro- scopy. Excellent yields of 87–99 % were given.
Similarly to above Michael addition, the strong acidity of 1a expanded the catalytic spectrum to the unactived ketones in the condensation reactions (Scheme 4). Acetone and butanone gave satisfactory 74–94 % yields (8a–8d, 8f–8i). The strong acidity of 1a successfully activated the aliphatic ketones. Some- what surprising, only moderate yield (42 %) of 4e was obtained. Various Brønsted acid catalysts were also used to catalyze the reactions, shown in Table 6. Under the similar conditions, 1a gave 91 % yield of 6a, 54 % yield for o-C12H25C6H4SO3H and 81 % yield for Cl(CH2)3SO2NHSO2C4F9, but no detectable yield for H2SO4 (Entries 1–4). The formation of hydrophobic location of the catalysts played a crucial role. Additionally, 1a exhibited more excellent catalytic ability than the other two due to its acidity superiority both in the reactions of anisaldehyde and acetone (Entries 5–7).
In our catalytic reactions, the careful purification by column chromatography and recrystallization were not obligated. This is significant, because synthetic chemistry encourages to reduce the reaction waste. The advantage was attributed to the local hydrophobic effect of the catalyst 1a. The hydrocarbon chain helped to enrich the substrates, and the fluorocarbon chain re- pelled away the excess water molecules and product molecules due to its hydrophobicity/lipophobicity. The waste generated from silica and toxic solvents was thus reduced. This is signifi- cant for searching environmentally benign reactions and reduce the E factor.[1d]
Conclusions
In summary, we demonstrated a designed Brønsted acid 1a en- ables Friedel–Crafts alkylation of indoles in water. The hydro- phobic aggregations of fluorocarbon chains, along with phenyl ring, of 1a protected acid sites from bulk water and enriched the substrates. The amphiphilic structure has been proven cru- cial for the high catalytic efficiency. The catalyst reasonably re- duces the employment of the fluorocarbon number by splitting the longer fluorocarbon chain into shorter, with strong acidity and hydrophobicity maintained. The strong acidity of 1a enabled the reactions of some unreactive substrates in water.
3-Bromo-5-butoxyphenylboronic acidCatalog No.:AA003BOJ CAS No.:1072951-84-8 MDL No.:MFCD08457637 MF:C10H14BBrO3 MW:272.9314 |
6-Bromo-2-fluoro-3-propoxyphenylboronic acidCatalog No.:AA003N14 CAS No.:1072951-85-9 MDL No.:MFCD09038422 MF:C9H11BBrFO3 MW:276.8952 |
3-Bromo-2-isopropoxy-5-formylphenylboronic acidCatalog No.:AA003IXT CAS No.:1072951-86-0 MDL No.:MFCD09750471 MF:C10H12BBrO4 MW:286.9149 |
2-[(2-Isopropyl-5-methylphenoxy)methyl]phenylboronic acidCatalog No.:AA003G4X CAS No.:1072951-87-1 MDL No.:MFCD08276821 MF:C17H21BO3 MW:284.1578 |
6-Bromo-3-butoxy-2-fluorophenylboronic acidCatalog No.:AA003N1B CAS No.:1072951-88-2 MDL No.:MFCD08276825 MF:C10H13BBrFO3 MW:290.9218 |
3-(4-Methoxybenzyloxy)phenylboronic acidCatalog No.:AA0084TO CAS No.:1072951-89-3 MDL No.:MFCD09038416 MF:C14H15BO4 MW:258.0775 |
3-[(4-Chloro-3-methylphenoxy)methyl]phenylboronic acidCatalog No.:AA003ION CAS No.:1072951-91-7 MDL No.:MFCD09265140 MF:C14H14BClO3 MW:276.5232 |
3,5-Dimethyl-4-(3',5'-dimethoxybenzyloxy)phenylboronic acidCatalog No.:AA007EP6 CAS No.:1072951-94-0 MDL No.:MFCD22421632 MF:C17H21BO5 MW:316.1566 |
2-Bromo-3-butoxy-6-fluorophenylboronic acidCatalog No.:AA003GJT CAS No.:1072951-95-1 MDL No.:MFCD08276824 MF:C10H13BBrFO3 MW:290.9218 |
4-(3'-Fluorobenzyloxy)phenylboronic acidCatalog No.:AA003JYC CAS No.:1072951-98-4 MDL No.:MFCD00010512 MF:C13H12BFO3 MW:246.0420 |
3-Formyl-4-isopropoxyphenylboronic acidCatalog No.:AA003BPN CAS No.:1072952-00-1 MDL No.:MFCD08705272 MF:C10H13BO4 MW:208.0188 |
3-(2'-Methoxybenzyloxy)phenylboronic acidCatalog No.:AA0084TN CAS No.:1072952-02-3 MDL No.:MFCD08276833 MF:C14H15BO4 MW:258.0775 |
3-(4'-Fluorobenzyloxy)phenylboronic acidCatalog No.:AA003I06 CAS No.:1072952-03-4 MDL No.:MFCD08705238 MF:C13H12BFO3 MW:246.0420 |
3-Ethylsulfinylphenylboronic acidCatalog No.:AA003BND CAS No.:1072952-07-8 MDL No.:MFCD03092933 MF:C8H11BO3S MW:198.0471 |
3-Carboxy-2-fluorophenylboronic acidCatalog No.:AA007EP5 CAS No.:1072952-09-0 MDL No.:MFCD03095128 MF:C7H6BFO4 MW:183.9295 |
2-Ethylsulfinylphenylboronic acidCatalog No.:AA0084TM CAS No.:1072952-11-4 MDL No.:MFCD03095262 MF:C8H11BO3S MW:198.0471 |
2-Amino-4,5-difluorophenylboronic acidCatalog No.:AA003BIP CAS No.:1072952-14-7 MDL No.:MFCD03095340 MF:C6H6BF2NO2 MW:172.9251 |
5-Hexenylboronic acidCatalog No.:AA003QSK CAS No.:1072952-16-9 MDL No.:MFCD10567048 MF:C6H13BO2 MW:127.9772 |
5-Chloro-2-fluoro-4-methoxyphenylboronic acidCatalog No.:AA007EP3 CAS No.:1072952-18-1 MDL No.:MFCD04112552 MF:C7H7BClFO3 MW:204.3911 |
2-Isopropoxy-4-trifluoromethylphenylboronic acidCatalog No.:AA007WFG CAS No.:1072952-21-6 MDL No.:MFCD04972374 MF:C10H12BF3O3 MW:248.0067 |
2-Boronofuran-3-carboxylic acidCatalog No.:AA0084TK CAS No.:1072952-23-8 MDL No.:MFCD06203510 MF:C5H5BO5 MW:155.9012 |
2-Fluoro-5-hydroxymethylphenylboronic acidCatalog No.:AA007WFF CAS No.:1072952-25-0 MDL No.:MFCD06656276 MF:C7H8BFO3 MW:169.9460 |
2,6-Difluoropyridine-3-boronic acid hydrateCatalog No.:AA003BIF CAS No.:1072952-27-2 MDL No.:MFCD06657881 MF:C5H6BF2NO3 MW:176.9138 |
5-Formyl-3-methylthiophene-2-boronic acidCatalog No.:AA003BVB CAS No.:1072952-28-3 MDL No.:MFCD06657888 MF:C6H7BO3S MW:169.9940 |
2-Picoline-5-boronic acid hydrateCatalog No.:AA008SSJ CAS No.:1072952-30-7 MDL No.:MFCD06657901 MF:C6H10BNO3 MW:154.9595 |
2-Picoline-3-boronic acid HClCatalog No.:AA0033CQ CAS No.:1072952-34-1 MDL No.:MFCD06659489 MF:C6H9BClNO2 MW:173.4052 |
3-Picoline-4-boronic acid HClCatalog No.:AA003BQ3 CAS No.:1072952-40-9 MDL No.:MFCD06659519 MF:C6H9BClNO2 MW:173.4052 |
5-Chloro-2-fluoro-4-methylphenylboronic acidCatalog No.:AA0084TJ CAS No.:1072952-42-1 MDL No.:MFCD07368241 MF:C7H7BClFO2 MW:188.3917 |
5-Hydroxy-2-methoxyphenylboronic acidCatalog No.:AA003NVO CAS No.:1072952-43-2 MDL No.:MFCD07368831 MF:C7H9BO4 MW:167.9550 |
3-Fluoro-5-methylpyridine-4-boronic acidCatalog No.:AA003BPJ CAS No.:1072952-44-3 MDL No.:MFCD07368843 MF:C6H7BFNO2 MW:154.9347 |
2-Fluoro-5-methylpyridine-3-boronic acidCatalog No.:AA003BKD CAS No.:1072952-45-4 MDL No.:MFCD07368857 MF:C6H7BFNO2 MW:154.9347 |
2-Bromo-5-methoxypyridine-4-boronic acidCatalog No.:AA003BJ3 CAS No.:1072952-48-7 MDL No.:MFCD07781222 MF:C6H7BBrNO3 MW:231.8397 |
(4,5-Dimethoxy-2-(methoxycarbonyl)phenyl)boronic acidCatalog No.:AA007WFD CAS No.:1072952-49-8 MDL No.:MFCD07781232 MF:C10H13BO6 MW:240.0176 |
2-Fluoro-3-(ethoxycarbonyl)phenylboronic acidCatalog No.:AA0084TH CAS No.:1072952-52-3 MDL No.:MFCD08064050 MF:C9H10BFO4 MW:211.9827 |
3-Chloro-4-formylphenylboronic acidCatalog No.:AA007EP1 CAS No.:1072952-53-4 MDL No.:MFCD08274473 MF:C7H6BClO3 MW:184.3847 |
BenzovindiflupyrCatalog No.:AA01DZFR CAS No.:1072957-71-1 MDL No.:MFCD30725523 MF:C18H15Cl2F2N3O MW:398.2340 |
Sr-3677Catalog No.:AA008RLJ CAS No.:1072959-67-1 MDL No.:MFCD16619390 MF:C22H24N4O4 MW:408.4504 |
1-Ethyl-1h-pyrazol-5-olCatalog No.:AA007EOZ CAS No.:107296-34-4 MDL No.:MFCD13151912 MF:C5H8N2O MW:112.1298 |
4-(6-Methyl-4,8-dioxo-1,3,6,2-dioxazaborocan-2-yl)benzaldehydeCatalog No.:AA01FGJ9 CAS No.:1072960-66-7 MDL No.:MFCD11215233 MF:C12H12BNO5 MW:261.0384 |
2-(4-Hydroxymethylphenyl)-2,3-dihydro-1h-naphtho[1,8-de][1,3,2]diazaborinineCatalog No.:AA00HAW4 CAS No.:1072960-84-9 MDL No.:MFCD20527131 MF:C17H15BN2O MW:274.1248 |
Cyclopropaneaceticacid, 2-methylene-Catalog No.:AA0084TG CAS No.:1073-00-3 MDL No.:MFCD11558999 MF:C6H8O2 MW:112.1265 |
1,3,2-dioxathiane-2,2-dioneCatalog No.:AA00HAW5 CAS No.:1073-05-8 MDL No.:MFCD00801144 MF:C3H6O4S MW:138.1423 |
1-Bromo-3-fluorobenzeneCatalog No.:AA0032MW CAS No.:1073-06-9 MDL No.:MFCD00000326 MF:C6H4BrF MW:174.9984 |
4,4-Dimethylcyclohex-2-enoneCatalog No.:AA008RLW CAS No.:1073-13-8 MDL No.:MFCD00009695 MF:C8H12O MW:124.1803 |
3-Amino-2,4-dimethylpyridineCatalog No.:AA0084TA CAS No.:1073-21-8 MDL No.:MFCD08235192 MF:C7H10N2 MW:122.1677 |
2,6-Lutidine-n-oxideCatalog No.:AA003G31 CAS No.:1073-23-0 MDL No.:MFCD00039715 MF:C7H9NO MW:123.1525 |
2-PropionylpyrroleCatalog No.:AA003HTP CAS No.:1073-26-3 MDL No.:MFCD01696449 MF:C7H9NO MW:123.1525 |
2-HydroxythioanisoleCatalog No.:AA003HDD CAS No.:1073-29-6 MDL No.:MFCD00002211 MF:C7H8OS MW:140.2028 |
Pyridine,4-chloro-3-methyl-, 1-oxideCatalog No.:AA007EKY CAS No.:1073-34-3 MDL No.:MFCD00128858 MF:C6H6ClNO MW:143.5709 |
4-BromobenzocyclobuteneCatalog No.:AA0033VJ CAS No.:1073-39-8 MDL No.:MFCD09029072 MF:C8H7Br MW:183.0452 |
(1-Bromoethyl)cyclohexaneCatalog No.:AA003BCG CAS No.:1073-42-3 MDL No.:MFCD12065565 MF:C8H15Br MW:191.1087 |
6-Methylpyrimidine-4-carbaldehydeCatalog No.:AA009QTH CAS No.:1073-53-6 MDL No.:MFCD09881197 MF:C6H6N2O MW:122.1246 |
2-Pyrimidinamine,4-(methylthio)-Catalog No.:AA0084N3 CAS No.:1073-54-7 MDL No.:MFCD18816603 MF:C5H7N3S MW:141.1942 |
(2-Chloroethyl)cyclohexaneCatalog No.:AA007EKF CAS No.:1073-61-6 MDL No.:MFCD11646261 MF:C8H15Cl MW:146.6577 |
Benzylhydrazine hydrochlorideCatalog No.:AA003O26 CAS No.:1073-62-7 MDL No.:MFCD01722685 MF:C7H11ClN2 MW:158.6286 |
Pyrimidine-4-carbaldehyde oximeCatalog No.:AA0094LI CAS No.:1073-65-0 MDL No.:MFCD18828136 MF:C5H5N3O MW:123.1127 |
4-ChlorostyreneCatalog No.:AA00389I CAS No.:1073-67-2 MDL No.:MFCD00000632 MF:C8H7Cl MW:138.5942 |
4-ChlorophenylhydrazineCatalog No.:AA007W84 CAS No.:1073-69-4 MDL No.:MFCD00038132 MF:C6H7ClN2 MW:142.5862 |
4-Chlorophenylhydrazine, HClCatalog No.:AA003L5B CAS No.:1073-70-7 MDL No.:MFCD00012943 MF:C6H8Cl2N2 MW:179.0471 |
4-(Methylthio)phenolCatalog No.:AA0033R1 CAS No.:1073-72-9 MDL No.:MFCD00002351 MF:C7H8OS MW:140.2028 |
2-Propanone, 1-(tetrahydro-2-furanyl)-Catalog No.:AA007EF1 CAS No.:1073-73-0 MDL No.:MFCD12153334 MF:C7H12O2 MW:128.1690 |
2,6-Dimethyltetrahydro-4h-pyran-4-oneCatalog No.:AA008RZB CAS No.:1073-79-6 MDL No.:MFCD01693965 MF:C7H12O2 MW:128.1690 |
1-(3-Bromophenyl)-1h-pyrroleCatalog No.:AA0084TF CAS No.:107302-22-7 MDL No.:MFCD02665243 MF:C10H8BrN MW:222.0812 |
4-(2-fluoro-1-hydroxyethyl)benzonitrileCatalog No.:AA01DX74 CAS No.:1073056-22-0 MDL No.:MFCD31666888 MF:C9H8FNO MW:165.1643 |
2-chloro-1-[4-(4-fluorophenyl)piperazin-1-yl]ethan-1-one hydrochlorideCatalog No.:AA019JE6 CAS No.:1073059-28-5 MDL No.:MFCD08445288 MF:C12H15Cl2FN2O MW:293.1647 |
2-(3,5-Dibromophenyl)-4,6-diphenyl-1,3,5-triazineCatalog No.:AA00942Z CAS No.:1073062-59-5 MDL No.:MFCD25562933 MF:C21H13Br2N3 MW:467.1560 |
(4-bromo-1,5-dimethyl-1H-pyrazol-3-yl)methanolCatalog No.:AA01BXKL CAS No.:1073067-93-2 MDL No.:MFCD30497696 MF:C6H9BrN2O MW:205.0525 |
1,3-dimethyl-2-oxo-1,2-dihydroquinoline-4-carboxylic acidCatalog No.:AA01CA6T CAS No.:1073071-78-9 MDL No.:MFCD24499224 MF:C12H11NO3 MW:217.2206 |
5-(2,4-Dichlorophenyl)pyridin-2-amineCatalog No.:AA007WFA CAS No.:1073114-78-9 MDL No.:MFCD16778826 MF:C11H8Cl2N2 MW:239.1006 |
Methyl 2-chloro-6-(trifluoromethyl)nicotinateCatalog No.:AA0094OZ CAS No.:1073129-57-3 MDL No.:MFCD00016047 MF:C8H5ClF3NO2 MW:239.5790 |
Methyl (1r,2r)-rel-2-aminocyclohexane-1-carboxylate hydrochlorideCatalog No.:AA01DMCO CAS No.:107313-17-7 MDL No.:MFCD28892334 MF:C16H32Cl2N2O4 MW:387.3423 |
Benzamide,N-[2-(1H-benzimidazol-2-yl)ethyl]-Catalog No.:AA007WF8 CAS No.:107313-47-3 MDL No.:MFCD00522697 MF:C16H15N3O MW:265.3098 |
2-(4-ethylphenyl)-2-[(trimethylsilyl)oxy]acetonitrileCatalog No.:AA01BA0T CAS No.:1073135-75-7 MDL No.:MFCD16786523 MF:C13H19NOSi MW:233.3816 |
DefactinibCatalog No.:AA008TCN CAS No.:1073154-85-4 MDL No.:MFCD25977806 MF:C20H21F3N8O3S MW:510.4927 |
1-(4-chlorophenyl)-2-(piperazin-1-yl)ethan-1-one dihydrochlorideCatalog No.:AA00VT5N CAS No.:1073155-04-0 MDL No.:MFCD16295341 MF:C12H17Cl3N2O MW:311.6352 |
N-(3-(Aminomethyl)pyridin-2-yl)-n-methylmethanesulfonamide acetateCatalog No.:AA0095N9 CAS No.:1073159-75-7 MDL No.:MFCD29044904 MF:C10H17N3O4S MW:275.3247 |
Defactinib hydrochlorideCatalog No.:AA008TIY CAS No.:1073160-26-5 MDL No.:MFCD28144730 MF:C20H22ClF3N8O3S MW:546.9537 |
Methyl 4-bromo-3-(trifluoromethyl)benzoateCatalog No.:AA0084TC CAS No.:107317-58-8 MDL No.:MFCD10566409 MF:C9H6BrF3O2 MW:283.0419 |
Methyl 5-amino-2-chloroisonicotinateCatalog No.:AA007WF6 CAS No.:1073182-59-8 MDL No.:MFCD11848213 MF:C7H7ClN2O2 MW:186.5957 |
3-Amino-6-chloro-4-methylpicolinic acidCatalog No.:AA00HAW9 CAS No.:1073182-76-9 MDL No.:MFCD18382760 MF:C7H7ClN2O2 MW:186.5957 |
3-Amino-4,6-dichloropicolinonitrileCatalog No.:AA0098G0 CAS No.:1073182-86-1 MDL No.:MFCD20701019 MF:C6H3Cl2N3 MW:188.0141 |
3-Amino-4,6-dichloropicolinic acidCatalog No.:AA009986 CAS No.:1073182-87-2 MDL No.:MFCD24499074 MF:C6H4Cl2N2O2 MW:207.0142 |
4,4'-Bis[N-(1-naphthyl)-N-phenylamino]-4''-phenyltriphenylamineCatalog No.:AA003KBP CAS No.:1073183-32-0 MDL No.:MFCD06797058 MF:C56H41N3 MW:755.9448 |
tert-Butyl 4-(4-methylbenzoyl)piperazine-1-carboxylateCatalog No.:AA00HAWC CAS No.:1073190-54-1 MDL No.:MFCD14635762 MF:C17H24N2O3 MW:304.3841 |
1-chloro-5-methylhexan-2-olCatalog No.:AA01BGMC CAS No.:107323-80-8 MDL No.:MFCD19232587 MF:C7H15ClO MW:150.6464 |
2-Benzyloxybenzyl acetateCatalog No.:AA008WSQ CAS No.:1073234-31-7 MDL No.:MFCD09038505 MF:C16H16O3 MW:256.2964 |
trans-1-benzyl-4-phenylpyrrolidin-3-aMineCatalog No.:AA0095N2 CAS No.:1073263-65-6 MDL No.:MFCD21608504 MF:C17H20N2 MW:252.3541 |
rac-(3R,4S)-1-benzyl-4-(4-fluorophenyl)pyrrolidin-3-amine, transCatalog No.:AA01DX75 CAS No.:1073263-80-5 MDL No.:MFCD21605249 MF:C17H19FN2 MW:270.3446 |
(1s,4s)-4-(trifluoromethyl)cyclohexan-1-amineCatalog No.:AA00IMIK CAS No.:1073266-01-9 MDL No.:MFCD19686543 MF:C7H12F3N MW:167.1721 |
Trans-4-(trifluoromethyl)cyclohexanamineCatalog No.:AA008UEV CAS No.:1073266-02-0 MDL No.:MFCD18914322 MF:C7H12F3N MW:167.1721 |
(R)-3-tert-Butoxycarbonylamino-4-(1h-indol-3-yl)-butyric acidCatalog No.:AA0094WR CAS No.:1073269-91-6 MDL No.:MFCD08276227 MF:C17H22N2O4 MW:318.3676 |
4,4-diMethyl-2-PyrrolidineMethanolCatalog No.:AA0092MB CAS No.:1073283-04-1 MDL No.:MFCD19227423 MF:C7H15NO MW:129.2001 |
2-Chloro-3-fluoropyridine-5-boronic acid pinacol esterCatalog No.:AA008STT CAS No.:1073312-28-3 MDL No.:MFCD08063077 MF:C11H14BClFNO2 MW:257.4968 |
(Trimethyl)pentamethylcyclopentadienyltitanium (IV)Catalog No.:AA003CML CAS No.:107333-47-1 MDL No.:MFCD00269851 MF:C13H29Ti----- MW:233.2364 |
5-(Hydroxymethyl)morpholin-3-oneCatalog No.:AA008ZD2 CAS No.:1073338-64-3 MDL No.:MFCD11044094 MF:C5H9NO3 MW:131.1299 |
5-(Ethoxycarbonyl)furan-2-boronic acid, pinacol esterCatalog No.:AA003Q8Z CAS No.:1073338-92-7 MDL No.:MFCD11855980 MF:C13H19BO5 MW:266.0980 |
3-iodo-5-(trifluoroMethyl)phenolCatalog No.:AA00953B CAS No.:1073339-06-6 MDL No.:MFCD12405423 MF:C7H4F3IO MW:288.0057 |
2,5-Dimethoxyphenylboronic acid, pinacol esterCatalog No.:AA007EKZ CAS No.:1073339-07-7 MDL No.:MFCD12405521 MF:C14H21BO4 MW:264.1251 |
2-(3,4-Bis(trifluoromethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneCatalog No.:AA00944F CAS No.:1073339-08-8 MDL No.:MFCD12405522 MF:C14H15BF6O2 MW:340.0691 |
2,3-Methylenedioxyphenylboronic acid pinacol esterCatalog No.:AA009454 CAS No.:1073339-10-2 MDL No.:MFCD12405524 MF:C13H17BO4 MW:248.0827 |
5-Bromo-2,3-difluorophenylboronic acid, pinacol esterCatalog No.:AA003EV1 CAS No.:1073339-12-4 MDL No.:MFCD11855989 MF:C12H14BBrF2O2 MW:318.9502 |
4-Chloro-2-fluoro-5-(methoxycarbonyl)phenylboronic acid, pinacol esterCatalog No.:AA0090C8 CAS No.:1073339-13-5 MDL No.:MFCD12026085 MF:C14H17BClFO4 MW:314.5448 |
2,2'-(4,5,6-Trifluoro-1,3-phenylene)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane)Catalog No.:AA00HAWO CAS No.:1073339-14-6 MDL No.:MFCD12407210 MF:C18H25B2F3O4 MW:384.0059 |
2,3-Difluorophenylboronic acid pinacol esterCatalog No.:AA009522 CAS No.:1073339-17-9 MDL No.:MFCD12405347 MF:C12H15BF2O2 MW:240.0541 |
2-(5-Bromo-2,3,4-trifluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneCatalog No.:AA00HAWQ CAS No.:1073339-18-0 MDL No.:MFCD12405350 MF:C12H13BBrF3O2 MW:336.9406 |
5-Bromo-2,3,4-trifluorophenolCatalog No.:AA0094EA CAS No.:1073339-19-1 MDL No.:MFCD11857741 MF:C6H2BrF3O MW:226.9787 |
2-Trifluoromethylphenylboronic acid, pinacol esterCatalog No.:AA008WMN CAS No.:1073339-21-5 MDL No.:MFCD06795676 MF:C13H16BF3O2 MW:272.0711 |
2-(4-Methoxythiophen-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneCatalog No.:AA009987 CAS No.:1073339-22-6 MDL No.:MFCD12405477 MF:C11H17BO3S MW:240.1269 |
3-Chloromethylphenylboronic acid pinacol esterCatalog No.:AA007EKX CAS No.:1073353-44-2 MDL No.:MFCD11053847 MF:C13H18BClO2 MW:252.5448 |
N-Methyl-4-benzenesulfonamideboronic acid pinacol esterCatalog No.:AA007EKW CAS No.:1073353-47-5 MDL No.:MFCD06657895 MF:C13H20BNO4S MW:297.1782 |
4-(2-Hydroxyethylcarbamoyl)phenylboronic acid, pinacol esterCatalog No.:AA007EKU CAS No.:1073353-51-1 MDL No.:MFCD06795648 MF:C15H22BNO4 MW:291.1505 |
4-Pyrrolidinylcarbonylphenylboronic acid, pinacol esterCatalog No.:AA007WF1 CAS No.:1073353-55-5 MDL No.:MFCD09027085 MF:C17H24BNO3 MW:301.1884 |
4-(N-Benzylaminocarbonyl)phenylboronic acid, pinacol esterCatalog No.:AA003SOM CAS No.:1073353-57-7 MDL No.:MFCD09266184 MF:C20H24BNO3 MW:337.2205 |
4-(N,O-Dimethylhydroxylaminocarbonyl)phenylboronic acid, pinacol esterCatalog No.:AA003T2P CAS No.:1073353-58-8 MDL No.:MFCD09953501 MF:C15H22BNO4 MW:291.1505 |
4-(Furfurylaminocarbonyl)phenylboronic acid, pinacol esterCatalog No.:AA003K5M CAS No.:1073353-59-9 MDL No.:MFCD09266168 MF:C18H22BNO4 MW:327.1826 |
4-(2-Methoxyethylcarbamoyl)phenylboronic acid, pinacol esterCatalog No.:AA0090CG CAS No.:1073353-60-2 MDL No.:MFCD09266188 MF:C16H24BNO4 MW:305.1771 |
3-Pyrrolidinylcarbonylphenylboronic acid, pinacol esterCatalog No.:AA007WF0 CAS No.:1073353-61-3 MDL No.:MFCD09027086 MF:C17H24BNO3 MW:301.1884 |
3-(Piperidine-1-carbonyl)phenylboronic acid, pinacol esterCatalog No.:AA0084T3 CAS No.:1073353-62-4 MDL No.:MFCD09027084 MF:C18H26BNO3 MW:315.2149 |
3-(Furfurylaminocarbonyl)phenylboronic acid, pinacol esterCatalog No.:AA003I5J CAS No.:1073353-63-5 MDL No.:MFCD09266173 MF:C18H22BNO4 MW:327.1826 |
3-(2-Methoxyethylcarbamoyl)phenylboronic acid, pinacol esterCatalog No.:AA003HY8 CAS No.:1073353-64-6 MDL No.:MFCD09266187 MF:C16H24BNO4 MW:305.1771 |
2,4-Bis(trifluoromethyl)phenylboronic acid, pinacol esterCatalog No.:AA007EKT CAS No.:1073353-65-7 MDL No.:MFCD09953467 MF:C14H15BF6O2 MW:340.0691 |
2-Fluoro-4-trifluoromethylphenylboronic acid, pinacol esterCatalog No.:AA008SFX CAS No.:1073353-68-0 MDL No.:MFCD08458187 MF:C13H15BF4O2 MW:290.0616 |
3-Chloro-2-fluoropyridine-4-boronic acid pinacol esterCatalog No.:AA003J3V CAS No.:1073353-71-5 MDL No.:MFCD09037476 MF:C11H14BClFNO2 MW:257.4968 |
1,3-Bis(4-boronophenyl)urea, bispinacol esterCatalog No.:AA0090D4 CAS No.:1073353-72-6 MDL No.:MFCD09972179 MF:C25H34B2N2O5 MW:464.1699 |
3-Chloro-2-methoxypyridine-4-boronic acid, pinacol esterCatalog No.:AA003J4A CAS No.:1073353-73-7 MDL No.:MFCD06798258 MF:C12H17BClNO3 MW:269.5323 |
5-Bromo-2-methoxypyridine-3-boronic acid, pinacol esterCatalog No.:AA008RUV CAS No.:1073353-75-9 MDL No.:MFCD07781157 MF:C12H17BBrNO3 MW:313.9833 |
4-Carboxynaphthalene-1-boronic acid, pinacol esterCatalog No.:AA003JZ3 CAS No.:1073353-77-1 MDL No.:MFCD09972180 MF:C17H19BO4 MW:298.1414 |
2,3-Dichloropyridine-4-boronic acid, pinacol esterCatalog No.:AA007WEZ CAS No.:1073353-78-2 MDL No.:MFCD06798257 MF:C11H14BCl2NO2 MW:273.9514 |
4-Methoxy-2-nitrophenylboronic acid, pinacol esterCatalog No.:AA003LJO CAS No.:1073353-81-7 MDL No.:MFCD10699701 MF:C13H18BNO5 MW:279.0967 |
6-Chloro-1-methylindole-2-boronic acid, pinacol esterCatalog No.:AA003N2G CAS No.:1073353-82-8 MDL No.:MFCD11504964 MF:C15H19BClNO2 MW:291.5809 |
2-Fluoro-4-nitrophenylboronic acid, pinacol esterCatalog No.:AA008SR8 CAS No.:1073353-89-5 MDL No.:MFCD09264075 MF:C12H15BFNO4 MW:267.0612 |
3-((Phenylamino)methyl)phenylboronic acid, pinacol esterCatalog No.:AA003HW7 CAS No.:1073353-90-8 MDL No.:MFCD09266198 MF:C19H24BNO2 MW:309.2104 |
3-(2-Bromoethoxy)phenylboronic acid, pinacol esterCatalog No.:AA0084T1 CAS No.:1073353-91-9 MDL No.:MFCD11044883 MF:C14H20BBrO3 MW:327.0218 |
3,3'-(Ethane-1,2-diylbis(oxy))bis(3,1-phenylene)diboronic acid, pinacol esterCatalog No.:AA003I8Q CAS No.:1073353-94-2 MDL No.:MFCD10699702 MF:C26H36B2O6 MW:466.1824 |
2,5-Dichloropyridine-4-boronic acid, pinacol esterCatalog No.:AA007WEY CAS No.:1073353-98-6 MDL No.:MFCD06798256 MF:C11H14BCl2NO2 MW:273.9514 |
5-Chloro-2-nitrophenylboronic acid, pinacol esterCatalog No.:AA007EKS CAS No.:1073353-99-7 MDL No.:MFCD11053894 MF:C12H15BClNO4 MW:283.5158 |
4-Boc-Aminopyridine-3-boronic acid, pinacol esterCatalog No.:AA003UG2 CAS No.:1073354-02-5 MDL No.:MFCD08063074 MF:C16H25BN2O4 MW:320.1917 |
3-Cyano-2-methoxypyridine-5-boronic acid, pinacol esterCatalog No.:AA0084T0 CAS No.:1073354-05-8 MDL No.:MFCD11504968 MF:C13H17BN2O3 MW:260.0967 |
(3-Bromomethyl-4-trifluoromethoxyphenylboronic acid, pinacol esterCatalog No.:AA003BON CAS No.:1073354-06-9 MDL No.:MFCD11504969 MF:C14H17BBrF3O3 MW:380.9932 |
2-(1,3-Dioxolan-2-yl)-1-ethylboronic acid pinacol esterCatalog No.:AA003EN6 CAS No.:1073354-07-0 MDL No.:MFCD03788722 MF:C11H21BO4 MW:228.0930 |
N-(2-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pivalamideCatalog No.:AA00HAWT CAS No.:1073354-10-5 MDL No.:MFCD05663849 MF:C17H26BNO3 MW:303.2042 |
2-Formylpyridine-5-boronic acid pinacolateCatalog No.:AA007WEX CAS No.:1073354-14-9 MDL No.:MFCD06659508 MF:C12H16BNO3 MW:233.0713 |