Boronic recrystallization

A solution of 2,3-dibromo-5-methoxyaniline (32 g, 0.17 mol) in CHjClj (300 ml) was stirred and cooled in an icc bath. Boron trichloride (1 M in CH2CI2, 180 ml, 0.18 mol), chloroacetonitrile (14.3 g, 0.19 mol) and TiC (1 M in CH CIj, 190ml, 0.19 mol) were added. The resulting mixture was refluxed for 1.5 h. The solution was cooled to room temperature and poured carefully on to a mixture of icc and 20% aq. HCl (700 ml). The organic layer was separated and the CH Clj removed by distillation. The residue was heated to 90°C on a water bath for 30 min. The solution was cooled and the solid collected by filtration. It was partitioned between ether (1.41) and 1 N NaOH (500 ml). The ether layer was washed with brine, dried over Na2S04 and evaporated. The residue was recrystallized from ethanol to give 2-amino-3,4-dibromo-6-methoxy-a-chloroacetophenone (55 g) in 90% yield. 

A solution of 6-bromoindole (O.lOmol) in toluene (200 ml) was treated with Pd(PPh3)4 (5mol%) and stirred for 30 min. A solution of 4-fluorophenyl-boronic acid (0.25 M, 0.15 mol) in abs. EtOH was added, followed immediately by sal aq. NaHCOj (10 eq.). The biphasic mixture was refluxed for several hours and then cooled to room temperature. The reaction mixture was poured into sat. aq. NaCl (200 ml) and the layers separated. The aq. layer was extracted with additional EtOAc (200 ml) and the combined organic layers dried (Na2S04), filtered and concentrated in vacuo. The solution was filtered through silica gel using hexane-CHjCl -hexanc for elution and evaporated. Final purification by recrystallization gave the product (19 g, 90%). 

A solution of 3 g of the nitrile, water (5 moles per mole of nitrile), and 20 g of boron trifluoride-acetic acid complex is heated (mantle or oil bath) at 115-120° for 10 minutes. The solution is cooled in an ice bath with stirring and is carefully made alkaline by the slow addition of 6 A sodium hydroxide (about 100 ml). The mixture is then extracted three times with 100-ml portions of 1 1 ether-ethyl acetate, the extracts are dried over anhydrous sodium sulfate, and the solvent is evaporated on a rotary evaporator to yield the desired amide. The product may be recrystallized from water or aqueous methanol. Examples are given in Table 7.1. 

Step 1 1-(p-Chlorophenyl)-3-Ethoxy-1 H-lsoindole - Crystalline triethyloxonium boron-tetrafluoride (21 g) (prepared from 23 g of borontrifluoride etherate and 11 g of epichlorohydrin) is dissolved in 100 ml of absolute methylenechloride. 3-(p-Chlorophenyl) phthalimidine (21 g) is added and the reaction mixture is stirred overnight at room temperature. The resulting solution is poured onto 50 ml of saturated Sodium carbonate, extracted with 500 ml of ether and dried. Upon evaporation of the solvent there is obtained crude material which is recrystallized from methylene chloride/hexane (1 1) to yield l-(p-chlorophenyl)-3-ethoxy-1 H-isoindole MP 102° to 103°C. 

Crystalline, diastereomerieally pure syn-aIdols are also available from chiral A-acylsultams. lhe outcome of the induction can be controlled by appropriate choice of the counterion in the cnolate boron enolates lead, almost exclusively, to one adduct 27 (d.r. >97 3, major adduct/ sum of all other diastereomers) whereas mediation of the addition by lithium or tin leads to the predominant formation of adducts 28. Unfortunately, the latter reaction is plagued by lower induced stereoselectivity (d.r. 66 34 to 88 12, defined as above). In both cases, however, diastereomerieally pure adducts are available by recrystallizing the crude adducts. Esters can be liberated by treatment of the adducts with lithium hydroxide/hydrogen peroxide, whereby the chiral auxiliary reagent can be recovered106. 

The parent hexathiaadamantane (185) is obtained preparatively when a solution of formic acid and hydrochloric acid in nitrobenzene is allowed to stand for several weeks in a hydrogen sulfide atmosphere the product which separated is almost insoluble in all common solvents and purification presents a problem. Only large volumes of dimethyl sulfoxide at reflux serve for recrystallization.224 The reaction of thioacetic acid with formic acid in the presence of zinc chloride gives tetramethyl-(186), monomethyl-, dimethyl-and trimethylhexathiaadamantane derivatives (187).225 Other variations include the reaction of thioacetic acid with a /i-diketone,226 and the use of boron trifluoride227 or aluminum chloride as a catalyst.228... 

Impurities from boron may be removed by successive recrystallization or volatdization at high temperatures. Removal of certain impurities such as oxygen, nitrogen, hydrogen or carbon from boron are more difficult and involve more complex steps. 

A flask was charged with 4-bromo-iodobenzene (0.079 mol), 4-methoxy-2-methyl-phenyl boronic acid (0.087 mol), palladium acetate (0.004 mol), and triphenyl phosphine (0.008 mol) and then treated with 200 ml acetone and 250 ml 2M NaHCO i. The mixture was refluxed at 65°C for 18 hours and was then treated with water and diethyl ether and the organic layer isolated. This layer was washed with 40 ml saturated sodium chloride solution and water, dried over MgSC>4, filtered, and concentrated. The residue was purified by column chromatography using silica gel with CH2C12/ hexane, 1 1, and then recrystallized in / , 7 3, respectively, and 16.4 g of product isolated. 

The BF2 chelates are hydrolytically stable (the majority of them may be recrystallized from water) whereas the BC12 chelates are easily hydrolyzed. The boric acid ester complex triptych boroxazolidines are also stable towards hydrolysis as are other aminoalcohol esters.83 A great number of the boron chelates are colored several spectrophotometric methods are based on chelate formation81 84 for the analytical determination of boric acid, organoboric acids and chelating organic compounds. The boron chelates are remarkable for their pharmacological properties as well.84 Various aspects of the boron chelates have been reviewed.81,83-86... 

The ability of the boron atom of 59 to engage in a donor-acceptor interaction was illustrated with DMAP and DABCO (DABCO = diazabi-cyclo-[2.2.2]-octane) that readily formed the corresponding Lewis adducts. Interestingly, a similar behavior was retained after coordination of the phosphorus atom to palladium. The formation of the Lewis base adducts 66a and 66b of complex 65 (Scheme 38) was supported by solid-state 31P and nB CP/MAS-NMR spectroscopy (<5 1 B = 5-6 ppm), although the occurrence of decomposition and/or dissociation processes impeded spectroscopic characterization in solution and recrystallization to obtain X-ray quality crystals. Compounds 66a and 66b substantiate the ability of ambiphilic compounds to engage concomitantly into the coordination of donor and acceptor moieties. Such a dual behavior opens interesting perspectives for the preparation of metallo-polymers and multimetallic complexes. 

The reaction of diols with alkylating agents can also be performed such that approximately the theoretical amount of monoalkylated product is obtained. Some substrates can even be monoalkylated [36, 41, 42] or monoarylated [43] with substantially higher yields than statistics would predict what must be due to the slowness of the second alkylation. This behavior, however, is not usually observed, and other strategies must usually be used to achieve clean monoalkylations. Use of excess diol will often furnish pure monoalkylated diol, but a suitable means of removal of excess diol will be required. In the examples sketched in Scheme 10.10 the products were purified by column chromatography, recrystallization, or distillation. As with acylations, the formation of monoalkylated diols can also be promoted by Ag20 [44] or by transient protection with boron [45] or tin [46] derivatives. 

Boron trifluoride etherate (37.9 ml) was added to a stirred solution of 3a-hydroxy-5a-pregnane-ll,20-dione (6.64 g, 20 mmol) and lead tetraacetate (10.1 g, 22 mmol) in dry benzene (280 ml) and methanol (15.1 ml) at room temperature. After 2 h the mixture was poured into water (2 L) and extracted with ether (1 L). The combined ether extracts were washed successively with sodium bicarbonate solution and water, dried over magnesium sulfate, and concentrated in vacuo to give a white crystalline mass. Four recrystallizations from acetone-petroleum (b.p. 40°-60°C) gave 21-acetoxy-3a-hydroxy-5a-pregnane-ll,20-dione as fine needles (4.22 g, 54%), melting point 172°-173°C. 

The tiyptophol was condensed with methyl propionylacetate using boron trifluoride etherate as the catalyst to produce tetrahyropyranoindole. Basic hydrolysis of the ester gave [3-14C] etodolic acid (overall yield 26% from the labeled starting material). The compound was recrystallized in presence of an antioxidant to prevent formation of peroxides and stored at -10°C. The radiochemical purity was determined to be 99%. 

The oxazaborolidine is finally made by heating diphenylprolinol (4) under reflux with a suitable alkyl(aryl)boronic acid or, better, with the corresponding boroxine in toluene in the presence of molecular sieves—the water can also be removed by azeotropic distillation. According to the literature, methyl-oxazaborolidine (Me-CBS) can be either distilled or recrystallized. The key point is that the catalyst must be free from any trace of water or alkyl(aryl)boronic acid because those impurities decrease enantioselection. 

Nucleophilic substitution with lithium hexamethyldisilazane (LiHMDS) proceeds with inversion to give silylated amino boronic ester 19.26 A solution of 19 is passed through a short plug of silica before its use in the desilylation reaction. Due to the instability of underivatized a-amino boronic esters,26 trifluoroacetic acid (TFA) is used to furnish the corresponding TFA salt 20.27 A second recrystallization from TFA and isopropylether further enhances the optical purity. A diastereomeric ratio (dr) > 97 3 is typically obtained from the process route. 

The double nitrates Mg3M2(N03)12, 24 H20 can be recrystallized in strong nitric acid and serve to separate the lighter lanthanides M = La, Pr, Nd and Sm (where Ce has been removed after oxidation to the quadrivalent state). Judd noted 109) that the fine-structure of the absorption band belonging to each /-level of M(III) was so peculiar that it looked as if the chromophore was icosahedral with N = 12 (which is almost unheard about, outside boron chemistry). The crystal structure 110) of the cubic crystals confirmed entirely Judd s proposal, it is indeed [Mg(OH2)6]3 ... 

Zeolite Y does not recrystallize in KOH solutions (24). Our results are in agreement with this for Y, but for dealuminated Y zeolite there is a decrease in the Si/Al ratio irtien treated with B2O3 in KOH solution (Table 3). We found a similar trend in the mordenite system. Apparently these zeolite structures are more susceptible to recrystallization when dealuminated. Preparation of boron substituted zeolite Y by post- synthetic substitution demonstrates that this method may be used to prepare materials which are not readily available by direct synthetic procedures. 

A mixture consisting of l-bromo-5-fluoro 2-nitrobenzene (4.5 mmol), 2,4-dichlorobenzene boronic acid (4.7 mmol), Na2C03 (13.5 mmol) in benzene, and 3 ml water was treated with tetrakis(triphenylphosphine)-palladium(0) (0.2 mmol) and heated at 75°C overnight. The mixture was partitioned between EtOAc and water and the organic layer separated, then washed with brine. It was dried with MgS04 and then concentrated. A brown solid residue was recrystallized and the product isolated in 80% yield as a white solid. 

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