Dean Stark trap synthesis

When comparing the stereoselectivity ofthe reductive amination products of (R) or (S) PEA, when using Ti(OiPr)4 (1.25 equiv) or Yb(OAc)3 (10mol%) or Y(OAc)3 (15 mol%) or Ce(OAc)3 (15 mol%) or Bronsted acids (catalytic or stoichiometric, e.g., AcOH), the de ofthe amine product is the same. Furthermore, taking the ketones used for these reductive amination studies and intentionally preforming and isolating the (R) or (S) PEA ketimines (Dean Stark trap synthesis) and reducing them in the same manner, albeit without the presence of the Lewis acid or Bronsted acid, the de is the same as that found for the reductive amination [34]. 

Synthesis of Unsaturated Polyester A. The unsaturated polyester oligomer A was prepared in a 500 milliliter 4-neck flask fitted with a variable speed stirrer, a heating mantle, a gas inlet tube, a thermometer, a Dean-Starke trap and a condenser. The flask was charged with 147.0 g (1.5 mol) of maleic anhydride (Amoco), 195 g (1.88 mol) of 1,5-pentane diol (BASF), about 35 ml of xylene and 0.3 g of Fascat 4100. Then heated slowly under a nitrogen blanket to 175° C while the water of condensation was removed... 

Cyclic acetals are useful and common protecting groups for aldehydes and ketones, especially during the course of a total synthesis [8]. The successful synthesis of acetals frequently relies on the removal of water, a by-product of the reaction between the carbonyl compound and the corresponding diol. A Dean-Stark trap is often used for the removal of water as an azeotrope with benzene, but this method is not suitable for small-scale reactions. In addition, the highly carcinogenic nature of benzene makes it an undesirable solvent. Many of the reported catalysts for acetal synthesis such as p-toluenesulfonic acid and boron trifluoride etherate are toxic and corrosive. 

We developed a method for the synthesis of a variety of cyclic acetals that utilizes bismuth triflate as a catalyst and does not require the use of a Dean-Stark trap for removal of water [102]. In this method, an aldehyde or ketone is treated with 1,2-bis (trimethylsiloxy)ethane in the presence of bismuth triflate. A comparison study using o-chlorobenzaldehyde showed that with ethylene glycol a low conversion to the dioxolane was observed after 2 h whereas the use of the 1,2-bis(trimethylsiloxy) ethane afforded the corresponding dioxolane in good yields. (Scheme 9). 

SYNTHESIS (fromMDA) A solution of 6.55 gof 3,4-methylenedioxyamphetamine (MDA) as the free base and 2.8 mL formic acid in 150mL benzene was held at reflux under a Dean Stark trap until no further H20 was generated (about 20 h was sufficient, and 1.4 mL H20 was collected). Removal of the solvent gave an 8.8 g of an amber oil which was dissolved in 100 mL CH,C12, washed first with dilute HC1, then with dilute NaOH, and finally once again with dilute acid. The solvent was removed under vacuum giving 7.7 g of an amber oil that, on standing, formed crystals of N-formyl-3,4-mcthylenedioxyamphetamine. 

Deng and Overman employed the aza-Cope-Mannich reaction in the enantios-elective total synthesis of (+)-preussin (21), a potent antifungal agent possessing a pyrrolidine skeleton8 (Scheme 1.6h). Conversion of the amino alcohol 22 to the oxazolidine derivative 23 was readily accomplished by reacting with decanal in hot benzene with removal of water using a Dean-Stark trap. Treatment of... 

The methods reported for the preparation of the oxazaborolidine include the reaction of diphenylprolinol with methylboronic acid 1) in toluene at 23°C for 1.5 hr with 4 A molecular sieves present and 2) in toluene at reflux for 3 hr using a Dean-Stark trap, bolh followed by evaporation of solvent and molecular distillation (0.1 mm, 170°C).5( An alternate method involved heating a toluene solution of 2-naphthylprolinol and methylboronic acid at reflux for 10 hr using a Soxhlet extractor containing 4 A molecular sieves.5 These methods afforded erratic results. The submitters therefore developed an alternate synthesis. 

Synthesis of D20 DiSiAn. A 2-L, three-neck, round-bottom flask equipped with a Dean-Stark trap, water-cooled condenser fitted with a nitrogen inlet, pressureequalizing addition funnel, and magnetic stirring bar was charged with 111.81 g (0.242 mol) of DiSiAn, 430.12 g (1.450 mol) of D4, and 260.0 mL of chlorobenzene. The mixture was heated to reflux, and 15 mL of solvent was removed by azeotropic... 

Synthesis of Siloxane-Polyimide Elastoplastics. In a typical polymerization, a 5-L, three-neck, round-bottom flask equipped with an overhead mechanical stirrer, a Dean-Stark trap with condenser and a nitrogen inlet, and a thermometer was charged with 484.00 g (0.2406 mol) of D2o-DiSiAn, 41.61 g (0.431 mol) of mPD, 19.52 g (3 wt %) of 2-hydroxypyridine, and 2 L of o-dichlorobenzene. The mixture was warmed to 100 °C for 1 h to dissolve the monomers and the catalyst. The polyamic acids precipitated and then redissolved when the mixture was warmed to 150 °C for 2 h. To the oligomer solution was added 99.13 g of BPADA dissolved in 200 mL of o-dichlorobenzene. The mixture was maintained at 150 °C for an additional 2-h period to ensure incorporation of the dianhydride and then warmed to reflux. After approximately 100 mL of a solvent-water mixture had been removed, the solution was maintained at 180 °C for 40 h. The mixture was cooled to room temperature and diluted with 1 L of methylene chloride. Polymer was isolated from the solution by a slow addition of the polymer solution to 4 L of methanol. The resulting slurry was filtered, and the polymer was redissolved in 4 L of methylene chloride, extracted three times with 2 N aqueous HCl to remove catalyst, washed with water, dried with magnesium sulfate, reprecipitated into methanol as before, filtered, and dried in vacuo at 100 °C to obtain 522 g (85%) of a rubbery material with an IV of 0.50 dL/g. IR, NMR, and Si NMR spectroscopic analysis indicated the absence of amic acid functionalities that could be present if imidization is incomplete. 

The total synthesis of the phenolic sesquiterpene (+)-parviflorine was accomplished by L.A. Maldonado and co-workers. The key step in the synthetic sequence was the reaction of an enamine with acrolein to form a bicyclic intermediate, which was subjected to a Grob fragmentation to afford the eight-membered ring of the natural product. The bicyclic ketone substrate was refluxed in benzene using a Dean-Stark trap and the resulting enamine was taken to the next step as crude material. 

The synthesis is conducted in a 500-ml. two-necked flask equipped with magnetic stirrer and a gas inlet. If hydrated bis(2,4-pentane-dionato)nickel(II) (ROC/RIC, 11686 Sheldon St., Sun Valley, Calif. 91352) is to be used, 5.88 g. (20 mmoles) of the dihydrate and 125 ml. of toluene are placed in the flask, and it is fitted with a Dean-Stark trap. The mixture is boiled under reflux under nitrogen until 0.72 ml. of water collects in the trap. 

Polycondensation of acid anhydrides (maleic and phthalic anhydrides) with diols (e.g. ethylene glycol) under microwave irradiation conditions has also been described for synthesis of unsaturated polyesters [52]. In addition to the previous procedure, the reaction temperature was increased to 200 °C and a Dean-Stark trap was used to remove water from the reaction mixture (Scheme 14.23). It was found that reaction times for the microwave and conventional procedures were comparable and depended on the rate of removal of water from the reaction system. 

SYNTHESIS A solution of 27.2 g anisaldehyde and 18.0 g nitroethane in 300 mL benzene was treated with 2.0 mL cyclohexane and refluxed using a Dean Stark trap until H20 ceased to accumulate. A total of 3.8 mL was generated over about 5 days. After the removal of the solvent under vacuum, the viscous red oily residue was cooled and it spontaneously crystallized. This was ground under an equal volume of MeOH, producing lemon-yellow crystals of 1-(4-methoxyphenyl)-2-nitropropene. The final yield was 27.4 g of product with a mp of 45-46 °C. Recrystallization from 4 volumes MeOH did not improve the mp. An excellent alternate synthesis with a comparable yield involved letting a solution of equimolar amounts of the aldehyde and nitro-ethane and a tenth mole of n-amylamine stand in the dark at room temperature for a couple of weeks. The product spontaneously crystal-lized, and could be recrystallized from MeOH. The more conventional synthesis involving acetic acid as a solvent and ammonium acetate as a catalyst, produced a poor yield of the nitrostyrene and it was difficult to separate from the white diacetate of the starting anisaldehyde, mp 59-60 °C. 

After filtering, Et20 washing, and air drying, there was obtained 6.2 g of 2,5-dimethoxy-N-methylamphetamine hydrochloride (METHYL-DMA) as fine white crystals with a mp of 117-118 deg C. The mixed mp with 2,5-DMA (114-116 deg C) was depressed to 96-105 deg C. An alternate synthesis gave the same overall yield of an identical product, but started with 2,5-DMA. It required two synthetic steps. The free base amine was converted to the crystalline formamide with formic acid in benzene using a Dean Stark trap, and this intermediate was reduced to METHYL-MDAwith LAH. 

In 1988 Cox and Robinson also reported a synthesis of the 1,2,3,4-tetrahy-dro-9a,4a-(iminoethano)-9H-carbazole core (Scheme 2). Starting with the cyclohexanone 87 and the phenylhydrazine 88, they first formed hydra-zone 89 via heating in mixture of benzene and catalytic amounts of acetic acid at reflux, while removing water with a Dean—Stark trap. A Fischer indolization sequence was next achieved via heating the derived hydrazone 89 at reflux in acetic acid to furnish indolenine 90. Aqueous ammonia was then added to the crude product to perform a nucleophihc attack at both the ester carbonyl and indolenine imine carbon to eHcit precipitation of pyrro-hdinone 91. Finally, reduction of the amide employing hthium aluminum hydride in hot tetrahydrofuran (THF) provided pyrroloindole 92. 

Scheme 7.1 Tada et al. synthesis of patulin (348). Reagents and conditions a) CICH2CHO, pyridine, 50°C, 24 h, 70% b) LiAlH4,80% c) MnOz, 56% d) PPTS, MeOH/benzene (1/2), reflux, 1.5 h, Dean-Stark trap, 91% e) m-CPBA, CH2CI2, 2 h f) CH2N2, 67% (two steps) g) Ca(OH)2, benzene, reflux, 0.5 h, Dean-Stark trap, 41% h) TFA/H2O (9 1), 50°C, 1 h, 78%...

The final example by Severin et al. indicates as to where the dynamic covalent synthesis of superstructures may lead to." Driven by a previous observation that boronic ester-based macrocycles with pendent aldehyde groups could be functionalized with amines, they investigated the possibility of performing boronic ester and imine condensation reactions simultaneously. In the first attempt, a mixture of 3-formylphenylboronic acid 14, pentaerythritol 15, and 1,4-diaminobenzene 16 in tetrahydrofuran/toluene was heated in a flask equipped with a Dean-Stark trap (Figure 8a). Analysis of the formed products revealed the formation of macrocycle 17 as a result of a [4-F2-F2] condensation with a yield of 44%. Prompted by this success, they performed the polycondensation reaction on a mixture of 4-formylphenylboronic acid 18, pentaerythritol 15, and tris(2-aminoethyl)amine 19, rather than the linear 1,4-diaminobenzene (Figure 8b). With a remarkable yield of 82%, the macrobicyclic cage 20 was spontaneously formed as a result of the condensation of six boronic acid molecules, three pentaerythritol molecules, and two triamine molecules. A total of 18 covalent bonds were... 

NaH has been recommended for the benzylation of carbohydrates Direct esterification of phenols occurs quite readily if the resulting water is removed by means of a Dean-Stark trap A simple preparation of ketenimines from amides and a convenient synthesis of azoxy compounds, including aromatic-aliphatic ones have been published. 

A mixture of phenylalanine, o-acetylbenzoic acid, acetic acid, and toluene refluxed 48 hrs., while the aq. condensate passes through a Dean-Stark trap -> N-protected phenylalanine (Y 82%) added to a mixture of 85%-hydrazine hydrate, acetic acid, and water, then refluxed 5 hrs. phenylalanine (Y 80%). F. e. s. C. A. Panetta and A. L. Miller, Synthesis 1977, 43. 

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