Sulfur trioxide-triethylamine

A variety of sulfating agents has been used for preparing sulfuric esters of polysaccharides.297 - 303 The methods employed include use of adducts of sulfur trioxide with such aprotic solvents as triethylamine,299 dimethyl... 

Transformations of Methyl 5-0-Benzyl-2-0-methyl-/3-I)-glueofuranosidurono-6,3-lae-tone (86) to Dimethyl (Z,E)-2-Methoxy-5-(phenylmethoxy)-2,4-hexadienedioatevl (87). ( Elimination employing DBU b oxidation with silver oxide-sodium hydroxide followed by diazomethane esterification c acidic glycoside cleavage, oxidation by dimethyl sulfoxide-acetic anhydride with formation of 5-0-benzyl-2-0-methyI-D-glucaro-1,4 6,3-dilactone, elimination by using DBU, followed by short treatment with diazomethane d elimination by DBU with subsequent diazomethane esterification e sodium borohydride in hexamethylphosphoric triamide 1 catalytic oxidation followed by short treatment with diazomethane " dimethyl sulfoxide-sulfur trioxide-pyridine-triethylamine.150)... 

A total of 10.0 g (8.9 mmol) SASRIN resin2 (note 1) was washed with N,N-dimethyIfonnamide (DMF 2 x 25 mL), methanol (MeOH 2 x 25 mL), and dichloromethane (DCM note 2 2 x 25 mL), and dried under vacuum (0.5 torr) at 70°C overnight. To a suspension of the dried SASRIN resin in lOOmL of methyl sulfoxide (DMSO note 2) and 25 mL of DCM was added 12.4 mL (89 mmol, 10.0 Eq.) triethylamine (note 2) followed by 7.1 g (44.5 mmol, 5.0 Eq.) sulfur trioxide-pyridine complex (note 2). The suspension was shaken on a radial arm at room temperature overnight (note 3) filtered on a glass frit and washed with DCM (3 x 100mL), DMSO (3 x lOOmL), DCM (3 x lOOmL), and tetrahydrofuran (THF 3 x 100 mL) and dried under vacuum (0.5 torr) at room temperature to give 10.0 g Ameba resin (notes 4 and 5). 

DCM (anhydrous), DMSO (anhydrous), triethylamine (99 + %), sulfur trioxide-pyridine complex, DMA (anhydrous), potassium tert-butoxide (95%), DCE (anhydrous), 2-(4-methoxyphenyl)ethylamine (98 + %), sodium triacetoxy-borohydride (95%), A/A-diisopropylethylamine (99%), p-toluenesulfonyl chloride (99 + %), and trifluoroacetic acid (99 + %) were obtained from Aldrich Chemical Company, Inc. 4-Hydroxy-2-methoxybenzaldehyde (>98%) was obtained from Fluka Chemie, AG. 

There are several methods reported in the literature for transforming vicinal diols into ct-diketones while avoiding the risk of C-C bond cleavage.26 Examples include the standard Swem conditions (dimethyl sulfoxide and oxalyl chloride followed by triethylamine), or the use of DMSO activated by acetic anhydride, pyridine-sulfur trioxide complex, or dicyclohexylcarbodiimide (Mq/J-att oxidation). Diones are also obtained by treatment with benzalacetone as a hydride acceptor in the presence of catalytic amounts of tris(triphenylphosphine)ruthenium dichlonde [(PPh RuCFl.27 Recent developments include the use of w-iodoxyben/.oic acid28 or the oxoammonium salt of 4-acctamidoletramethylpipcridine-1-oxyl and y -toluencNulfonic acid.29... 

To the product from Step 2 (26.0 g) containing with triethylamine (15.6 g) was added sulfur trioxide pyridine (37.6 g) slurried in 50 ml of DMSO over 15 minutes at 22 °C. Thereafter, 100 ml 2.5 M HCl was added, the mixture stirred 15 minutes, 100 ml EtOAc added, and the mixture again stirred 15 minutes. The aqueous layer was separated, concentrated, and the product isolated in 95% yield. 

One of the best activators fw dimethyl sulfoxide is the complex of sulfur trioxide/pyiidine, which in the presence of triethylamine rapidly oxidizes primary and secondary alcrdmls to aldehydes and ketones in very good yields at ambient temperature. This reagent also allows the very useM crmversion of allylic alcohols to the corresponding a, unsaturated carbonyl compounds. A further advantage of this procedure over many of the others is the ease of woiit-up, especially over the dimethyl sulfoxide-dicy-clohexylcarbodiimide method. 

Goh and Harvey effected the oxidation of the m-diol (3) to the o-quinone (4) efficiently by use of the sulfur trioxide-pyridine complex in DMSO-triethylamine. Use of DMSO-acetic anhydride (I, 305 2, 163-165 3,121-122) gave fair, but erratic yields of the quinones. Other reagents were completely unsuccessful. Note that oxidation... 

Boron trifluoride-triethylamine effects a ring-opening elimination of 4,4-difluoro-3-trifluoromethyl-l,2-oxathietane 2,2-dioxide to give fluorosulfonyl-trifluoromethylketene. Eliminations occur from intermediate 3-sultones, obtained by addition of sulfur trioxide to alkenes, to give alkenesulfonic acids. ... 

Bis-trifluoromethylmethylene)-1,2,4-thiadioxetane 1,1-dioxide (hexafluoro-isobutenylidene sulfate) (499) is a stable, colorless liquid obtained by treatment of bis(trifluoromethyl) ketene, 3,3,3-trifluoro-2-trifluoromethylpropanoic acid, or the anhydride of the latter with sulfur trioxide. It is said, on the basis of F nmr data, to be in equilibrium with a cyclic, eight-membered dimer (/Teq = 0.1321iter/mole at 34.5°C), analogous to the structure of the above-mentioned methylene sulfate . Hydrolysis of 499 gives 3,3,3-trifluoro-2-trifluoromethyl-propanoic acid. The cyclic sulfate is a powerful donor of sulfur trioxide, as exemplified by its reactions with fluoride, bromide, and iodide ions (but not chloride ions), triethylamine, dioxane, sulfolane, and alkenes (See... 

In a typical example, 10 mmol of an alcohol, 11 mmol of oxalyl chloride, and 24 mmol of DMSO in 40 mL of dichloromethane react at -60 °C. The mixture is then made alkaline with 50 mmol of triethylamine [1023] (equation 262). In other instances, the molar ratios of the alcohol to DMSO and to the activator (benzoic anhydride) were 1 47 and 1 17, respectively with phosphorus pentoxide as the activator, the respective molar ratios were 1 47 and 1 1 [1009], and with pyridine-sulfur trioxide, they were 1 70 and 1 3 [1018]. Dichloromethane and toluene [1012] are the best solvents. 

The sulfur derivative (87) is 1000 times as sweet as sugar and without the bitter after-taste of saccharin however, it was discovered that N-alkylation of (87) removed the sweetness. On the other hand, in the saccharins (88a)-(88e) containing substituents in the 4-position and 6-position, sweetness was retained after N-alkylation. Many sulfamic acid derivatives are sweet, and there have been numerous studies of structure-taste relationships which have highlighted the importance of molecular shape and stereochemistry (see Chapter 9, p. 162). Two sulfamates which are commercial, non-nutritive sweeteners are cyclamate (85) and acesulfame potassium (86) (Figure 11). Cyclamate (85) is manufactured by refluixing cyclohexylamine either with triethylamine-sulfur trioxide in dichloromethane or with sulfamic acid (see Chapter 9, p. 162). 

A certain number of recognition phenomena involve sugar sulfates. Synthetic examples are found in Chapter 17. Hydrogensulfates are prepared by treating an alcohol dissolved in DMF with sulfur trioxide in the presence of triethylamine (reaction 5.9). 

The complex formed by pyridine-sulfur trioxide was shown to activate DMSO for oxidation, when a base such as triethylamine is present.The presumed intermediate is 72. Reaction of the alcohol generates the usual complex (52). Deprotonation by triethylamine gives 65, and this gives the carbonyl product. Stereo-... 

On treatment with methyl sulfoxide activated by sulfur trioxide and triethylamine, " various partially acetylated hexopyranosides give 4,5-unsaturated 4-deoxy-6-aldehydo pyranosides by oxidation of the primary hydroxyl group. For instance, 131 gives 133 by way of the aldehyde 132. Chromatographically pure methyl 2,3-di-0-acetyl-4-deoxy-6-aZde-... 

Similar vinylog -elimination was observed on pyranoid and furanoid sugar derivatives. Perlin and coworkers described a double j8-elimina-tion on 2,3,4,6-tetra-O-acetyl-a-D-mannopyranose by treatment with methyl sulfoxide activated by sulfur trioxide-pyridine-triethylamine. 

Typical procedure. l,5-Dimethyl-4-methoxycyclohexa-2,4-dienylacetaldehyde 1884 [1399, 1401] To a solution of 2-(l,5-dimethyl-4-methoxycyclohexa-2,4-dienyl)ethanol (450 mg, 2.47 mmol) in anhydrous triethylamine (5 mL) and anhydrous dimethyl sulfoxide (5 mL) was added a solution of sulfur trioxide-pyridine complex (1.90 g,... 

Chlorosulfonic acid reacts with aliphatic and aromatic tertiary amines to form the corresponding amine-sulfur trioxide complexes 148 (Equation 58). " The dropwise addition of a solution of chlorosulfonic acid (one equivalent) in an inert organic solvent (e.g. chloroform or dichloromethane) to a stirred solution of the tertiary amine (two equivalents) in the same solvent at low temperature yields the complex (see Chapter 4, p 101), This procedure provides a convenient synthesis of the triethylamine-sulfiir trioxide complex in 75% yield. The complex is... 

E.E. Gilbert, Chem. Rev., 1962, 62, 549 (reviews the sulfonation of organic compounds by sulfur trioxide and its adducts with, for example, dioxan, pyridine, triethylamine). 

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