Sulfur trioxide with pyridine

Furan is resinified by sulfuric acid but it can be sulfonated with the complex of sulfur trioxide with pyridine or dioxane. Depending on conditions the 2-sulfonic or the 2,5-disulfonic acid may be obtained. Furan-2-carboxylic acid can be sulfonated with oleum. Benzo[6]furan is polymerized by sulfuric acid. The 2-sulfonic acid has been obtained by oxidation of the sulfinic acid available in turn by treatment of the lithio derivative with sulfur dioxide. Benzo[6]furan with the sulfur trioxide-pyridine complex allegedly affords the 3-sulfonic acid. 

The complexes of sulfur trioxide with various nucleophiles (dioxane, pyridine etc.) are mild sulfonating reagents. Unlike other complexes of sulfur trioxide, dimethyl sulfide-sulfur trioxide readily adds to conjugated multiple bonds. Consequently, not only the sulfo group but also the dimethyl sulfide group add at the multiple bond. The reactions of dimethyl sulfide-sulfur trioxide complex with butadiene, isoprene and 2,3-dimethylbutadiene take place as conjugated l,4- -additions of dimethyl sulfide and sulfonate groups at the double bonds of the diene (equation 103).124... 

Fuming sulfuric acid and sulfur trioxide are more reactive than sulfuric acid, frequently leading to polysulfonation. Formation of addition compounds of sulfur trioxide with suitable Lewis bases (nitromethane, pyridine, 1,4-dioxane), however, moderates its reactivity allowing clean monosulfonation. 

Formamide. Bottles containing a modified Karl Fischer reagent (pyridine, iodine, and sulfur trioxide) with formamide replacing methanol developed gas pressure during several months and exploded.6... 

Renilla luciferin was converted to luciferyl sulfate (204) by treatment of the diacetate (203) with sulfur trioxide in pyridine followed by removal of the acetyl group with ammonia (77TL2685). 

Peptide aldehydes can be synthesized by backbone attachment of the corresponding amino acetal to a BAL resin 30.b A modification of this method involves the preparation of a peptide alcohol (with the free alcohol group) by side-chain attachment, and after elongation of the peptide chain the alcohol is converted into the aldehyde using sulfur trioxide and pyridine.t l... 

Esterification of starch dialdehyde with chlorosulfonic acid in formamide gave a sulfate ester that could be transformed into an amide and methyl ester.532-536 The classical method of sulfonation, namely, by the action of sulfur trioxide in pyridine, is also applicable.537,538 Hemiacetals of starch dialdehyde result upon treatment with suitable alcohols in the presence of an acidic catalyst. In acetic media amides condensed with the carbonyl groups. Acetylation of starch dialdehyde with acetic anhydride is an obvious reaction. Esters with hexanedioic (adipic) acid were also prepared.537 Starch dialdehyde undergoes etherification with monochloroacetic acid in an alkaline medium.538... 

Chlorosulfonic acid, and in particular adducts of sulfur trioxide with dioxan or pyridine have been used for aliphatic sulfonation. These adducts, which are to be considered as betaine-like internal oxonium salts, very easily transfer... 

Form Supplied in crystalline white solid widely available. Preparative Methods reaction of chlorosulfonic acid and pyridine in CHCls or reaction of sulfur trioxide and pyridine. Handling, Storage, and Precautions corrosive reacts quantitatively with hot H2O to give pyridine and sulfuric acid. Use in a fume hood. 

Sulfur trioxide reactivity can also be moderated through the use of SO adducts. The reactivity of such complexes is inversely proportional to their stabihty, and consequentiy they can be selected for a wide variety of conditions. Whereas moderating SO reactivity by adducting agents is generally beneficial, the agents add cost and may contribute to odor and possible toxicity problems in derived products. CeUulosic material has been sulfated with SO.—trimethyl amine adduct in aqueous media at 0 to 5°C (16). Sulfur trioxide—triethyl phosphate has been used to sulfonate alkenes to the corresponding alkene sulfonate (17). Sulfur trioxide—pyridine adduct sulfates oleyl alcohol with no attack of the double bond (18). 

Both pyrrole and furan can be sulfonated in the 2-position by treatment with the pyridine-sulfur trioxide complex (Scheme 14). Furan can be further sulfonated by this reagent to give the 2,5-disulfonate. 

Sulfur trioxide pyridine complex [26412-87-3] M 159.2, m 155-165°, 175°. Wash the solid with a little CCI4 then H2O to remove traces of pyridine sulfate, and dry over P2O5 [Chem Ber 59 1166 1926 Synthesis 59 1979]. 

Sulfonation with sulfur trioxide, pyridine sulfur trioxide, pyridine bis-sulfur trioxide, and dioxane sulfur trioxide, which are useful sul-fonating agents for acidophobic substances, have been applied to the thiophene seriesd At room temperature the 2-monosulfonic acid (isolated as the barium salt) is obtained in 86% yield. Higher temperatures lead to a disulfonic acid. However, sulfonation with chloro-sulfonic acid appears to be more convenient,as the sulfonyl chloride obtained can be used directly for the preparation of derivatives. 

The sulfonating actions of pyridine-sulfur trioxide, pyridine-bis sulfur trioxide and dioxane sulfur trioxide on 2,5-dimethyIthiophene have been compared. Yields of 95% monosulfonic acid were obtained with the latter two reagents, whereas pyridine sulfur trioxide yielded only 75%. 2-Methyl-3,5-diphenylthiophene resists formylation and SnCl4 Catalyzed acylation in contrast to 2,3,5-trimethylthiophene, which is formylated and acylated quite easily. 

To a stirred solution of 4.6 g (0.01 mol) of anhydrous oxytetracycline in 40 ml of dry tetrahydrofuran is added 3.5 g (0.021 mol) of pyridine-sulfur trioxide complex. After 16 hours of stirring at room temperature, the resulting suspension is filtered, and the solid is slurried with 25 ml of 2% hydrochloric acid for 10 minutes, filtered and thoroughly washed with methanol followed by ether. The pale yellow crystalline 5-oxytetracycline-6, 12-hemiketal-12-sulfuric acid ester melts at 210°C. 

Using Sodium Iodide with Trifluoroacetic Anhydride or Sulfur Trioxide-Pyridine... 

Although the most characteristic reaction of the pyrrole nucleus is the predominant addition of electrophiles to the C-2 position, it is interesting to note that contrary to previous assumptions, sulfonation of pyrrole and its 1-methyl derivative with sulfur trioxide-pyridine complex affords mainly the 3-sulfonated pyrroles <00TL6605>. As Mizuno wisely points out, it is likely that some of the pyrrole-2-sulfonates reported previously are actually pyrrole-3-sulfonates. 

Interesting selectivity has been observed with some substituted carbohydrates. On treatment with sulfur trioxide-pyridine complex in A/,A/-dimethylformamide, methyl 4,6-O-benzylidene-a-D-... 

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). 

Numerous workers have demonstrated the applicability of electrospray ionization mass spectrometry (ESI/MS) for the detection and analysis of biomolecules with highly electronegative groups (reviewed by Wood et al., 2003, and for neutral steroids by Higashi and Shimada, 2004). The sensitivity of detection of neurosteroids can also be enhanced by derivatization when they are analyzed by nano-electrospray/mass spectrometry procedures. Neurosteroid sulfates can be easily prepared in a single-step reaction in pyridine with the N,N-dimethylformamide complex of sulfur trioxide (Chatman et al., 1999). Another elegant... 

Replacement of an allylic hydroxyl without saturation or a shift of the double bond was achieved by treatment of some allylic-type alcohols with triphenyliodophosphorane (PhjPHI), triphenyldiiodophosphorane (PhsPIj) or their mixture with triphenyl phosphine (yields 24-60%) [612]. Still another way is the treatment of an allylic alcohol with a pyridine-sulfur trioxide complex followed by reduction of the intermediate with lithium aluminum hydride in tetrahydrofuran (yields 6-98%) [67 J]. In this method saturation of the double bond has taken place in some instances [675]. 

Methacycline Methacycline, 4-dimethylamino-l,4,4a,5,5a,6,ll,12a-octahydro-3,6,10, 12,12a-pentahydroxy-6-methylen-l,ll-dioxo-2-naphthacencarboxamide (32.3.6), is synthesized from oxytetracycline (32.3.2), which is reacted with a sulfur trioxide— pyridine complex, resulting in an oxidation reaction. Simultaneous sulfonation gives a naphthacen-snlfotetrahydrofuran derivative intermediate (32.3.5), which when reacted with hydrofluoric acid forms methacycline (32.3.6) [222-225]. 

Indeed, where reactions at a ring carbon take place under relatively mild conditions, special circumstances are at work. For example, 2,6-tert-butylpyridine combines with sulfur trioxide in liquid sulfur dioxide at -10 C to give the corresponding 3-sulfonic acid (Scheme 2.3). An explanation is that the bulky tert-butyl groups prevent access of the large electrophile to N-1. Steric hindrance is much less at C-3 and sulfonation is diverted to this site using the free pyridine as the substrate. 

For example, 3-bromopyridine is formed when pyridine is reacted with bromine in the presence of oleum (sulfur trioxide in cone, sulfuric acid) at 130 °C (Scheme 2.4). Direct electrophilic substitution is not involved, however, aszwitterionic (dipolar) pyridinium-A-sulfonate is the substrate for an addition of bromide ion. Subsequently, the dihydropyridine that is formed reacts, possibly as a dienamine, with bromine to generate a dibromide, which then eliminates bromide ion from C-2. It is notable that no bromination occurs under similar conditions when oleum is replaced by cone, sulfuric acid alone instead, pyridinium hydrogensul-fate is produced. 

Sulfation with Pyridine/Sulfur Trioxide Complex... 

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