Sulfur with pyridine

Another important example of a redox titration for inorganic analytes, which is important in industrial labs, is the determination of water in nonaqueous solvents. The titrant for this analysis is known as the Karl Fischer reagent and consists of a mixture of iodine, sulfur dioxide, pyridine, and methanol. The concentration of pyridine is sufficiently large so that b and SO2 are complexed with the pyridine (py) as py b and py SO2. When added to a sample containing water, b is reduced to U, and SO2 is oxidized to SO3. 

These precursors are prepared by reaction of fuming nitric acid in excess acetic anhydride at low temperatures with 2-furancarboxaldehyde [98-01-1] (furfural) or its diacetate (16) followed by treatment of an intermediate 2-acetoxy-2,5-dihydrofuran [63848-92-0] with pyridine (17). This process has been improved by the use of concentrated nitric acid (18,19), as well as catalytic amounts of phosphoms pentoxide, trichloride, and oxychloride (20), and sulfuric acid (21). Orthophosphoric acid, -toluenesulfonic acid, arsenic acid, boric acid, and stibonic acid, among others are useful additives for the nitration of furfural with acetyl nitrate. Hydrolysis of 5-nitro-2-furancarboxyaldehyde diacetate [92-55-7] with aqueous mineral acids provides the aldehyde which is suitable for use without additional purification. 

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). 

Isoxazole compounds can be converted into the corresponding isothiazoles by successive catalytic hydrogenation, sulfuration with phosphorus pentasulfide and oxidation with chloranil (72AHC(14)l, 75SST(3)541). 2,1-Benzisoxazoles give the 2,1-benzisothiazoles directly, by the action of phosphorus pentasulfide in either pyridine or molten imidazole (73SST(2)556, 77SST(4)339). (See also Chapter 4.16 for further discussion of these topics.)... 

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. 

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

Reaction of compound 37 with bromine in chloroform results in mono-bromination a to the sulfur. Treatment of this brominated derivative with NaBH3CN in AcOH gives a mixture of products resulting from reduction of the C=N double bond and of elimination of HBr. Reaction of 44 with sodium ethoxide results in the ethoxy-substituted derivative 45, whereas reaction with pyridine gives the dehydrobrominated derivative 46. Reaction of either 44 or 46 with sodium cyanide in dimethyl sulfoxide (DMSO) gives the cyano-derivative 47 <1983HCA971> (Scheme 13). 

This intramolecular interaction of heteroatoms may be distorted by introducing different substituents onto the 4,6-positions of the ring. In the case of acceptor substituents, (CC13) dioxaboraphosphorinane (97) is not alkylated at the phosphorus atom and is inert to sulfur at the same time it forms a stable complex with pyridine [Eq. (96)]. In the case of donor substituents (Aik) (93)—(94), by contrast, the corresponding sulfides have been obtained and the pyridine complex is formed only with four-coordinated phosphorus derivatives. 

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). 

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]. 

Figure 5.8 Three recognition motifs based on (a) hydrogen bonding interactions between 2,6-diaminopyridine and thymine, (b) metal coordination of suUur-carbon-sulfur (SCS) Pd pincer with pyridine, (c) pseudorotaxane formation between dibenzo[24]crovvn-8 (DB24C8) and dibenzylammonium ions, and (d) fuUy functionaUzed terpolymer 5.

Sulfation with Pyridine/Sulfur Trioxide Complex... 

Scheme 4 Sulfation of the N -Protected CCK-Heptapeptide with Pyridine/Sulfur Trioxide Complex1881 Ac—Tyr—Met—Gly—Trp—Met—Asp—Phe—NH2 5...

Figure 6 Rates of Sulfation of the Hirudin-Peptides with Pyridine/Sulfur Trioxide and of Epimerization of the C-Terminal Asu Residue1931"...

Scheme 12 Postsynthetic Protection of Unsulfated Human CCK-33 at Amino and Hydroxy Groups prior to Sulfation with Pyridine/Sulfur Trioxide Complex Followed by Suitable Deprotection Steps 551...

Nitration of pyridines in other than nitric or sulfuric acids is of little interest here because either no reaction or N-nitration takes place (see Section 2.05.2.10). However, pyridine 1-oxide is considerably more reactive and treatment with benzoyl nitrate ultimately leads to the 3-nitro derivative (Scheme 25) (60CPB28). Annelation of a benzene ring bestows greater reactivity on the 3-position in quinoline, compared with pyridine, and reaction with nitric acid in acetic anhydride furnishes the 3-nitro derivative (ca. 6%) (Scheme 26). This isomer has also been obtained, again at low yield (6-10%), by treatment of quinoline with tetranitratotitanium(IV) in carbon tetrachloride (74JCS(P1)1751>. Nitration of benzo analogues of pyridine occurs much more readily in the benzene ring, and Chapter 2.06 should be consulted for these reactions. 

---