Penta pyridines

Bromopyridine has been made by direct bromination of pyridine - from N-methyl-2-pyridone with phosphorus penta-bromide and phosphorus oxybromide from 2-aminopyridine by diazotization with amyl nitrite in 20% hydrobromic acid from sodium 2-pyridinediazotate by solution in concentrated hydrobromic acid and from 2-aminopyridinc by diazotization in the presence of bromine and concentrated hydrobromic acidd The method described here is essentially that of Craig. 

Abbreviations aapy, 2-acetamidopyridine Aik, alkyl AN, acetoniuile Ar, aryl Bu, butyl cod, 1,5-cyclooctadiene COE, cyclooctene COT, cyclooctatetraene Cp, cyclopentadienyl Cp , penta-methylcyclopentadienyl Cy, cyclohexyl DME, 1,2-dimethoxyethane DME, dimethylformamide DMSO, dimethyl sulfoxide dmpe, dimethylphosphinoethane dppe, diphenylphosphinoethane dppm, diphenylphosphinomethane dppp, diphenylphosphinopropane Et, ethyl Ec, feirocenyl ind, inda-zolyl Me, methyl Mes, mesitylene nb, norbomene orbicyclo[2.2.1]heptene nbd, 2,5-norbomadiene OTf, uiflate Ph, phenyl PPN, bis(triphenylphosphoranylidene)ammonium Pi , propyl py, pyridine pz, pyrazolate pz, substituted pyi azolate pz , 3,5-dimethylpyrazolate quin, quinolin-8-olate solv, solvent tfb, teti afluorobenzobaiTelene THE, tetrahydrofuran THT, tetrahydrothiophene tmeda, teti amethylethylenediamine Tol, tolyl Tp, HB(C3H3N2)3 Tp , HB(3,5-Me2C3HN2)3 Tp, substituted hydrotiis(pyrazol-l-yl)borate Ts, tosyl tz, 1,2,4-triazolate Vin, vinyl. 

Likewise, azepine-2-thiones, e. g. 18, obtained by treating azepin-2-ones with phosphorus penta-sulfide in refluxing pyridine, yield the 2-(ethylsulfanyl) derivatives.77,227... 

Alternatively, penta-O-acetyl-galactose can be converted to the known 2,3,4,6-tetra-O-acetylgalactopyranosyl azide59 which after treatment with sodium methoxide in methanol and subsequent pivaloylation with pivaloyl chloride in pyridine, also furnishes the O-pivaloylated galactosyl azide60. 

Chloro-1 -methyl-3-trifluoromethyl- //-[ 1,3,4]oxadiazmo[5,6-fc]quinoxaline (570) suffered thiolytic ring fission in refluxing pyridine (containing phosphorus penta-sulfide) during 1 h to provide 7-chloro-3-[7/-methyl-A( -(triiluoroacetyl)hydrazino]-2(17/)-quinoxalinethione (571) in 87% yield. ... 

Halo-substituted phthalazines react with two equivalents of ynamines to give penta-substituted pyridines 17 through N-N bond cleavage of the pyridazine ring <96H(43)199>. 

DL-Valiolamine (205) was synthesized from the exo-alkene (247) derived from 51 with silver fluoride in pyridine. Compound 247 was treated with a peroxy acid, to give a single spiro epoxide (248, 89%) which was cleaved by way of anchimeric reaction in the presence of acetate ion to give, after acetylation, the tetraacetate 249. The bromo group was directly displaced with azide ion, the product was hydrogenated, and the amine acety-lated, to give the penta-A, 0-acetyl derivative (250,50%). On the other hand. 

Preparation of acetylated nitriles from oximes with pyridine-acetic anhydride. Penta-acelyl-n-glucosaminonitrile. One gram of D-glucosamine oxime hydrochloride was treated with 6 ml. of pyridine and 6 ml. of acetic anhydride and kept at 20° until solution had occurred. The solution was then concentrated and the crystalline residue was recrystallized from ethanol yield 1.8 g. (84%), m. p. 126°. 

The Glaxo synthesis of zanamivir (2) started with the esterification of commercially available A-acetyl-neuraminic acid (88) with methanolic HCl to give the methyl ester as shown in Scheme 7.14 (Chandler and Weir, 1993 Chandler et ah, 1995 Patel, 1994 Weir et al., 1994). Global acetylation of all the hydroxyl groups with acetic anhydride in pyridine with catalysis by 4-(dimethylamino)pyridine (DMAP) led to the penta-acetoxy compound 89. Treatment of 89 with trimethylsilyl triflate in ethyl acetate at 52°C introduced the oxazoline as well as the 2,3-double bond to provide 86. Addition of trimethysilyl azide to the activated allylic oxazoline group led to the stereoselective introduction of azide at the C-4 position to afford 83 as in Scheme 7.13. 

Only a little 3,5-di- and penta-iodopyridine is obtained when pyridine reacts with iodine in the vapour phase. Treatment of pyridine with iodine in 50% oleum furnishes 3-iodo-(18%) and some 3,5-di-iodo-pyridine. This is probably the result of electrophilic substitution by I+, with oleum performing in the role already discussed (57JCS387). The products of iodination of quinoline are not well defined however, a reviewer (77HC(32-1)319) has pointed out that one such product (formed by heating quinoline with iodine and potassium iodide at 160-170 °C in the presence of mercury(II) chloride) has a melting point identical with that of 3-iodoquinoline. 

Pyridine-3-sulfonic acid is converted to the sulfonyl chloride with phosphorus penta-chloride and the 2-isomer results from treatment of the corresponding sodium sulfonate... 

When maltose was treated with 8 molar equivalents of benzoyl chloride in pyridine at —40°, it afforded octa-0-benzoyl-/3-maltose, l,2,6,2, 3, 4, 6 -hepta-0-benzoyl-/3-maltose, and l,2,6,2, 3, 6 -hexa-0-benzoyl-/3-maltose in yields of 3, 79, and 12%, respectively.69 Similar treatment of methyl /3-maltoside with 7 molar proportions of benzoyl chloride in pyridine gave crystalline methyl 2,6,2, 3, 4, 6 -hexa-0-benzoyl -/3 - maltoside and methyl 2,6,2, 3, 6 -penta-O -benzoyl -/3 -maltoside in yields of 71 and 23%, respectively.69 Analysis of the relative yields of the products of these reactions suggests that, after HO-3, the 4 -hydroxyl group in maltose and methyl /3-maltoside is the most hindered. Benzoylation of methyl 4, 6 -0-benzylidene-/3-maltoside with 10 molar proportions of reagent gave 2,6,2, 3 -tetra-0-benzoyl-4, 6 -0-benzylidene-/3-maltoside (71%) and an equimolar mixture (22%) of the 2,6,2 - and 2,6,3 -tribenzoates. These results indicated that the order of reactivity of the hydroxyl groups towards acid halides in pyridine is HO-2, HO-6 > HO-2 HO-3 > HO-3. 

Replacement of a hydroxy with a thiol group, using phosphorus penta-sulfide in refluxing pyridine, has been reported for pyrazolo[4,3-c]pyrid-4-(54-75%)144,146 and pyrazolo[3,4-c]pyrid-7-ones (67%). 10... 

The transformation of one hetero substituent into another is a reaction frequently observed in the 1,2,4-triazine series. Oxo group transformations are indicated in Scheme 8. They can be transformed into thioxo groups by phosphorus pentasulfide or Lawesson s reagent. Pyridine seems to be the best solvent for the phosphorus pentasulfide reaction and a small amount of water (0.1% or less) seems to improve results. An oxygen in the 5-position is more easily replaced than one in the 3- or 6-position. Transformation of the oxo (hydroxy) group into a chloro substituent is achieved by phosphorus oxychloride, phosphorus penta-chloride, or thionyl chloride and DMF. In this reaction also the oxygen is most reactive in the 5-position. 

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