3-Methyl-7-iodo pyridine

Fig. 11-1. Intramolecular electronic effects in the adsorption of meta- and para-% ih-stituted pyridines on (a) alumina and (b) silica (15,24). 1, 4-amino 2, 3, 4-dimethyl 3, 4-methyl 4, 4-ethyl 5, 3-methyl 6, pyridine 7, 3-hydroxy 8, 4-chloro 9. 4-aldehyde 10,3-acetyl 11,3-iodo 12,3-aldehyde 13, 3-chloro 14, 3-bromo 15. 4-cyano 16, 3-cyano 17, 3,5-dichloro. [The plots do not include points for the compound 3-aminopyridine see discussion of Ref (/5).]...

Chloro- and bromoaminopyridines are oxidized by persulfuric acid at 0° to their nitro derivatives thus, 3-chloro-, and 3-bromo-4-aminopyridine are converted to the respective 3-halo-4-nitropyridines. However, 4-araino-3-iodo-pyridine is not oxidized under these conditions. 4-Amino-2,3,5,6-tetrafluoro-pyridine is difficult to oxidize and requires refluxing peroxytrifiuoroacetic acid for 22 hours in order to yield the 4-nitro derivative. Potassium bromate has been used to oxidize S-amino-3-methyl-2-pyridone, but the product was not a nitro compound instead 3-hydroxy-6-methyl-2-aza-l,4-benzoquinone-4-(2,6-di-hydroxy-5-methyl-3-pyridyl)imine (IX-S7) was obtained. ... 

Methyl-5-(4-pyridyl)-7-aza- 2-Araino-3-iodo-6-methyl-,S- (4-pyridyl)pyridine Trimethylsilylethyne. Pd(PPh,)jCl4, Cut 96,40 ... 

Halothiophenes, which are not activated through the presence of —I—M-substituents, undergo substitution smoothly under more forcing conditions with copper salts in pyridine or quinoline. Hence 3-cyanothiophene and 5-methyl-2-cyanothiophene have been obtained from the corresponding bromo compounds. 2-Bromothiophene reacts readily with aliphatic cuprous mercaptides in quinoline at 200°C to give thioethers in high yields. The use of the copper-catalyzed Williamson synthesis of alkoxythiophenes from iodo- or bromo-thiophenes and alcoholate has been mentioned before. The reaction of 2-bromothiophene with acetanilide in nitrobenzene in... 

Methyl 5-deoxy-2,3-0-isopropylidene l3-T>-erythro-pent-4-enofurano-side (43). A solution of methyl 5-deoxy-5-iodo-2,3-0-isopropylidene-/ -D-ribofuranoside (42) (30) (1.0 grams) in pyridine (10 ml.) was shaken for 7 hours at room temperature with anhydrous silver fluoride (1.5 grams). Isolation of the product as described previously afforded the 4-ene (43) as a sirup (414 mg., 70%) which distilled at 40°C. (bath) at 0.1 mm. G.l.c. showed the presence of a major component (95%) together with 5% of another component which was not investigated. [ ]D21 + 26.3° (c, 2.3). Anal Calcd. for C9H1404 C, 58.05 H, 7.6. Found C, 57.9 H, 7.7. 

Pyrrolo[3,2-f]pyridine can be readily substituted with a variety of electrophiles at C-2 or C-3 after protection of the ring nitrogen atom. Derivatives can be synthesized with substituents such as iodo, methyl, trimethyltin, formyl, and allyl groups. The reactions proceed with excellent yields (47-95%) <200583581 >. 

The Michaelis-Arbuzov reaction of methyl 5-deoxy-5-iodo-2,3-0-isopropylidene-/ -D-ribofuranoside38 (43) with diethyl ethylphosphonite gave,35 in 80% yield, the 5-C-[(ethoxy)ethylphosphinyl] derivative which, on treatment with SDMA and then mineral acid, yielded (30%) 5-deoxy-5-C-[(RS)-ethylphosphinyl]-D-ribopyranose (44) as a mixture of diastereoisomers. These compounds showed no mutarotation in methanol during 24 h. Upon treatment with acetic anhydride-pyridine, the product, 44, was converted (90% yield) into a syrup, presumably consisting of four diastereoisomers of the peracetate 45, separation of which was not attempted. Treatment of 45 with sodium methoxide in methanol regenerated 44 quantitatively. 

The iodo derivative is a useful intermediate for the preparation of a wide variety of different types of compounds. Primary mesyl esters also react with sodium iodide in acetone, but the selectivity of this cleavage is less because of the greater reactivity of secondary mesyl esters. oa( ) Methyl 2,3,4-tri-0-acetyl-6-0-mesyl-a-D-glucopyranoside is converted into methyl 2,3,4,6-tetra-O-acetyl-a-D-glucopyranoside with acetic anhydride and potassium acetate. Replacements of a primary mesyloxy group with fluorine by use of potassium fluoride in methanol,106 with chlorine by use of lithium chloride,102 and with pyridine to form a pyri-dinium deoxy derivative,106 have been reported. Primary tosyloxy groups have been replaced by hydrogen,106 by thiocyanate,107 and by... 

Barluenga et al.565 have reported the selective monoiodination of arenes with bis (pyridine)iodonium(I) tetrafluoroborate [I(py2)BF4] in excess superacids (2 equiv.) [Eq. (5.210)]. Comparable results were found for activated compounds with both HBF4 and triflic acid, whereas triflic acid was more effective in the iodination of deactivated aromatics. For example, nitrobenzene and methyl benzoate are unreactive in HBF4 but give the corresponding iodo derivatives in triflic acid (83% and 84% yields, respectively, in 14 h). Iodination of phenol required low temperature (-60°C). 

Compound 85 was dehydrogenated at 300° over palladium black under reduced pressure to a pyridine derivative 96 which was independently synthesized by the following route. Anisaldehyde (86) was treated with iodine monochloride in acetic acid to give the 3-iodo derivative 87. The Ullmann reaction of 87 in the presence of copper bronze afforded biphenyldialdehyde (88). The Knoevenagel condensation with malonic acid yielded the unsaturated diacid 91. The methyl ester (92) was also prepared alternatively by a condensation of 3-iodoanisaldehyde with malonic acid to give the iodo-cinnamic acid (89), followed by the Ullmann reaction of its methyl ester (90). The cinnamic diester was catalytically hydrogenated and reduced with lithium aluminium hydride to the diol 94. Reaction with phosphoryl chloride afforded an amorphous dichloro derivative (95) which was condensed with 2,6-lutidine in liquid ammonia in the presence of potassium amide to yield pyridine the derivative 96 in 27% yield (53). 

One of the earliest reported preparations of the requisite glycosidation precursor 5-deoxy-l,2,3-tri-0-acetyl-p-D-ribofuranoside (17) was published by Kissman and Baker in 1957.23 D-Ribose was heated at reflux in a methanol/acetone mixture in the presence of concentrated HCI to provide methyl 2,3-O-isopropylidene-D-ribofuranosidc (21), which was in turn converted to the corresponding 5-O-mesyl ribofuranoside 22 with methanesulfonyl chloride in pyridine in 63% yield. The sulfonate moiety of 22 was then displaced with sodium iodide in refluxing DMF to provide 5-deoxy-5-iodo derivative 23 in 76% yield on a multigram scale. Reductive dehalogenation of 23 was accomplished under heterogeneous catalytic hydrogenation conditions to provide the reduced 2,3-0-protected intermediate 24 in 56% yield, which was subjected to hydrolysis conditions in... 

Pyridine and its derivatives react with 1,3-pentadienes forming cyclic products. This type of cyclization was observed by the authors of 95JFC(72)49. They showed that in the reaction of (Z)-1,1,2,5,5,5-hexafluoro-4-phenyl-3-trifluoromethyl-1,3-pentadiene 117 with pyridine the products are [ S,9aR]- and [lS,9tfS]-3-fluoro-9<2-hydro-l,2-bis(trifluoro-methyl)-l-phenyl-4//-quinolizin-4-ones 118 and 119 with 54 and 21% yields, respectively. The structure of the compounds was confirmed by X-ray analysis. Similarly, the reaction of (Z)-l,l,2,5,5,5-hexafluoro-4-iodo-3-trifhioromethyl-l,3-pentadiene 120 with 4-substituted pyridines gives the derivative of 4//-quinolizin-4-one 121 with quinoline, the product is derivative 122. 

An interesting study of conformationally mobile systems involves iodo-methylation of nicotine derivatives 47, where steric effects of substituents at position-2 and -6 modify the alkylation rate at the pyridine nitrogen and at the two nitrogens (N trans and N cis) of the pyrrolidine conformers (80JA7741 81JOC3040) (Scheme 26b). 

Regio- and stereo-controlled iodocyclizations of allylic trichloroacetimidates provide a route to cw-hydroxyamino sugar from hexenopyranosides. For example, conversion of the hydroxyl of compound 117 into the trichloroacetimidate 118 followed by IDCP-mediated intramolecular cyclization, gives iodo-oxazoline derivative 119, which is reduced (Bu3SnH) and hydrolyzed (pyridine, TsOH) to afford IV-acetyldaunosamine methyl glucoside 120 (O Scheme 57) [95]. 

---