By pyridine hydrochloride

A mixture of 6 g. of dry pyridine hydrochloride and 3 g. of cannabidiol (M. P. 66-67°) was heated at 125° for one hour The Beam test (purple color with 5% alcoholic potassium hydroxide) had entirely disappeared after a relatively short time. The product was then washed with water to free it from pyridine hydrochloride, extracted with ether and the ether solution washed with water. After evaporation of the solvent, the product was distilled in high vacuo, whereupon hydrogen chloride was evolved. The distillate was a highly viscous, colorless oil with a B.P approximately the same as that reported in the experiments using hydrochloric acid in ethanol for cyclization. Upon separating into six fractions, the specific rotations were as follows [a]32D—235 °, - 236 °, - 235 °, —241 °, —244 °, —249 °. 

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On heating, the chlorosulfinate is catalytically decomposed by pyridine hydrochloride to the corresponding alkyl chloride and sulfur dioxide (see Eq. 6). Secondary chlorosulfites give olefins even under the mildest conditions [11], The use of excess pyridine reduces the yield of sulfite by the method described in Eq. (4). 

The methoxy derivatives may be treated directly o-methoxyphenyl-acetone, heated with hydrobroniic acid in acetic acid, gives 2-methyl-benzofuran.326 o-Methoxylated phenylacetones are readily prepared by glycidic synthesis from o-methoxylated aromatic aldehydes the intermediate glycidic ester (127) can be directly converted by pyridine hydrochloride into a 2-alkylbenzofuran in 40-80% yield.105... 

A variant of this method produces xanthones from 2-halogeno-2 -methoxybenzo-phenones, cyclization being brought about by pyridine hydrochloride (72BSF2948). 

The 3-methoxy-5-phenyl isomer (114) was synthesized from the thio compound59 197 (113), which was hydrolyzed to 115 by pyridine hydrochloride. Diazomethane, acting on 3-hydroxy-5-phenyloxadiazole (115)... 

Hydroxybenzo[6]thiophene has been isolated from coal tar.42 It may be prepared from 6-aminobenzo[fr]thiophene by standard procedures.241 6-Methoxybenzo[h]thiophene may be prepared by decarboxylation of the corresponding 2-carboxylic acid,341 and 6-ethoxybenzo[6]thiophene is obtained by reduction of 6-(ethoxy)-thioindoxyl (Section VI, 1,2). 6-Methoxy-5-methylbenzo[6]thiophene is obtained by cyclization of (3-methoxy-4-methylphenylthio)-acetaldehyde dimethyl acetal (Section IV,B).617 The product previously described542 as 6-hydroxy-3-phenylbenzo[6]thiophene has now been shown to be the 2-phenyl isomer.307 6-Methoxy-818 and 6-methoxy-5-methyl-benzo[6]thiophene617 are demethylated by pyridine hydrochloride. 

For practical reasons, hydrochloric acid was sometimes replaced by pyridine hydrochloride. Acetylcyclopropane (27) gave 5-chloropentan-2-one (28) in high yield when treated with this... 

Klemenc14 observed fission when melting aniline hydrochloride with ethers,13 this method being especially suitable for ethers that afford volatile alkyl halides the reaction occurs more readily if dry, gaseous hydrogen chloride is passed through the mixture.15 The aniline hydrochloride may be replaced by pyridine hydrochloride or hydrobromide at temperatures around 200°. 

Cleavage of a tricyclic ether. The tricyclic ether (1) is cleaved by pyridine hydrochloride mainly to 9a-acetoxypinene (2) fenchyl chloroacetates, (3a) and... 

Cleavage of methyl ethers. Methyl ethers of methoxyformylbenzofuranes such as (1) are cleaved to the corresponding phenol in higher yield by pyridine hydrochloride in quinoline at the boiling point than by neat reagent. ... 

Selective N-dealkylation in the presence of N-aryl linkages may be induced by pyridine hydrochloride, and selective N-debenzylation by thiophenoxide anion. ... 

Chloromethyl)pyridine hydrochloride [1822-51-1] M 164.0, m 170-175°, 172-173°, pK , -5.6. Purified by recrystn from EtOH or EtOH-dry Et20. It melts between 171° and 175° and the clear melt resolidifies on further heating at 190° and turns red to black at 280° but does not melt again. The picrate-hydrochloride (prepared in EtOH) has m 146-147°. The free base is an oil, [Mosher and Tessieri J Am Chem Soc 73 4925 1951.]... 

Typically in such a process the bis-phenol A is dissolved in about ten times its weight of pyridine and vigorously stirred at 25-35°C. Phosgene is then bubbled into the solution and in a few minutes the pyridine hydrochloride starts to precipitate. As polymer is formed the viscosity of the solution increases and eventually becomes too great for stirring. The polymer is then recovered by the addition of a solvent such as methyl alcohol which dissolves the pyridine hydrochloride but precipitates the polymer. 

The striking effect of the catalyst is exemplified by the reaction of pregna-4, 16-diene-3,20-dione (10) with benzyl mercaptan. In the presence of piperidine only conjugate addition occurs to give (11) whereas with pyridine hydrochloride only the 3-benzyl thioenol ether (12) is formed. In the presence of p-toluenesulphonic acid both reactions take place to yield (13). 

Reaction of the potassium salt of salicylaldehyde with chlo-roacetone affords first the corresponding phenolic ether aldol cyclization of the aldehyde with the ketonic side chain affords the benzofuran (1). Reduction of the carbonyl group by means of the Wolf-Kischner reaction affords 2-ethyl-benzofuran. Friedel-Crafts acylation with anisoyl chloride proceeds on the remaining unsubstituted position on the furan ring (2). The methyl ether is then cleaved by means of pyridine hydrochloride (3). lodina-tion of the phenol is accomplished by means of an alkaline solution of iodine and potassium iodide. There is thus obtained benziodarone (4)... 

The mixture was cooled to 7°C, extracted with two 500-oc portions of ice water to remove pyridine hydrochloride, and the benzene solution of 3-o-methoxyphenoxy-2-hy-droxypropyl chlorocarbonate was added to 500 ml of cold concentrated ammonium hydroxide. The mixture was vigorously stirred at 5°C for 6 hours, then the crude white precipitate of 3-o-methoxyphenoxy-2-hydroxypropyl carbamate was filtered off, dissolved in 1,500 ml of hot benzene and completely dried by codistillation of last traces of water with benzene, treated with decolorizing carbon and filtered while hot. On cooling 160 g of product crystallized as white needles melting at 88° to 90°C. 

The combined liquors, which comprise an aqueous hydrochloric acid solution of 3-amino-methyl-pyridine hydrochloride, are then heated to a temperature of 60° to 65°C, and ethyl nitrite gas is passed into the heated solution. The ethyl nitrite is generated by placing 20 liters of 90% ethyl alcohol in a suitable vessel, diluting with 200 liters of water, and, while stirring, adding to the dilute alcohol 18.3 kg of nitrosyl chloride at the rate of 2.25 kg per hour. (The process using methyl nitrite is carried out by substituting a stoichiometrically equivalent quantity of methyl alcohol for the ethyl alcohol.)... 

A solution of 2 grams of A -19-norandrosten-3,17-dione and 0.4 gram of pyridine hydrochloride in 50 cc of benzene free of thiophene was made free of moisture by distilling a small portion 4 cc of absolute alcohol and 4 cc of ethyl orthoformate were added and the mixture was refluxed during 3 hours. 5 cc of the mixture were then distilled and after adding an additional 4 cc of ethyl orthoformate the refluxing was continued for 2 hours longer. The mixture was evaporated to dryness under vacuum and the residue was taken up in ether, washed, dried and evaporated to dryness. The residue was crystallized from... 

A solution of 82 parts by weight of 7-chloromethyl-pyridine-hydrochloride in 60 parts of water is added dropwise, at 0 to 5°C, to 250 parts by weight of a 50% aqueous ethyl amine solution. The mixture is stirred for 1 hour at 60°C, whereupon it is cooled down and separated in the cold with solid potassium hydroxide. The oil formed is separated off, dried over potassium hydroxide and distilled. The ethyl-(7-picolyl)-amine formed boils over at 103° to 104°C under a pressure of 13 mm Hg. Its dihydrochloride melts at 198° to 200°C. 

A selective introduction of a chlorine atom at C-6 could be achieved (65) by treating 11 (and the / -anomer) with sulfuryl chloride in pyridine at — 70°C. followed by treatment of the resulting tetrachlorosulfate (83) with one mole of pyridine hydrochloride which gave 84. Heating of 84 with pyridine hydrochloride in chloroform resulted in further substitution by chloride to give 78 after dechlorosulfation. The above illustrated transformations support the proposed mechanism (65) for... 

Acidic treatment of prechilenine (139) (Section III,C) afforded the imino keto acid 377 via the imminium salt 140 (Scheme 68). Neutralization and work-up furnished the known y-lactol 371 in 90% overall yield from 139 (96, 181). Kondo et al. (183) obtained 139 from the epidioxide 122 by treatment with pyridine hydrochloride in pyridine along with 377 and norhydrastine. The acid 377 was converted to the known imino ester 373 through N,0-dimethylation. 

B. l-Eihyl-3-(3-dinuthylamino)propylcarbodiimide hydrochloride. A suspension of 34.6 g. (0.300 mole) of pyridine hydrochloride (Note 7) in 280 ml. of methylene chloride is prepared in a 1-1. Erlenmeyer flask. To this is slowly added 46.5 g. (0.300 mole) of l-ethyl-3-(3-dimethylamino)propylcarbodiimide. The resulting solution is diluted with anhydrous ether (Note 8) and stored at 0-5° for 16-20 hours. The crystalline product is collected by filtration in a dry atmosphere (Note 9), washed with a little anhydrous ether, and dried under reduced pressure over phosphorus pentoxide. The yield is 50.5-55.5 g. (88-96.5%), m.p. 104-109° (Notes 10 and 11). This material is sufficiently pure for most purposes. 

Wittig olefination of 2-nitro-Z-cinnamaldehyde (1300) with the phosphonium bromide 1301 led to the diene 1302. The Diels-Alder cycloaddition of 1302 with maleimide (1303), followed by dehydrogenation with DDQ, afforded the phthali-mide 1304. Double deoxygenation of 1304 with triphenylphosphine (PPhs) in collidine gave O-methylarcyiiaflavin B (1305). Finally, heating of 1305 with molten pyridine hydrochloride led to arcyriaflavin B (346) (759) (Scheme 5.215). 

Bromination of pyridine is much easier than chlorination. Vapour phase bromination over pumice or charcoal has been studied extensively (B-67MI20500) and, as with chlorination, orientation varies with change in temperature. At 300 °C, pyridine yields chiefly 3-bromo-and 3,5-dibromo-pyridine (electrophilic attack), whilst at 500 °C 2-bromo- and 2,6-dibromo-pyridine predominate (free radical attack). At intermediate temperatures, mixtures of these products are found. Similarly, bromination of quinoline over pumice at 300 °C affords the 3-bromo product, but at higher temperatures (450 °C) the 2-bromo isomer is obtained (77HC(32-1)319). Mixtures of 3-bromo- and 3,5-dibromo-pyridine may be produced by heating a pyridine-bromine complex at 200 °C, by addition of bromine to pyridine hydrochloride under reflux, and by heating pyridine hydrochloride perbromide at 160-170 °C (B-67MI20500). 

A mixture of 56.5 mmol of the 2/7-3,l-benzoxazine-2,4(l//)-dione 1 (R1 = H, CH3), 6.53 g (56.5 mmol) of pyridine hydrochloride and 7.15 g (62.2 mmol) of (S )-2-pyrrolidinecarboxylic acid is refluxed in pyridine for 6 h. After cooling and evaporation of the pyridine in vacuo, the resulting semisolid is partitioned between water and CHC13. The organic extract is washed with two 15-mL portions of 1M aq hydrochloric acid, followed by brine, and then dried over MgS04, filtered and concentrated to give a solid which, when triturated with ethyl acetate, gives the analytically pure product. 

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