Chloro-, hydration

The reaction mixture is boiled for half an hour under reflux. Thereafter the ether is removed by distillation, until the inside temperature reaches 65°-70°C. The resulting benzene solution is added to 95 cc concentrated hydrochloric acid containing ice for further processing. Thereby, 3-piperidino-1-phenyl-1-[A5-bicyclo-(2,2,1)-heptenyl-2]-propanol-1 of the summary formula C2iHj,ON is obtained. The compound melts at lOTC and its chloro-hydrate has a melting point of about 238°C. The compound is difficultly soluble in water, slightly soluble In ethanol, and readily soluble In methanol. 

The formula for sulphuric acid was confirmed by Williamson by the discovery of chlorosulphonic acid (chloro-hydrated sulphuric acid) by the action of phosphorus pentachloride on sulphuric acid (the final product being sulphuryl chloride) ... 

The anhydrous chloride is prepared by standard methods. It is readily soluble in water to give a blue-green solution from which the blue hydrated salt CuClj. 2H2O can be crystallised here, two water molecules replace two of the planar chlorine ligands in the structure given above. Addition of dilute hydrochloric acid to copper(II) hydroxide or carbonate also gives a blue-green solution of the chloride CuClj but addition of concentrated hydrochloric acid (or any source of chloride ion) produces a yellow solution due to formation of chloro-copper(ll) complexes (see below). 

Dissolve 10 g. of chloro- 2,4-dinitrobenzenet in 50 ml. of dioxan in a 250 ml. conical flask. Dilute 8 ml. of hydrazine hydrate with an equal volume of water and add this slowly with shaking to the dioxan solution, keeping the temperature between zo " and 25°. Heat under reflux for 10 minutes to complete the reaction and then add 5 ml. of ethanol and heat again for 5 minutes. Cool and filter oflF the orange 2,4-dinitrophenylhydra-zine. Recrystallise the dry product from ethyl acetate m.p. 200° (decomp.). Yield, 7 g. 

Hydroxyphthalazin-l(2//)-one is obtained in a smooth reaction between phthalic anhydride and hydrazine hydrate and this is again the starting compound for many 1-substituted and/or 1,4-disubstituted phthalazines. The transformations of 1,4-dichloro-phthalazine, which is prepared in the usual manner, follow a similar pattern as shown for pyridazines in Scheme 110. On the other hand, phthalonitrile is the preferential starting compound for amino- and hydrazino-phthalazines. The most satisfactory synthesis of phthalazine is the reaction between a,a,a, a -tetrachloro-o-xylene and hydrazine sulfate in sulfuric acid (67FRP1438827), alt iough catalytic dehalogenation of 1-chloro- or 1,4-dichloro-phthalazine or oxidation of 1-hydrazinophthalazine also provides the parent compound in moderate yield. 

Isothiazolium salts (59) react with phenylhydrazine to give pyrazoles (60) (72AHC(14)l) (see Section 4.02.1.6). When treated with hydrazine hydrate, 3-chloro-l,2-benzisothiazole gives di-(o-cyanophenyl) disulfide (73SST(2)556), but 2,1-benzisothiazole gives o-aminobenz-aldehyde azine (72AHC( 14)43). 2-Substituted saccharins give the expected o-sulfamoyl-benzohydrazides. 

Alkylquinazolines are catalytically reduced to the corresponding 3,4-dihydro derivatives/ The only example of a 4-substituted quin-azoline which was reduced to its 3,4-dihydro derivative is 2-chloro-4-phenylquinazoline which gave 4-phenyl-3,4-dihydroquinazoline/ 4-Methylquinazolines are susceptible to oxidation, as is shown by the attempted nitration of 2,4-diraethylquinazoline which causes the removal of the methyl group with formation of 4-hydroxy-2-methyl-6-nitroquinazoline/ When the 4-substituent is —C(Et) (C02Et)2 recrystallization of the picrate from ethanol is sufficient to convert it to 4-hydroxyquinazoline/ Similar hydrolyses occur in acid solution and the mechanism undoubtedly involves a hydrated intermediate/... 

Besides acetophenone, this reaction was also applied to p-chloro- andp-methoxyacetophenone, and even to an aliphatic ketone, acetone (although the yield was stated to be only half as large as that obtained from mesityl oxide, i.e., less than 30%, Dorofeenko and co-workers reported a 45% yield of 2,4,6-trimethylpyrylium perchlorate from acetone, acetic anhydride, and perchloric acid), and is the standard method for preparing pyrylium salts with identical substituents in positions 2 and 4. The acylating agent may be an anhydride in the presence of anhydrous or hydrated ferric chloride, or of boron fluoride, or the acid chloride with ferric chloride.Schneider and co-workers ... 

Reactivity in this ring system is sufficient for facile hydrolysis (20°, 2 hr or 100°, 1 min) of the 2-, 4-, 6-, and 7-methoxypteridines in high yield and for easy substitution (75-90% yields) of the 7-methylthio group with methanolic hydrazine hydrate (65°, 15 min), dimethylamine (65°, 30 min), and ethanolic ammonia (125°, 6 hr). The 7-acyloxy intermediate in thionation of 7-oxopteridine with phosphorus pentasulfide is readily substituted (80°) to form pteridine-7-thione. The chloro group in 6-aryl-2,4-diamino-7-chloro-pteridine still reacts readily with hydrazine (100°, several minutes) in spite of the two deactivating amino substituents. 

Reaction of 5-chloro-l,2,4-triazolo[l,5-c]pyrimidines (165) with sodium hydroxide, thiourea, or hydrazine hydrate (79AJC1585) or with sodium azide (85EUP152841) also caused the displacement of the chlorine atom to... 

Chloro-2-hydrazino-4-phenylquinoline A stirred mixture of 2,6-dichloro-4-phenylquino-line 12.7 g,0.01 mol) and hydrazine hydrate (6.8 g) was refluxed under nitrogen for 1 hour and concentrated in vacuo. The residue was suspended in warm water, and the solid was collected by filtration,dried and recrystallized from ethyl acetate-Skelly B hexanes to give 1.81 g (67% yield) of 6[Pg.46]

A mixture of 3.4 parts of 7-chloro-4-fluorobutyrophenone, 4 parts of 1-(4-piperidyl)-2-benzimidazolinone hydrochloride, 6 parts of sodium carbonate and 0.1 part of potassium iodide in 176 parts of 4-methyl-2-pentanone is stirred and refluxed for 48 hours. The reaction mixture is cooled and 120 parts of water is added. The separated organic layer is dried over magnesium sulfate and the solvent is evaporated to leave an oily residue which is dissolved in dilute hydrochloric acid and boiled. The acidic solution is filtered and cooled at room temperature whereupon there crystallizes from solution l-<1-[ y-(4-fluorobenzoyl)-propyl]-4-piperidvl>-2-benzimidazolinone hydrochloride hydrate melting at about 134°-142°C. 

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