None
Meconic Acid, C,H,O, = C,HO,(OH)(CO,H),., oxypyrone dicarboxylic acid, occurs in opium in union with morphine. The opium extract is saturated with marble, and calcium meconate precipitated by calcium chloride (Anna/en, 83, 352). The salt is afterwards decomposed by hydrochloric acid. ‘The acid crys- tallizes with 3H,O in white laminz, which dissolve readily in hot water and alco- hol. When heated to 120° it decomposes into carbon dioxide and comenic acid. Ferric salts color the acid solutions dark red. In forming salts the acid generally combines with two equivalents of the bases, although with an excess of base, the salts are tribasic and yellow in color. Meconic acid also unites with ammonia, forming Comenamic Acid (Berichte, 17, 2081). re Acid, C, H,O, = CH,.C O —— C.CH, I | ? (See Berichie, CH — CO — C.CO,H. 23, Ref. 463; Annalen, 257, 253.) This is a by-product in the preparation of aceto-acetic ester. It can be obtained by long continued boiling of the ester, using at the time a return condenser. It dissolves with difficulty in cold water and alcohol. It crystallizes in needles from ether; these melt at 108° and boil at 269°. Being a ketonic acid it can unite with both hydroxylamine and phenylhydrazine (Berichie, 18, 453). It forms (1, 5)- dimethylpyrone on being heated with hydriodic acid. Iso-dehydracetic Acid, C,H,O,, is isomeric with the preceding and may be obtained by the decomposition of the condensation product, C,,H, 0, (Annalen, 222, 9), produced by the action of sulphuric acid upon acetoacetic ester. It is identical with carbaceto-acetic acid (Berichte, 19, 2402), derived from the aceto- acetic acid by means of hydrochloric acid. It is very probably mesiten-/actone carboxylic acid (Berichte, 23, Ref. 734). | Dimethyl Pyrone Dicarboxylic Acid, C,H,O, Carbonyl Diacetic Acid. Its ethyl ester is produced when COC], acts upon the copper compound of aceto-acetic ester. Water is eliminated from the carbonyl diacetoacetic ester which is formed at first (Berichte, 19, 20) :-— CH,.CO CO.CH, Cie 6 — CCH, l d yields | I RO,.C.CH — CO — CH.CO,R RO,C.C — CO — C.CO,R. The diethyl ester is crystalline, very readily soluble in alcohol and ether, and melts at 80°. Ammonia converts it into dimethyl pyridone-dicarboxylic ester (Berichte, 20, 154). OF THE b VERSITY SALEORNIA. 7 Se 960 ORGANIC CHEMISTRY. 2. QUINOLINE GROUP—C,H,,_,,N.* QUINOLINE, C,H,N. Lepidine, C,,H,N = C,H,(CH;)N—Methyl quinoline. Cryptidine, C,,H,,N = C,H;(CH,;).N—Dimethyl quinoline, etc. The quinoline bases occur with those of pyridine in bone-oil (p- 938), and are also obtained by distilling alkaloids (quinine, cinchonine, strychnine) with potassium hydroxide. The com- pounds /eucoline, C,H,N, tridoline, CyH,N, etc., separated from coal-tar are identical with the quinoline bases (Berichte, 16, 1847). As regards synthetic methods and isomerides, quinoline is a naphthalene in which a CH-group is replaced by N (p. 937). TES gis tak shown by synthesizing quinoline from allyl aniline (p. 602), by passing the latter over ignited lead oxide. This is perfectly analogous to the syn- thesis of indol from ethyl-aniline (p. 827, and of naphthalene from pheny! bu- tylene (p. 905) (K6nigs) :— Fae! i Cf C,H,.NH.CH,.CH:CH, = C,H,¢ | Sb OH. Che: CH Quinoline is also produced in the distillation of acrolein-aniline (p. 602). A more direct proof of the constitution of quinoline was effected through its forma- tion from hydrocarbostyril (p. 755); PCI, converts the latter into a dichloride, which upon heating with hydriodic acid. yields quinoline (just as isatin yields indigo, p. 836) (A. Baeyer, Berichte, 12, 1320) :— /CH,.CH,\ /CH:CCl\, /CH:CH\, CHC yy 2 CO) CHa CCL OH CH. Hydrocarbostyril. a8-Dichlor-quinoline. Quinoline. Here, as with naphthalene and pyridine, we represent the three replaceable-hydrogen atoms of the pyridine nucleus by a, § and 7; ~ ee 3, \7\ 8 | NSS fo z5-4N those of the benzene nucleus with 1, 2, 3 and 4. ‘The positions 1, 2, 3 correspond to the ortho-, meta-, and para-positions of the — benzene derivatives. 4 corresponds to the second meza position (referred to N), and is known as the Aza-position. These posi- * A. Reissert, Das Chinolin und seine Derivate, 1889. + Another nomenclature designates the affinities of the pyridine nucleus as Py-t, -2, and -3; those of the benzene nucleus as B-1, -2, -3, and -4 (Berichte, 17, 960). QUINOLINE. 961 \ tions are designated as the affinities of the benzene nucleus with 2@-, m-, ~- and a-. Consequently, seven mono-derivatives of quinoline are possible (Berichte, 19, Ref. 443). Of the great number of new synthetic methods of preparing quinoline and its derivatives the following are the most important : 1. The condensation of the ortho-amido-compounds of such benzene derivatives as have an oxygen atom attached to the third carbon atom of the side-chain (p. 755) (A. Baeyer). In this way we obtain quinoline from o-amido-cinnamic aldehyde, a-methyl- quinoline from o-amido-cinnamic ketone, and a-oxy-quinoline from o-amido- cinnamic acid (p. 812). Further, o-amido-benzyl acetone yields a-methyl-hydro- quinoline (p. 730), o-amido-pheny] valeric acid, B-ethyl hydrocarbostyril (p. 814), and from these compounds the normal quinoline derivatives—a-methyl quinoline and (-ethyl quinoline—can be obtained by the withdrawal of 2H or O. 2. The production of quinoline and its derivatives by heating anilines (or amido-benzene compounds) with glycerol and sulphuric acid to about 190°. This method is of universal application and can be very readily executed (Skraup, Berichte 14, 1002) :— C,H;.NH, + C,H,0,= C,H,N(C,H;) + 3H,0+H,. It is very probable that acrolein first results, this then combines with the aniline derivative yielding acrolein-aniline (see above), which is oxidized to the quinoline derivative by the elimination of two hydrogen atoms by sulphuric acid. Hence, the reaction proceeds more easily and rapidly by using a mzxture of aniline with nitrobenzene, which only oxidizes. Similarly, from the three toluidines (and nitrotoluenes) we obtain the three methylquinolines (toluquinolines), C,,H,N = C,H,(CH,)N(C,H,), from the naphthylamines (and nitronaphthalenes) the naphthoquinolines, C,,H,N, and from the diamidobenzenes (and dinitrobenzenes) the phenanthrolines (p. 974). It is not necessary to apply the corresponding nitro-compounds together with the amido-derivatives; nitro-benzene mostly suffices as an oxidizing agent (Berichte, 17, 188). Likewise, the chlor-, brom-, and nitro-quinolines result from the corresponding aniline derivatives. The nitranilines yield both nitro-quinolines and phenanthro- lines ( Berichte, 14, 2377). From the amido-sulphonic acids arise the quinoline sulphonic acids; from the amido-benzoic acids, quinoline carboxylic acids; from the amido-phenols oxyquinolines, etc. The Kekulé benzene formula confirms the course of these quinoline syntheses (p. 563) (Berichte, 23, 1020). 3. An analogous reaction is the condensation of anilines with paraldehyde, aided by sulphuric or hydrochloric acid. Here a-methyl quinolines (quinaldines) are produced (Doebner and v. Miller) :— : CH: CH C,H;.NH, + 2C,H,O = C,H, 8 NN: cir, oe a-Methyl as ine, All aldehydes of the formula CHO.CH,R react like ferric 962 ORGANIC CHEMISTRY. aldehyde with anilines. The first step in the reaction consists in two molecules combining to unsaturated aldehydes, CHO.CR:CH. CH,R, or condensing to aldols corresponding to them. These then act upon the anilines and form quinoline bases. Two aldehyde molecules always act. Their condensation is due to the influ- ence of the CH, group attached to the aldehyde greup. Acetaldehyde yields crotonaldehyde, CHO.CH:CH.CH,, propyl aldehyde yields methyl ethyl acrolein, CHO.C(CH,):CH(C,H;), and ethyl propyl acrolein is formed from normal butyraldehyde. These unsaturated aldehydes (or the aldols) then react with the anilines in such manner, that the aldehyde group attacks the benzene nucleus (and not the amido-group). Thus, a- or aZ-alkyl quinolines (Berichée, 17, 1713; 18, 3360) result. Acetaldehyde (crotonaldehyde) forms a methyl quinoline (see above), a(-ethyl-methyl quinoline (Berichte, 21, 299) is derived from propyl aldehyde :— C,H,.NH, -+- CHO.C(CH), //CH:C.CH, | ire oy | + H,0 + H,. CH(C,H;) N=C.C,H,. aB-Ethyl Methy] Quinoline. In oxidizing these dialkyl quinolines with a chromic acid mixture it is only the a-alkyl that is changed to carboxyl; the resulting carboxylic acids eliminate carbon dioxide and yield 3-alkylquinolines (Berichte, 18, 3370). Unsaturated aldehydes, therefore, react (with one molecule) directly with the anilines. Acrolein (glycerol, see above) yields quinoline, while a-phenyl quino- line (Berichte, 16, 1664) is derived from cinnamic aldehyde, CHO.CH:CH.C,H,. m-Nitrocinnamic aldehyde reacts similarly (Berichte, 18, 1902). Acetone (two molecules) reacts in the same manner as the aldehydes with aniline hydrochlorides when aided by heat. It is very probable that mesityl oxide, CH,.CO.CH:C(CH,),, is the first product; therefore, as there is a simultaneous splitting off of one mesityl group, the products are ay-dimethyl quinolines (Berichte, 18, 3296; 19, 1394). The mixture of an aldehyde and ketone (each one molecule) re- acts the same as the aldehydes upon anilines. The intermediate products are unsaturated ketones, R.CO.CH:CH.R (or f-aldol ketones, R.CO.CH,.CH(OH)R (C. Beyer, Berichte 20, 1767 ; 19, Ref. 327). In this way ay-dialkyl quinolines are produced. Acetone and acetaldehyde, or acetylacetone, and aniline yield ay-dimethy]l- quinoline (Berichte, 21, Ref. 138) :— CH, CH, | rs Gat we Geach 2 cH7 “cH 4 HOt, CHO.CH, N=C.CH, ; The £-diketones react similarly (Berichte, 20, 1770; also a mixture of two different aldehydes, Berichte, 20, 1908, 1935).. _ a-Alkyl-quinoline-y-carboxylic acids are produced by the interaction of a mixture QUINOLINE. 963 of pyroracemic acid and an aldehyde upon aniline (Berichte, 20, 277; 21, Ref. 12):— CO,H CO,H : ; C,H,.NH, £CO.CH, =C,H,“ ‘SCH + 2H,0 +4 H,. CHO.R go’ N The carboxylic acids lose carbon dioxide and in this manner the a-alkyl quino- lines are produced. Pyroracemic acid alone when heated with aniline yields the same a-methyl quinoline-y-carboxylic acid (aniluvitonic acid, p. 972); this is be- cause aldehyde is formed from one molecule of the pyroracemic acid (Berichte, 20, 1769). 4. The direct condensation of amido-benzaldehyde with alde- hydes and ketones (by the action of caustic soda). The ortho- amido-derivatives of the unsaturated homologous benzaldehydes and ketones are the first products. These immediately give up water (see p. 721) (Friedlander, Berichte, 16, 1833). , Thus, with acetone we get a-methyl-quinoline :— — CHO CH, CH:CH CBee = CoH ee + 2H03 NH, — CO.CH, N: 3 with acetophenone, CH,.CO.C,H,, a-phenyl quinoline; with phenyl-ethyl aldehyde, C,H;.CH,.CHO, 6-phenyl quinoline; with aceto-acetic ester, a-methyl quinoline-G-carboxylic acid ( Berich/e, 16, 1833); with malonic ester a-oxyquino- — line-3-carboxylic acid (Berichte, 17, 456). o-Amidobenzophenone (p. 859) reacts just like o-amidobenzaldehyde; it yields ay-methyl phenyl quinoline with acetone and caustic soda (Berichte, 18, 2405) :— CO.C,H, CH, C(C,H,):CH 4\ — CoH NH, CO.CH, N—— .CH, -- 2H,0. In acid solution it is only the amido group that takes part in the reaction ; ac- cording to Miller’s reaction benzoyl-a-methyl quinoline results. 5. The condensation of aceto-acetic esters with primary and secondary anilines (L. Knorr, Berichte, 17, Ref. 147; Annalen, 236, 112). There are two phases in this reaction : (@) aceto-acetic anilide (from aniline and aceto-acetic ester when heated to 110°), when acted upon with concentrated acids, forms a-oxy-y-methyl quinoline (y-methy] carbostyril, p, 968) :— CO(CH,)CH, og CH): CH is pe iF 0: C,H,(NH).CO *“\n=—c(oH) ” — Methyl aceto-aceti¢ anilide by the same treatment yields By-dimethyl carbostyril (Berichte, 21, Ref. 628). (4) On the other hand (-phenyl-amido-crotonic ester, formed at the ordinary 964 ORGANIC CHEMISTRY. temperatures, yields y-oxy-a-methyl quinoline (y-oxyquinaldine, p. 970) when heated to 240° (Conrad and Limpach, Berichte, 20, 945, 1397) :— C,H,0.CO.CH /C(OH):CH | = CHS l + C,H,.OH. C,H,.NH.C.CH, N——C.CH, Phenyl-lutidone carboxylic ester is formed simultaneously. Anisidine, C,H, (O.CH,).NH,, also affords methoxy-y-oxyquinaldine (Berichie, 21, 1649, 1655). Aceto-acetic ester and methylaniline condense to ~-methyl lepidone (= pseudo- carbo-styril, p. 968) (Annalen, 236, 105; Berichte, 19, Ref. 827) :— CH,-CO.CH, ACH;):CH ore tinged CoHyC | + H,0. C,H;.N(CH,)-CO N(CH,).CO Acetone dicarboxylic ester (p. 435) reacts in an analogous manner with aniline (and methyl aniline) ; the products in this instance are esters of y-oxyquinaldine- $-carboxylic acid (Berichée, 18, Ref. 469). At the ordinary temperature benzoyl acetic ester and aniline yield (-phenyl- amido-phenylacrylic ester, which heated to 250° forms y-oxy-a-phenyl quinoline (Berichte, 21, 521, 523). 6. By the rearrangement of the aniline malonates or the malonanilides with PCl,; triquinolines being produced (analogous to the formation of a-naphthol from phenylisocrotonic acid, Riigheimer, Berichte, 18, 2975) :— /O=CCl C,H,.NH.CO.CH,.CO,H yields C,H, ee \w—=cca The toludines react similarly to aniline ( Berich¢e, 18, 2979), and ethyl malonic acid deports itself the same as malonic acid (Berichte, 20, 1235). Hippuric acid, C,H,.CO.NH.CH,.CO,H, under like treatment, yields chlorisoquinoline, (p. 976). 7. By rearranging the anil benzenyl compounds, from benzanilid-imide chlorides and sodium malonic or aceto-acetic ester, by the aid of heat (Just, Berichte, 19, 979, 1462, 1541) :— RO.OC.CH.CO,R pe) s= C.CO,R | ae CoH. C,H,;.N:C(C,H,)_ . N C.C,H, a-Phenyl-y-oxy-8-quinoline carboxylic acid. + ROH. 8. The conversion of indol and alkyl indols into quinolines (p. 830) is rather re- markable. It occurs in consequence of the introduction of methyl, dihydroquino- lines resulting (E. Fischer, Berichte, 21, Ref. 17). Chlor- and brom-quinolines are similarly obtained by heating methyl ketol with chloroform or CBr,H and sodium ethylate (Berichte, 21, 1940).. The quinoline bases are liquids which dissolve with difficulty in water, alcohol and ether, and possess a penetrating odor. Like pyridine they are not readily attacked by nitric or chromic acid ; QUINOLINE. 965 potassium permanganate, however, destroys the benzene nucleus in them, with production of af8-pyridiné dicarboxylic acid (quinolinic acid, p. 947). The homologous quinolines, containing the alkyl groups in the pyridine nucleus (a, #, 7), and those containing the substitutions in the benzene nucleus (0, m, ~, @), are oxidized by chromic acid in the presence of sulphuric acid to the corresponding quinoline car- boxylic acids, while potassium permanganate on the other hand usually oxidizes those substituted in the benzene nucleus, with the formation of pyridine carboxylic acids (Berichte, 19, 1194; 23, 2252). Potassium permanganate converts the #- and y-alkyl quinolines (by decomposing the benzene nucleus) into the corresponding pyridine tricarboxylic acids, while the a-alkyl quinolines have their pyridine nucleus destroyed, and acid derivatives of o-amidobenzoic acid result. By this treatment a-phenyl quinoline yields benzoyl anthranilic acid, CHK Nih.CO.CH, (Berichte, 19, 1196). If two methyl groups are present in quinoline, the y-position will be oxidized with the most ease, then the , and finally the a-position (Berichte, 23, 2254). In the case of the a-dialkylquinolines, obtained by the action of aldehydes (2 molecules) upon the anilines, chromic acid only attacks the higher a-alkyl with the formation of 3-alkyl-a-carbonic acids (see above). Only the most important of the many derivatives of quinoline will receive notice in the succeeding paragraphs. , Quinoline, C,H,N, occurs in bone oil and coal tar. It results when many alkaloids are distilled, and is best prepared syntheti- cally. In preparing quinoline, digest a mixture of 38 grams aniline, 100 grams sul- phuric acid, 24 grams nitrobenzene, and 120 grams glycerol, until the reaction commences. Boil them for several hours, dilute with water, distil off the nitro- benzene in a current of aqueous vapor, supersaturate with alkali, and distil the quinoline with aqueous vapor. To purify it thoroughly convert it into the acid sulphate (Berichte, 14, 1002). See Berichte, 14, 1769, for the reactions and physiological action of quinoline. Quinoline is a colorless, strongly refracting liquid, with pene- trating odor. It boils at 239°; its sp. gr. = 1.095 at 20°. It forms crystalline and very soluble salts with one equivalent of acids; the characteristic bichromate, (C,H,N,)Cr,O,H,, dissolves with difficulty and forms yellow needles, melting at 165°. With the alkyl iodides quinoline, as tertiary base, produces crystalline, yellow ammonium iodides, which may be converted into peculiar bases (ammonium hy- 966 ORGANIC CHEMISTRY. droxides), soluble in ether, on warming with caustic soda (Berichte, 17, 1953, and, 18, 410, 1015). Tertiary dihydroquinolines also afford bases soluble in ether, while the iodomethylates of tertiary tetrahydroquinolines are stable towards alkalies (Berichte, 21, Ref. 17). Potassium permanganate oxidizes the ammonium chlo- rides, the pyridine nucleus being decomposed, and derivatives of o-amidobenzoic acid are produced (see above). Cyanine (C,,H,,N,I) is a blue dye, and was formerly prepared by heating quinoline amyl iodide with potassium hydroxide. It is only produced in the presence of a-methyl quinoline (Berichte, 16, 1501, 1847); the same is true of the red-dye (Berichte, 16, 1082) obtained from quinoline with benzotrichloride. Quinoline betaine, C,H,N To ae (the HCl-salt), is formed from quinoline and chlor-acetic acid; the free betaine melts at 171°. Nascent hydrogen (tin and hydrochloric acid) produces Dihydro-quino- line, C,H,N (melting at 161°), and liquid Tetra-hydro-quinoline, C,H,,N ee CHC NetcR> boiling at 245° (Berichte, 16, 727, 23, 1142). Both are secondary bases and form nitrosamines. The tetrahydronitrosamine rearranges itself quite readily to the paranitroso compound, which yields / amidoquinoline when reduced (Serich/e, 21, 862). The alkyl iodides and tetrahydroquinoline yield #-alkylhydroquinolines. 2-Methyl tetrahydroquinoline, C,H,,N.C,H,, so-called Kairoline, obtained by means of methyl iodide, is said to have the same action as kairine—a febrifuge. Tetrahydroquinoline (unlike piperidine, p. 950), does not react with bromben- zene. When heated with nitro-benzene it is readily oxidized to quinoline (Ze- richte, 22, 1389). In tetrahydroquinoline the four hydrogen atoms are attached to the pyridine nucleus, therefore like the a7.tetrahydro naphthylamines it possesses the character. of an aromatic base (of an aniline), Decahydroquinoline, C,H,,N, of alicyclic character, is produced when the preceding compound is further reduced by heat- ing with hydriodic acid. It is strongly alkaline, with a penetrating, conine-like odor. It melts at 48° and boils at 204° (Berichte, 23, 1142). The diquinolyls, C,H,N.C$H,N, result from the union of two molecules of quinoline. They are analogous to the dipyridyls. They consist either of two pyridine nuclei, two benzene nuclei or one pyridine nucleus and one benzene nucleus. Seven isomerides have been prepared thus far, partly through the con- densation of quinoline by sodium, or by conducting it through a tube heated to redness. Skraup has succeeded in synthesizing them from benzidine and dipheny- lin (p. 961), or from amidophenyl quinolines. On heating quinoline with sodium in air we get a-Diquinolyl, melting at 176° (Berichte, 20, Ref. 327.) The two pyridine nuclei in it are united to each other at the a-positions (Py a-Py a) C,H,: C, H,N—C,H,N: C,H, (Berichie, 19, Ref. 7553 20, Ref. 471). The chlor-, brom-, and nitro-quinolines, with the substitutions in the benzene nucleus, are prepared synthetically, by Skraup’s reaction, from the chlor-, brom-, and nitro-anilines. @-Chlorquinoline, C,H,CIN, is obtained from a-oxyquino- line with PC], and PCI,0; it consists of long needles, fusing at 38°, and boiling at 266°. Itis a feeble base. Its halogen atom, in the a-position, is very reactive. When heated to 120° with water it regenerates a-oxyquinoline; alkyl ethers appear when it is acted upon by sodium alcoholates, It reacts in the same manner with anilines (Berichte, 18, 1532). See Berichte, 21, Ref. 232 for the action of bleaching lime upon quinoline and the chlorquinolines. Consult Berichie, 23, Ref. 110 upon bromquinolines - Ortho and meta (or ana)- Nitroguinolines, C,H, (NO,)N, are produced when quinoline is nitrated at 80° with a mixture of nitric and sulphuric acids. The OXYQUINOLINE. 967 ortho- and para- have been obtained from the ortho- and paranitranilines by means of glycerol and sulphuric acid, while -nitraniline yields phenanthroline (p-974). The ortho melts at 89°, and the meta- (or ana-), when anhydrous, at 72°. Amido-quinolines, C,H,(H,N)N (substituted in benzene nucleus), are pro- duced in the reduction of the nitroquinolines with tin and hydrochloric acid and upon heating the oxyquinolines, C,H,(OH)N, with ammonia-zinc chloride. I- and 4- Quinoline Sulphonic Acids (ortho- and ana- Berichte, 20, 95), are formed when quinoline is heated with fuming sulphuric acid; at 300 the para acid is almost the exclusive product, the ortho acid apparently being converted into this (Berichte, 22, 1390). Ana and fara- quinoline sulphonic acids have been synthetically prepared from meta- and para amido-benzene sulphonic acid with nitrobenzene, glycerol and sulphuric acid (Berichte, 20, 1446). When the three quinoline sulphonic acids (their alkali salts) are distilled with po- tassium cyanide in a vacuum (Berichte, 22, 1391), they yield the corresponding cyanbenzguinolines, C,H,N(CN) (1, 3 and 4). The ortho- cyanide melts at 84°, the fara (3) sublimes in needles and melts at 131°, the ava (4) melts at 87° (Berichte, 20, 1447). The cyanides can be saponified by heating them together with concentrated hydrochloric acid in a sealed tube, when they yield the corres- ponding quinoline benzcarboxylic acids, Cj, H,N(CO,H). Oxyquinolines, CsH,(OH)N. The oxyquinolines containing the hydroxyl in the benzene nucleus, called also quinophenols (1, 4, and 3, or ortho, meta, and para), are synthesized from the three amidophenols by Skraup’s reaction. 1I- and 4-Oxyquinolines have also been prepared from the quinoline sulphonic acids by fusion with caustic potash. They resemble the phenols and like them combine with diazo-salts forming azo- dyes (Berichte, 21, 1642). 1-Oxyquinoline (ortho) is also produced from r-chlorquinoline (see above) and is most readily prepared from 1-quinoline sulphonic acid (Berichte, 16, 712). It crystallizes in white needles, has the odor of saffron, melts at 75°, boils at 266°, and is volatile insteam. Ferric chloride imparts a dark-green color to its alcoholic solution. Nitrous acid converts it into #itroso-oxyguinoline, yellow-green needles, that by reduction yields amido-oxyguinoline. 1-Oxyquinoline, like the phenols and naph- thols, is changed by chlorine to chlorketoguinolines ( Berichte, 21, 2977). Tin and hydrochloric acid convert it into 1-Oxytetra-hydroquinoline, C,H, (OH)NH. This forms shining leaflets or needles, melting at 120°. It yields oxytetra-hydro-7-methyl-quinoline, C, H,(OH)N.CH,g, melting at 114°, when it is acted upon by methyl iodide, The hydrochloric acid salt of this base, C,)H,,0N.HC1+-H,0, is Kairine (erichte, 16, 720), which is applied as an antipyretic. 3 Oxyquinoline (para), from para-amidophenol, melts at 190° (Berichie, 15, 893). Its methyl ester, para-quinanisol, is prepared from /-amidoanisol by the reaction of Skraup. It boils at 305°. Nitrous acid converts it into o-sztroso- p-oxyquinoline, which, upon reduction, and further oxidation by ferric chloride, forms gutnoline guinone, CJH,(O,)N, crystallizing in red-brown needles (Berichie, 21, 1887). Tin ae hydrochloric acid convert 3-oxyquinoline into ¢e¢ra-hydro-para-quinan- tsol, CsH, 9(O.CH3)N, crystallizing in stout prisms, melting at 42° and boiling at 283°. Most oxidizing agents (¢.g. ferric chloride) color the base and its salts green. The sulphate and lactate serve as antipyretics, under the name 7ha//in (Berichte, 18, Ref, 613, 72.) : 968 | ORGANIC CHEMISTRY. _ 4-Oxyquinoline (ana), from para-amidophenol and from 4-quinoline sulphonic acid, crystallizes in needles or prisms, melting at 235-238° with decomposition. Ferric chloride imparts a brown-red color to its solution. Tin and hydrochloric acid convert it into a tetrahydro-compound. The oxyquinolines, with hydroxyl in the pyridine nucleus, are more feeble bases and phenols than the oxybenzquinolines. a-Oxyquinoline, C,H,(OH)N, Carbostyril, the lactime of o-amido-cinnamic acid (pp. 810, 812), is most readily obtained by digesting o-nitro-cinnamic ester with tin and hydrochloric acid or alcoholic ammonium sulphide (Berichte, 14, 1916). It may also be prepared from a-chlorquinoline by heating it with water, and by digesting quinoline with a bleaching lime solution (Berichte, 21, 619). It crystallizes from hot water (1 : 100) in fine needles, from alcohol in large prisms. It melts at 198-199° and sub- limes. Water decomposes its salts with alkalies and acids. Carbon dioxide separates it in the form of shining needles from its alkaline solution. Potassium permanganate oxidizes it to oxalyl anthranilic acid (p. 749). Sodium and alcohol reduce it to tetrahydroquinoline (Berichte, 19, 3302). o-Nitrocarbostyril is produced when o-nitrocoumaric acid (p. 819) is heated together with alcoholic ammonia. It melts at 168°. As in the case of oxypyridine or pyridone (p. 945), it is undetermined whether the lactime or lactam form should be ascribed to a-oxyquinoline; the ethers, how- ever, of the two forms, of carbostyril and pseudocarbostyril exist :— CH:CH CH:CH lt ha | bah Ce -N:C.OR NNR.CO Carbostyril Ether. Pseudocarbostyril Ether. The cardbostyril or lactime ethers, with the group, N:C(OR), are produced by the action of the alkyl iodides upon the undecomposed (Na- or Ag-) salts of carbo- styril ; the pseudocarbostyril or lactam ethers, however, by the action of the alkyl iodides upon free carbostyril in the presence of alkalies (Berichte, 18, 1528; 20, 2009). ‘The lactam ethers differ from the lactime ethers in being solid crystalline bodies, not decomposed when heated with hydrochloric acid. ‘The methyl ether melts at 71°, and the ethyl at 54°. The lactime ethers are also formed when o-amidocinnamic esters are digested with alcoholic zinc chloride (p. 812) and by the action of sodium alcoholates upon a-chlorquinolines. They are aromatic oils, that volatilize in a current of steam. There are perfectly anologous isomeric ethers of Hydrocarbostyril, derived from tetrahydroquinoline, C,H,,N. a -Oxy-y-methyl quinoline, y-Methyl carbostyril, or Lepidone, C,H, C(CH,):CH “ad | , from acetoacetanilide (p. 963), manifests a similar behavior. - \—NH—CO Methyl lepidone, from acetoacetic ester and methyl aniline, melts at 131°, whereas methoxy-y-methyl-quinoline is a liquid (Berichte, 19, Ref. 828). y- Oxy-a-methyl Quinoline, y- Oxyquinaldine, from phenylamidocrotonic ester (p. 963), also forms two isomeric ethers (Berichte, 20, 948; 21, 1965). METHYL-QUINOLINE. 969 When methyl iodide acts upon y-oxy-quinaldine, it forms an zodomethy/ate, or HI- CO CH / | *\N(CH),.C(CH, salt, from which alkalies separate n-methyl quinaldone, C,H melting at 175° (Berichte, 22, 78). Compare lutidone. Kynurine, £- or y-oxy-quinoline, C,H,(OH)N, is made by heating cynu- renic acid (oxyquinoline carboxylic acid, p. 973), and by oxidizing cinchonine and cinchoninic acid with chromic acid (Berichte, 22, Ref. 758). It crystallizes in needles, containing three molecules of water, and when anhydrous melts at 201°. It forms quinoline when heated with zinc dust. Potassium permanganate oxidizes it to oxalylanthranilic acid (cynurenic acid, p. 749). PCI, converts it into chlor- quinoline, melting at 34°. Dioxy-quinolines, C,H,(OH),N. Two isomerides have been obtained from chlorcarbostyril. A rather noteworthy formation of ay-dioxyquinoline is that from o-amido-phenylpropiolic acid (p. 816). Nitrous acid converts it into trioxyquino- line, C,H,(OH),N, which may be oxidized to quinisatinic acid by ferric chloride and this by loss of water yields quinisatin, C,H;.NO, (p. 765). Quinoline Homologues, The monoalkylquinolines exist in seven isomeric forms (p. 961). (1) The seven isomeric methyl quinolines are all known. The four quinolines methylated in the benzene nucleus, called Toluquino- lines, methyl benzquinolines, or lepidines, are obtained by Skraup’s reaction on heating the three toluidines with nitrotoluenes, glycerol and sulphuric acid. In this way o- and f-toluidine yield o- and f-methyl quinoline, while #-toluidine affords both the meta- and ana-quinolines. The latter can be separated by means of their acid sulphates (Berichte, 19, Ref. 442). The isomerism of place of the meta- and ana-compounds is obtained from the carboxylic acids, corresponding to them (p. 972). Chromic acid oxidizes all four methyl quinolines to quinoline benzcarboxylic acids; while potassium permanganate converts the four isomerides (by destruction of the benzene nucleus) into @Z-pyridine dicarboxylic acid (p. 947). Ortho. methyl quinoline (1), from o-toluidine, boils at 248°, the meta- (2) boils at 250°, the para- (3) at 257°, and the ana- (4) at 250°. The following are methylated in the pyridine nucleus :— a-Methyl-quinoline, C,H,N = C,H,:C,;H,(CH;)N, Quinal- dine, is formed in the condensation of o-amido-benzaldehyde with acetone when warmed with sodium hydroxide (p. 963); by the reduction of o-nitrobenzal acetone (p. 806); from y-oxyquinaldine, and by fusing ethyl acetanilide with zinc chloride (Berichie, 23, 1903). It may also be obtained from aniline by means of ethyl aldehyde. The most advantageous course to procure it consists in digesting 1 part of ani- line with 1% parts of paraldehyde and 2 parts crude hydrochloric acid, and then distil the product with sodium (Aerichfe, 16, 2465, 2600). As much as 25 per cent. of quinoline is found in coal-tar, but it cannot be isolated from it (Berichte, 16, 1082). Quinaldine is a liquid with a faint odor resembling that of quino- line, and boils at 238°. When acted upon by potassium perman- ro 97° ORGANIC CHEMISTRY. ' ganate the pyridine ring is broken and acetyl-anthranilic acid results. Chromic acid oxidizes it to a@-quinoline carboxylic acid. Tin and hydrochloric acid reduces it to Tetrahydro-quinaldine, C,,H,,N, which also results by the reduction of o-nitrobenzyl acetone (p. 730). It boils at 247°, is a strong base, and is colored blood-red by oxidizing agents (FeCl,). Alkyl iodides and quinaldine (also the lepidines) unite to Peete or am- monium iodides; the caustic alkalies liberate the ammonium bases, C,)H, (NR),O from the latter (Berichte, 21, Ref. 14). When the iodomethylates ate heated in air contact with the concentrated alkalies peculiar red and blue dyestuffs—the Cyanines—are produced (Berichfe, 18, Ref. 17). Concentrated nitric acid converts quinaldine into o- and m- nitro-quinaldines, C,,H,(NO,)N, which form o- and m-amido-quinaldine by reduction (Lerichde, 22, 224). y-Oxyquinaldine and m-methyl-quinaldone (p. 969). The CH,-group of quinaldine is very reactive. It enters readily into condensa- tion products with aldehydes (paraffin or benzene class) (Berichte, 20, 2041). Chloral yields the compound, C,H,N.CH:CH.CCl,, melting at 144°; boiling potassium carbonate converts it into a quinoline acrylic acid, C,H,N.CH:CH. CO,H, while potassium permanganate oxidizes it to a-quinoline aldehyde, C,H,N.CHO. MWHydrobromic acid and soda convert quinoline acrylic acid into a-quinoline-lactic acid, C,H,N. CH(OH).CH.CO,H and its /actone (Lerichte, 21, Ref. 635). Consult Berichie, 22, 271, upon quinoline acrylic acids and quino- line aldehydes. Quinaldine and phthalic anhydride yield a beautiful yellow dye—quinophthalone or quinoline yellow, C,H,(C,O,):CH.N.C,H, (p. 880), which may be sublimed in golden-yellow needles, melting at 235°. The sodium salt of its sulphonic acid is the quinoline yellow of commerce. It dyes silk and cotton a beautiful yellow. 8-Methyl Quinoline, C,H,(CH,)N, is produced by heating 3-methyl-a-quino- line carboxylic acid (from a 3-ethyl-methyl quinoline, from aniline and propionic aldehyde, p, 962). and by the condensation of aniline together with propionic aldehyde and methylal (p. 962, Perichies 20,1916). It boils at 250°. It solidifies in the cold and melts at 10-14°. Chromic acid oxidizes it to {-quinoline car- boxylic acid. y-Methyl-quinoline, C,H,(CH,)N, Lepidine, occurs together with quinoline and quinaldine in coal-tar, and is obtained on distilling cinchonine with caustic potash. It may be synthetically prepared by the condensation of aniline with methylal (3 parts) and acetone (3 parts), aided by hydrochloric acid, by the method of vy. Baeyer (p. 962). It possesses an odor like that of quinoline, and boils at 257°; it solidifies below 0°. Chromic acid oxidizes it to y-quinoline-carboxylic acid. Potassium permanganate first produces methyl-pyridine-dicarboxylic acid, and afterwards pyridine-tricarboxylic acid (ay). (2) Dimethyl- and Ethyl-quinolines. aB- Dimethyl Quinoline, C,H,;(CH;),N, is obtained from a mixture of acet- and propionic aldehydes (or from tiglic aldehyde) with aniline (Derichie, 22, 267). By-Dimethyl Quinoline, from y-dimethyl-carbostyril, melts at 65° and boils at 290°. o- and f-Oxy-ay-dimethyl Quinolines, C,H,(OH)(CH,),N, have been prepared from o- and g-amidophenol with acetone (Berichte, 22, 209). o- and /- Toluquinaldine, C,H,(CH,),N, containing the methylene groups in the benzene and pyridine nuclei, are obtained from o- and -toluidine by means of paraldehyde (Berichte, 23, 3483). a- and 6-Ethyl Quinoline, C,H,(C,H,)N, are produced (similar to the alkyl pyridines, p, 942) by heating eine jodoethylate t to 280° PHENYL-METHYL-QUINOLINE. 971 (Berichte, 19,2995). $8-Ethyl Quinoline is obtained from $-ethyl hydro-carbo- styril (p. 814), just as quinoline is prepared from hydrocarbostyril (p. 961); and from /3-ethyl quinoline-a-carboxylic acid (from af-propyl ethyl quinoline, prepared from aniline and butyraldehyde, p. 962) ( Berich¢e, 18, 3371). a-Ethyl Quinoline boils at 255—260°, 6-Ethyl Quinoline at 265°, and y-Ethyl Quinoline at 270-275°. These compounds yield the corresponding quinoline carboxylic acids when oxidized with a chromic acid mixture. Consult Berichte, 21, Ref. 138 upon the ¢rimethyl-guinolines. Phenyl-quinolines, C,H,(C,H,)N. a-Phenyl-quinoline is obtained from cinnamic aldehyde and aniline upon heating them with hydrochloric acid to 200° ; also by the condensation of o-amido- benzaldehyde with acetophenone. It consists of brilliant needles, melting at 84°, and boiling above 300°. Potassium permanganate oxidizes it to benzoyl anthrani- lic acid (p. 749) (Berichze, 19, 1196); while tin and hydrochloric acid convert it into a tetrahydro-compound C,H,,(C,H,;)N. $-Phenyl-quinoline is pro- duced in the condensation of o-amido-benzaldehyde with phenyl-acetaldehyde. It is an oil, which solidifies on cooling, y-Phenyl-quinoline is formed by heating y-phenyl-quinaldinic acid (from y-pheny] quinaldine, see below) to 180° ( Berichte, 19, 2430). It crystallizes from pure alcohol in white flakes, melting at 61°, and distilling at that temperature. It apparently is the parent substancé of the quinia alkaloids (Berichte, 20, 622). y-Phenyl-a-Methyl Quinoline, C,H,(C,H,) (CH,)N, y-phenyl quinaldine, results in the action of hydrochloric acid upon aniline mixed with acetophenone and paraldehyde (p. 961), as well as by the condensation of o-amido-benzophe- none and acetone by means of sodium hydroxide (p. 963) (Berichte, 18, 2406), also by the condensation of benzoyl acetone, CSH,;.CO.CH,.CO.CH,, with aniline, according to Beyer’s method (Berichte, 20,771). It melts at 99° and yields y-phenyl quinoline-a-carboxylic acid when its phthalone is oxidized - with chromic acid. This new acid affords y-phenyl quinoline (see above). a-Phenyl-y-methyl Quinoline, C,H,(C,H,;)(CH,)N, is produced by con- densing o-amido-acetophenone, C,H, NH, °» 2nd acetophenone with caustic 2 soda (p. 963) (Berichte, 19, 1036), as well as by distilling flavenol with zinc dust. It crystallizes in white leaves and melts at 65°. . = Upon heating acetanilide, C,H,.NH.CO.CH,, with zinc chloride to 270° (by condensation of 2 molecules of the ortho-amido-acetophenone which is produced first), we obtain Flavaniline, C,,H,,N,, applied as a beautiful yellow dye ( Berichte, 15, 1500). It is -Amido-a-phenyl-$-methyl-quinoline. It also results in the condensation of o-amido-acetophenone and /-amido-acetophenone when digested with zinc chloride (Berichte, 19, 1038). Flavaniline forms colorless crystals that become yellow on exposure to the air. Its monacid salts are yellow in color and have been used as dyes (Berichte, 15, 1500). Nitrous acid converts it into so-called Flavenol, C,H,(C,H,OH)(CH,)N, a phenol, which when heated with zinc dust becomes ay-Phenyl-methyl-quinoline. Potassium permanganate oxidizes flavenol to ya-methyl-quinoline-carboxylic acid (p. 972), and then to methyl pyridine tricarboxylic acid and pyridine tetracarboxylic acid. 972 ORGANIC CHEMISTRY. Quinoline Carboxylic Acids, These acids exhibit the character of amido-acids and yield salts with both bases and acids. (1) Quinoline Monocarboxylic Acids, C,,H,NO, = C,H,N.CO,H. There are four quinoline benzcarboxylic acids or those containing the carboxy] groups in the benzene nucleus. Of these the ortho, meta and para are obtained by oxidizing the corresponding methyl quinolines with chromic acid in a sulphuric acid solution. The ortho, para and ana-acids are prepared from o-, Z- and m- amido-benzoic acids by Skraup’s reaction, heating them with glycerol and sul- phuric acid to 140°, further, by heating the three cyanquinolines with hydro- chloric acid (p. 967). The place-isomerism of the ana-acid (melting about 360°) is evident from its formation (together with the ortho-acid) from amido-terephthalic acid by Skraup’s reaction (Berichte, 19, Ref. 548), from (1, 2, 3)-amidophthalic acid (together with the meta-acid) (Berichte, 19, Ref. 548), and from ana- quinoline sulphonic acid (p. 917) by means of the cyanide (Berichte, 20, 1446). The meta-acid has also been obtained by oxidizing 6-di-quinolyl (Berichie, 19, 2473). Ortho-Quinoline-Carboxylic Acid (1) is the most soluble in water and alco- hol. It crystallizes in white needles, melting at 187°. The meta (2) acid crys- tallizes in needles, melting at 284-250°. The fara-acid (3) is a white powder, and melts at about 291°, charring at the same time. The ama-acid (4), also pre- pared from meta-amido-benzoic acid, is almost insoluble in water, sublimes as a cyrstalline powder, and melts about 360° (338°) (Annalen, 237, 328). The acids containing the carboxyl in the pyridine nucleus are prepared by oxidizing a-, 8-, and y-methyl-quinoline with chromic acid in sulphuric acid solu- tion. Those acids, with a carboxyl in the a-position, are colored reddish-yellow by ferrous sulphate. a-Quinoline Carboxylic Acid, C,H,N(CO.H), Quinaldinic Acid, crystallizes from hot water in needles containing 2H,O; it effloresces in the air, melts at 156°, and further decomposes into carbon dioxide and quinoline. B-Quinoline Carboxylic Acid is produced by heating Acridic acid to 130°. It crystallizes, in small plates, melts at 171°, and when oxidized with potassium permanganate yields (a, 3, y)-pyridine tricarboxylic acid (p. 949). y-Quinoline Carboxylic Acid, C,H,N(CO,H), Cinchoninic Acid, was first produced upon oxidizing cinchonine with potassium permanganate or nitric acid. It crystallizes in needles, containing 2H,O, in thick prisms, or plates with 2H,O (Berichte, 20, 1609). It melts when anhydrous at 254°. When distilled with lime it affords quinoline; potassium permanganate oxidizes it to afy-pyri- dine tricarboxylic acid. Methylquinoline Carboxylic Acids, C,H,(CH,)N(CO,H). y-Methyl-a-quinoline Carboxylic Acid is obtained by oxidizing flavenol (p. 971) with potassium permanganate, and melts at 182°, with decomposition into CO, and y-methy] quinoline. a-Methyl-y-quinoline Carboxylic Acid, a-Methyl Cinchoninic Acid, is Aniluvitonic Acid, obtained by the condensation of pyroracemic acid with aniline QUINOLINE-DICARBOXYLIC ACID. - 973 (p. 962) (Berichte, 22, 1769). It crystallizes in delicate needles containing one molecule of water. It melis at 240°, and breaks down into carbon dioxide and quinaldine (Berichte, 14, 2249). The homologous a-a/kyl cinchoninic acids result in the condensation of pyro- racemic acid and aldehyde with anilines (p. 962) (Berichte, 22, 23) a-Methyl-8-quinoline Carboxylic Acid, C,H,N(CH,).CO,H results from the condensation of o-amido-benzaldehyde with aceto-acetic ester (p. 962), and melts about 234°, with decomposition into carbon dioxide and quinaldine. The Quinaldine Carboxylic Acids (quinaldines with carboxyl in the ben- zene nucleus), a-Methyl quinoline-carboxylic acids (ortho, meta and para), are produced by the condensation of the three amido-benzoic acids with aldehyde and hydrochloric acid. (2) Oxyquinoline Carboxylic Acids, C,H ,(OH)N)CO,H. a-Oxyquinoline-3-Carboxylic Acid, Carbostyril-3-carboxylic Acid, results in the condensation of o-amido benzaldehyde with malonic acid (p. 963), melts above 320°, and on heating its silver salt yields CO, and carbostyril. a-Oxyquinoline-y-carboxylic Acid, Oxycinchoninic Acid, is formed on melting cinchoninic acid with potash. It melts at 310°,and decomposes into CO, and carbostyril, if its silver salt be distilled. Kynurenic Acid is also an oxy-quinoline carboxylic acid. It occurs in the urine of dogs. It consists of needles containing 1H,O, becomes anhydrous at 140°, and melts at 257°. Fusion with caustic potash converts it into CO, and kynurine. o-Oxy-quinoline-m-carboxylic Acid, C,H,(OH)N(CO,H), with the hy- droxyl group in the ortho position of the benzene nucleus, is produced when the sodium salt of o-oxyquinoline (Berichte, 20, 1217) is heated with CO, under pres- sure (analogous to the formation of salicylic acid) :— C,H,(ONa)N + CO, = C,H,(OH)N(CO,Na). p-Oxyquinoline by the same treatment yields p-oxy-guinoline carboxylic acids (Berichte, 20, 2695). The ortho and para acids have also been obtained from o- and g-oxyquinoline by means of CCl, and caustic potash (Berichée, 20, Ref. 564). In the same manner o-oxyquinaldine yields 0-oxyguinaldine carboxylic acid, C,H ,(CH,)(OH)N.CO,H (Berichte, 21, 883). Para-oxycinchoninic Acid, C,H,(OH)N(CO,H)(3, y), Xanthoguinic acid, results on fusing parasulphocinchoninic acid (on heating cinchoninic acid to 260°, with sulphuric acid) with KOH. It crystallizes with 1 molecule of H,O, and melts at 320° with decomposition into carbon dioxide and paraoxyquinoline. Its methyl phenol ether Quininic Acid, C,H,(O.CH,)N(CO,H), is obtained by oxi- dizing quinine and quinidine with chromic acid in sulphuric acid solution, crys- tallizes in long, yellow prisms, dissolves in alcohol with a blue fluorescence, and melts at 280°. When heated to 230° with hydrochloric acid it decomposes into methyl chloride and para-oxycinchoninic acid. 3. Quinoline Dicarboxylic Acids, C,H;N(CO,H),. a$-Quinoline-dicarboxylic Acid, Acridic Acid, is produced when acridine is oxidized with potassium permanganate, crystallizes in needles with 2H,O, or plates with 1H,O, and decomposes at 120-130° into CO, and (-quinoline-carbox- ylic acid. ; ay-Quinoline-dicarboxylic Acid results when a-cinnamenyl-cinchoninic acid (from cinnamic aldehyde, pyroracemic acid and aniline) is oxidized with 974 . ORGANIC CHEMISTRY. potassium permanganate. It melts with decomposition at 246° (Berichte, 22, 3009). (1, 4)-Quinoline Dicarboxylic Acid is obtained from amidoterephthalic acid by the action of glycerol and sulphuric acid. It crystallizes in long needles contain- ing 2H,O, melts at 268-270°, and breaks down into carbon dioxide, and ortho- and ana- quinoline carboxylic acids (p. 972). Complex Quinolines. Just as pyridine, C;H,N, and quinoline, C,H,N, are derived from benzene, C,H,, and naphthalene, G 1e%2¢9 90 corresponding quinolines result from the higher, condensed benzenes. The so-called Naphtho-quinolines, C,,H, N, are derived from phenanthrene by the replacement of a CH-group in a terminal "benzene ring by nitrogen, whereas in phenanthridine the N-atom is present in the middle benzene mucleus :— N ty CAS ain ® SN, | ig ER Ee Te OE ea, eh eat ee ay ea Ae a tire a-Naphtho-quinoline. B-Naphtho-quinoline, N Phenanthridine, They are produced when a- and / naphthylamines are heated with glycerol, nitrobenzene and sulphuric acid.. a-Naphtho-quinoline melts at 50°, and boils at 251°. $-Naphtho-quino- line, melts at go°. When they are oxidized, they yield two (a- and §-) phenyl- pyridine dicarboxylic acids, C,H,(CO,H).C, H, N(CO,H) (this i is like the forma- tion of diphenic acid from phenanthrene, p. 92 5), which split off two molecules of carbon dioxide and become a- and 3-phenyl-pyridines (950). $-Naphtho-quinoline may also be obtained by removing bromine from a-brom-$-naphthylamine, or by the elimination of the nitro group from a-nitro. $-naphthylamine (BerichZe, 23, 1018). 8 Naphthomethyl Quinoline, C,H,,N = C,,H,(CH,)N, -naphtho- quinaldine, is analogously, produced by the action of paraldehyde and sulphuric acid upon #-naphthylamine. Potassium permanganate oxidizes it to P-naphtho- quinoline carboxylic acid, C,,H,N.CO,H (Berichte, 22, 254; 23, 1231). Phenanthridine is isomeric with naphthoquinoline, In it one of the interme- diate CH-groups of phenanthrene is replaced by nitrogen. It results from the pyrogenic condensation of benzylidene aniline on conducting the latter through a tube heated to redness (Berichfe, 22, 3339) :-— C,H,.CH C,H,CH [ts ee, ee C,H,.N C,H,.N It crystallizes in delicate white needles, melting at 104° and boiling without decomposition at 360°. Its salts are yellow in color. CH oN.CH Two Phenanthrolines, C,,H,N,, = | || , have been prepared by U;H,N.CH heating m- and g-diamidobenzene with glycerol, etc. These are derived from phenanthrene by replacement of 2 CH-groups of the terminal benzene ring by 2 nitrogen atoms (Berichte, 16, 2522; 23, 1016). ISOQUINOLINE GROUP. . 975 Phenanthroline, melting at 78°, is obtained from meta-nitraniline and meta- amido-quinoline by means of glycerol and sulphuric acid. Isomeric Pseudo- phenanthroline is also derived (in slight amount) from paranitraniline and melts at 173°. Potassium permanganate oxidizes the phenanthrolines to two dipyridyl dicarboxylic acids (Berichte, 19, 2377)- CRN. CECH Anthraquinoline, C,,H,,N = CoHa cH /CoHa, ee is obtained from anthramine (p. 895) on heating with glycerol, nitrobenzene and sulphuric acid. It sublimes in colorless leaflets, melts at 170°, and boils at 446°. Its solu- tions fluoresce very intensely. By oxidation with chromic acid in glacial acetic. acid, it yields a quinone corresponding to anthraquinone; the dioxy-compound of the latter is alizarin blue. When m-nitro-alizarin or amido-alizarin is heated, according to Skraup’s re- action, with glycerol and sulphuric acid we obtain a/izarin-blue, C, ,H,,NO, (Be- richte, 18, 445):— C,,H;(O),(OH),NH, + C,H,O; = C,H;(O),(OH),N.C,H, + 3H,0. The same occurs in trade in the form of a bluish-violet paste, and like alizarin is applied in dyeing. Since reducing agents decolorize it (zine dust, grape sugar) and it again separates on exposure to the air, it is adapted to the vat-dyeing. It combines with sodium sulphite, yielding a compound soluble in water (same as quinoline)—the so-called soluble alizarin-blue (Berichte, 22, Ref. 368). Alizarin-blue crystallizes from benzene in metallic, blue-violet needles, which melt at 270° and sublime. Heated with zinc dust it forms anthraquinoline, C,,H,,N (see this); it is, therefore, a derivative of the latter, and is similarly obtained from nitrealizarin and glycerol, just as quinoline is derived from nitro- benzene and glycerol. It unites with acids and bases to form salts; those with the bases are stable. ISOQUINOLINE GROUP. Isoquinoline is isomeric with and perfectly analogous to quinoline, Its N- atom- occupies the meta-position with reference to one of the two C- atoms, which are common to-both rings. It corresponds to the following scheme :— This constitution seems evident from the fact that when isoquinoline is oxidized — it forms cinchomeronic and phthalic acids (see below); the syntheses of the iso- quinoline nucleus also argue in its favor :— CH,.CO (1) By heating homophthalimide, CHK | (p. 791) with POCI, and then CO.NH reducing the resulting dichlorisoquinoline by heating it with hydriodic acid (Berichte, 19, 2354), or by heating homophthalimide with zinc dust (Berichée, 21, 2299). In a like manner dimethyl homophthalimide (p. 791) and zine dust yield methylisoguinoline (Berichte, 20, 1105; 21, 2300); isophthalamidine, CH:C.C,H,. HN une , forms f-pheny/ isoquinoline (Berichze, 18, 3477; 19, 830); q7e ORGANIC CHEMISTRY. and o-cyanbenzoyl cyanide is converted into benzyl chlor- oxyisoguinoline (Be- richte, 21, 2679). (2) Heating hippuric acid (p. 744) with phosphorus pentachloride and then reducing with hydriodic acid (Berichte, 19, 1172). This is analogous to the for- mation of quinoline from malonanilide (p. 964). Isoquinoline, C,H,N, occurs together with quinaldine and ordinary quinoline in the crude quinoline from coal tar. It is separated from the accompanying com- pounds by the crystallization of the sulphates (Berichte, 18, Ref. 384). It is very similar to quinoline, solidifies however at 0° to a crystalline mass, melting at 20— 22°, and boils at 237°. Potassium permanganate oxidizes it to phthalic acid (de- _ stroying the pyridine nucleus) and By- pyridine dicarboxylic acid (by destroying the benzene nucleus), whereas quinoline yields a$- pyridine dicarboxylic acid; phthalimides, C,xH,(CO),NR (Berichte, 21, Ref. 786), result if the oxidation be moderated. A beautiful red dye—Quinoline Red—is produced by condensing benzotrichlo- ride, C,H;CCl,, with molecular quantities of quinaldine and isoquinoline when they are heated with zinc chloride. This compound, in all probability, has a consti- ; / CyoH,.N S : iad me CO: C H, (CH,)N, analogous to that of malachite-green (Hofmann, Berichte, 20, 4). In addition to its coloring properties, it possesses the remarkable power of render- ing photographic plates orthochromatic. $B-Phenyl isoquinoline, C,H,(C,H,;)N (see above), crystallizes in leaflets, and melts at 104°. BENZO-DIAZINES. These are analogous to the benzopyrrols (p. 826) and denzo-diazoles (p 571). They contain both the benzene nucleus and the diazine nucleus, with two carbon atoms in common (p. 860). They exist, in accordance with the positions of the N- atoms, in three isomeric forms :— CH=CH CH=N /N=CH C,H” Op 2) 2 and § CH Py \ NEN \ Nee OH \. N=CH Ortho-benzdiazines Metabenzdiazines Parabenzdiazines. Cinnoline. Quinazoline. Quinoxaline. zr. Cinnoline Group. The Cinnoline nucleus, C,H,N,, the first representative of the ring-chains containing two nitrogen atoms, is known in very few derivatives. It has been ob- tained by a closed ring being formed from the diazo-compounds; a nitrogen atom enters the side chain occupying the ortho-position. Thus, Oxy-cinnoline Carboxylic Acid (v. Richter, Berichte, 16, 677,) is ob- tained from the diazo-chloride of o-amidopheny] propiolic acid (p. 815), when its aqueous solution is heated to 70°:— /&iC-CO,H /C(OH):C.CO,H ; C,H H,O — C,H HCL * ea it NN = : C(CH,):CH Methyl Cinnoline-carboxylic Acid, CyH,(CO,H) he os (Wid- NN PHENYLENE-DIAZOSULPHIDE. 977 mann, Berichte, 17, 724), is obtained in the same way, from the diazo-chloride of o-amido-propenyl benzoic acid (p. 778), CgH,(CO,H) { X\Cp 2 Oxycinnoline-carboxylic acid, C,H,(OH)N,(CO,H), melts at 260°, with the separation of CO, and formation of Oxycinnoline, C,H,(OH)N,, which melts at 225°, and when heated with zinc dust yields cinnoline. o-Phenylene-diazosulphide, oh He NON (p. 683), may be viewed as a cin- noline derivative, in which a sulphur atom replaces the group CH : CH. It sustains the same relation to cinnoline that thiophene bears to benzene or benzothiophene to naphthalene (p. $24). 2. Quinazoline Group. The quinazolines contain the benzene nucleus and in addition the same ring as the pyrimidines. They are produced by analogous condensations. (1) Di-hydroquinazolines (and quinazolines) are obtained from the acidyl de- rivatives of 0-amido benzylamine, C,H,(NH,).CH,.NH, (p. 710), by condensation, effected by mere distillation (Gabriel, Berichte, 23, 2808). Thus, o-amidobenzyl- acetamide yields methyl dihydro quinazoline :— CH,.NH CH,.NH CHS) = C,H + H,0; ". NNH,.CO.CH, .” SNe Cl@RE ee and o-amidobenzyl formamide, C,H,(NH,).CH,.NH.CHO, dihydroqguinazoline, c while o-amido benzyl benzamide forms pheny/quinazoline, C,H, :. with simultaneous elimination of water and hydrogen. N= C.C,H; (2) Analogous acidyl compounds are produced by the action of sodium form- anilides (not acetanilides) upon o-nitro benzyl chloride :— CH,Cl ee CH NCH | + Na Ne waft NaCl. Cc ; CHZ as (ae HO NNO, CHO *\No, When these are reduced, condensation takes place, and #-phenyl dihydro- quinazolines are produced (Paal, Berichte, 22, 2683). The o nitrobenzyl anilines yield such acidy] derivatives by the introduction of formyl and acetyl. Thus, o-nitro-benzyl-acetanilide forms mechyl-phenyl-dihydro- guinazoline (Paal, Berichte, 23, 2635, Ref. 530) :— CH,.N.C,H CH,.N.C,H CH FC tie ya CA gts xs -\NO,.CO.CH, ‘“N = C.CH, Condensation does not follow the action of nitrous acid upon the amido-benzyl anilines ( Berichte, 23, 2188, 2636). (3) Xeto-derivatives of the dihydroquinazolines are obtained from o-amido- benzamide, C,H,(NH,).CO.NH, (from anthranil carboxylic acid, p. 749, by the action of ammonia), by introducing acid radicals into it, and then condensing the resulting acidyl-amidobenzamides (Weddige, Berichte, 20, Ref. 630; Kérner, ibid.) :-— //CO.NH, // CO—NH C.H ae CNS | + H,O. *. ° NNELOOLCH, te 5,: Sy ia ort Acetyl-o-amido-benzamide. Methyl-keto-dihydroquinazoline. 82 978 ORGANIC CHEMISTRY. Benzoyl-amidobenzamide under similar treatment forms phenyl-ketodihydro- quinazoline. ied (4) Keto-derivatives of tetrahydroquinazoline are analogously obtained from o-amidobenzyl alcohol (p. 709) by converting it into urea derivatives (with CNK and HCl), and condensing the latter by digesting them with hydrochloric acid (Widmann, Berichte, 22, 1668, 2933) :— //CH,.0H / CH, NH CoH = CHC bas kG. NH,.CO.NH, NH—CO Oxytolyl Urea. Keto-tetraquinazoline. The ¢hioguinazolines are prepared by digesting o-amido-benzyl alcohol with mustard oils :— /CH,0H N.C,H, CH,.N.C,H, C,H + || oe | + H,O. * “\NH, Cs °*N NHLCS Mercuric oxide will convert these new compounds into ketoquinazolines. 