None
IsMntrides, The deriratiTes produced by the replacement of (he hydrogen atoms in pyridine can easily be deduced in their possible isomerisms from the given structural formulas, and are perfectly analogous to the isomerisms of the benzene derivatives. Representing (he five hydrogen atoms, or the affinities of the pyridine nucleus, with numbers or letters, corre- sponding to the diagram— 21 /?! a, 4 5 /^i «t then the positions, l and 5, also 2 and 4 (as in benzene), are similar (p. 33). Tlic first may be designated the ortho-, the latter, the meta-|X)siti()iis — while the position 3, occur- ling only once, corresponds to the para of benzene. From this we conclude that the mono-derivatives of pyridine, C5H4(X)N, can exist in three series, while six isomerides are posuble with the di-derivatives C2H,(X,)N. This is verified by the existence of three methyl, three propyl- and phenyl -pyridines, CjH4(R)N, of three pyridine-mono- carboxylic adds, CjH^(CO,H)N, of six dicarboxylic acids, etc. The determination of place for the pjrridine derivatives usually follows from their conversion into carboxylic adds of pjrridine. CatutUutioH of the Pyridine Monocarboxylic Acids. — Tlie constitution of pyridine-a- carboxylic add or picolinic acid and pyridine-/?-carboxylic acid or nicotinic acid is evi- dent from its production in the oxidation of a- and /3-phenylpyridines. These latter bodies have been obtained from a- and /3-naphthoquinoline. \Vhcn these are oxidized the first products are a- and ^-phenylpyridine dicarboxylic acids, which upon the loss of 2CO, become phenylpyridines. This proof of constitution prcsup|K)ses, therefore, the constitution of a- and /3-naphthoquinolines. The diagram represents the derivation of the constitntion of picolinic add s •^Naphtbo^ulnoUne A-Phenylpyridine opphenyl Pyridine Pyridine-a-carboxylic Dicarboxylic Acid Acid, a^Picolinic Aciil. The behavior of the pyridine dicarboxylic acids leads to a simpler deduction of (he position of their atoms (B. 18, 2967). Quinolinic acid (pyridine dicarboxylic acid), Ibnned by the oxidation of quinoline, has the position (1,2), and cinchomeronic acid, from isoquinoline, has the position (2,3). Quinolinic acid loses one molecule of carbon dioxide when heale<l and forms nicotinic acid, while cinchomeronic acid yields nicotinic add and isonicotinic acid ; therefore nicotinic acid is /? = 2 and isonico(inic acid >- = 3. Pyridine, C»H|N, boiling at i^.S*', with sp. gr. 1.003 (o*')* c^" ^ prepared from bone-oil, and is obtained from all the pyridine-carlK)xvlic acids on AvsMWsLiion with lime. Its hydtocYAouA^, C^^ ^ViSlX^ \^ 532 ORGANIC CHEMISTRY. dcliciiicscent, and with platinum chloride it forms a double salt, (C|H»- N . HCI),PiCl4, melting at 240°. See B. ag, R. 295, for pyridine mer- cury compounds. Its hhUnethylate melts at 117® (B. ag. R. 994). .CILCO Pyridine dciaine,^i^h'^(^ > , melting with decomposition at 150°, is formed by the interaction of pyridine and chloracetic acid (B. 23, 2609). Compare i, 521 ; B. 26, R. 54, for the action of pyridine upon acetyl chloride and benzoyl chloride. Sodium and alcohol reduce it to ])iperidine, while normal pentane is produced when it is heated with hydriodic acid. I. Homoloe^ous P3rridines. Methyl Psrridinet, C|H4(CHg)N, Picolines (from /ix, tar ; because they were obtained from coal-tar) : u-Picoline U>ils at 130° ; its sp. gr. is 0.965 at o^, and it b oxidized by potassiuin |>ermaiiganate to picolinic acid. /i^-Picoline boils at 143^; its sp. gr. is 0.977. It is formed when stryclniine is distilled (R. 13, 3555), and upon heating glycenil with P,Oj and aninioniuni phosphate ; aKso by heating trimethylenediamine hydrochloride (B. 23, 2730). It yields nicotinic acid on oxidation. }'-Picoline boils at 144°. Its sp. gr. is 0.974 at 0°. It has also been prepared by heating pyridine iodmethylate (p. 531). It yields isonicolinic acid when it is oxidized. Dimethyl Pyridines, Littiiiines^ ^(^(^s)s^ Is^ • Bone-oil contains mainly : aa^-Luti- liine^ l>oiling at 142°, with sp. gr. 0.942; a,) -Z»//<//>/^, boiling at 157®, with sp. gr. "■9493; and /i,>-ZM/i(/iW, boiling at 164° (H. ai, 1006 ; ag, 2996). ^fi^-Lutidint^ from the corres|X)ndinj; carboxylic acid, boils at 170° (B. 23, III3). a Ethyl Pyridine, C5H^(C,Il5)N, boils at 148° ; its sp. gr. is 0.949 at o«. >-Ethyl Pyridine boils at 165®; its sp. gr. is 0.952 at 0°. These two compounds result apoD lieatinj; pyriiline ethyl iodide. ,f Ethyl Pyridine has been obtained, together with the } IkmIv. from cinchonine and brucine on heating with caustic potash. It Ixuls at 166®. Sym. (1,3,5) Tiimethyl Pyriiiiney C^H, ( CI 1,),N, collidine, is obtained from synthetic diliydrocollidine dicarlx>xylic ester (p. 528) by oxidation, saponification, and the elimi- nation of carbon <lioxi(lc. It lK>ils at 172°. 1,3,4-Collidine, boiling at 165-168®, occurs in coal-tar (li. 29, 2998). (1,4) Methyl- Ethyl Pyridine, C5Hj(CIIj)(C,ll5)N,has been prepared from various aldehyde compounds, hence called aUehydine or ald^hydcollidine. It boils at 178**. « Propyl Pyridine, Conyrine, €5(03! I,) H^N, is produced on heating conine with zinc-dust. It l)oils at 167°. '/-Isopropyl Pyridine is jiroduced, together with the y-compoand, when pyridine projtyl iodide or isopropyl iodide is heated. It boils at 158^. Parvuline, v-Tetramethyl Pyridine, boiling at 227-230°, occiub in coal-tar (B. 28, 796). /^„V,-Dibenzyl P)rridine, C5Hj,(C-H^),N, boiling at 89®, is formed in the condensation of benzaldehyde with benzoyl pi[)cndine (p. 540) (A. a8o, 36). a- and ,i Phenyl Pyridine, C5(C,H5)n^N, boiling at 269** and 270®, result from the elimination of 2C(J, from their carl)oxylic acids, the decomposition products of a- and /^napllthoqninoline. The a-body can also be made by heating the corresponding a-pyridone with zinc-dust (IJ. 29, 1 678). p-Nitrophenyl Pyridine, melting at II7°» is obtained from nitrosodiazobenzene and pyridine. By reduction it yields p-amidophenylpyridine, melting at I02°, which yields rt-phenyl pyridine (B. 29, 167). Dinitrophenyl Pyridine melts at I18® (B. ag, 279). }'-Phenyl Pyridine, melting at 77° and boiling at 374°, results from a transposition of the condensation product of acetoacetic ester with benzaldehyde and ammonia (p. 528). a,n,-Phenyl Methyl Pyridine, C5(C8H5)(CH3)HjN, boiling at 28l<>, is obtained from cinnamylidenc acetoximc (p. 529 and B. 28, 1727). a,a}-Diphenyl Pyridine, melting at 82°, has been obtained (i) by distilling the oxime of cinnamylene-accto- plienone (metln^l 3. p. 529) ; (2) from a,o,-diphenyl->'-pyridine-carboxylic acid . produced on heating dij)heuacyl-ma\on\c acid ni'wXy ammoivYaL*, mA VSN Vpj ^^utUxiu^ a-phcnyl- NITRO-PYRIDINKS. 533 naphthocinchoninic acid (B. 29, 798; 30, 1499) Tetra- and Pentaphenyl Pyridines, melting at 179^^ and 240°, are produced from desoxyben/oVn hen/ylidene acetopluiione, and from benzamarone and NIIjOH (p. 529) (A. 281, 50; li. 26, 440). y-y-Dipyridyl, (CjH^N), -|- 2H,0, melting at 73° (114°) a"^ l>oiling at 305°, is produced, together with an oily, polymeric pyridine (CglijN)x, when sodium acts upon pyridioe (B. 24, 1478). /3,^-Dipyridyl, melting at 68° and boiling at 287°, is obtained nom its dicarboxylic add, an oxidation product of phenanthroUne (p. 554). Compare B. ai, 1077, for another dipyridyl. Vinyl Pyridine, C(H4(C,H3)N, results when pyridine vapors are conducted, together with ethylene, through a tulw heated to redness, as well as from a-picolyl alkine by the loss of water, and from pyridyl-j3-brompropionic acid (p. 538) by the exit of CO, and HBr. It boils at 160° (B. ao, 1644; A. a65, 229). a-AUyl Pyridine, C(IL(C^H5)N, is produced when picoline and paraldehyde are heated to 200^ (A. a47, 26). It boils at 290°. Sodium and alcohol convert it into propyl piperidine (inactive Conine, p. 562). Styryl Pyridine, SiilbazoU, C.(CH : CHC,H2)H^N, melting at 61° and boiling at 325^, is formed from a-picoline with benzaldehyde and zinc chloride. 2. Halogen Pyridines : The pyridines containing halogens in the nucleus are ob- tained with difficulty by the direct action of the halogens u|)on the pyridines. Bromine particulariy replaces the alkyl group in the homologous pyridines very easily (B. 25, 2985; 28, 1759). The replacement of the pyridine hydrogen atoms is more easily effected npon heating pyridine or the oxyp3rridines with phosphorus or antimony penta- chlorides. a-Chlor-pyridine, melting at 166^, results on treating a-oxypyridine with PCl^. ^-Chlor-pyridine, boiling at 148°, and /3-Brom-pyridine, boiling at 170°, are formed when CCn,H orCBr,H acts upon pyrrol-potassium (p. 530). a-Phenyl-a-chlor-pyri- dine, melting at 34°, is obtained from phenylpyridone (B. 29, 1679). Dichlor-p3rri- dine, melting at 67®, and trichlor-pyridine, melting at 50**, result from the action of PCL upon barium pyridine disulphonate. a,y-Dichlor-picoline, boiling at 206*', is obtained from dioxypicoline (B. 28, R. 644). Tetrachlor-pyridine, melting at 80- 85®, and Pentachlor-pyridine, C5CI5N, melting at 124-125°, are prepared from pyridine and phosphorus pentachloride. The same reagent converts dioxypyridine (glutaconimide) into perchlorpyridine (Kekul^, p. 527). 3. Pyridine Sulphonic Acids are formed, together with pyridine, on heating piperi- dine with concentrated sulphuric acid. /9-Pyridine Sulphonic Acid, C5H4(SO,II)N, also results on treating pyridine with snlphoric acid. ^-Cyan-pyridine, melting at 49°, is formed when its sodium salt is dis- tilled with potassium cyanide. It is the nitrile of nicotinic acid (p. 536) and yields /3-oxypyridine on fusion with caustic potash. 4. Nitro-pyridinea : Nitration of the pyridine nucleus seems only possible when NH,-, OH-, or similar groups are present, which, as in the case of benzene, facilitate the nitration (p. 149). The nitration of j3-oxypyridine (p. 534) in the form of its acetyl ester with nitric acid containing N,0, gives rise to two nitro-ox3rpyridinea, melting at 21 1** and at 295-298° with decpmixMiition ; also a dinitro-ox3rpyridine, melting at 133° (B. 28, R. 911). See nicotinic acid (p. 536) for the nitroamidonicotinic acids. 5. Amido-pyridines have been obtained from the pyridine acid-amides with bromine and caustic potash (Hofmann's reaction), and also by the exit of CO, from amidopyridine caifooxylic acids. o-Amido-pyridine, melting at 56^ and boiling at 204°, is obtained from the amide of a-picolinic acid; also from a- and a|-amido-nicotinic acid (B. 27, 1317, R. 410 ; A. 288, 253). /S-Amido-pyridine, melting at 64° and lx>iling at 251^, is formed in the I of bromine and caustic potash upon the amide of nicotinic acid (B. 28, R. 322). y-Aniido-a,aj-lutidine, C«H,(CH3),(NII,)N, melting at i^d^ and boiling at 246°, is obtained from amido-lutidine dicarlx>xylic acid (B. 27, 1325). Ciilorinated a-amido- pjrridines have been obtained by the action of PCI5 ufmn /^-oxyglutaramide. Trichlor- a-amido-pyridine, C5HC1,(NH,)N. melts at 143-144®. 6. Oz3fp]rridinea : They correspond to the amidophenols, as they form salts both with bases and ncids. They are formed with speciaX east (xocn ^^ oi.YV^T\d\\!A. ^-k^^^:^^ 534 ORGANIC CHEMISTRY. acids by the elimination of the carboxyl groops. The most of these adds haive been produced by the action of ammonia upon the corresponding pyrone deriTatiTes. Ferric chloride imparts a red color to nearly all their solutions. On Uie other hand, the a- ud )oxypyridines manifest the deportment of cyclic imides or lactams. They must be ▼iewed as kefo or <>j:^compounds of the hydropyridines, and are called, therefore, Z^'- dones. The following formulas have been considered for the a- and x-moooxypyridioes: a-Ozypyridine y-Oxypyridine a-Pyridone y-Pyridone. Although it is undetermined which of the two possible representations belongs to (he free oxy-l>odies, alkyl derivatives are obtained from both in which the alkyl residue replaces the imide or hydroxy 1 hydrogen (B. 24, 3I44) (l, 363). The following formulas should also be considered for the a,a]-dioxypyridines or glutaconimides : -<;;:^!o;;> -"ds...,)"- "■■<h;s>» (Compare the pyrazolons, the isoxazolons, benzimidazolons, indoxyl, isatin, etc.) (i) Monoxypyridmes: i-Oxyp3rridine, a-Pyridone, C^HgON, melting at 106° and boiling at 281°, is obtained from oxyquinolinic acid (p. 537^ and from oxy-nicotinic acid. Bromine water converts it into a dibromox pyridine, CjH,Br2(OIl)N, melting at >^CH — C(>\ 206®. With ethyl iodide it yields n-ethyl-a-pyridone, ^H^ _ ^N . QH^, lx)iling at 247°, while the silver salt of a-oxypyridine and the same reagent yield a-fthoxy- /.Cli — C(()C,lL):iv pyridimS'^^i , ^N, Iwiling at 156°. a-Methoxypyridine zzj\7^sQ\i^ prepare*! from a pyridone and diazomclhane (p. 445 ; B. 28, 1625). 1.3 Dimelhyl-a-pyridone, rscudolutidoatyril^ Mesitene Lactam^ melting at 180**, results from the action of ammonia upon dimethyl coumalin or mesilene lactone (p. 522), as well as from its c:irl>oxylic acids (r, 363). a-Phenyl Pyridone, melting at 197°, is formed from |)heiiyl coumalin and ammonium acetate. With aniline it yields a,n-di- phenylpyridone, melting at 145° (B. 29, 1677). 2 Oxypyridone, ('ijn^(()II)N, melting at 124°, distils without decomposition. It is produced when .^pyri(li^e sulphonic acid is fused with caustic potash (B. 28, R. 911), or by the acti<Mi of nitrous acid upon /^anndopyridine. Its ethyl ether, C5H^(OC,Hj)N, results from the interaction of /'MJrompyridine and alcoholic potash. 3 Oxypyridine, y-Pyridone, CjlIgONf-f- 1I,0), melting at 148®, is produced by heating oxypicolinic acid and ammon chelidonic acid. Methyl iodide converts it into the hydroiodide of n-methyl^-pyridone, OC<^[J ^ ^[J>NCH„ melting at 89**. ,^CII — CIl:^ . ^. y- Methoxv pyridine. (ClLOjC'' ^N, is isomeric with it. This compound / , IJ y \ z ) ^(,jj -_-CIl/ ^ may be j)repared by heating } -chlorpyridine with sodium ethylate. It boils at 190®, and, unlike its isomeride, is broken down, when heated with hydriodic acid, into methyl iodide and } pyridone. 2.4 Dimethyl-3-oxypyridine, >-Lutidone, C5(CH,),H,0N(-|- l>iH,0). melting at 225°, is obtained from lutidone dicarlwxylic acid (p. 538), as well as from dihydracetic acid (p. 521) on heating with ammonia (H. 28, R. 644). 7-Ethoxylutidine, boiling at 207°, results upon diazotizing ; -amidolutidine (p. 533) in alcoholic solution (B. 27, 1328). (2) Dioxy pyridines: i, S-Dioxypyridine, /^/u/aconinndet CjHeOjN (i, 467), melting at 183-184®, is obtained from oxyjrlutarimide, glutaconamic acid, or glutacondiamide. Its salts (chlofidef -f- H,0; sulphate ^ \ iW{^\ are decom^^ed by much water. It PYRIDINE CARBOXVLIC ACIDS. 535 yie]Js pyridine upon <listill:iti«)n wiili zinc dust. Pho^iilioriis jK'ntachloride ct»nvrrts it \x\\.K) f's^nta.hlorpyyidinc (compare p. 527 j. 2 Methyl-l,5-dioxpyridine, C^i^ClIjjII^OjX, inching at 191^, 2-Ethyl-l,2 Benzyl- dioxypyridine, etc., have been prepared by the action of ammonia upon methyl-, ethyl-, and benzyl -glutaconic esters (B. 26, R. 318, 587). These dioxypyridines correspond to resorcinol of the benzene series, and like it they fonn dya with phthalic anhydride (see p. 364 and 6. a6, 1559). Consult B. 25, R. 793 ; a8, R. 644, for 1,3-diozypicoline. Different isomeric dioxypyridines have, furthermore, been prepared by the fusion of pyridine disnlphonic acids with caustic potash (B. 17, 1832) and by the removal of CO, from oomenamic or dioxypicolinic acid (p. 538) (B. 18, R. 633), etc. (3) Trioxypyridinei: 1,3,5-Trioxypyridine, Triketopiperidine^ CjHjOjN, decomposes at 220-230®. It corresponds to phloroglucin (p. 165). It can be obtained by boiling glutazine with hydrochloric acid. Heated with ammonia it reforms Glutaxine, p-Imido- ghaarimide.^H : C<^[|*^^q>NH (?), melting with decomposition at 300®, which may be prepared by heating acetone dicarboxylic ester with ammonia (B. 20, 2655). Psrromecaxonic Acid is an isomeric trioxypyridine, obtained from pyromeconic acid with ammonia. Ferric chloride colors it a dark indigo-blue. 7. Pyridyl Alcohols: These are sometimes called //riV/|//rt/itiii«. They arise (i) in the ddol condensation of a-methyl pyridines with aldehydes on boiling with water ; (2) bom. theur HBr-esters, the homologous pyridines brominated in the side-chain ; (3) by the reduction of the corresponding ketones : l-Picolyl Alkine, C.H.N(CH, . CH,OH), boiling at I79«> (22 mm.), and i-Picolyl ' aH^NCH,(CHOI - and acetaldehydes (B 22, 2583; 23, 2709, ^725). i-Picolyl Trichlor-methyl Methyl AjUdne, C.H4NCH,(CIiOH)CH,, are obtained from a-picoline with formic Alkinc,C,H^NCH,CH(OH)Ca„ melting at 87**, is formed from a-picoline and chloral. Alcoholic potash converts it into a-pyridyl acrylic acid (p. 538). P)rridyl-a-ethyl Alkine, C^H4NCH(OH)C,H5, boiling at 213® to 218®, is isomeric with a-picolylmethyl alkine. It is made by reducing pjrridyl ethyl ketone with sodium amalgam. I-Picolyl- 4-methyl Alkine, C5H,(CH,)NCH(OH)CH„ boiling at 240°, results upon boiling bromcollidine with water (B. 28, 1759). 8. Pyridyl Ketones : Ketones of the pyridine series are obtained in the distillation of pyridine carboxylic acids with fatty or aromatic acids (Engler, B. 24, 2525). They yield secondary alcohols, together with pinacones. by reduction. I-Pyridyl Methyl Ketone, (CH,CO)C5H^N, boiling at 192®. is prepared from calcium picolinate and acetate. Its oxime melts at 120°. Its phcnylhvdratone melts at 15S«. 2- Pyridyl Methyl Ketone, boiling at 220°, is obtained from calcium nicotinate and acetate. l-Picoline-4-methyl Ketone, C5H,(CH,)(COCH,)N, boiling at 233°, results upon oxidizing the corresponding alkine (B. 28, 1764). i-Pyridyl Ethyl Ketone, (CjHjCOjCjH^N, boiling at 205®, is changed by sodium and amyl alcohol to aethyl piperyl alkine^ CjHjCHrOH) . CjH^NH, which is identical with the pseudoconhydrint present in the conine alkaloids. 2-Phenyl Pyridyl Ketone, CjII^CO. CgH^N, boiling at 307® (B. 20. 1209), forms two isomeric oxinus^ melting at 142® and 162° TB. 29, R. 832). /i,>-Diacetyl a.a,- lotidine, C^H(COCH.)|(CH|).N, is produced by tne action of ammonia upon metlienyl- bisacetylacetone, (CH,CO),CH . CH : C(COCH,),— compare i, 478). i-Acetacetyl Pjrridine, (C^H^NjCO . CH, . CO . CH„ melting at 50° and boiling at 137-143'* (15 mm.), is obtained from picolinic ester, acetone, and sodium ethylate (B. 29, R. 846). 9. Pyridine Carboxylic Acids.— These acids of pyridine result upon oxidizing the homologous pyridines with potassium permanganate, when alkyl as well as phenyl groups are converted into carboxyl. The condensed pyridine derivatives — e,g., quinoline, isoquinoline, etc. — ^are similarly decomposed, the benzene rings being ruptured and oxidized to carboxyl. Hence, most alkaloids, being pyridine derivatives, yield these acids upon energetic oxidation. 536 ORGANIC CHEMISTRY. The lower acids can be prepared from the pyridine polycarbozylic acids by heating them with hydrochloric acid. Usually, in this treatmcDt it is the COOHgrou]>s, occupying the a-position, which are split off. Uix)n heating with lime all the carboxyl groups are eliminated and pyri- dine is formed. The pyridine carboxylic acids, like the other pyridiDe derivatiTes, are reduced by sodium and alcohol to piperidine carboxylic acids. A number of pyridine carboxylic acids are reduced by sodium amalgam in aqoeoos- alkaline solution to laciomc adds of the fatty series. The group — CH = N — CH =i$ then converted into —CO— O — CH, — (B. 25, R. 904; a6, R. 8; ay, R. 193, etc.). As the pyridines are bases, their acids manifest the chanicter of amido-adds. Tbe basic properties disappear with the polycarboxylic acids. The methods of determining position or place in the monocarboxylic acids have been given on p. 531. Of the dicarboxylic acids, quinolinic acid, because of its formation from quinoline (p. 527), must be the «,/?-(]! carboxylic acid, and cinchomeronic acid, because of its production from isoquinoline (p. 554), must be the /?,y'-di carboxylic acid. A. Pyridine-mono-carhoxylic Acids : I -Pyridine Carboxylic Acid, Picolinic Acid, C5H^N(CO,H), is obtained by the oxiilatiun of a-picoline. It melts at 135-136°, and sublimes. I'crrous sulphate imparts to its solutions, as well as to those of all pyridine carboxylic acids having the carboxyl group in the a -position, vl. yelltnu-red co\or. 2- Pyridine Carboxylic Acid, Nicotinic Acid, was first obtained by oxidizing nicotine. It is also prepared from /^-picoline, as well as from /3-cyanpyridine. It melts at 228-229°. Its iodmethylate forms a bffaffte^ C5H^(COO)N . CH,, which is identical with the alkaloid trigonelline (p. 564). 5-Chlornicotinic Acid, melting at 199°, is olttniried from oxyiiicotinic acid, and when heated with ammonia becomes 5-Amido- nicotinic Acid, which changes to a-amidopyridine on heating, and by nitration yields 4,5-nitroamidonicotinic acid, melting at 280°. The reduction of the latter yields 4.5-diamidonicotinic acid. i-Amidonicotinic Acid, from quinolinamic acid, also yields a amidopyridine on the application of heat, and by nitration becomes nitroamido- nicotinic acid (B. 27, 1317; A. 288, 253). 3 Pyridine-carboxylic Acid, Isonicotinic Acid, is obtained from > -methyl pyridine, or from cinchomeronic acid, by the spliuing-off of CO,. It melts at 304°. Homolo}^ous Pyridine Monocarboxylic Acids : 3-Methyl- 1 -pyridine Carboxylic Acid is obtained on heating uvitonic acid when iCOj splits off. It sublimes without previously fusing. 3 Methyl-nicotinic Acid results on heating methyl quinolinic acid. It melts at 210°. 1,3 Dimethyl-nicotinic Acid, C5H,(CH,)2N(CO,H). Its ethyl ester results in the condensation of acetoacetic ester with aldehyde and aldehyde-ammonia. The free acid contains two molecules of water of crystallization. H. Pyridine Dicarboxylic Acids : 1,2 Pyridine Dicarboxylic Acid, Quinolinic Acid, CjH,N(COOH),, melting at 190° with decomiK)sition, is obtained from (]uinoIine and from I- and 2-methyl -quinoline by oxidation with ix)tassium permanganate (H. ig, 293). llie oxidation of p-oxyquino- line with bleaching lime yields an intermediate product, carbopyridyl glyceric acid, ('jIIjN :",.!. Qjjv rnrOincOOH' ^^^^^ changes with ease to acetonicotinic acid^ ^^^^^.rc\c\\ (compare II. 26, 1501, and decomposition of /3-naphthol and naphtho- quinone, pp. 392, 393). The anhydride melts at 134° and the imide at 230® (A. 288, 257). 2j-Pyridine Carboxylic Acid, Cmchorci^tomc Kcxd^v^oVAaiuedftomcinchooine qXYPYRIDINE CARBOXYLIC ACIDS. 537 •nd ctnchooidme by oxidation with nitric acid and by the oxidation of isoquinoline with potassium pennanganate. It mehs at 266^ with decomposition. It yields an unhydridi^ C^H.N(CO),0, melting at 67^. Sodium amalgam reduces it to cinchonic add, C^HgOf, whicn breaks up into CO,, and hydrocinchonic acid or dimethyl maleic anhydnde on application of heat (B. z8, 2968 ; i, 465). The methyl betalne of cinchomeronic acid is Apophyllenic Acid. 1,3-PyTidme Dicarboxylic Acid, Lutidinic Acid, C^II,N(C(X)H), -f 2H,0, melts at 235^* ^A. 247, 37). 1,4-PyTidine Dicarboxylic Acid, isocinchomeronic acid^ crystallixing with i-i>^ mols. of water, melts at 236^ (B. 19, 1311). 1,5-Pyridine Dicarboxylic Acid, Dipicolinic Acid, melts at 225^ (A. 247, 33). 2,4-F^dine Dicarboxylic Acid, Dinicotinic Acid, melts at 314^ (B. 19, 2S6). Homologous Pyridine Dicarboxylic Acids : 3-Methyl-quinolinic Acid, 05113(01!,) N(C0,II)3, is produced upon oxidizing y-methyl-quinoline with potassium permanganate. It mells about 186^ with decomposition. I-Mcthylpyridine 5,3-dicarboxylic Acid, Uvitonic Acid, 05(01!,) I I,N(0OOH)„ is formed when alcoholic ammonia acts upon pyroracerruc acid. It melts at 244^. LfUtidine Dicarboxylic Acid, i,5-Dimethyl-2,4pyridine Dicarboxylic Acid, C|H(CH,),N(0OOH)j, melting at 316°, is formed from methenylbisacetacetic ester and ammonia (compare i, 483, and A. 241, 31). (1. 3. 5 )-Trimethyl-pyridine-( 2,4) -dicarboxylic Acid, CoUidine DicarboxyUc Acid^ C^(CH,),N(0O,H),. The diethyl ester is prepared by the oxidation of dihydro-collidine dicarboxylic ester in alcoholic solution with nitrous acid. It is the starting-out substance for the preparation of a series of higher and lower pyridine carboxylic acids. C. Pyridine Tricarboxylic Acids: 1, 2, 3- Pjrridine Tricarboxylic Acid, Carbo-cin- chomironic Acidy 05H,N(OOOH)3 -f i)^H,0, melting at 250°, results ujKm oxidizing quinine, cinchonine (p. 572), various decomposition products of these alkaloids, and }'-methyl quinolinic acid, etc., with potassium pennanganate. Oonsult 0. 1897, ii, 308, for the esterification of this acid. 1, 3, 5 -Pyridine Tricarboxylic Acid, meltin}^ with decomposition at 145^, is obtained from symmetrical collidine (p. 532) or from uvitonic acid (A. 228, 29). 1, 3,4- Pyridine Tricarboxylic Acid, Bcrberonic Acid^ obtained by the action of nitric acid upon the alkaloi<1 berberine, melts at 235° (B. 25, R. 582), i,2,5-P3rridine Tricarboxylic Acid, ( -f 211,0), decomposes at 130° (B. 19, 1309). D. Pyridine Tetracarboxylic Acids: 1, 2, 3, 5 -Pyridine Tetracarboxylic Acid, CjHN(0OOH)4(-f- 2H,0), melting at 227°, is obtained from collidine carboxylic acids, or iiomjlavenol (p. 546), a quinoline derivative (B. 17, 2927). Oonsult B. 19, 1309, for the 1,2,4,5-tfriV, etc. E. Pyridine Pentacarboxylic Acid, 05N(00,H)5 -|- 2H,0, decomposing at 220°, is formed by the oxidation of collidine dicarboxylic acids. 8. Oxypyridine Carboxylic Acids: The views expressed on p. 534 relative to the oxypyridines or pyridones apply to the constitution of the oxypyridine carboxylic acids. The latter are obtained with re- markable ease from the corresponding pyrone carboxylic acids by the action of ammonia. When heated they break down, as a rule, quite readily into carbon dioxide and pyridones. A. Monoxypyridine Carboxylic Acids : I -Oxyp3rridine-4- carboxylic Acid, Oxy nico- tinic Acid, 05H4ON(0OOH), melting at 303®, is produced when ammonia acts upon coumalic acid ester, and by the elimination of carbon dioxide from oxyquinolinic acid. i-Ozypyridine-2-carboxylic Acid, melting with decomposition at 255°, is made from i-amidonicotinic acid (p. 536), and in various other ways (A. 288, 265 ; M. 9, 145). 3- Oxypyridine- 1 -carboxylic Acid, Oxypicolinic Acid, (-f 1 1,0), melting at 250°, is produced by the action of ammonia upon comanic acid (p. 522). i-Oxyp3rridine-4,5- dicarboxylic Acid, Oxyquinolinic Acid, 05!lsON(0O(JH),, decomposing at 254^, is obtained from quinolinic acid by the potash fusion, or from its methyl ether, methoxyquino- linic acid, melting at 140^, which results when potassium permanganate acts upon amido- carbostyril ether. 3-Oxypyridine-i,5-dicarboxyV\c Kcvd, AmmonchcUdomc Ac\d^ Ckelidamu Add, is obUuDed by the action of ammoniai w^n c^«\v\oiC\c v^ia^ V^. V^> 533 ORGANIC CHEMISTRY. i,3-Dimethyl-5-pjrridone Carbozylic Acid, Pseud&lutidaOyrU Carh^xylU AcH C.(C'n,),II,ON(C(X)II), results upon heating HCI-/)-amidocrotooic ester to lyiP (B. 14, R. 632). n-Phenyl Lutidone Carbozylic Acid, CjH(CH,),(C,H.)ON(C00H), b similarly produced, together with y-oxyquinaldine» upon heating jS-anifidocrotonic etfer. 1,5 Lutidone-2,4^icarboxylic Acid, C5(CH,),HON^CCK>H)„ melting at 267<>, result! when ammonia acts upon dimethyl pyrone dicarboxyhc ester. Pentachloride of phoi- pliorus converts it into 3-chlorlutidine dicarboxylic acid, melting at 224^, whidi yields 3aniidolutidine dicarboxylic acid with ammonia at 150° (B. 27, 1323). K. Dioxypyridine Carbozylic Acids : Dioxypicolinic Acid, C5H^O^(C00H). Cornenamic Aiufy is derived from comenic acid (p. 522) by aid of ammonia. 1,5-Diozyisonicotinic Acid, Citrazinic Acid^ is formed when dtnmide, CONH,C (On)<^.{ j> * ^'qJJ|{'. is heated with concentrated sulphuric acid. An aldehyde dicarbozylic acid, C5H,(),N(COOH),(CHO) (B. ag, R. 110$), is obt.iine<l in the action of chloroform and caustic potash upon citrazinic acid. 9. Pyridyl sul>stituted acids of the fatty series are not very numerous. Certain pfridjl lactic acids, because of their relations to the alkaloids, have been investigated : a,2Pyridyl Lactic Acid, C^H^N . CrOH)(CH.)COOH, b formed, along with tri- methylnniine, in the decomposition of the i\VM\ov\ pilocarpine (p. 564). Phosphorus tri- l»romi(le converts it into pyridyl brompropionic acid, CHiNCBrCH, . COOH. The homoIoRous picoline-a lactic acid, [C5(CII,)H,N]C(OH)(CH,)C(X)H, is obtained liy sa|)onifyinfT its nitriU^ the cyanhydrin of picolylmethylketone (p. 535) (B. 28, 1765). /^.i Pyridyl-lactic Acid, C^ILN . CHjCH (OH )COOH, melting at I25^ is preparoi by decomposing its ^rM<>-<AA>r/<?(f, trichlormeihyl picolyla1kine,C5H^NCH2CH(OH)CCl| (p 535)t ^'i(^ so<la, whereas with alcoholic potash the product is — Pyridyl a-acrylic Acid, CjH^N . CH : CH . COOH. Bromine converts this acid into pyridyUibrompropionic acuf, and hydrobromic acid changes it to pyridylmonobronKfro- pionic acid, ^^M^. CllHr. CH, . COOH (A. 265. 22i). a,2-Picoline Acrylic Acid, [('5(('n5)n,NjClI( :CIl2)COC3H, is obtained from picoline brompropionic acid, the reaction product of PBr, and picoline lactic acid. HYDROPYRIDINB DERIVATIVES. Hydropyridincs, and, indeed, the perhydrogenized products,— the pipnidint'Sy — are produced when the pyridines are reduced with zinc and hydrochloric acid, or, l)etter, with sodium and boiling alcohols, and by eicrlrolysis (H. 29, R. 1122 ; C. 1897, I, 388). a. llantzsch obtained dihydropyridine derivatives in the p3rridine syntheses from aceto- acctic ester and aldehyde ammonias. They part verj' readily with two atoms of hydrogen and revert to pyridines. Further, several dihydropyridines have been obtained as liquids* with {)enetratin}; mlor and easily rcsinitied, by the action of caustic potash upon alkyl' pyridinium iodides (It. 14, 1497). 1). Tetrahydropyridines^ Fipnidelues : Tetrahydropicoline, C5TIg(CHj)N, boiling at 132°, is ol>taincd from rf-amidobutylmethyl ketone by ring-formation (B. 25, 219O * A. 294, 135) : CHj.CHj.NH, ^CH,.CH,.NH CH, . CH, . CO . CH, CH, . CH : icH, ' The letrahydropyridines include a series of bases, which have been prepared from th ^ pilH-ridincs by the action of bromine and sodium hydrate, or iodine and silver oxide, c?* by the exit of water from the oxypipcridines. Thus, the conicelnes result from th^ action of phosphorus pcntoxide ui>on conhydrin (p. 5^^)* The n alkyl derivatives of the pyridones (p. 534) and the dioxypyiidines or glutacon. ' imides arc to be viewed as >&^/^-derivatives of di- and tetrahydropyridines. c. IlexahydropyridineSy Piperidines : Hexahydropyridine, Piperi-^ dine, FeniamethyUntimidc^ ^^»<^Ch\- c!a*^^"> boiling at 106^, is ^ PIPERIDINE DECOMPOSITION. 539 dissolving quite readily in water and in alcohol. Its odor is like pepper. It occurs attached to piperic acid (p. 285) as piperine in y and is produced when piperine is heated together with alcoholic . It may be synthesized (i) by heating pentamethylene diamine :hloride ; (2) by heating e-chlor- and e-bromamylamine with caustic (previously mentioned) ; and (3) by the reduction of pyridine, bich it passes when heated with sulphuric acid to 300^, or, better, itrobenzene to 260®, or by boiling with silver oxide or silver ; in glacial acetic acid (6. 25, 1620). ymposition of Piperidine.-^The piperidine ring is ruptured in the followiDg s : nben piperidine (i) is heated to 3CX>** with hydriodic acid it is converted into am- nd n-pentane. lien piperidine is oxidized with hydrogen peroxide it changes to (5-amidovaleric e (3) and n-glatarimide (4). The decomposition by means of hydrogen per- ith the formation of (5-amidoaldehydes is observed also with the homologous MS. The (f-amidoaldehydes regenerate the piperidines with caustic potash, and livm bisulphite form piperidine sulphonic acids (H. 28, 1459, 2273). itric acid oxidizes piperidyl urethane (5) to y-carbethoxyl-amidobutyric acid (6), ields y-amidobutjrric acid or piperidic acid with caustic potash. )€issiam permanganate oxidizes benzoyl piperidine (7) to d-benzoyl-amido-n- icid (8), which is changed by caustic potash to d-amido-n- valeric acid (9) or leridic acid (B. 17, 2544). peridine and methyl iodide form dimethylpiperidinium iodide (10), which moist cide converts into dimethylpiperidinium hydroxide (ll). This breaks down, on on, into dimethylpiperidine, the A^-pentenyldimcthylamine (12) and water. If ^nyIdimethytamine be converted into A^-pentenyltrimethylammonium hydroxide id the latter be distilled, it will break down into piperylene (i, 99) or [1,4-pen- (14), trimethylamine, and water (A. W. Ilofmann, Ladenburg, B. 16, 2058; ; the decomposition of the pyrrolidines, p. 461). The diagram  ' \ / r, CH, CH, [, CH, CH, CO,H CH, CH, (3) NH, CH, CHO I I CH, CH, \ / CH, t (7) N— C0C,H5 / \ CH, CH, CH, CH, X/ CH- (4) NH / \ CO CO I I CH, CH, \ / CH, NH, CO,H CH, CO,H CH, ciu (8) NHCO.CgHj CH, CO,H ^ I I -" CH, CH, \/ CH, (9) NH CHj "I CH, CH, CO,H CH, :h, I .1/ N I, CH, I, CH, CH, (11) CHj CH, OH X|/ N /\ CH- CH, CH, CH, \ / Cl^ (12) CH, CHj \/ N / CH, CH, \ CH, CH, CH / (13) N(CH3),OH (14) N(CH,), CH, CH, ■> I X / CH. CH CH 540 ORGANIC CHEMISTRY. Piperidine, being an imide base, is capable of fonning a nitroso-oompooiid, iMdkyt- and n-acid-derivatives : Nitro80pip«ridine, CHj^N . NO, boiling at 218^, resolu from the action of nitroBS acid upon piperidine. By reduction it becomes Fiperylhydnsine, C^HmN.NH^ 1x)iling at 146^. See B. 30, 535, for the electroljrtic redaction of nitrosopiperidine ind the formation of dipiperidyl. n- Methyl Piperidine, C^H^qN . CH,, t»ik at 107'. n-Ethyl Piperidine boils at 128^ n,x-Brompropylpipendine and trimethylm C\\ piperylium bromide, QH,,: NBr<^|j«>CH,. See B. ag, 2389. The great reactivity of piperidine with brom- and iod-benzenes, resalting in the pro- (luctiun of n-phenylpiperidine (B. ai, 1921), is very peculiar. This power is ▼eryms- terially reducctl in the case of a-methyl piperidine (B. 23, 1388). n-Phenyl Piperidine, CjHipNCfll,, boib at 250^*. n-a- and /9-Naphthyl Piper- idine, boiling at 215° and melting at 56^, are obtained without difficulty from the naph- thols and pii)eri(line (B. 29, II 75). n- Acetyl Piperidine, CglljoNCOCH,, boils at 226^. n-Benaoyl Piperidine, CgllioNCOC^H}, melting at 48^, condenses when heated with benzaldehyde to dibenxrl- pyridine (p. 532). Piperidyl Urethane, C.H,^NCO,C,H,, boils at 2li». The oxidatitm of benzoyl pi]>eridine and piperyl urethane leads to the rupture of the piperi- dine nucleus. See p. 539. Piperine, the alkaloid, is the piperide of piperic acid. Tlie fiomohi^ous piperidinfs result when the homologous pyridines are reduced with sodium and alcohol. They are called pipecolines, C.H0(CH,)NH, lupetidines, C5l^(Cn,),NH, copellidinea, C5H8(CH,)(C,H5)NH, etc. (compare B. 28,2270.) The alkyl pi|)eridines contain asymmetric carbon atoms, hence different members of this class of bases have l>een decom{X)sed, by means of their bitartrates, into optically active comiMinents — e, ,^^, a-pipecoline (B. 29, 43, 422), the copellidine, boillDg at 163^ (ii. 29, 1959), ol)tained from aldehyde collidine, and /3-propyl piperidine, Uiiling at 174° (B. 30, 1060), isomeric with conine, which has been synthetically pre- pare<l from f-chlor-/?propylamylamine. a,a|-Diphenyl Piperidine melts at 69^ (B. 30, 1499). n Methyl apipecolyl Alkine, C5H,[CH(()I1)CH,]NCH„ boils at 215®, ind 11 Methyl «-vinyl piperidine, C5H,(C,H,)NCH„ boils at 162° (C. 1897, 1, 386). Triacetonamine and vinyl diacetonamine (1,219) ^'^ keto-derivatives of the pil>eridine series : p.. .CHj — QCIIj),. j,jT p^ XH, — CH(CH,) «.. xTu ^^<CIlj — qcilj),-'^" ^"<CII, — CH(CH,),-^^"- They are produced in the action of diacetonamine upon acetone and benzaldehyde. The oxiffte of the vinyhliacetonaraine, melting at 151°, yields upon reduction, depending upon the prevailing conditions, two stereoisomeric >-Amidotrimethyl piperidines, NH,CII<^J^«~^[Jij^^J*^>NH (n-^rt// melting at 26° and Iwiling at 84-86° (20 mm.) ; the pbady^ an oil, boiling at 82-84° [22 mm.]), which nitrous acid clianges to two stereoisomeric vinyldiacetonalkamines, or }-ozy- trimethyl piperidines, C5ll7\(On)(CIl5)j, melting at 138° and i6l«*. The latter is rearranged by sodium amylate into the first (A. 294, 336). Sotlium and alcohols reduce the pyridine carboxylic acids to piperidine carhoxylii at ids : Pipecolinic Acid, C5H,oN(COOH), melting at 261®, is resolved by the bitartrates into d- and l-pii-tocolitiic acids, melting at 270° (B. 29, 2887). Hexahydroquinolinic Acid, CjIItpNiCXJOil), has been obtained, similar to the hydrophthalic acids, in two stereo- isomeric forms, melting at 227° and 253**, of which each in the form of its niiroso- com{K>und can be decomitosed into two optically active forms (consult B. 29, 2665). Hexahydrocinchomeronic acid melts with decomposition at 256° (B. 29. 2187). Eucaine, derived from triacetonamine, is an oxycarboxylic acid derivative of the piperi- dine series. It is a tetramethyl-n-inethyl-)'-benzoxypiperidine->'-carboxylic ester, (CIl3)N<^J^,j^Y ~ iru > ^ ""^CC^OcIl *• ^^"^** ^■^ **^" recommended as a substi- tute for cocaine as an anxslV\e\AC ^C. \^^,\\,iw^. QUINOLINE GROUP. 541 Coninfy or a-propyl pii>eridinc, tropint\ and t\\\^onine arc other impor- tant pi{x.*ridine compounds. They arc alkaloids or dec (;mi)osition proihicts of the latter. They will be discussed later, in the chapter relating to alkaloids. Ccmdensed nncld, obtained from pyridine, have been prepared in great numbers, and are arranged in the following groups: II. Quinolines. HI. Coruiensed Quinolines —. /. ^., nrnpotboaoinolines, anthraquinolines, phenanthrolines, quinoquinolines. IV. ho- ptmoima, V. Phenanihridines, VI. Naphthyridines and Naphlhinolines. VII. Acridimes (carbazacridines, quinacridines). VIII. Anthrapyridines, 'Ilie alkaloids ■Itodi themseWes as a distinct chapter to the preceding bodies. II. QUINOLINE GROUP. The quinoline bases, or benzopyridine group, occur with those of pyri- dine in bone-oil (coal-tar), and are obtained by distilling different alka- loids with lime. The parent substance of the group was first obtained by Gerhardt (184a) from the alkaloids quinine and cinchonine. As regards synthetic methods, transpositions, and isomerides, quinoline is a naphthalene in which an a-CH-group is replaced by N. Uris was first shown by synthesizing quinoline from allyl aniline. This is perfectly analogous to the synthesis of naphthalene from phenyl butylenc (p. 390) (Kdnigs) : q.H,. NH . CH. . CH : CH. = C,H,/^j^-gJ AUyl Aniline Quinoline. A more direct proof of the constitution of quinoline was effected through its formation fifom hydrocarbostyril (p. 391) ; PQ^ converts the latter into a dichloride, which u|X)n heating with hydriodic acid yields qumoline (A. Baeyer, B. 12, 1320) : Hydrocarbostyril o/S-Dichlor-quinoline Quinoline. A *< diagonal formula" has been suggested for quinoline because of its production in the distillation of acridine : Owing to the intimate genetic relations prevailing l)ctween the quinoline and pyridine derivatives we most assume for the pyridine nucleus of quinoline the same linkages as in pjrridine itself (see p. 526). Furthermore, later researches upon the formation of quino- qninolines (p. 553) from quinolines afford additional proof against the "diagonal Isomerisms of the Quinoline Derivatives : Wc represent the three replaceable hydrogen atoms of the pyridine nacleus in quino- line by a, fif and y ; those 01 the benzene nucleus with i, 2, 3, and 4. CO 542 ORGANIC CHEMISTRY. The positions i, 2, 3, referred to the N-atom, correspond to the ortho-, metm-. and ytn- |N>sitions uf the benzene derivatives; 4 is known aa the ^ita-position. These positiou are <lesitpiate<l as the aflinitics of the benzene nucleus with o-, in-,-p-, and a. Anotlwr nomenclature desi(;nates the affinities of the pyridine nucleus as I^-l, -2, and -3; those of the lienzene nucleus as U- 1, -2, -3, and -4. Consequently, seven mono-derintiTesof quinoline are possible (B. 19, K. 443). Syntheses of the Quinoline Derivatives : 1. The coiulensalion of the ortho-amido-compounds of such beDzene derivatives as have an oxygen atom attached to the third carbon atom of the side-chain. In tills way we obtain quinoline from o-amido-cinnamic aUekydet Q^ ' 4 r 1 1 * . r 1 1 C(~)H " *"^^^^y' -quinoline from o-amiJo- cinnamu mtthyl ketone^ and u-oxy-quinoliue (carbustyril) from o-amido-cinnamic acid. 2. Tlic condensation of o-amidobenzaldehyde or o-amidobenzoketones with sul)stances containing the group — CHj — CO — (^. ^., aldehydes, ketones, acetoacetic ester, nialonic ester) to quinolines by means of sodium hydroxide is dc{)endent upon the intermediate formation of such o aniido-derivalivcs (Friedlander, B. 16, 1833; ^Si ^750 • /Clio CII, /CH = CII ^•"*\Nn, "^ CO. CII, ■^^•"*\N^(^CH, o-AniKl(ibvnzalilch)cle Acetone a-Methyl Quinoline. ^-()xy<iuinolincs arc similarly formed from anthranilic acid (p. 211) wiih aldehydes, ketones, etc. (Ch. Zt. 17, Rep. 258; see also B. 28, 2S09). The synthesis of (juinoline from o-toluidine and glyoxal and that of /?-<ixv(]Minaldinc from o-toluidine and pyroracemic ester are similar (H. 27,628; 28, R. 743): /CIL OCII /CH = CH 3. The i)r()duction of (luinoline and its derivatives substituted in the ])enzcnc nucleus by heating anilines with glycerol and sulphuric acid to about 140°, with the addition of nitrobenzene, or, better, arsenic acid ( 1>. 29, 70.^) as the oxidizing agent. This method is of universal appli- cation, and can be very readily executed (Skraup) : C„II,. NH, -f C,II«03 = C,IT,N(C3H,) -f 3H,0 + H,. Aniline Glycerol Quinoline. It is very i)robal»le tlint acrolein first results, this then combines with the aniline <l<.*rivjitive yiehlinj^ acroleln-aniline, which is oxidized to the quinoline derivative by the elimination uf two hydro>^cn atoms l)y sulphuric acid. The halogen, nitro-, oxyanilines. toluidiiies, etc. , beliavc similarly. The naphthylamines yield the naphthoquinolines ; and the (liamidobcnzcncs, the phenanthrolincs. Instead of using a mixture of the aromatic aniline and nitrobenzene, the correspond- ing; nitro b(Mly alone can be employed, which then is reduced in part by the hydrogen arising; in the reaction. T)ic first synthesis of this description was the preparation of alizarin blue (p. 554) from nitroalizarin (p. 427), glycerol, and sulpliuric acid (A. 201, 333)- SYKTHESES OF QUINOLINE DERIVATIVES. 543 The following may be regarded as further generalizations of these syn- 4 (a). Quinolines substituted both in the benzene and pyridine nucleus U€ produced in the condensation of anilines with aldehydes, aided by sulphuric or hydrochloric acid {Quinaidine syntJuses of Doebner and v. Miller). Aniline and acetaldehyde yield a-methyl quinoline or quinal- dine: C;H,. NH, + 2C,H,0 = C.H,/^"J ™j ^ + 2H,0 + H, a^Methyl Quinoline. All aldehydes of the formula CHO . CHjR react like acetaldehyde. The first step in the reaction consists in two molecules combining to un- saturated aldehydes, CHO . CR : CH . CHjR, or condensing to aldols corresponding to them. These then act upon the anilines and form quinoline bases with a CHs-group in the a-position. It is very probable that alkylidene anilines formed at first change to dimolecular, aldol-like condensation-products, which split off aniline and become quinaldines (B. 25, 2^^ \ 39> 59 * compare formation 2 of the indols, p. 466) : •™.-<=«-<^«.— ^5":™-!!j|-.c„.=^=^^<'i6c„.- The hydrogen set free sometimes occasions a partial reduction of the reaction-product to tetrahydroqainoline derivatives (p. 550). (b) Instead of two molecules of the same aldehyde, a mixture of two aldehydes, or an aldehyde with a ketone, may be used ; in the latter case a,x-di- or a,/3,7-tria1kyl quinolines are formed (C. Beyer, B. 20, 1908) — e, g.: CH, CHj C.H.. io.CH. > ch/^ = ?' ^NH, 4- CHO . CH, • *\N = C.CH, a,Y-Dimethyl Quinohne. (c) a-Alkylcinckoninic acids (a-alkyl-quinoline-y-carboxylic acids) are produced by the interaction of a mixture of pyroracemic acid and an aldehyde upon aniline (p. 549) (B. 281, I) : CO.H ?'" A C,H, . NH, -h CO . CH, = C;H/ ^CH + 2ll,0 + H,. CHO.R \ ^C.R This is a reaction which, particularly when naphthylamine is substituted for aniline, proceeds so smoothly that the production of naphtho-cinchoninic acids may be applied as a test for the detection of aldehydes in mixtures. I'yroracemic acid alone, when heated with aniline, yields the a-methyl quinoline-y-carboxylic acid (aniluvitonic acid), together with phenyl latidone ; thb is because aldehyde is formed from one molecule of the pyro- ncemicadd. 5. Oxyquinoline derivatives are obtained from aniline derivatives of /9-ketonic acids and /9-dicarboxylic acids by a ring formation (L. Knorr^ B. 17, R. 147; A. 236, 112). zus hexed u iio"i, -mtfhyl Gv- JiTi. :t -C 2SS- r I^ Z54J : . .. . : :h =c.co.r r: J. -. i*. . . 1 1 i: 1.=. : ^ : : i . * . ■ vi. i.1- 'juiu.'.int -. D. " i. » ■ •:•! :i<. ijj :■«= :*icr.:^-: upcn p. 4r'7- ...ri .c Viiiiz* =iet2v" ke:o'. wrJi sodium alco- ire '. :_ is whicr. ciss-jive wiihdiffi- i: i n'.'rt'. ir.i p.-j-^e^s a jeretrating ^ :T::.ir-. ':j.>es. iwc like ihem form: --:■:::.-' >i>^^. B. 28, R. 617). The ::i-ur.ii5 are rVrmed by their union with • :":r alkv". :-:^:de> is, however, limilai 1'^ I resent in ihe quinolines (R 24, -■r a\\.\'. -uir.iliriium i<x]ides are unstable. ju>t lik« tl. •- rr! ly srtaiium hydroxide that dihydnvjuinoinn :.- ari; furmed side by side (A. 282, 363) : ^n, OH CH / CH CH _/" \N(CH,)— CO M;i(Miihriiif |i|ii/- dyrs, the Cyatiines, which, however, are unstable, and the constitu- ii'.ii i,\ whif h \\ not flrJiniirly known, arc obtained by treating mixtures of alkyl quino- hnniiii iiHliflis iiiid InmioloKouR alkyl quinolinium iodides with caustic potash (B. 18, R. QUINOLINE. 545 When the quinolinium hydroxides are treated with alcohols, water splits off, and ah 0- kOaUs (— N <^^ \ remain. 3. Quinoline, like pyridine, is but slightly attacked by nitric acid or chiromic acid. Potassium permanganate, however, destroys the benzene nucleus in them, with production of a,P-pyndine dicarboxylic acid (quino- linic acidy p. 536). The homologous quinolines, containing the alkyl groups in the pyri- dine nucleus, and those containing the substituents in the benzene nucleus are oxidized by chromic acid in the presence of sulphuric acid to the corresfxinding quinoline carboxylic acids, while potassium permanga- nate, on the other hand, usually oxidizes those substituted in the benzene nncleus, with the formation oi pyridine polycarboxylic acids (B. 23, 2252). PoUssiam peniumganate converts the a-alkyi quinolines, by the destruction of their pyri- dine nndetts, into tcid derivatiTes of o-amidobenzoic acid. By this treatment a-phenyl qiiiiioliiie yields benzoyl anthranilic acid (B. 19, 1 196). The pyridine nacleas is similarly ruptured by the oxidation of the quinolinium com- 4. The pyridine naclens of the quinolines, when reduced with zinc and hydrochloric add, takes np four atoms of hydrogen, with the pro<luction of tetrahydroquinolines. DeaihydroquinoHne finally results by more energetic reduction. The number of known quinoline derivatives is very great. To a cer- tain extent they have a technical value as antiseptics, antipyretics, dyes, etc. Only the more important members of this group will receive con- sideration in the succeeding {)aragraphs. Quinoline, C»H|N, is a colorless, strongly refracting liquid, with penetrating odor, which possesses a powerful antiseptic action. It boils at 239®; its sp. gr. = 1.095 ^it 20**. It occurs in bone-oil and coal-tar. It results when many alkaloids are distilled, and is best prepared syn- thetically by Skraup's method — /. ^., boiling a mixture of 38 grams aniline, 100 grams sulphuric acid, 24 grams nitrobenzene or arsenic acid, and 120 grams glycerol for several hours (B. 14, 1002 ; 27, 574 ; a9t 704). It forms crystalline and very soluble salts with one equivalent of acids; the characteristic bichromate, (Q,H7N,)Cr20,H2, dissolves with difficulty and forms yellow needles, melting at 165^. Its iodmethylate^ C,H,N . ICH3, melting at 72°, is converted by sodium hydroxide into n-methyldihydroquinoline and n-methyl-a-ciuino- line. Quinoline betahu, Q^^ . CH, . CO . O, melts at 171**. Its hydro- chloride is formed from quinoline and chloracetic acid. Di-, tetra-, kexa*^ and decahydroquinoline result from the reduction of quinoline (p. 550- HomolofOas Qoinolines. — The seven isomeric methyl quinolines are all known. The four qainolines, methylated in the bcnzenb nucleus, sometimes caile<l toluquinolines Oi wtahyatnzqMinoiines, are obtained by the reaction of Skraup from the three tolu- idiMs: o-methyl quinoline boils at 24&^, ihtpara at 257<*, the meta at 248<>, and the MM at 250^. 11—46 546 ORGANIC CHEMISTRY. a-Methyl-quinoline, Quinaldine, C,H9N(CH,), boiling at 247®, occnn in coal-tar (25 percent.) (B. 16, 1082). It is produced by the various sjrnthetic methods, by the reduction of y-oxyquinaldine, and by fusing ethyl acetanilide, CLHjN(C,H5) . CO . CH^ with zinc chloride (B. 23, 1903). It may also be obtained by digesting aniline, paralde- hyde, and crude hydrochloric acid for several hours (B. 16, 2465). Chromic acid oxidizes ii to a-quinoline carboxylic acid (see p. 545). The CH, -group of quinaldine is very reactive. It enters readily into condensation products with aldehydes (paraffin or benzene class) (B. ao, 2041). It combines with formaldehyde to a-oxethyi quitioline^ which by loss of water forms a-vinylfuinoline. C,He(C,H,)N (B. 27, 2689). Chloral yields the compound, C,H,N . CH : CH . CCl,. melting at 144° ; lx)iling potassium carbonate converts it into a-quinoline acrylic acid, CIH^N . CI I :CIl.CO,II, while potassium permanganate oxidizes it to a-quinoline aldehyde, C.IIfN.CHO. Hydrobromic acid and soda convert quinoline acrylic acid into a-quinoline-lactic acid (B. 21, K. 635; 28, R. 752^. Consult B. 22, 271, upon quinoline acrylic acids and quinoline aldehydes. Quinaldine, oxalic ester, and sodium elhylate yield quinaldim oxalic acid, (dH,N)CH, . CO . COOH (B. 30, 1479). Quinaldine and phthalic anhydride yield a beautiful yellow dye — quinophthalone or quinoline yellow, C^H^fC^O,) : CH . N . C^H, (p. 240), melting at 235®. The sodium salt of its sulphonic acid is the quinoline yellow of commerce. It dyes silk and cotton a beautiful yellow. See B. 29, 187, for the action of quinaldine upon phthalaldehydic acids. /3-Methyl Quinoline, CgH0(CH,)N (B. 20, 1916), boils at 250^* and melts at io-i4<>. y-Methyl-quinoline, Lepidine, occurs, together with quinoline and quinaldine, in coal-tar, and is obtained on distilling cinchonine with caustic potash. It may be syn- thetically prepared. It boils at 257°. Chromic acid oxidizes both methyl quinolines to the corresponding quinoline monocarboxylic acids. Potassium permanganate produces pyridine tricarboxylic acids. n,/i Dimethyl Quinoline, C9H5(CH,),N, boils at 261® (B. 22, 267). n,}^- Dimethyl Quinoline, l)oiling at 266^, is made from acetyl acetone and aniline, as well as from dihydrotrimethyl quinoline, which is produced by the interaction of indol and methyl iodide (p. 550). /^,} -Dimethyl Quinoline, from /?,> -dimethyl carbostyril, melts at 65° and boils at 290°. o- and p-Toluquinaldine, C,H5(CH,),N (B. 23, 3483). a-Ethyl Quinoline, CaHj(C,H.)N, boils at 255-2600, /?■ Ethyl Quinoline at 265<». I1iey result on beating ethyl quinolinium iodide to 250° (analogous to the formation of alkyl pyridines, p. 528). y- Ethyl Quinoline boils at 270-275®. Consult B. 21, R. 138, upon the trimethyl-quinolines. a-Phenyl-quinoline, C9Hg(CjH5)N, is obtained from cinnamic aldehyde and aniline upon heating them with hydrochloric acid to 200®. It melts at 84** and boils above 300®. Potassium permanganate oxidizes it to benzoyl anthranilic acid. /3-Phenyl- quinoline is an oil, which solidifies on cooling (B. 16, 1836). y-Phenyl-quinoline is formed from its acid. It melts at 61°. It is closely re- lated to the quinia alkaloids (B. 20, 622). See B. 27, 907 (p. 571), for T'-Quinoline Phenols. Nitrophenyl Quinoline, NOjC^H^. C^H^N, melting at 159®, is formed from iso- diaznnitrobenzene and quinoline (B. 29, 160). y-Phenyl-a- Methyl Quinoline, y-phmyl quinaldine, C,H5fC^H^)(CHj)N, results by the condensation of benzoyl acetone with aniline (B. 20, 1771). It melts at 99® and yields >- phenyl quinoline-a-carboxylic acid when its phthalone is oxidized with chromic acid. This new acid affords y-phenyl quinoline. a-Phenyl-x-methyl Quinoline is produced (B. 19, 1036) by distilling flavenol with zinc-dust. It melts at 65°. Its p-amido-derivative, Flavaniline, applied as a beautiful yellow dye (B. 15, 1500), is a-Amidophenyl->'-methyl-quinoline, CjH5(CH,)(C^H.NH,)N. It results in the condensation of o-amido-acetophenone and |vamido-acetophenone when digested with zinc chloride (B. 19, 1038). Its monacid salts are yellow in color and have been used as dyes (B. 15, 1500). Nitrous acid converts it into so-called Plavenol, C^H5(C^H4- OH) (CI f J ) N, a ,p. Phcny\-> tnclYiv\-<V>3^^^o\\T\^. OXYQUINOLINES. 547 Varioos ifomeric diquinolines, (C^IIfN),, have been prepared by boiling quinoline with sodium ; further, by conducting its vapors through tubes heated to redness, and finally from benzidine and other diamidodiphenylenes through Skraup's quinoline syn- thesis (M. 8, 121 ; B. 17, 1965 ; 20, 634, etc.). Diquinolyl Quinoline, QH.N. QH^. C^H^N, melting at 151^, is formed from y>acetacetyl quinoline, C^H^N . COCH,^OCH, (p. 549), with two molecules of o-amido- benzaldehyde (B. ag, R. 845)- Triqninolyl Methane, CH(C0H^N)„ melting at 202^, is obtained from pararosani- line by the reaction of Skraup (B. 24, 1606, 2267). Consult p. 357 for the opinion that aldehyde green is a quinoline derivative. 