PLACE IN RETURN BOX to remove this checkout from your record. TO AVOID FINES return on or before date due. MAY BE RECALLED with earlier due date if requested. DATE DUE DATE DUE DATE DUE 6/01 cJCIRCJDateDuepes-p. 1 5 Somo Chloro Derivatives of the Benzylphenola Some Chloro Derivatives of Benzylphenols BY Wayne Neel Headley Thesis Submitted to the Faculty of.Michigan State College of Agriculture and Applied Science in Partial Fulfillment of the Requirements for the Degree of’Maeter of Science. 1929 Acknowledgment The writer wishes to express to Dr. R. C. Huston his sincere appreciation for assistance and inspiration received during this work. Contents Page Historical (l) The Work or Claisen.,.................... l (2) The Werk or Friedel and Cratts,.......... 5 (3) Theory of Action of Aluminum.Chloride,... 7 (4) The WOrk of Huston,.....................o ll (5) Chlorination of Benzene Derivatives,..... 15 (6) Chloro Derivatives of the Benzylphenol Ether.,oeeeeoeeeeoo0.0900000000000006... 1-7 The Problem.Defined,...........................o. 18 Experimental,.................................... 19 summaryuuuuuunun"so..."no.”an"... 32 Photographs,......o........................... 33-36 Sch.” Of Condenaatipn,oeeeoeoooeeoeo090600006000 3" I... O c e o e e a a Q I a e O o 00.! D O O I O a DO.‘ '. COCO-OI. o \ Some Chloro: Derivatives of the Benzylphenols 1. The Iork of Claisen Claisen (Ber., 20, 646-650; Claisen and Low- man, Ber., 20, 651-654) in 1877 published his first mrk on the effect of sodium, sodium ethoxide, sodamide, or similar agents in effecting condensations between carboxy- lic esters with a ketone or carboxylic esters. His theory of the mechanism of this reaction as applied to the synthesis of acetoacetic ester may be illustrated as follows: -0 ' N8 ,ONa on. .c + ' __._ 7 CH; .C-0.C2H5 ' \0.C2He 0-02H5 0-CaHs ,ONa H\ , . . /0Na CH; .C~0 .0235 + H-C .COOCsHB __ CH: .C‘\ \0 eCBHS H/ 7 CH.COOCBH5 ' + ZCsHSOH The importance of this work to the present pro- blem is in Claisen's (Ann. 442,212) application of this method to the preparation of benzylated phenols. In this metknd, sodium phenolate is first prepared and dissolved, or suspended in a suitable medium and treated with the benzyl halide. The resulting product is a mixture of the possible mono or di-benzyl phenols, and an ether which may be removed by shaking the methyl alcoholic potassium hydroxide solution of the phenols with petroleum ether. Claisen states that while the other is the pro- duct one would expect to be formed, the benzyl phenol formed is the result of ring alkylation, whai one would naturally expect the benzyl group to take the place of the metal atom displaced. His discussion of the ortho substitution is based on Michael's Theory (J. pr. 31, 486; 46, 189) of the ,reaction between silver cyanide and methyl iodhie. This as applied to the reaction of a sodium.phenolate and an alkyl halide may be illustrated as follows: x'I - C - OH R___. - - N t v a 4. I 7 (:TONI J? -C-H - C-HR - c - o _____;r v - C - 0H - CHR > '5 R The most important factor in this reaction is the medium in which the reaction occurs. A.dissociating medium.yields mainly the other, while a non-dissociating medium.yields mainly the ring alkylation product. Thatthe nature of the medium.ie the main factor in determining oxygen or carbon alkylation is further support- ed by Claisen and Tietze (Ber., 583, 275,1925) who showed that when alkali phenolates were treated in non-dissociating media with unsaturated alkyl halides, such as allyl, there is obtained almost entirely carbon alkylation. Also by Ulaisan, Kremers, Bath and Tietze (Ann. 442, 210) who found from.the condensation of sodium.p-cresylate and allyl bromide in methyl alcohol, 90% oxygen alkylation while with benzene , I . ' . ' ‘ . . . k - - ‘ n U “I ' -‘ 4 ,.« -‘ h‘ A. . I. v - - - . - - - . o t‘ l‘ I _ A ~ . . r. H ‘ ‘ A ‘- r r - ‘ v , c, c g A: ‘L M e ‘ ‘. . .- §' - ‘ A ‘ e ' - . .‘- . a x g - : N . — u“ A‘ ' r I v . — ‘ i ' . - ‘ ' . . t. .4 .J . A, gs. . A : r i ' _ . - - - t I‘ . r , . t . -. ~._a - . . ' r . ‘ . ' . r- ‘ ’ . A ,. e . A. a ’ e ‘1 as the medium, 30% oxygen and 60% carbon alkylation. K. von Auwers, G. Wegener, and Th. Bohr (Chem. Z entr. 1, 2347-8, 1926) eXplain the formation of carbon sub- stituents from salts of keto-enols and alkyl halides. They discuss the following hypotheses: (1) (2) (3) "The initial formation of addition pro- ducts with subsequent splitting" (Michael). "The initial formation of normal oxygen derivatives, with rearrangenent of these into carbon derivatives". "The separation of the metal as a metallic halide, formation of free alkyl and enol radicals - -9=°L——>-2 ~9L O 0 and with.the slight reactivity of the alkyl group partial or complete rearrangement of the enol to keto radical, and finally union of the radical. (Wislicinus) The course of the alkyl ations of a keto-enol -depends upon its character and upon the alkyl' ation agent. Saturated alkyl halides promote the formation of oxygen der- ivatives,and allyl or benzyl halides promote the formation of carbon derivatives. These facts are well explained by the first hypothesis, which is also used by Claisen as the basis of his thsaries. The second hypothesis is inadequate, for it is not comprehensible why an oxupn derivative Should be transformed into a carbon derivative in benzene more easily than in alcohol. The third hypothesks, states that the oxygen derivatives should be formed with allyl and benzyl radicals because of their great reactivity. It is assumed that great reactivity indicates a large requirement for valence, while the opposite view is Just as probable and is upheld by the facts that allyl and benzyl groups are dis- tinguished by their slight valence requirements and so carbon substitution may be expected. Claisen's views also confirm.this, for he states that unsaturation in the allyl and benzyl radicals result in a comparatively loosely hell halogen, and furthermore that reaction mediums such as toluene ‘exert a loosening effect on the valence bonds between the alkyl or benzyl radical and the halogen. My Busch (Z. Angew Chem. 38, 1145-6, 1925) states that the tendency of benzyl radicals toward carbon alkyltion of phenols increases with the increasing substitution of the methane carbon. I. Busch and B. Knoll (Ber., 60 B, 2243—57, 1927) found that diphenylbronmethane with phenol, with or without a solvent in the presence of heat, gives the para hydroxy car- bon derivative, while sodium.phenolate under similar conditions gives the corresponding ortho derivative. K. von Auwers and Th. Bohr (Ber. 61B, 408-16, 1928) state that the halides of such radicals as are characterized by a small affinity consumption, such as allyl and benzyl, yield chiefly carbon derivatives; while true alkyls like ethyl and prOpyl, favor the formation of oxygen derivatives. 2. The Work of Friedel and Crafts The synthesis of organic compounds received an impetus in 1876 when Friedel and Crafts (Compt. rend., 84, 1392-95) in a study of the action of a1uminum.and its salts on organic substances, discovered the remarkable condensing powers of the a1uminum.halides. They investigated the condensation of alkyl halides and aromatic hydrocarbons in the presence of aluminum chloride. Further work has shown that aluminum.chloride may be put to the most diverse applications and consequently the react- ion has been used very extensively. The mechanism of the Friedel-Crafts reaction de- serves some attention here on account of its general application to aluminum.chloride condensations. Boeseken (Rec. trav. chime, (a) 19, 19-26, 1900; (b) 20, 102-106, 1901; (c) 22, 301-314, 1905; (d) 23, 98, 1904, (e) 50, 148-150, 1911) has put forward the view that the react- ions take place according to the following scheme: R C 0.01 + A101. - R C 0 Cl, AlCls R C 0 Cl, A101. + R'H - R C O R', A1013 + HCl R c o R', 1101. + IHgO a R c o R' + A101. +IxH20 where R'H represents an aromatic hydrocarbon or one of its derivatives. Schaarschmidt (Z. Angew. Chem. 57, 286-8, 1924) bases his explanation on the activation of the aromatic hydro- carbon (by the aluminum chloride) effecting a loosening of the bonds of the organic halogen compound. A primary complex is formed consisting of'metallic chloride, hydrocarbon, and addend, in which the metallic chloride is held by auxiliary valences . . O « . J . . " ' s ,. — r T I . ' e4! )J _ L ‘\ .~. T’ ‘ r _. I. ‘ . I .1 . h 2' ~ 1 I r . r ' ' . . . ‘c r . _. . , .‘ .. ‘ .f . r ‘ s ‘l l 9 J 'o‘ , ~ . . l ‘ .Ai. . r " l r .59, u . . . and the addend by ordinary valences. The stability of this complex depends upon the division of the inner valences and may pursue one of two courses, - the "mol course" or the "catalytic course". Several other theories have been advanced, but all are based on the formation of an addition compound bet- ween aluminum.chloride and the organic material. The reality of these intermediate addition products of aluminum chloride has been established by Gustavson (Ber., 11, 2151, 1878) who isolated an addition product of benzene, A1013, 3Cgfig; benzene and ethyl chloride, AlClso(Ucefle)2o5CeHg, (Comp. rend. 136, 1065, 1903; 140, 940, 1905). The work of Gustavson has been confirmed by Schleiehen (J. pr. Chem., 11, 105, 355, 1922). Other workers who have shown.the presence of ' addition compounds with aluminum chloride are Boeseken, (Rec. trav. chime, 20, 102-106, 1901; 23, 98-109, 1904). Kronberg, (J. pr. chem. ii, 61, 494-496, 1900) and.Menschutkin (J. Ruse. P Nye. Chem. 800., 41, 1053, 1089; 1909). Friedel and Crafts (J. Chem. Soc., 41, 116, 1882) stated that their reaction is usually impossible in the pre: """ sence of compounds containing the group OH or OR. MI 5’ 3. Theory of Action of Aluminum Chloride Agents commonly used in effecting condensations are:- zinc chloride, sulphuric acid, sulphuric and acetic acids, hydrochloric acid, ferric chlorhie, and aluminum chloride. Condensation processes are usually divided into two classes (Cohen-Part I, P 196): (1) Those in which the combining molecules are induced to unite by being rendered artifx3ally unsaturated as the result of withdrawing certain elements. (2) Those already unsaturated which axmbine either spontaneously or with help of a catalyst. The exact nature of the effect of aluminum chloride in condensations is not definitely known. The possible action may be one or a combination of all of the followirg general theorhes: (1) catalytic action (2) intermediate compounds (3) dehydration The catalytic action of aluminum chloride has been explained by Sabatier (catalysis in organic chemistry, p 794). His theory is the temporary production of a combination between the chloride and the organic substance. The latter would re- act immediately on the halogen derivative, yielding the product and regenerating the chloride. The use of largr amounts of aluminum.chloride in effecting condensations has caued some f0 doubt to the catalytic action of aluminum chloride. This, however, is due to the tardiness of the reaction in some cases and the desire to hasten it by formation of large amounts of the required intermediate compound, or in other cases, to the fact that aluminum.chloride is withdrawm.from.the reaction by the formation of stable compounds. I. Boeseken (Rec. trav. chim. 30, 148-50) de- scribes the catalytic action of aluminum. chloride as one made possible by the loss of free energy. Norris (Ind. Eng. Chem., 16, 184,1924) has studied the catalytic action of aluminum.chloride between tri- phenyl methyl chloride and ethyl ether and other similar re- actions. The action of aluminum.chloride infbrming inter- mediate addition compounds has been previously discussed in the work of Gustavson, Boeseken and.Menschutkin. The dehydrating action of aluminum chloride is illustrated by the work of Mars and‘Weith (Ber., 14, 187,1881) who prepared di-phenyl ether by the action of zinc or aluminum chloride on phenols. Scholl and Seas (Ann. 394, 111-177, 1912) found that, by means of anhydrous aluminum chloride, aromatic nuclei can be satisfactorily united, particularly in case of Eatones where elimination of hydrogen is accompanied by formation of new rings. By heating phenyl alpha naphthyl hatone and anhy- drous aluminum.chloride at 1500 for two and one-half hours they 'obtained benzathrone. In 1901 Jaubert (compt. rend. 132, 841-842) and Graebe (Ber., 34, 1778—1781) independently prepared aniline by the action of hydroxylanine on benzene in the presence of aluminum chloride. Frankforter and Kritchevosky (J. Am. Chem. Soc. 36, 1614-29, 1914) condensed pentane, benzene, resorcinol, etc., with chloral. Frankforter and Kokatnur (J. Am. Chem. Soc. 36, 1529, 1914) worked on the action of trioxymethylene on various hydrocarbons. This work was also extended by Frankforter ( J. Am. Chem. Soc. 37, 385, 1915 to include polycyclic hydrocarbons. Nametkin and Kursanov (J. Russ. Phys.—Chem. Soc., Chem. Pt. 60, 917-20,l928) have prepared diphenylmethane and di-benzyl-benzene by the dehydrating action of phosphorus pentaoxide on benzyl- alcohol in the presence of benzene. Other workers have used various condensating agents to split off hydrogen chloride. The earliest of them.was prob- ably E. Paterno (Gazz. Chim. ital. i, 589; ii, 1-6) who, in 1872 prepared benzylphenol and benzyl anisol respectively by the action of benzyl chloride on phenol and anisol in the pre— sence of zinc. In the following year Paterno, in connection with Fileti, (Gazz. Chim. ital. 5, 381-833) prepared benzyl phenol by means of acetic and sulphuric acids, also in 1879, in connection with Mazzara (Gazz. Chim. ital. 8, 303-305) he prepared benzylated cresol in the presence of zinc turnings. Perkins and Hodgkenson (J.C.S. 37, 721,1880) pre- pared benzyl phenyl acetate by the condensation of benzyl chloride and phenyl acetate in the presence of aluminum chloride. 10 Peratoner and Vitali (Gazz. chim. ital. 28, 197-240, 1898) treated benzylphenol prepared by Paterno's method with.su1phany1 chloride and obtained a chlor-benzyl- phenol. They were working with Nef's views on the addition of halogen and subsequent elimination of hydrogen chloride, according to which the chlorine atom aitered the hydroxy- pheny ring probably in the ortho position. J. Boeseken (Rec. trav. chum. 27, 10-15) con- densed dihalogen derivatives of benzene with acetyl and benzoyl chlorides in the presence of aluminum chloride. 11 4. The Work of Huston In 1916 Huston and Friedmann (J.A.C. Soc. 38, 2527) applied the dehydrating action of aluminum chloride to the condensation of aromatic compounds. They prepared diphenylmethane by condensing benzyl alcohol with benzene in the presence of aluminum chloride. They state that the yield of the product is greatly influenced by the amounts of the reagents and the temperature. As to the mechanism.of the reaction, they observed the formation of an intermediate product resembling the intermediate Iroduct of Friedel and Crafts reaction. . Two years later Huston and Friedmann ( J. A. C. Soc. 40, 785) extended this reaction to include secondary alcohols. They also studied the effect of aryl and alkyl groups upon the reaction and concluded that alkyl groups have a depressing effect (ethy1_r7methy1) while aryl groups, such as phenyl, have a stimulating effect. Huston (Science 52, 206-7) applied this reaction to the condensation of aromatic alcohols and phenols , pre- paring benzylphenol as follows: CeHsCHaOH + C3H50H A101. CaHsCcheHAOH + H20 2 This condensation had previously been accomplished by Paterno (Gazz. chim. ital. 2, 2; Ber. 5, 288) using zinc as a catalyst; Paterno and Mazzura (ibid 8, 303) in tin presence of’a mixture of sulphuric and acetic acids; Paterno-and Fileti (ibid 5, 381); with zinc chloride by Liebman (Ber. 15, Cs l2 Huston (J. A. C. Soc. 46, 2775, 1924) con- densed benzyl alcohol with phenol, anisol and phonetal in the presence of aluminum.chloride. He also condensed benzyl chloride with phenol in presence of aluminum.chloride and states that no definite date (c. f. Millers Chem., 55h Edition, revised by Armstrong and Groves, Part III, P 772) on this condensation is found in the literature. Huston and Sager (J. A. C. Soc . 48, 1955, 1926) applied the dehydrating effect of aluminum.chloride to saturated and unsaturated aliphatic and aromatic alcohols with benzene, and concluded: (1) that saturated aliphatic alcohols up to and including amyl alcohol do not react. (2) that unsaturated aliphatic alcohols, as allyl, do react. (3) that of the alcoholic derivatives of the aromath: hydrocarbons, only those having the hydroxyl group on the carbon atom adjacent to the rug react. Huston, Lewis and Grotemut (J. A. C. Soc. 49, 1365, 1927) extended the series of condensation of scanndary alcohols with benzene to include that d?secondary alcohols with phenol, in the presence of aluminum chloride. They ale: found additional evidence of the tendency of unsaturation on the alpha carbon atom to increase the yield of the product. l3 5. Chlorination of Benzene Derivatives Early workers in this field as Korner, (Gazz. chim. ital. 4, 305, 446, 1874) Hubner, (Ber. 8, 873, 1875) and Nolting (Ber. 9, 1797, 1876) concluded that acid groups direct a new substance to the meta positions, while the halogens, the hydroxyl group, and basic groups direct to the ortho-para positions. Thb hypothesis has been extended by Armstrong (J. c. Soc. 51, 258, 1887); Crum-Brown and Gibson, (J. C. Soc. 61, 367, 1892); Vorlander (Ann. 320, 122, 1902) and Holleman. For the purpose of this paper the work of Hal le- man ("Die directs Einfuhrung von substituenten in der Benjolk- ern" 1910) is sufficient. He states that the rule of Bell- stein (Handbuch der organischen chemie, II, 10; 3 edition) can hardly be described as very helpful. "If a substituent C enters into a compound CefllAB, hath A and,B exert an influence, but the group (A or B) whose influence predominates directs C to the place it will occupy”. He has suggested that if we knew the velocities of the two reactions - CgflsA + C - CeHaAC and CsHsB + C - CeHeBC we might be able to predict the course of the reaction. CsHaAB + C . CeHaABC and the ratio of the isomerides formed. He assumes in this postulate that A and B keep their ”directing influence" when the second substituent is introduced or that the "directing influence" of each is changed proportionally. He his shown 14 that the introduction of a third substituent into a di- substituted benzene derivative reveals for ortho-pars directing substituents the following diminishing series: 03711113) 1781-7 01 >011. and similarly for the meta directing substituents: coon) SOROH?N02 With this knowledge and the quantitative ratio in which the isomerides are formed, it is possibka to predict the action or C on a compound c.8118. A partial list or workers in this risk}; follows: 1. Directive influence a. Holleman Ber. 44,725, 2504, 3556, 1911; J. Am. Chem. Soc. 36, 2495, 1914; Chem. Rev. 1, 187, 1924. b. Fry 1. Am. C. Soc. 36, 1035-47; ibid 37, 855. c. Prins Chem. Weckblcd 15, 571-80, 1918. d. Fraser and Humphries Chem. News 126, 161-8, 241-3, 257—61, 1923. e. Pastak Rev. glu. sci. 36, 70-6, 1925. t. Blanksms Rev. trav. Chim. 21, 282, 1902. 8. Pfeiffer and Wiezflner Ann. 461, 152-34, 1928. 15 2 . Mechanism a. Boeseken ; Pros. Acad. Wetenschappen 14, 1066-81. b. Barnett and Cook Rec. trav. chim. 43,.262-5; 897-8, 1924. c. Prins - ‘ Rec. trav. chim. 44, 166-72, 1925. d. von Alphen . Rec. trav. chim. 46, 799, 1927; ibid 47, e. Blanksms Rec. trav. chim. 23, 200, 1904. t. Vorlander Ber. 58’ 1893’ 1925. A careful review of literature has shown.no very definite data regarding the chlorination of C>-<':- C>°H l (c.f. Peratoner and Vitali, Gazz. chim. ital. 28, 197-240, 1898). However, Zinche and Wilhelm.(Ann. 1904,334, 367,385) have brominated 4-hydroxydiphenyl methane yieldirg 5:5 di- brcm-4-hydroxy diphenylmethane, ' Br C) C H2C>B<3H but they do not state any proof of this structure. All: van Alphen (Rec. trav. chim. 46, 799-812, 1927) ins brominat- ed 4-hydroxy triphenylmethane yielding Br “080: H (C8 Hs)a 16 which he gives the name of 2 : 6 - dibrom 4-hydroxytriphenyl- methane. His designation of the position of the bromine atoms as 2 : 6 is misleading and evidently a mistake, flar with the hydroxyl group in the 4 position the bromine atoms as illustrated would occupy the 3 : 5 positions. His proof of this structure is that a similar brominated product cauld not be obtained from.bromine and 2 : 4 : 6 tri (diphenyl- methyl) - phenol, so it must be assumed that bromine is introduced into these positions. The above work lends confirm tion to tie hypoth- esis that in halogenation of groups of this nature the halog- em. enters first into the group containing the hydroxyl group, but no definite proof has been given. An attempt to determine the correctness of this theory will be part of the object of this paper. 17 6. Chloro Derivatives of the benzyl-Phenyl Ethers A careful review of literature reveals only a few preparations of such derivatives. Sintenis (Ann. 161, 345) prepared benzylchloroPhenyl other by adding chlorine to an alcoholic solution of the ether in which fredily pre- cipitated mercuric oxide was suspended. The bromoderivative was also similarly prepared. Auvers (Ann. 1907, 357, 85-94) has prepared 2, 4, 6 tri-chlorphenyl benzyl ether by boiling the substituted phenol with benzyl chloride and sodium ethoxide in an alcoholic sol- ution. He has also prepared the corresponding tri-bromo der- ivative and two di-brom.derivatives by the same method. Barv (Quant. J. Indian Chem. Soc. 3, 101-4, 1926) prepared by the means of leucotrOpe, the following ethars: (l) Benzyl o-chlorophenyl ether (2) Benzyl m-chlorophenyl ether (3) Benzyl p-chlorOphenyl ether (4) Benzyl, 2, 4 di-chlorphenyl ether Raiford and Colbert (Proc. Iowa Acad. Sci. 31, 287-8, 1924) have worked on the activating and retarding influence of groups in rings on the formation and reduction of others. 18 The Problem Defined The object of this work may be briefly outlined as follows: ~ (1) To determine the influence of chlorine in the benzyl and phenyl rings in regard to conicnsati cm of their derivatives. (2) To establish definitely that o-substitution accompanies the p-substitution in condensations with aluminum chloride and the ratio of such substitution. (3) To establish the position of halogens entering into the groups; H “CD-9"-“ H cnxd. ti o CH1©CJ 19 Experimental The Chloro-benzyl chloride used in these experiments was prepared by first making para chloro- toluene according to the method of Marvel and Mc.E1vain (Org. Syn. Vol. 3, pp. 33, (1923) ). This was then chlorinated according to the procedure used by Jackson. and Field (Ber. 11, 904, (1878) ). ' The product formed compared exactly in preperties with those given in the literature. ' The first condensation attempted was that of chlorobenzyl chloride and phenol in the presence of al- uminum.chloride. The method used was similar to that at Hustonfs (J. A. C. 800., 46, 2775, 1924) preparation of benzyl phenol, which procedure is quoted from the Journal. "Fifty grams of benzyl chloride and fifty grams of phenol were added to 100 cc. of petroleum.ether in which they completely dissolved; thirty grams of aluminum chloride was then added in small portions. The reaction was quite vigorous and was retarded by placing the vessel in cracked ice. The temperature rose to 350. Two layers were formd, the lower one of which was dark red and rather viscous. After twenty-four hours, the entire mixture was decompcn ed: "The third refraction gave 28.4 g. at 150-2000; 26 g. at 120-1800 (4 m); 10.2 g. at 180-2300 (4 m); and 21.2 g. of residue. The fraction obtained at 120-1800 was para benzyl phenol”. In the condensations carried out the reactants were of the following proportions: 0‘ 20 M01.Eq. Grams Chloro-benzyl chloride 1 50 Phenol 3 87 Aluminum chloride .5 21 Petroleum other 200 cc. The reaction preceded similarly to the one quoted above with the exception that the temperature re- mained at 18 - 209 without controlling by means of ice. The crude condensation product was allowed to stand over- night and decomposed with ice and.hydrochleric acid (1 ; 1). This yielded a dark red oil which was extracted with ether and the ether extract was dried over anhydrous potassium car- bonate for twenty-four hours. The ether was distilled off and the remaining residue fractionally distilled. First Fractionation 70-1500 14 mm. 45.5 3. 80-1900 ' e " w 5.5 - 180-2500 5 a a. 55.5 a 250-5200 5-19 m.m. 15.0 n Residue 5.7 ' O. 21 Fourth Fractionation (another condensation) 60-1400 14 m.m. phenol 47.0 g. /140-l6l° 5 n w 4.2 -” 161-169° 5 n n 2.8 " 169-1900 5 a n 24.1 ' [190-2500 5 n n 1.5 a 230-2650 5 n n 4.7 n Residue (total) 16.0 7 The fraction 140-1610 and 169-1900 gave evidence of being different compounds. It was thought one fraction might be a para derivative while the other might be an ortho derivative. The fraction 140-1610 we will call compound A and the fraction 169-1900 compound B. ;A condensation of’chloro-benzyl chloride and phenol by Claisen's method was next carried out. The amounts used were: Phenol 14.6 Bo Chloro benzylchloride 25.0 g. Sodium 3.5 ' Toluene 50 cc. The sodium.was added to a solution of the phenol in toluene, forming sodium.phenolate, a white cheesy mass. Thb mixture was allowed to stand over night. To this was added the chloro benzylchloride and the resulting mixture heated at 150° (thermometer in oil bath) for eight hours while connected to a reflux condenser. This product was shaken out with two portions of water to remove the salt and the toluene distilled off. The residue was treated with Claisen's alcoholic potash which dissolves any free 22 hydroxyl groups. This mixture was shaken out with petroleum.ether to remove any possible ethers and the remainder acidified. A dark rod 011 separated out which was taken up with ether and the ether extract dried over anhydrous potassium.carbonate for twenty-four hours. The ether was then distilled off and the residue fraction- ated. Third Fractionation 80-1500 18 mam. phenol 5 g. 160-1760 5 " 7 . 9 7 176-2500 5 " " 1.5 ' Residue 8 ' The fraction 160-1760 was pressed between filter papers and recrystallized from.petroleum.ether, high test gasoline, or ligroin. The compound had a melting point of 60-610 and a boiling point of 157-1580 at 3 m.m. The yield of the product in this condensation was 25% of the theoretical. The yield, however, was increased considerably in subsequent condensations. For the appearance and char- acteristic growth of'the crystals consult photographs, - Figures 3, 4 and 5. This compound must be: HI 0 .CH. 01 2-hydroxy 4' chloro di-phenyl methane. 23 The mother liquor of the recrystallization of the 2-hydroxy 4' chlor diphenyl nethane yielded a few crystals (rhombohedronal plates) having a melt- ing point of 86.5-87.59. There was not a sufficient amount of these for further recrystallization. A Parr Bomb determination for chlorine carried out on tin 2-hydroxy 4' chloro diphenyl methane gave the following results: Sample % 01” data. $01.. oalc. 0.2045 16 .36 16 .22 0 .2794 16 .27 16 .22 The theoretical was calculated for one atom of chlorine and the experimental results bear out this statement. The 2-hydroxy 4' chloro diphenyl nethane was chlorenated by dissolving in chloroform and 1a ssing into this solution a ten percent excess of the theoretical amount of chlorim required to form the compound. H 01 0. on. Q 01 l The resulting compound on purification melted at 68.5 - 69.5°. The amount was to small to recrystallize further. A condensation of 2 : 4 d1 chloro phenol and chloro benzyl chloride was carried out by Claisen's method. The procedure was similar to the preparation of tie 2- 24 hydroxy 4' chloro diphenyl methane previously de- scribed. The condensation yielded, as usual for this type of reaction, a petroleum ether extract con- taining possible others and the main product which when recrystallized from high test gasoline or ligroin, melted at 69 .5 - 70.50. The compound from its method of preparation must have the following formula: I c1.<: >08 “Ii! c1 2- -hydroxy 3 : 5 : 4' chloro diphenyl methane. For the appearance and the manor of crystal growth consult the photograph, FigureL A small amount of a compound melting at 200- 2100 was also obtained by fractional crystallization. This product was not identified. A Parr Bomb determination for chlorim carried out on the 2-hydrexy 3 : 5 : 4' tri chloride phenyl methane gave the following results: Sample 6 detn. ‘ ' i calc. 0.1826 57.02 57.01 0.1959 236.85 57.01 The theoretical percent of chlorine was cal- culated for three atoms of chlorine and the experimental data verifies this statement. The melting point of the 2-twdroxy 3 : 5 : 4' tri chloro diphenyl methane of 69 .5 - 70.50 checks within one degree with that obtained by chlorinating 2-hydroxy .i 1 _ e O . O . .’. 4 e. " U Q i - . _. h . V . . f \ _-. . wl‘ . J a‘ l h ' w . . 1 1 . l r .. ' I ' 1 -. ,. fl . I ‘ . . '- . , - I - S .- ) L I ’ s 25 4' chloro diphenyl methane. This is further evidence that the compound resulting from 0181 son's condensation of phenol and chloro benzyl chloride is 2-hydroxy 4' chloro d iphenylmsthane . We have now proven that the substitution deriv- ative formed by a condensation of chloro benzyl chloride and phenol by the Claisen nathod is 2-hydrcxy 4' chloro diphenyl methane having a melting point of 60-610 am! a boiling point of 157-1580 at 3 m.m. In the condensation of chloro benzyl chloride and phenol with aluminum chloride, we stated that we found evidence of two compounds; - compound A, fraction 140-161 and compound B, fraction 169-1900. The prepe rti es of 2-hydroxy 4' chlorodiphenylmethane suggest that com- pound A may be the ortho derivative. Therefore, compouni B would be the para derivative or 4 chloro 4' hydroxy di phenyl methane. Compound B was pressed between filter paper and recrystallized fran high test gasoline or ligroin, yielding a compound having a melting point of 87 - 87.50 and a boil- ing point of 169-1700 at 2 m.m. For the appearance am nature of the crystal growth, consult photographs, Figure _fl. .. 1 . f 26 Compound B was analyzed for chlorine by the Parr Bomb method with the following results: sample % C14 detn. % 013 0810. 0.2517 15.97 15.22 K 0.2419 16.15 16.22 The theoretical percentage of‘chlorine was calculated for'the compound 4 chloro 4' hydroxy diphemyl methane. The experimental results verify this assimption. Compound B was chlorinated by dissolving in chloroform and passing in a ten percent excess of the the- oretical amount of chlorine required to form.the compound. ‘01 01 The resulting oil crystallized immediately upon seeding with a crystal of 3 : 5 : 4' tri chloro 4- hydroxy methane. The crude compound was pressed between filter paper and recrystallized from.petrolsum.cther. Upon repeated recrystallization it melted at 55.5-58° and with the amount available could not be purified further. A condensation of 2 : 6 di chloro phenol and chloro benzyl chloride in the presence of aluminum ‘uohloride was carried out in a similar manner to the con- densation of phenol and chloro benzyl chloride previously described. This condensation yielded a product melting at 61.5 - 62.59. The yield obtained was approximately 35%. The appearance, nature of crystal growth, and occurreice of the crystals in two ferms may be seen by consulting the k‘. \x. photographs, Figures 7 and 8. 27 The method of preparation of this compound allows only one possible formula: Cl 01 3 : 5 : 4' tri chloro 4-hydroxy diphenyl methane A Parr Bomb determination for chlorine on 5 : 5 : 4' tri chloro 4-hydroxy diphenyl methane supports the above statement by showing that three atoms of chlorine are present. Sample % Cl. detn. % Cl- calc. 0.2100 36.90 37.01 0.2539 37.08 37.01 Compound B on chlorination gave a product whose solubility, crystal growth, crystal structure, and melting point showed it to be crude 3 : 5 : 4' trichloro 4-hydroxy diphenyl methane. Therefore we assign the following formula to compound B. mC>cm-on In order to complete the avid ence of the format- ion of compound A, several more com ensations of chloro- benzylchloride and phenol were carried out in the presence of aluminum.chloride. The fractions were collected after four distillations at 140-1610, lei-169° and 169-190°. Tho as at 140-1610 (compound 1) were combined and upon standing a short time in the ice chest solidified. This product was pressed between filter papers and recrystallized from.petroleum ether yielding a compound having a melting point of 87-87.50. 28 We therefore gave the compound A the same formula as com- pound B, 4 chloro 4' hydroxy diphenyl methane, and conclude that no ortho substitution occurred in the condensation of phenol and chloro benzyl chloride by aluminum chloride. The yield for'd chloro 4' hydroxy diphenyl methane as re- presented by the fractions from 140 - 1900 after four distill- ations is forty-six percent.of the theoretical. In the preparation of the ortho derivative, 2- hydroxy 4' chloro diphenyl methane, by Claisen's methad, we obtained a few crystals, rhombohderonal plates, c.f. Figure 6. These melted at 86.5 - 87.50 and we concluded that ther are the para derivative, 4 chloro 4' hydroxy diphenyl methane. Para substitution with Claisen's method has previously been observed by Huston and Bank who obtained a trace of parzfggi benzyl cresol where only théfiorthc dibenzyl cresol was ex- pected. The occurrence of 4 chloro 4' hydroxy diphenyl meth- ane in two forms can be seen by consulting the photographs, Figures 1 and 6. The petroleum ether extract of the condensation of phenol and chloro benzylchloride by Claisenfs method was concentrated and fractionally distilled. The fraction 100- 1650 at 6 m.m. of 3.9 g. solidified and when recrystallized from.alcchol gave a compound melting at 85.5-86.50. This was expected from.Claisen's theories to be 01 Q CHe-o- 4 chloro-benzyl phenylether. O. ‘ 29 In order to obtain further evidence of the structure of this compound; a condensation of chloro benzyl chloride and sodium phenolate was carried out in a dissociating medium, methyl alcohol. The resulting compound was found to be identical with that obtained as a by-product in Claisen's condensation. A Parr Bomb determination for chlorine on this compound gave the following results: Sample % Cl detn. % Cl calc. 0.2155 ' 15.50 15.22 0.2514 15.87 15.22 The low percentage of the eXperimental is pro- bably due to the difficulty of obtaining the crystals in a pure state. The theoretical was calculated for the compound 4 chlorobenzyl phenyl ether and the experimental confirms the formula as containing one atom of chlorine. With the evidence offered by the two metln ds of preparation and the analysis, the formula of the compound may Cl CHaO 4 chldro-benzylphenylether. be gim as, The- petroleum ether extract of the condensation of 2 : 4 di chlorOphenol and chloro-benzylchloride by Claisen's method was concentrated and fractionally distilled. The fraction 120 - 210° at 5 m.m. of 2.:4g‘. solidified in the ice chest and on recrystallization yielded a compound meltirg at 54.5 - 55.5°. This was expected from.Claisau'e theary to be, 30 Cl 01 ~- CHs-o- c1 4 chlorobenzyl 2 : 4 dichlorophenylether. The compound 4 chloro-benzyl 2 : 4 di chloro- phenylether was also prepared by coniensing the sodium salt of 2 : 4 dichlorophenol.and chloro benzyl chloride in a dissociating solvent, methyl alcohol. The melting point was 64.5 - 65.5°, showing that two methods yield identical compounds. A Parr Bomb determination for chlorine on 4 chlorobenzyl 2 : 4 dichlorophenylether, gave the flallowing results: sample % Cl. detn. % Cl calc. 0.1155 56.40 37.01 This was the total sample of sufficient purity for analysis, and while the eXperimsntal is low, there can be no doubt to the amount of’chlorine present in the obmpound. The benzoyl derivatives of (l) 4 chloro 4' hydroxy di phenylmethane, (2) 2-hydroxy 4' chloro di phenyl methane, (3) 5 : 5 : 4' tri chloro 4-hydroxy di phenyl methane, and.(4) 2-hydroxy 5 : 5 : 4' tri-chloro-diphenylmethane were prepared by diss>lving 2 g. of the phenols in pyridine and adding a ten percent excess of the calculated amount of benzoyl chloride. The following formulas indicate the compounds res- pectively formed: ‘1’ c1 OCH- Q mop. 115 "' 116° 51 (2) c - 0 t 0 1 -CH2 (3 51 Did not crystallize (3) ’01 9' ‘01 m.p. 115-117° (4) c -- 0 t 0 01 CHs‘Q 01 did not crystallize Cl 32 Summary (1) A comparison of the yields of 4 chlor- 4' hydroxy diphenyl methane and 4 hydroxy di phenyl methane (Huston, J‘.A.C. Soc. 46, 2775) shows that the introduction of a chlorine atom increases the activity of the benzyl group. A ten percent larger yield: being obtained. (2) Were not able to establish the presence of ortho substitution in the aluminum chloride condensations. 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