NIERENSTEM THE CONSTITUTION OF CATECHIN. PART 11. 1151 CXXX.-The Constitution of Catechin. Part IT By MAXIMILIAN NIERENSTEIN. IN the previous communication (this vol. p. 971) prowisional formulze wetre suggested for ca;teclhin (I) and for the methylated relducltim profduct' (111) obtained by Kostaneclri and Lamps (Ber., 1907 40 720) fro'rn. oadechin tetrarnelthyl ether. At- the same time it was shown that Kostanecki and 1,ampel's substance may be olxidiseld to 3 4 21 41 6~-pelntametho~xydiphenyla~tic acid (IV). 0 \A/ HO CH 'i L O H OH >JeO/\OBre M e d ' OMe I ICH-CII,.CH !,),H*C02H ()OMe ()Me MeO/ \/ I MeO/ OMe 0 Mo (111. ) ( IV. 1 The preeent communication describes the synthe'sis 3 4 21 41 6/-pentrnethoxy-aa-&phemylpro~pne (111)) which of Wa 11 52 NIERENSTEIN THE CONSTITUTION OF CATECHIN.PaRT 11. found ~ Q I be identioal in evelry respelat with t'he melthylahid reldue tiofn product of Kost8anefcki amnd Lanpe. The1 synthesis was ca'rrield olut a,aclording ttol the folllolwing scheme 3 4 21 41 6I-plen'tam.eth-olxydiphemylacetyl chlo&de (V) oip? t.re~atment with dia,zolme8tlha,ne (compare Clibbens a'nd Nierenstein T. 1915 107 1491) yie1de.d 3 4 21 41 6~-pentalmethoxydipF,enyhzethy2 ke:tone (VI) which oln reductlion wit'h metallia soldium and adaohol gave 3 4 21 41 6~-psntaune.t~hoxy-u~diphenylpropane (111). chlovromethyl M ~ O ~ ) O M ~ MeO/)OMe (/CH*CO*CH,CI MeO/ \/YH*CC)C1 M&/\ I )OMs \/ I lOMe OMe \/ OMe (V-1 VI.1 The interrneldia,te 21-hyd~oxy-3 4 41 6f-te8traim,ethozy-au-di-phemy@ropn~~ (11) has prelviously noit been investligated ; thus, Koistla.neicki and Larnpei (loic.cit.) only refelr t a itl as an oil with-out further mentioln. It has now beeln obt,a8ineld as a crystlalline substla.nos which yields oln onida,tioa 21-hydrolxy-3 4 41 6I-tetra;-rnethoix~~i~heinylacetic acid (VII). The la,tcter substance behaves normally towards m&hyl sulpha,te dia,zomethane and acetyl ohlolride a8nd pyridinei yielding the c;ocresponding delrivativels. On digelstlion wit'h acetia aahydridel and anhydrolus sodium a,aelt8aftle, howelver 3 5 31 4 ~ - t e t r a ? n e t h o ~ x y - 2 - p h e n ? / l ~ o ! u ~ ~ ~ ~ ~ ~ - ~ - o ~ ~ ++ (VIII) is formeid which is a,lso pro\duc;crd whea 3 4 21 41 61-pent8ameth-o,xydiphelnylamtia a,cid (IV) is t4rea;ted with a8celt8yl ahlorida ac,oolrd-ing to Stoerrner and Friderici's method (Ber.1908 41 340). 0 M~O/\OH MeO/\/\CO I 1 ICH M e O / j Met /\, \/- I I ,,!CH.OO,H I b & l e OMe \/ (VII.) (VIII.) OMe * The numbering of the coumaran nucleus is as suggested by Stoermer (Annalen 1900 312 258) MERENSTEIN THE CONSTITUTION OF CATECKIN. PART II. 1153 E x P E R I M E N TAL. 3 4 2' 4/ 6/-Pentarnzetholxy&phenylecetyl Chlo.ride (V). Six and achalf grams oB 3 4 21 4' 6~-pentlme~tho~xydiphanyI-acetia acid are heateid on a water-bath for three hours with 10 grams of thionyl chloride. As muoh as pomible olf the un-ohanged t'hioayl chloride is distilled olff under diminished preesure and the residue dissolved in dry benzeae.The sollid obtained by elvapocating the benzene is left olvelr solid poltassium hydrolxide in a vitouurn folr some time sol as to remolve the adhelring t'races of thiolnyl ohloride. The product crystallises from benzem in small clusters olf prisma,tia nesdles which meltl a,t 76.5'. The1 yielld is 98 pelr mat. of the thelotretical (Found C1=9.6. CI9Hz,O6C1 requirea C1=9*3 per aent.). 3 4 2/ 4/ 6f-Penta;methoxyd~pFYe.nylmeth~~ Chlogomethyl getone (VI). Tot a sol-ation of 6 grams of the acyl chloride in dry ether (accorcling to1 Grignard) an elthelreal solution of freshly prepared diaeomethane from 30 O.C. of nitrosomethylurethane is added. Wheln the evollution of nihrogen teasels the same amoant of diazo-meltlhana is again added and the solution allowed to remain folr several days moisture1 being excludeld.The1 ether which colntains an excess of diazomethanel is distilled off and tlha residue cirystal-lised from benzenei. Large glistening platee separate which malt a t 1 0 2 O and hatvet the characteristic odour of the ohlolroimethyl ketlones. The yield is 94 pelr cent. olf the theoretical (Foand*: C=60*6; H=5.9; C1=8.9. C,,H,,O,Cl requires C=60-9; H=5.8; C1=9*0 per cent.). 3 4 2' 4' 6/-Pen~tametko~xy-aa-diphenyZpropme (111). A sollution 09 6 grams of the1 lreltone in about 200 C.O. alcohol is hela,tefd on a water-bath with 20 grams of m~ttallio soldium until the latter disappelars. The solution is subsequently reduced to abolut 50 c.a. and diluted with water. The precipitate crystadlisee from alcohol in small needleis which melt ah 83-84O.This mellt-ing point is not depresseid when mixed with the methyla,ted rsduo-tion product of Kostaneicki and L a m p (Found* C=69*2; €3 = 7.7. Cala. a. C = 69.3 ; 13 == 7.5 per cent.). * Dried ovcr paraffin in a vacuu 1154 NIERENSTEIN THE CONSTITUTION OF CATECHIN. PART II. 2/-Hydrolxy-3 4 41 6 f - t e t r a m e t ~ o c y - a a - ~ ~ ~ h e n l ~ l ~ o ~ ~ e (11). By distdlling Kostla8nec!ri a'nd Lampei's relductdoa prolductl (deoixy-hydrooatechin tet,ramethyl elthelr) under diminished prmsurel tlh,e grelater propostioln is obtaineid as an olil boiiling a t 235-238O/ 10-11 mm. After remaining on ice folr a' sholrt t'irne itn readily solidifieis. A felw c;ryst,als of this subst,ance a8re sufficient t'ol ca'use the1 ail of olth.elr prepa,rations t.01 become semi-soilid without previous distilla,tlon.Prepred by t'his melthod a.ny adheiring obl may be removed by washing with light peltroleurn and subsequeat drying o1n a polroas plafel. Three prepara,tions from 10 grams of catelchin telt-ramethyl e1thclr ga,vve 7.8 6.2 and 8.1 grams relspe&vedy olf the1 sotli d.* It oryst8alliseIs frolm alcohol in rect'angulas pla.tes which feel oily a,nd meflt atl 106O. The su.bst,ance 1s solluble in the usuaJ olrga,nic sollvelntlsi witlh the1 eixcelptciofn 09 light peltrolcnm in the1 colld. The a,lcolhollic solut'io'n turns violet1 with ferric chlolride (Found f : C = 68.5 ; H = 7-4. C,,H,O relquires C = 68.7 ; H = 7.2 pes oelntl.). On tsea,tmelntl with met.hy1 sulphate t,he t.helolretticd yielld olf 3 4 2' 41 6/-pe1nt~ame~tho~xy-aa-diphenylpr~o~pa~ne1 (111) is obtaine'd.It melts a.t+ 83-54O a,nd this melltiiig point is iiolt depresseld when mixed wit,h thei me,thyla.teid reduction pro,duct of Kosta,necki and L,ampe. 2/-Hyd~oixy-3 4 41 6 / - t e t r a m e t h o l z y ~ ~ ~ h ~ y l ~ c e t i c Acid (VII). Nine grams of 2/-hydraxy-3 4 41 6/-tetlramelthoxy-aa-diphenyl-propanel suspelnded in 300 G.C. off a 20 pelr sent. solution of poltassium hydrobxidel in water are midised on a boiling-watelr bath folr four holurs with 9 grams of potassium permanga>nate dissolved in 200 a.0. of water. The solution is filtemd while hotl and after aoloding aoidifield with dilute sulphuric acid. The dark-coburad preclipitatle is not filteaed butl the solution eatraoted several times with eltheir in whioh the precipitate dissolveis.The ethereal extract dried over anhydrous soldiuin sulphatel leavea a solid on eivapoiration which after selvelral orystlallisaltions from water, * The reduction of catechin tetramethyl ether according to the method of Kostanecki and Lampe (Zoc. cit.) is apparently accompanied by some decomposition since the cruds reduction product has an odour of acetic acid. Several attempts were made t o isolate some of the disintegration products by extracting the porour plate with alcohol. A small crop of needles was obtained from the alcoholic extract. They melted a t 178-180" which is the melting point given for veratric acid but there was not enough material t o establish their identity.t Dried over paraffin in a vacuu MERENSTELN THE CONSTITUTION OF CATECHIN. PART 11. 1155 animal charcoal being used yields lolng prismatic needles mellting at 168-169' carbon dioxide being evolved. By prolonged drying olvelr phosphoric oxide in a vacuum or heating a t l l O o onel mole-oule of water is lost (Found* H2Q=5.0. Calo. H,O=4-9 per mint.). The anhydrous product is powdery in appearance and mellts at 172-173" carbon dioxide Feing eivolvcd. The substanoe is also soluble1 in alcohal o r ethyl acetatei but insoluble1 in benzene or toluene. Both the aqueous and alcoholic solutions turn bluish-violet with ferria chloride. The yield is 78 per cent. of tlhe theoretical (Found ++ C == 62.2 ; 13 =5*9. Cl8H2,0 requires C = 62.1 ; H=5.7 per oent.).On metlhylatioii with methyl sulphate 3 4 21 4' 61-pe1nta-mettholxydiphenylacetia acid (IV) melting a t 150-151° is formeld. Diazoinethanel colnverts 2/-hydroxy-3 4 41 61-htrametholxydi-pheayladia aoid quantitatively into the colrrelsponding methyl ester which mdts at 119O. Neither of these melting polints is depresseid when the compounds are mixed with ths corresponding substances previously described (Zsc. cit. p. 879). The acetyl derivative is prepared by the action of acmtyl ohloride (3 grams) a,nd pyridine (30 grams) on the anhydrolus acid (3 grams). It crystallisels from alcolhol in prismatio needlee which melt at 183-184O carbon dioxide being evollved (Found * : C=61*5; H=5-7. C2,H,,Q require@ C=61-5; H=5*6 per mnt.). 3 5 31 4 f - T e t ~ ~ ~ m e t h o z y - 2 - ~ ~ ~ e n y T c o u l t l a l .n l e (VIII). One gram of 2f-hydroq-3 4 4/ 6/-tetirametho~sydiphenylace~tic acid is digested with 30 C.C. of acietic anhydride aiid 3 grams of anhydrous sodiuin aceiate aiicl t h e niisture subsequelntlly diluted with water. The1 precipitate1 obtained in this way crystallises from absolute alcohol in stoat prismatic needles whioh melt a t 117O. The yield is 85 per cent. of the theoreticlal (Found -f C=65*4; H = 5 - 5 . C18H180 requires C=65.5; H=5.4 per mnt.). The same! product is also1 olbtainecl when 3 grams of' 3 4 2/ 4' 6/-penta-nzethoxydipheiiyla~ltic acid dissolved in 20 C.C. oif glacial acetic acid are kept at the1 oirdinary temperature1 f o r forty-elight hours with 50.4 O.C. of a solution of 100 U.C.glacial acetic acid and 2.12 grams off acetyl chloride (1 mol. od acetyl chloride). The greater part of the aeetia acid is removeld under diminished pressure1 and the residue precipitated with watelr. The product cry~t~allises from absolute1 alcohol id stout prismatic needles which melt at 117O, * Dried at 110". f Dried o w r paraffin in a v&cuurn 11 56 NIERENSTEIN THE CONSTITUTION O F CATECHIN. PART II. and this metlting point is not1 altelred on mixing with t'he preiviolus prepa'ratim. The yield is 91 per oent. oC the theolretical. The autholr is indebted to1 the1 Colston Society of the University of Brisbol for a grantl which has colvereld the etxpelnses of this research. BIO OHEMICAZ LABORATORY, C m MI CAL DEPARTMENT, UNIVERSITY OF BRISTOL.[Received September 9th 1920.1 Note added Octolber l s t 192Q.-Since this c80~mmunica8tio~n was submitted a p a p r by ,Frelu.delnbelrg (Ber. 1920 53 [B] 1416) has appeased in which he desaribes 3 4 21 41 6f-pe~nt~ame~tlhoxy-ay-diphenylpropaael as meilting ah 87-88O which is t'he melting point given b.y the autholr (this vol. p. 972) folr this subst'ance. Freudelnbeirg states furt?lier thatl Kost,aneicki and Lampe's methylated retduct,iovn prolduc,tl alsot melts at 87-88O which is not mrrel&. This subst8atnce melt8 a t 83-84O' as givea by Kostlanecki and Lampa (Ber. 1902 $0 720). The aut'hor has o1n five separab olaaasiolns prepreld t,his prolductl a'nd has alwa,ys folund it to melt at 83-84O. No diff etrelncx od t'hel melting polint has b,een re,colrdeNd by Ryan and Walsh (Sci.Pmc. Roy. Du,bZin Sofc. 1916 16 lZO), who have1 allsol prepred Roet,amneicki and Lampe's prolduct. In vielw of Freudelnberg's aesumption t,hat Kot&anelcki and Lampe's methylated relductlioin productl is ideIntdc!aJ wit$ 3 4 2/ 41 6/-peata-meltholxy-a,y-diphelnylprolpa,nel t,hel follolwing mixeld meiltdng points welrel tla$eln. They clela,rly dis,prolve his colntentlions. (1) Koe-ta(necki and Lampel's m,et?hyla.ted re8duotioIn produck (m. p. S3-84O) and 3 4 2' 41 6f-pe~ntame1t~hoxy-a,y-diphe1nylproipa,ne (m. p. 87-88O) giving a delpretssiotn of 9 to1 11 delgrew. Similar relsult8s were o;bt.adnetd (Augustl 11 t,h 1919) when three mixeid meltdng points of thelsei t8wol substances welres takeln. (2) On the olthelr hand, a mixture olf Kost8a,nelcki a'nd Lampe's product (m. p. 83-84O) with 3 4 21 41 G~-pe~ntlalm~e~tboay-aa-diphenylpropane (m. p. 83-8'4O) described in the prewnt communicatioln melted a t 83-84O wit'hout t,he slight,eat depressioa as alrea8dy obselrved (April 26t,h 1920) when tlwot mixed mellting poiintls of these subst'anceis were taken