the willgerodt reaction study of reaction conditions with ketones

8/3/2019 The Willgerodt Reaction Study of Reaction Conditions with Ketones

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Oct., 1946 STUDYF WILLGERODTEACTION ONDITIONSITH KETONES 2025Summary

1. Ultraviolet absorption spectra measure-ments are recorded for aqueous solutions of D-glucosyl-N-butylamine and are compared withthose for si:milar solutions of D-glucose inalkali.2 . The above data are interpreted as demon-strating that the incipient coloration appearing

when aqueous solutions of D-glucosyl-N-butyla-mine are allowed to s tand a t room temperature, iscaused by hydrolysis of the compound followedby the action of the liberated hydroxyl ions uponD-glucose. It is probable that this is a generalreaction of sugar-amino condensation products inthese relatively high pH ranges.COLUMBUS,HIO RECEIVEDUNE 14,1946

[CONTRIBUTION FROM THE DEPARTMENTF CHEMISTRY AND CHEMICAL ENGINEERINGF THE UNIVERSITY O F PENNSYL-VANIA]

The Willgerodt Reaction. 11. A Study of Reaction Conditions with Acetophenoneand Other KetoneslTaB Y DELOSF. D E T A R ~ND MARVIN ARMACK

Although the Willgerodt reaction4 has been ap-plied to a large number of ketones for the prepara-tion of carbonamides, no systematic study of theeffect of variations of reaction conditions appearsto have been published. The at temp t of Willger-odt and Scholtz5 o replace the aninioniuni poly-sulfide reagent with colorless ammonium sulfidegave poor results. One useful variant of theoriginal procedure, introduced by Fieser andKilmer,6 involves the addition of dioxane to thereaction mixture; the presence of the organicsolvent generally permits the use of lower reac-tion temperatures, and yields are often greatlyimproved.I n an effort to improve the usefulness of theWillgerodt synthesis of amides and to throw lighton the reaction mechanism, we have made a studyof the effect of the time, temperature, composi-tion of the reagent, and presence of organic sol-vents on the reaction of acetophenone to formphenylacetamide. As a result of this study a

modified procedure was developed which gave atotal of 85.67&of phenylacetamide and phenyl-acetic acid as compared with the total of 63% bythe original procedure of Willgerodt and Merk.The improved methods were applied also to thereactions of a number of other ketones accordingto the general equationAryl-CO(CR&CHa+ ryl-CHz(CHz),CO,NHzThe results are summarized in Tables I1 and I11in the Experimental.(1) For l.he previous paper of the series, see Cavalieri, Pattison(2) From the Ph 11. Dissertation of DeLos F. DeTar, University(3) Present addres s: Chemistry Department, Cornel1 University ,(4)Willgerodt, Ber., 20,2467 (1887); 21,534 (1888).(5) Willgerodt and Scholtz, J . p ra k f .Chcm., [2 ] 81,382 1010).(6) Fieser and KJmer, TEIS OURNAL,2, 1354 (1940); a hibliog-

raphy of earlier references to the Willgerodt reaction appears inthis paper.

and Carmack, THISOURNAL,7, 1783 (1945).of Pennsylvania, 1944.Ithaca, N. Y .

(7 ) Willgerodt and Merk, J . prakt. Chcm., 12180, 102 (1909).

According to the classical procedure the am-monium polysulfide reagent is prepared by dis-solving an excess of sulfur in concentrated am-monium hydroxide which has been previouslysaturated with hydrogen sulfide. Althoughthe published procedures are rather indefinitethe molecular proportions of reactants haveprobably been of the following order: ketone(1)) mmonia (7), hydrogen sulfide (4) nd sulfurUsing a standardized procedure for small-scaleruns with acetophenone, we determined that thetemperature range of 160-190 gives the highestyields within a convenient reaction time of fourto six hours. Using combinations of sulfur, ke-tone, and analyzed solutions of ammonium sul-fide-ammonium hydroxide in varying proportions,we found tha t the highest yields of amide wereobtained when a large excess of sulfur was used;the optimum ratio appeared to be approximately10 gram-atomic weights of sulfur for each mole ofketone.When th e concentration of ammonium hydrox-ide and the proportions of sulfur and ketone wereheld approximately constant and the concentra-tion of hydrogen sulfide added t o the startingmixture was varied, the interesting result emergedtha t the best yields of amide were obtained whenonly low concentrations of hydrogen sulfide wereadded initially . Higher concentrations of hydro-gen sulfide in the reagent markedly lowered theyields of amide. This finding suggested the de-sirabili ty of omitt ing hydrogen sulfide entirelyfrom the reagent, a modification which gave verysatisfactory results with acetophenone. Runsin which only concentrated ammonium hydroxide,sulfur and acetophenone were present initiallyproduced higher yields than runs using compar-able proportions of the same reagents with addedhydrogen sulfide.It is apparent from a consideration of t he stoi-chiometry of the Willgerodt reaction that theover-all process involves a net oxidation which isalmost certainly at t he expense of the added

( 2 ) .


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2026 DELOSF. DETARAN Dsulfur. Soirie hydrogen sulfide is therefore formedas a reaction product, and will be prescnt duringmost of the reaction period whether m y is addedto the mix ttre initially or not. I t is iiot surpris--ing therefore that t he results obt:iiiietl with low(0-1 -11) initial concentratioris of Iiydrogen sill-fide were n:)t greatly tliffereiit frotii those ob-tained with concentrated aniiiioiiiuiii hytlrositl(~an d no added hyd rqe n sulfide.I t is not known whether hydrogen siilficle pluysan essential role in the course of the IVillgerotltreaction. If i t is :I iiecessary coinpoiient of thereaction mixture t h e cridence iiitlicntcs clearlyth at the amount of hytlrogen sulfide generated bythe reaction itsel1 is sufiicient in the case of aceto-phenone. This does n o t appear to be true for alltypes of ketones sirice it.was shown th at the bestyields of amide were obtained from purely ali-phatic ketones when the reagent initially con-tained enough hydrogen sulfide to convert all ofth e ammonium hydroxide to atiimoniuiii sulfide.With alkyl aryl ketones derived from phenaii-threne, pyrenc, biphenyl and similar polyc~clichydrocarbons, a reagent containing approxi-mately 0.7 111Iiydrogen sulfide (or the equivalentin atnmonitiiii sdfidej gave very sntisfactoryresults and is convenient to prepare. The pres-ence of lo w concentrations of sulfide greatly- in-creases the sdubil ity o f sulfur in conipnrisoii withthe solubility in aiiinioniurn hydroxide, an t1 i t ispossible that: the increase in the solubility of sul-fur partially- offsets the tendency of hydrogensulfide to decrease the yields of amide.A study of the effect of th e concentration ofammonia 011 the yield of phenylacetamide fromacetophenone showed that the yields increasedwith increasing concentration and leveled off inthe range of 12 to 15 moles of ammonia (or ani-moniuni salt) per liter of reagent.Th e effect of eth:iiiol, pyridine or dioxane addedto the rextioii inistures was iiivestigntecl.Ethanol iniprovctl thc [vicltls slightly, but pyridine an d tliosaiic~wet-(: iiiorc cf fect i \ - r . Ihcrcis nct evidence that orgaiiic solvelits take Itart i i ithe cheiriical reactions, :im1 i t is :issunlet1 thattheir effect is rluc t o tlie iiicrcasetl solubility of thestart ing ketones in the iiiisture of organic solventand aqueous reqcri .. I i i runs wj h cert:ki acylderivatives o th e liiglicr polycyclic hydrocarbonsa practical atlvant;tge in the u se of dioxane ratherthan pyridinc was uotctl. The amides oftensep:tr:itc>tl i i i fairly Inire crystalline stat? tlirectlyfrioiii i l l ( - cc 1 1 ~ ~ 1.;icLioii iiiistures coiitxiiiing

diusclnc, \ ) t i t t t ~ i ~ i x i ~ i t diiostlv i i t siilutioii i i i t l i ~pyridine rnixtures, iircessitatilig :I slightl!, n i t rtxelabora.tr ti iethod oi isolation.ExperimentalReagents.--l3ydrogeii sulfide gas was passed with cool-ing into concentrated arrimoniunl hydroxide (15M)o formsolutions of crdorless ammonium sulfide 5 A dispersing(8) As hydrogen sulfide di.sulves t he t i ter of amniut l id Id115 s loniyfrom approximately 1 .I! t o :ibout 12 I f :sn i l tlir ctmr?ntr:iticin r j f

sulfide rises grar1ii;illy tu n h u i 7 JI.

___--.-

MARVIN ARMACK Vol. 68disk consisting of a coarse fritted glass disk was found toincrease the ra te of solution. Stock solutions containingtliffereiit relative concentrations of ammonia an d hydrogensulfide were made up and analyzed in order to give a ranget if concentratioris for the experiments with acetophcnonc.The concentration of ammonia in the various solutions wasdetermined by titration with standard hydrochloric acid,tisiiig methyl ~ - r ds indicator. Concentrations of sulfidew r e deterniiiictl by a procedure similar to that describedIiy Treadwell and Hall.3The colored solutioiis formed by niixitig ammoniumhydroxide, hydrogen sulfide, and sulfur are extremelycomplex mixtures contailling many molecular and ionicspecies and a number of equilibrium systems which areiiot well understood. In order to express the compositionof our reageiits in a simple, if somewhat empirical, manner,ire have recorded the total molar ity of ammonia a ndmolar ity of hydrogeu sulfide in the solutions of ammo-nium sulfide, as determined directly in the titrations, with-out attempting to evaluate the relative amounts of thesesubstances with respect t o their sa lt forms.Immediately before use in a reaction, a known volumeof analyzed ammonium sulfide solution was mixed witha weighed quantity of finely powdered sulfur to form thepolysulfide reagent . Since hydrogen sulfide was notalways used and since consequently the sulfur was notalways completely in solution, it seemed preferable notto express the amount of added sulfur in terms of molarityor an empirical formula for polysulfide. Instead, th erat io of gram-atoms of sulfur to moles of ketone was re-corded. This value has been referred to as the moleratio of sulfur in the subsequent discussion.Procedure for the Small-Scale Runs with Acetophenone.-Redistilled acetophenone (Eastman Kodak Co.) (1.000g. ) was weighed into a 5-inch soft-glass test-tube, the ap-propriate weight ( t0.02 9.) of flowers of sulfur was addedan d 5.00 ml. of analyzed ammonium sulfide of the desiredcomposition was introduced. Organic solvent, when used,was pipetted into the mixture at this point. The tubeswere sealed and heated in a gas-heated Carius furnace,the temperature of which was held within + 5 . Usuallya number of tubes in a given series were heated simultane-ously in the furnace so that results would be directly com-parable in spite of possible fluctuations in the temperature.Unless otherwise specified, th e time of heat ing was fourhours, not counting the time required to reach the statedtemperature or cool to room temperature.The tubes were allowed to cool to room tempera ture inthe furnace. In experiments with acetophenone no resid-ual pressures were observed after the tubes had cooled.The contcnts of each tube were evaporated to dryness inn 400-ml. beaker on a water-bath to remove volatile ani-lnonium sulfide, leaving as a residue phenylacetamide,sulfur, ammoniutn phenylacetate, and small amounts of1)y-products. It was determined tha t losses of amide byvolatilization were negligible. The residue in each beakerwas extracted with six 10-m1. portions of boiling water,the hot solutions were clarified with charcoal, filtered,:mtl evaporated to dryness in a tared flask. The crystal-line residue was found to consist of phenylacetamide withvery small amounts of phenylacetic acid and ammoniumphenylacetate. The values in duplicate runs showed goodreproducibility.Determination of Optimum Time and Temperature.-I II a series of preliminary runs with acetophenone, follow-itig the procedure described above, it was determined thats t temperatures of 160 arid higher the nmximurn yield ofamide was obtained i n a heating period of two to threrhours, and th at longer heating in most cases did not changetlie yield of amide great ly. A standard reaction time offour hours was adopted to ensure complete reaction with-out uunecessarily prolonging the period of heating andp-ornotirig hydrolysis of the amide. It is not certain tha tth e runs at temperatures of 130were complete within thefour-hour periods, but at 160and higher there seems little...___ -

(9) Treadwell and Ifall, Analytical Clieiuistry, ( < , I . I I , JohuTViley aud Sans, X e w \ork, N . Y., 1935.p. 630


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Oct., 1946 STUDY F WILLGERODTEACTION ONDITIONSITH KETONES 2027reason to believe that longer heating would have in-creased the amount of amide.Effect of the Mole Ratio of Sulfur:Acetophenone.-Theexperiments shown graphically in Fig. 1were made with anammonium sulfide solution which was 12.8 AI in ammoniaand 2 .4 .I1 i n liydrogeri sulfide and to which varyingproportioris of sulfur were added to give the mole ratiosshown in the ab:,cissa The three curves in Fig. 1 repre-sent, in ascending order, the results a t 130 * 5 ', 160 * 5'and 190 f ', respectively, all runs involving a heatingperiod of four hours. The highest yield was obtained at190" with a su1fur:ketone ratio of 10.

00 4 8 12 16 20

Mole ratio of sulfur: ketone.0 ,130 * 5", 4, 160 =t 5'; 0, 90 * 5". All experiments

with 1.000 g. of CeH6COCH3 and 5.00 ml. of ammoniumsulfide solution (12.8 211 in ISH8 and 2.4 M , in H&) withadded sulfur as indicated; time, four hours.

Fig. 1.--Effect of mole ratio of sulfur to ketone:

Effect of Initial Concentration of Hydrogen Sulfide.-The experiments shown in Fig. 2 were made at 160'for four hours. The initial concentration of ammoniai n the ammonium sulfide solution was in every case withinthe range 11.3-11.9 M, ut the concentrations of hydrogensulfide varied froin 0 to slightly over 5 . The three curves,in ascending order, represent sulfur :ketone mole ratios of3, 5, and 10 , respectively. It can be seen that for initialconcentrations of hydrogen sulfide in the range 0-1 M

20

0 1 2 3 4 5Initial J I of hydrogen sulfide.

Fig 2.---Effect of initial concentration of hydrogensulfide: 0 , S:CsHaCOCHs mole rat io 2 : l ; A , S:C&I5-COCH? mole ratio 5:l ; E, S:C6HbCOCH3 mole ratio10: l . All experiments with 1.000 g. of C6HsCOCH3,5.00ml. of ammonium sulfide solution (11.3-11.9 Jf in SH3and as indicated i n H P S ) ,and sulfur in t h r ratios shown;160" for four hours.

there is little change in the yield of amide, but at higherconcentrations of sulfide th e yields fall off sharply.Effect of the Initial Concentration of Ammonia.--Theexperiments shown in Fig. 3 were carried out a t 160"for four hours in concentrated arnmoniuin hydrouidc (15M ) without hydrogen sulfide. T h e three curves represent,in ascending order, mole ratios of sulfur: ketone of 2, 5, and10, respectively. The yields are seen to reach a maximumin the concentration range of reagent ammonium hydroxide(12-15 M). Under the conditions of these experiments asolution initially 1.67A1 in ammonia would contain exactlythe theoretical amoun t of ammonia to convert all of theacetophenone to amide.

10 4 8 12 16Initial M of ammonium hydroxide.

Fig. 3.-Effect of init ial concentration of ammoniumhydroxide: 0 , S:CaHbCOCH3 mole ratio 2:l; A , S:C6H&!OCHJ mole ratio 5:l; 0 , S: CsHbCOCHs mole ra tio1O:l. All experiments with 1.000 g. of C6HjCOCH3,5.00ml. of ammonium hydroxide of indicated M, nd sulfurin ratios shown; 160" for four hours.

Effect of Added Organic Solvents.-Table I shows theresults of a series of experiments with 1-g. quantit ies ofacetophenone and 5-ml. quantities of ammonium sulfide.In all runs except the one with dioxane the ammoniumsulfide contained 12.8 M ammonia and 2.4 ill hydrogensulfide, with su1fur:ketone ratios as shown; 2 . 5 ni l . ofTABLE

EFFECTF ADDEDORGANICOLVENTS1 HEWILLGERODTEACTIONIT H ACETOPHENONE

Mole rat io Organic Yield ofTemp., sulfur: solvent phenyl-O C . ketone added acetamide, %130 * 5" 5 Sone 14

130 * 5" 3 Ethanol 1130 * 5" 3 Pyridine 27130 * 5" 10 Sonr 4*5130 * 5' 12 Ethaiiol i 1130 f " 12 Pyridiiir 9IJ158 * 5' 5 Sone ti2158 * 5' 3 Ethanol 60

5 Dioxane i 658 * 5"158 =t 5' 3 Pyridine i i158 * j3 10 None 72158 . j 0 12 Ethanol RO158 *


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2028 DELOSF. DETAR ND MARVINARMACK Vol. 68ethanol or pyridine was added, where indicated. In theexperiment with dioxane, the ammonium suliide was ini-tially 12.3 M n ammonia and 0.69M in hydrogen sulfide,and 2.0 ml. of dioxane was used. The best yield was ob-tained with a sulfur ratio of 12, a t 158* 5" , n the presenceof added pyridine.Phenylacetamide from Acetophenone (Preparative Pro-cedure).-Acetophenone (25.0 g., 0.208 mole), 37.5 g. ofsulfur (1.17 gram atomic weights), 50 ml. (0.76 mole) ofconcentrated (15 M ) ammonium hydroxide, and 30 ml.of pyridine were sealed in a 22-mm. 0.d. hard glass (notPyrex) bomb tube and heated to 157 * 6' for approxi-mately four and one-half hours. The tube was allowed tocool to room tempera ture and opened (no residual pres-sure). The reaction mixture was transferred to an evapo-rating dish and evaporated to dryness on a water-bath.The dry residue of sulfur and reaction product was leachedwith a tota l of about 500 ml. of boiling water in severalportions. The clarified filtrate was cooled, whereupon20.0 g. of phenylacetamide, m. p. 156-158" cor., separatedfrom the solution. Concentration of the filtrate yieldeda second crop of 2.7 g. of amide. The filtrate from thesecond crop was evaporated to dryness and extracted withether, yielding an additional 0.32 g. of amide and 1.2 g.

TABLE1ALKYL PHEN YL ETONESN TH E WILLGERODTEACTION

M. P. . M. P. ,o c . % o c .Amide (COT.) Yield (cor.)Keto ne obtained amide amide acidPropiophenone 6-Phenylpropionarnide 97 .,5- 98. a 82n-Butyrophenone y-Phenylbutyramide 83 - 84b 42 49-5OCn-Valerophenone 6-Phenylvaleramide 107.5-10Sd 29

a A sample prepared by another method melted a t 99.5-100.2' cor. Reported m. p. 84.5.7 A specimen of theacid, m. p 49-50' cor., was prepared by hydrolysis anddecarboxylation of ethyl 8-phenethylmalonate, then con-verted to the amide, m. p. 83-83.5" cor., not depressedby admixture with the product of the Willgerodt reaction.c Reported m. p. 51", Fischer and Schmitz, Ber., 39,2212 (1906). **Reportedm. p. 104-105", Eijkman, Chem.Weekhlad, 5,655 (1908); Chem.Zentr., 79 ,II , 1100 (1908).

a mixture of 2,4- and 2,5-diphenylthiophenes preparedby heating phenylacetylene with sulfur.lOReactions of Alkyl Phenyl Ketones.-Several straight-chain alkyl phenyl ketones were treated according to themodified Willgerodt procedure using concentrated am-monium hydroxide, sulfur, and pyridine under conditionsfound to be optimum for acetophenone, i. e., approximately5 ml. of concentrated ammonium hydroxide, 2.66 g . ofsulfur and 2.5 ml. of pyridine for each gram of ketone, at165' for four to five hours. The products were isolatedas described for phenylacetamide, and were purified byrecrystallization from appropriate solvents. In one casethe amide was converted to the solid acid. The resultsare shown in Table 11.Reactions of Acyl Derivatives of Polycyclic Hydrocar-bons.-Several acyl derivatives of polycyclic hydrocar-bons were treated with a reagent prepared in the followingmanner. Powdered sulfur was suspended in ten times itsweight of concentrated ammonium hydroxide and hydrogensulfide was passed into the suspension with agitationjust long enough to cause all of t he sulfur to dissolve.Analysis of a typical solution showed that it contained12.3 M of ammonia an d 0.69 M hydrogen sulfide. Ineach of t he experiments from one to three grams of ketonewas heated with the reagent and dioxane in a sealed glasstube at 160' for approximately six hours. The propor-tions were usually 5 ml. of polysulfide reagent and 4-6ml. of dioxane for each gram of ketone. The amidegenerally crystallized partially or completely upon cool-ing, but additional product could be recovered afterevaporation of the filtrate t o dryness to destroy ammo-nium sulfide. Some of the amides were hydrolyzed to t hecrystalline acids. The results of several typical experi-ments are summarized in Table 111. Melting points aregiven for the purified specimens.It is to be noted th at t he products in all cases had thestructures expected from the usual formulation of theWillgerodt reaction, i. e., no rearrangement of the carbonskeleton or loss of carbon atoms was noted , with oneinteresting exception: in the case of 9-propionylanthracenethe side chain was lost an d anthracene was recovered in85% yield. No similar example of the complete loss ofa side chain appears to have been noted previously in theWillgerodt reaction.

TABLE11ACYLDERIVATIVESF POLYCYCLICYDROCARBONSN THE WILLGERODTEACTION

M. p., "C. (cor.) % Yield M. p.. O C . (cor.),Retorie Amide obtained amide amide acid2-Acetylphenanthrene' %Phenanthreneacetamide* 247 -248 822-Propionylphenanthrene' P-(2-Phenanthrene)-propionamided 189.3-189.5" 66 176 -178'4-Ace ylbipheny1O 4-Biphenylacetamide' 242.5-243.5' 84 160.8-161.8'9-Propionylanthracenek None'

Calcd. forClsHIJNO: N, 5.95. Found: N, 5.89, 5.87. Prepared by the procedure of Bachmann and Struve, THIS OURNAL,58 , 1659 (1936). Anal. Calcd. for CI~HNNO:N, 5.62. Found: N, 5.65, 5.57. M. p. in an evacuated capill?.f Reported m. p. 177.2-178.4', Riegel, Gold, an d Kubico, THIS OURNAL,5, 1775 (1943); reported m. p. 177-177.5 ,Bachmann, ib id . , 57, 1381 (1935). Anal.Calcd. for C1,HlaNO: N, 6.63. Found: N, 6.51,6.56 . M. p. in an evacuated capillary. i Reported m. p. 161-162",Lesser, German Patent, 658,114 (1938); C. A . , 33,4798 (1938). k Prepared by t he procedure of L iittringhaus and Kacer,U. S. Paten t 1,766,433 (1930).(4.2%) of phenylacetic acid. Th e combined yields of Summaryphenylacetamide and phenylacetic acid amounted to85.8%. The acid, after crystallization from water, A critical study was made of the effectOf time,melted a t 76.3--77.3 cor. temperature, composition of the reagent, and th eThe residue of sulfur remaining from the original re- presence of organic solvents on the yield of phenyl-action mixture after extraction with hot water was ex- acetamide from acetophenone in the Willgerodttracted further with alcohol. A small amount of oil wasisolated from the alcohol, and treatment of the oil with reaction- A modified procedure thesuccessive portions of ether, petroleum ether, and meth- use of concentrated ammonium hydroxide, sulfuran01 eventually afforded a few milligrams of powdery and pyridine without hydrogen sulfide was de-crystalline mat.eria1, m. p. 141-143 ' or. Recrystalliza- veloped which gave higher y.ields than the classicaltion of the solid from methanol gave pale yellow plates,m. p. 145-146 , which were insufficient for further puri- reagent, ammonium polysdfide-fication. The material behaved, however, very much like (10) Carmack and DeTar, THISOURNAL, 68, 2029 (1948).

a Prepared by th e procedure of Mosettig and van de Kamp, THIS OURNAL,5, 3444 (1933). b A n d .

0 Prepared by the procedure of Long and Henze, ibid., 63 , 1939 (1940).Cleavage to anthracene occurred (85% recovery).


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Oct., 1946 AMIDESRO M ACETYLENESND OLEFINS 2029The modified procedures were applied to thereactions of several straight-chain alkyl phenylketones and several acyl derivatives of polycyclichydrocarbons. PHILADELPHIA,ENNSYLVAXIA

high yield of anthracene under conditions of theWillgerodt reaction.

9-Propionylan thracene was cleaved to give a RECEIVEDEPTEhlBER 15, 1945

[CONTRIBUTIOX F R OM TH E DEPARTMENTF CHEhlISTRY AND CHEMICAL ENGINEERING O F THE UNIVERSITY O F PENNSYL-VANIA]The Willgerodt and Kindler Reactions. 111.Studies Relating to the Reaction IM echanisr n~ '~~~~Amides from Acetylenes and Olefins;

BY MARVIN ARMACKND DELOSF. DETAR'In the course of our investigations of the Krill-gerodt5 and Kindler6 reactions we have foundth at acetylenes and olefins7 behave similarly toketones, forming carbonamides and thioamidesin the two procedures, respectively. Thus, inanalogy with tlie conversion of acetophenone tophenylacetarnide,2 phenylacetylene and styreneboth give good yields of phenylacetamide

Paralleling the reaction of propiophenone, bothI-phenylpropync and 1-phenylpropene yield p-phenylpropionainide

'The unsaturated hydrocarbons thus share witht h e ketones the most remarkable feature of theWillgerodt. reaction-the disappearance of an un-saturated group and t he oxidation of a terminalmethyl group. Under standard reaction condi-tions which had previously been found2 to give(1 ) EDITOR'SoOTsOTE.-The origina l manuscr ipt of this paperwas received September 1.5, 1945. A manuscript by King and Mc-

Millan containing some closely related material and an interpreta-tion of the mechanism of th e Willgerodt reaction was received Sep-tember 22, 1945. I t was piauned that both papers would appear inth e same issue of THE) OURXAL. As th e result of a clerical error inthe Editor's Office, however, the paper by King a nd McMillan waspublished (THIS O U X N A L , 68, 63 3 (1946)) before the condensationand revision of t he p.%perby Carmack and DeTar had been com-pleted, In view of tlie prior publication of Kin g and McM illan'spaper, th e article by Carmack and DeTar has been further revised toeliminate some historical material and t o call attention t o the re-sults independently arrived a t by King and AfcMillan.

(2 ) For the previous paper of this series see DeTar and Carmack,THIS O URXAL, 68 . 2025 (1946).

(3) From the Ph.D . dissertation of Debs F. DeTar, accepted bythe Gra duat e Schuol of the Un iversity of Penn sylvania, 1944.(4)Present addresr.: Department of Chemistry, Cornell Uni-

versity, Ithaca, 3. Y .( 5 ) For a bibliography of references to the Willgerodt reaction

consult Fieser and Kiiiner, THIS OURNAL, 62, 1364 (19401, and ref. 2.(6) For refprences t o the Kindler reaction, consult Schwenk andBlocb, ih id . , 64 , 3051 (1942). and ref. 15.(7 ) King and McMillan have observed independently that olefinsyield carbonamides under Conditions of the Willgerodt reaction;

cf. footnote 1 and also ibid., 68, 5 25 (1946).

optimum yields of amide from alkyl ary l ketones,the three types of compounds were found toproduce amides in the following order of decreas-ing yields : ketones, acetylenes, olefins.Phenylacetylene and styrene react with mor-pholine and sulfur to produce phenylacetothio-morpholide. Th e yield of purified product isabout the same in each case as tha t obtained fromacetophenone by the procedure of Schwenk andBloch6C6Hb-COCHz O ( C H ? C H $ ) * K H + SCeHj-c~cHaC6Hs--CH=CHz +140-150 . s

'N (C H Z C H P )0C6Hj-CH,C 'A marked evolution of hydrogen sulfides acconi-panies the reaction of styrene.These reactions appear to be applicable to awide variety of substituted acetylenes and olefins.We are exploring their scope and will report ourfindings in la ter publications.Several further experiments carried out in thisLaboratory are of interest in connection with thedevelopment of a general theory of the course ofthe Willgerodt reaction. Phenylacetaldehydegives phenylacetamide under the same conditionsas acetophenone, phenylacetylene and styrene.P-Phenylpropionaldehyde and phenylacetone8each give P-phenylpropionamide under t he sameconditions as propiophenone, 1-phenylpropyne,and 1-phenylpropene. However, methylphenyl-carbinol,* P-phenylethyl alcohol,* /3-phenylethylacetate, and methylbenzylcarbiriol fail t o yieldappreciable amounts of amide when heated witha typical Willgerodt reagent a t 160".Using the ammonium polysulfide-dioxane re-agent recommended by Fieser and Kilmer,5 wewere able to confirm the formation of a-methyl-y-phenylbutyramide from isobutyl phenyl ketone,as reported originally by JVillgerodt and Merkgand recently reinvestigated by Fieser and Kilmer.

(8) Also investigated by King an d McRIillan (footnotes 1 an d 7).(9) Willgerodt and Merk, J . puakl . Chcm , [ Z ] 80, 19 2 (19091.

the willgerodt reaction study of reaction conditions with ketones

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