hours, during which crystals were deposited, the solution was filtered hot. The filtrate was evaporated gradually with filtration of the solution from the crystals from time to time. The resF1ts were as follow*s: Fraction I , 0.675 g., m. p. 292-293 ; fraction 11, 0.320 g., in. p. 210" (riot sharp); fraction 111, 0.280 g., m. p . 210" (not Shdrp); fraction IV, 0.300 g., m. p. 210" (not 4iarp); fraction V, ~ ) ! . 2 5g., 0 m. p. 195' (not shaip); fraction VI, 0.260 g 'n.p. 190" (not sharp). Fraction I was recrystailized from gILiciL31:tcetic &(-i(i, :n p . 292-293' (cor.), .Inel. Calcd. for Cp2Hz2N2O4C1&: C , 51.46; 13, 4.32: S.5.46. Found: C, 51.49; 11, 4.28; S , 5.67. Fraction \' mas refrdctionatrd and the more soluble part crystallized thrice from ethanol, ni. p . 203 -204 O (cor.). .Inel. Calcd. for C22HZ2N10CC1PS2: C , 51.46; 11, 1 3 2 ; S. 5.46. Found: C, 51 62; 11,4.52; S , j.3. This lower-melting isomer after melting solidified at 205-206° and melted again a t 290-292'. A larger quantity of product heated for one hour above its melting point was then recrystallized from glacial acetic acid a i d proved t o be the higher melting form. To observe satisf;tctorily the melting point of the lower-melting form, it
.
was found desirable to preheat the bath to 195" and 111troduce the melting point tube with only a small quantity of product present.
Summary 1. N-Carboxymethyl-o-benzenesulfonaniidotol-
uene could not be resolved. Cis and trans isomers could not be obtained from N,N'-dimethylS,.f-dibenzenesulfonaniido-m-xylene, S,N'-diinethyl-2,6-dibenzenesulfonamido-m-xylene,antl N,N'- dimethyl-2,.5-dibenzenesulfonamido-p-x)-lene. I t appears that merely one methyl group in the benzene ring ortho to the amino group is inAdequate to restrict the C S rotation when the nitrogen atom is suhstitutrtt with the groups intiicated. 2 . X,iK'- Dimethyl-z',ci- dibenzenesulfonamidci3,B-dichloro-p-xylene was obtained in cis antl trans forins. ~ r R H 4 ' i A , IT.I,I\OIS
RECEIVED MARCH17, 1950
ICONTRIBL I l O S FROM THE UIVKSIOY OF ORGAUIC CHEMISTRI O F THh O R C H O KtiStiAXCH I i O l UDATIOX!
The Reaction of Isoprene with &Butyl Hypochlorite in Hydroxylic Solvents 73u IVILL1.w O K ~ S I I N IARN D ROBERT-\. ~ I A L L O R T
The intermediate carbonium ion can react a t either carbon-2 or carbon-4, producing a pair of isomers. The literature, however, is a t variance as to whether a 1,4-adduct can actually be obtained. Petrov,j who observed only 1,2-adducts, questioned the validity of the claim of Ingold and Smith4that the 1,3-bromohydrin can be obtained in this reaction. An isoprene chlorohydrin obtained through the action of t-butyl hypochlorite and water has been described in a German patent. Although no indication was made as to its struc-
ture, comparison with the product obtained in the present work showed i t to be a 1,2-adduct. The present work was prompted by a need for the 1,4-chlorohydrin of isoprene in a synthesis of vitamin A.R The hypochlorination method used was the elegant one discovered by Harford? and extended by Irwin and HennionS wherein t-butyl hypochlorite is added to a solution of olefin in a reactive solvent. It was found in the present study that this reagent reacted smoothly with isoprene in glacial acetic acid t o give two easily-frxtionated isomers, which were shown to be 1,3- and 1 ,&-adductsby the reactions shown. The non-allylic nature of the chlorine in I, its facile rearrangement to IV, and its conversion to 111, left no doubt as to its structure. In establishing the structure of the 1,4-isomer, the terminal chardcter of the chlorine and acetoxyl groups was first demonstrated by conversion to the diacetate 17, and thence to tiglic aldehydea9 Catalytic dehalogenation of IV, followed by hydrogenation, gave isoamyl acetate, thereby establishing the exact position of the acetoxyl group in IV. -11 though VI analyzed very poorly, the alcohol obtained from i t by alcoholysis gave the correct de rivatives for prenoI.lo Conclusive confirmation of the structure of IV was furnished by the excellent yield of chloroacetone upon ozonolysis. Up011 extension of the reaction to the homolo-
(1) P. D. Bartlett end D. S. Tarhell, Tms JOURNAL, 58, 486 119381, G Williams, Trans Far Soc , 87,j'49 (1941) (2) P. D B d e La hrare, E 11 Hughes and C IC Ingold -r C h m ~Soc , 18 (19481. 13) A. Pctrov, J . Gcn Chem 5 X ) , 13, 181 481 (194?' 1) C K Ingold and I1 G th J l-/,eau Snr , 2752 '1'1'31 ( ' u n i C n P a t e n t 540 I ? ?
(8) W Oroshnik, THISJOURNAL, 67, 1627 (1945) (7) C G Harford, U S Patent 2,054,814, 2,107,788, 2,207,983 48) 2 ' R Irwin dud G P Hennion. THIS JOURNAL, 68,858 (1941 1) A F hhepard .tnd J R Johnson, rbrd , 54, 4388 (1932) 10) 1 he m n ~ eprenol has heen siiggested for y,y-dimethplall) I i l ~ u l i i i ltiy 1- Sp.lth . i r d J Iiru'k t o Indlc.cti ~ t , d e r i L a t i o n I t o m >c, )r T I ( I?*, 71 270') flu361
According to the prevailing ionic theory, the hypochlorination of isoprene would be expected to proceed by electrophilic initiation a t carbon-1, as f OllOWS'~2 CH,
C '
. -
1
CH,
X
+
CICH~--Cyr.CH
CH?
LH
CICIi2 --C--CII=-CHz
(Izoi1___3
Solvent ROH
4-
OR CIi;
I
ClCHZ-C=CH-CH20R
.)
4- S H
Oct., 1950
ISOPRENE WITH
&BUTYL HYPOCHLORITE
4609
butanol, and a product CeH17C10, giving the same 149’ isothiourea picrate, was indeed obtained. However, in addition, a 1 OAc small quantity of an 1°3 KOAc . l H ~(Raiiey SI) ClCH2COCH3 isomeric picrate of CH? m. p. l G O o was isoI CH3 lated from the mother CICHz-C-CzH, I1 liquors of the derivatization. Its infrared spectrum indicated that i t was derived 1 - chloro - 2from methyl-4-t-butoxybutene-2, the “normal’’ 1,4-adduct of isoprene. This was confirmed as follows : ether fission of CgH17C10 with acetic anhydride gave tbutyl acetate and a gous series of carboxylic acids, i t was found that chloro-acetoxy mixture which -likewise furnished although the expected isomers were obtained, two isomeric isothiourea picrates. That formed in their yield increasingly diminished as one went up lesser quantity was, in fact, identical with the one in the series, while a new and unexpected allylic obtained from the acetate IV. Catalytic dehalochloride appeared in increasing proportions. genation of the chloro-acetoxy mixture, followed First observed in small quantities in acetic acid, i t by hydrolysis, gave a mixture of alcohols consistactually constituted the major product in butyric ing chiefly of 2-methylbutene-2-01-1,tiglyl alcohol. and isobutyric acids. The nature of this product This established the structure of the predominant isomer in CgH17C10 as l-t-butoxy-2-methyl-4will be discussed below. The hypochlorination of isoprene in methanol chlorobutene-2. It was subsequently found that also gave 1,2- and 1,Padducts. The former this isomer results almost exclusively upon direct proved to be quite inert and could not be rear- reaction of t-butyl hypochlorite with isoprene in ranged to any other isomeric form as in the case of the absence of solvent. This “abnormal” addition to isoprene opens to the acetate I. In spite of its allylic-ether structure, i t failed to react a t room temperature with speculation some possible competing mechanisms. acetic anhydride containing anhydrous ferric The ionic mechanism shown above predicts the chloride, although its hydrogenated analog reacted appearance of chlorine predominantly a t carbon-1 spontaneously to give the corresponding acetate. and hence is untenable here. However, if one Conversion of the latter to I11 demonstrated the may assume an initial attack by the t-butyl hypostructure of the 1,2-adduct. The structure of the chlorite a t its oxygen atom rather than its chlorine, 1,4-isomer was shown by ozonolysis to chloroace- i t is possible to formulate a cyclic oxonium salt tone and dehalogenation to methyl prenyl ether. through an electron-sharing process similar to that Similar hypochlorinations in ethanol, propanol, involved in the formation of the cyclic sulfone isopropyl alcohol and n-butanol likewise gave the from isoprene and sulfur dioxide.’l The vinylo1,2- and 1,4-isomers, in yields comparable to those gous electron-repelling effect of the 2-methyl obtained in methanol. In no instance was the group in this cyclic ion would tend to bring about allylic by-product obtained above with the car- a ring-opening shift of the bonding electron-pair boxylic acids, detected. In water, however, this from carbon4 to the oxygen, leaving the former compound was formed in major proportion along with a residual positive charge. with the two isomeric chlorohydrins. Phenol Hac gave complex side reactions, and no well-defined H3C .1 1 products were obtained. F C H C-CH2 c1The above-rnentioned allylic chloride by-product 1 4 - 1 I CHz CHI CH2 CHz+ yielded an isoprene 1,4-dihalide with hot hydro\ bromic acid and also gave an isothiourea picrate, \O< 0 m. p. 149”,whose analysis showed the parent I i t-CdHg t-CIHg compound to have the formula CgH17C10. Since this suggested a chloro-f-butoxy-adduct of iso(11) C. M. Suter, “Organic Chemistry of Sulfur,” John Wiley 8. prene, the hypochlorination was performed in t- Sons, Inc., N e w York, N. Y.,1944, p. 729.
I 7
-
with ether or petroleum ether. After neutralizing with aqueous bicarbonate and drying over anhydrous potassium ;-C&O- C'FII C- CH -CI*>Cl carbonate, the solution was distilled. In the alcohol reactions troublesome labile halides were formed as impuriThe explanation for the absence of the "abnormal" ties which decomposed during distillation. These were reaction in the primary and secondary alcohols effectively removed before distillation by stirring the pewould then be in terms of stronger competition troleum ether concentrate with anhydrous potassium carat 70" for eight hours. The results are sumfor the electron pair of oxygen by the available bonate marized in Table I . For characterization, the l,4-adducts protons; i. e., solvation of the t-butyl hypochlorite were converted into isothiourea picrates by the mzthod of Brown and Campbell .I6 This derivatization failed with in such solvents by hydrogen bonding. It has been shown that reactions of "positive the 1.2-adducts. The results a r e summarized in Table 11. Proof of the Structure of the 1,2-Adducts halogen" compounds might be explained in many Hydrogenation of the 1,&Adducts: (a) l-Chloro-2cases by a free radical rnechanism,l2 initiation resulting from the homopolar dissociation of the re- methyl-2-acetoxybutane (11) .---A solution of 65.0 g. (0.4mole) of the acetate I in 200 ml. of methanol containagent. Such a mechanism might equally explain iiig 30 g. of calcium carbonate and 3.0 g. of Raney nickel the formation of the above "abnormal' ,idduct. was sh:iken in a Parr apparatus under hydrogen a t an initial pressure of 45 lb. Absorption ceased abruptly t-C4H&Cl J_ t-C4Hq0 t ('1 when 0.41 mole of hydrogen had been absorbed. The C'H mixture wis filtered and worked up with water and ether. After drying with anhydrous potassium carbonate, distillation yielded 52 g. (79%) of product a t 60-fSo (11 rum.), n22u 1.4312. ..Lncil. Calctl. for C,HI:lC102: C1, 21.X. Found: C1, I-C,JI,O --CH! 4 -zCI1 CH21.66; 21.59. ih'i l-Chloro-2-methyl-2-methoxybutane. -The niethoxy analog of I was reduced in the same way as above. ClCH&=Cfl --CHXl t-CJIsO The yield was 867,. b. p. 67-68" (55 mrn.), ~ z * ~1.4313. D CH ) i l n d . Calcd. for C6H1:&lO: C, 52.71; H, 9.59; CI, 45.93. Found: C,52.98; H, 9.60; C1, 25.%, 25.78. ~ - c ~ HCII, ~ o --~-CH-CH~CI I-C,H~O The reduction product was converted into I1 in the folCH, lowing manner: 25.3 g. of the methoxy compound was dissolvetl in 73 ml. of acetic anhydride. On adding 0.20.R g. of anhydrous ferric chloride, i t mild exothermic re/-C4HoO, H*C==C--CH==CH + cH itctipn set in, the temperature rising to 50' before dropping again. The opaque red-browii solution was then warmed t-C,H@O-CH, -C-CH-C H? :it 50-6flo for one hour, cooled, and worked up with water iiiid ether, the exce'is acetic anhydride being removed by Initial attack upon isoprene by the free radicals 6-8 snccessive washer; with lOoh brine and it final wash a t carbon-1 is postulated here, for, of the two pos- with bicarbonate solution. Distillation yielded 16.8 g. sible intermediates ,4 and B, resulting from a t t x k (5.W;) of product, b. p. 65-68' i mm.), ~ * Z D 1..1318. .-btnZ, Calcd. for CrH13ClO::: 51.07; H , 7.96; C1, a t carbon-1 or carbon4 21.54. F o m d : e. .it.44. -51.44; €1. x.02, 7.86; CI. CI-I1 Lit 2l.1O921.lX. I This acetate yielded compound 111 after :tlcoholysis and .\CHZ-C.ICH---CH~ ( A I CH, -C=CH -CH:X P, diethylamination as described beloN-. Alcoholysis of I1 : 1-Chloro-2-methylbutanol-2.-A structure '4 is by far the more stable, having seven solution of 49 g, of the acetate 11, prepared from I, in 250 possible resonance forms through hypercon juga- nil. of methanol containing one drop of concentrated hytion as compared to only three for structure B.13 drochloric acid was slowly distilled during eight hours The free radical mechanism as shown above pre- through R 12" Vigreux column ;tt such a rate that 50-70 dicts the formation of some isoprene 1,4-dichlo- ml. of distillate was collected. After standing overnight ~ with a little anhyride. This compound was indeed identified in the the reinhiiig solution T V neutralized drous potassium carbonate, filtered and distilled, yielding foreruns, by conversion to isoprene l14-diisothiou- 22 g. of product, b. p. 74-78' (62 mm.), 1.4421. red picrate, The same. chlorohydrin was also prepared as follows: t o :E solution of ethylmagnesium chloride prepared from Experimental 52.4 g. of magnesium in 2000 ml. of ether was added 185.6 Hypochlorination of Isoprene.--ThL procedure usecl g. of chloroacetoiie a t -30". After hydrolysis with dilute acid and working up in the usual manner there were ob\vas essentially the same 111 all cases. One mole of t-butyl hypochlorite" was added during two hours t o J well- tained 186 g. of chlorohydrin b. p. $0-81' (73 inm.), stirred solution of 1.25 moles of isopreneI5 dissohed in ill ?726D 1.1442. 1-Diethylamino-2-methylbutanol-2 (111).-A solution moles of the reacting solvent. The redclioii mixture \\a\ then poured into a l'rrge \olume of w'iter .irid e.\trxted of 10.8 g. of the chlorohydrin obtained from the alcoholysis of 11, 20 g. of diethylamine and 20 mf. of 95% ethanol was (12) W. 4 Waters, "Chemistry of Free Kndicdlz," Uxford I. I U heated i u a pressure bottle for four hours a t 100". 0 1 1 versity Press, London, England, 2nd edition, 1948,p 2.52 cooling, the dark brown solution solidified to a crystallirie (13) A E Rcmick, "Electronic Interpretatlorib of Organic Chemmush. ilfter adding twice the volume of 20% potassium '15try." John Wiley &Sons, Inc , Ken York N Y 2nd edltion, l'llcr hydroxide, extracting with ether, and drying over potaspp 505, 629 sium carbonate, distillation yielded 9.8 g. (70cY,)of aminc., (14) hepared b) t h c mtthod of b U Ch.rttaw,iy rnd 0 The prenol obtained by methnnolysi5 of this .m tatc was separated into 3.7 g. of a picrate in. p . 148.5-149.5" hati 11. p . 80-82" (75 mm.i, n 2 0 ~1.4434. and 2.3 g . of a more soluble picrate in. p . 159.5161". d w a i Calcd. for C6Wl0O: C, 69.72; I I , 11.70 I'ouiiti: Although thc two picrates analyzed alike, a mixture of the C, 69.51, 69.55; H, 11.65, 11.75. two melted at 132-135'. The higher melting picrate was The p-'t,romopheiiylurethari meltrd a t 7? 5 -7:3 .i^ (from shown by infrared analysis to belong t o the homologous series of picratw rlcrircci from the 1,l-chloro-alkoxy 3dligroin). ducts (T:tble IT). C, 50.72; H, 4.97; Snal. Calcd. €or C12Hl~BrXO~: S , 4.93. Found: C , 50.87, ii0.86; H, 4.79, 5.01; S,
Ocl., 1950
1SOPRENE WITH BUTYL
A solution of 25 g. of the above chloride mixture in 75 ml. of acetic anhydride was treated with 0.1-0.2 g. of anhydrous ferric chloride. There was an immediate mild exothermic reaction lasting a few minutes. The mixture was kept below 60" by intermittent immersion in cold water, and then was maintained a t 50-60" for one hour. The solution was then evaporated under vacuum to two thirds its volume, condensing the volatiles in a Dry-Ice trap. This condensate was fractionated $nospherically and yielded t-butyl acetate, b. p. 95-97 , n a 6 1.3838, ~ dzol 0.876. The literature gives constants for t-butyl acetate: b. p. 97.8", nZ5D 1.3840, dz640.8620.*O The remainder of the reaction mixture was worked up with petroleum ether and water, washing several times with the latter to remove excess acetic anhydride. Distillation gave 13.6 g. of acetate (59%), b. p. 91-96' (10 Iilm.), ?224D 1.4633. And. Calcd. for C7H11C102: C, 51.70; H , 6.80; C1, 51.81. Found: C, 52.03, 52.11; H, 6.82, 6.93; C1, 80.87, 21.17. From 5.0 g. of this chloro-acetoxy compound there was obtained 11.3 g. of crude isothiourea picrate. Fractional crystallization starting with 70% methanol and ending with 50y0 methanol yielded 3.8 g. of a picrate, m. p. 1600162", and 1.6 g. of a more soluble picrate m. p. 131132 . The latter did not depress the melting point of that from IV (see Table 11). Both picrates gave the same elementary analysis. Anal. Calcd. for C ~ ~ H I ~ N ~C,O ~38.98; S: H, 3.97; S , 16.24. Found: C, 39.10, 39.34; H , 4.14, 3.98; N, 16.29, 16.31. A methanolic solution of 17.0 g. of the above chloroacetoxy mixture was catalytically dehalogenated in the same manner as described above. The crude acetate obtained was hydrolyzed with a very slight excess of methanolic sodium hydroxide at room temperature. The yield was 6 . i g. of alcohol, collected a t 83-88' (100 mm.), n% 1.4346. It yielded a p-nitrophenylurethan m. p. 112.5-113.5" and a p-bromophenylurethan m. p. 97-98', neither of which depressed the melting points of the corresponding derivatives of tiglyl alcohol. Authentic tiglyl alcohol was prepared by the Meerwein-Ponndorf reduction of tiglic aldehyde using aluminum isopropoxide. The yield of product collected a t 139-145", %*D 1.4420, was
37yo. Anal.
Calcd. for C5HIoO:C, 69.72; H, 11.70. Found: C, 69.95,69.86; H , 11.53, 11.62. The p-nitrophenylurethan melted a t 112.5-113.5' (from ligroin). Anal. Calcd. for ClzHlaNz04: C, 57.59; H , 5.64; S , 11.20. Found: C, 57.41, 57.42; H, 5.54, 5.61; N, 11.013,11.13. (20) J. F. Norris and G. 11939.
W. Rigby, THISJOURNAL, 64, 2088
HYPOCIILORITE
4618
The #-bromophenylurethan melted a t 100.5-101.5° (from ligroin). Anal. Calcd. for ClaHl4BrNO2: C, 50.72; H, 4.97; K, 4.93. Found: C, 50.86, 50.63; H , 4.80, 4.94; N, 5.03, 5.08. (b) In the Absence of Solvent.-Two moles of t-butyl hypochlorite were added with stirring, to one liter of isoprene a t 32-34" during ninety minutes. The reaction mixture gave a negative test for acetone and for free acid. It was then distilled directly, giving 206 g. of product b. p. 57-65' (2.2 mm.). C'pon refractionation there was obtained 164 g. of product, b. p. 54-55' (1.5 mm.), nzaD 1.4568. Anal, Calcd. for CgH&10: C, 61.18; H , 9.70; C1, 20.07. Found: C, 60.68; 60.64; H, 9.86, 9.53; C1, 20.19,20.32. A 10-g. sample yielded 21 g. of isothiourea picrat: which upon fractional crystallization gave 16 g. of 149 picrate and only 0.8 g. of 156-158' picrate. These were identical with the corresponding salts obtained under (a). The foreruns gave a small yield of picrate, m. p. 226227', which did not depress the melting point of that obtained from isoprene 1,4-dibromide (m, p. 229.5-230'). The same compound was also obtained from the foreruns from (a). Anal. Calcd. for ClsHz&0S2O14: C, 33.73; H, 2.98; K, 20.71. Found: C, 33.89, 33.89; H, 2.96, 2.86; K, 20.65,20.81. All melting points were determined on a Fisher-Johns melting point block, heating a t the rate of 2' per minute.
Acknowledgment.-The authors are indebted to hlr. A. D. Mebane for his helpful discussions and the preparation of many of the derivatives, Mr. W. Haffcke for the ozonizations, and Mr. J. Grodsky for the microanalyses. Summary 1. Isoprene reacts with t-butyl hypochlorite in hydroxylic solvents to give 1,2- and 1,4-adducts. 2. Orientation of the addenda follows the same course as other electrophilic additions to isoprene. 3. As the hydroxylic nature of the solvent diminishes, i t plays a progressively lesser role in the reaction, and t-butyl hypochlorite then apparently adds directly to isoprene. Under such conditions the orientation of the chlorine and alkoxy1 groups is the reverse of that in the electrophilic additions. 4. Two alternative mechanisms have been suggested to account for the "abnormal" addition. RARITAN, NEWJERSEY
RECEIVED MARCH 15, 1950
