Indian Journal of Chemistry Vol. 38B , July 1999, pp. 777-782

Stereoselective chlorination of non-conjugated heterocyclic alkenes

Shadpour E Mall akpour* Organic Polymer Chemi stry Research Laboratory, College of Chemi stry, Isfahan Uni versi ty of Tech nology .

Isfahan 84 156. IR , Iran E- mail : Mallak:@CC. IUT.AC.JR

and Mohammad Ali Zolfi gol

Chemi stry Department . Co ll ege of Science. Bu-Ali Sina Uni versity. Hamadan 671 74. I R. Iran

Received 13 Jalll/a ry 1997; accepted (revised ) 15 September 1998

Diels- Alder adducts of 4-suhsti tuted tri azo linediones (4-Ph. 4-II -Pr) with cyclopellladienes have heen reacted with chl orine in carbo n tetrac hl oride. When R = Ph onl y. cis-di chloride adduct is obtained in a stereos pecific man ner. However. when R = II-Pr, two products. the cis-dichl oride addoct and the rearrangement adduct are obtained in a steremelectivc manner. The adducts of these triazol inediones with IJ-cyclohexadiene have also been reacted with ch lorine. Whe n R = Ph . the trails-dichlo ride is formed with a high degree of stereoselecti vity (98%). Howeve r. when R = II-P I'. twn products . the trails-dichl ori de and the rearrangement adduct are obtained ill 4: I ra ti o.

Although the electrophilic additi on of hal ogens to carbon-carbon doubl e bonds is a fairl y well -known reaction, the study of its mechani sm has been the subj ect of ex tensive in vestigati onsla-j . Considerable insight has been ga ined into the mechani sm of halogen addition through studies on the stereochemistry of the reac ti on. For brominati on, Ctllti ­addition is preferred for alkenes th at do not contain substituents which would strongly stabili ze a carbocation intermediate, or other groups th at provjde steric hindrance agai nst (tll li-face attack. When the alkene is conjugated with an aryl group or the bromonium ion is stabili zed by the neighbouri ng groups, the ex tent of sYII -addition becomes much larger, and hence syn-additi on can beco me the dominant pathway.

Ch lorinati on is not as stereospecific as bromination , but tends to fo ll ow the same pattern . The tendency to fo rm tralls-dihalides fall s in the sequence h, Br2, C1 1· The additi on of bromine to cis-I ­phenyl propene gives mainly the tralls-dibromide, whereas chl orine forms a mi xture of nearl y equal quantities of cis- and lIwls-addi tion products2

.

Bromination of acenaphthene and phenanthrene produces the lrans-di hal ides'.4. ch lorination gives a substanti al quantity of th e cis-adduct together with the trans- isomer'.5. Such variati on is explained in terms of polar addition by the stronger tendency of bromine to form bridged structure in the cati on6

. Furthermore,

the larger size of iodine and bromine atoms niay prevent formation of cis-isomers. Chl orine on the other hand would be ex pected to be a so mewhat poorer bridging than bromine because it is less polari sable and more relu ctan t to become pos itively charged.

Ch lorinati on can be accompani ed by reactions that are characteri stic of carbonium intermediates. Branched olefins can give a product as a result of the eliminati on of a proton from a cati onic intennediate7

.

Skeletal rearrangement s ha ve also been reported in I

. . 7X systems t lat are prone to mt gratl on . .

In a previous paper brominati on of non-conjugated heterocyclic alekenes la , 1 b. 2a . and 2b has been reported'!. Brominati on of the heterocycli c alkelles la and tb was stereospec ific and yielded olll y cis­dibromide adducts. Thi s unusual rormati on or cis­dibromide was ex plained in terills of neighbouring group effect. However, the bro illination of alk enes 2a

n = 1 11 = 2

a R = C6i-i,

b R= n-Pr

778 INDIAN 1. CHEM. SEC B, JULY 1999

and 2b gave a substantial quantity of the trans­dibromide together with cis-dibromide.

The purpose of this investi gati on was to examine the reaction of these non-conjugated heterocyclic alkenes towards additi on of chlorine identification of the chl orinated adducts and mechani sm of their formation.

Compound la was allowed to react with excess chl orine in carbon tetrachloride in the dark at room temperature. After 12 hr only one product was fornied in quantitative yield (Scheme I). The elemental analyses of the resu ltant adduct was in agreement with the dichloride 3.

Its IH NMR spectrum showed all peaks that are in agreement with the cis-dichl oride adduct 3.

The above reaction is stereospecific and formation of the cis-dichloride 3 requires intermediacy of the intimate ionpair, zwitterion , or chlorocarbonium ion and subsequent sYII -attack by cr. But, formati on of such intermediates are unl ikely since trails-d ichl oride and rean'angement adducts were not formed at all. Therefore, we proposed the mechani sm, as shown in Scheme II, for the formation of the cis-dichloride 3. The fi rst step involves the format ion of a chl oronium ion 6 from the CH2 bridged side (e.w-addition). The absence of trans-dichloride adduct can be explained in terms of a large non-bonded interaction between chl orine and carbonyl group in the elida-configuration which provides a large steric factor opposing the formation of a trails-dichloride adduct. The second step is the neighbouring group effect via attack of the carbonyl group through oxygen atom from the anti­face to produce the intermedi ate 7. Although the intermedi ate 7 can have two resonance structures, but the structure which has pos iti ve charge on the nitrogen atom has more contribution, and therefore it is more important. From an inspecti on of molecular models, there is no question that the triazo le moiety via carbonyl group can form the intermediate 6 and subsequent sYIl-attack by cr gives the cis-dichloride adduct in a stereospecific manner. Stereospec ificity of the compound la can be explained in terms of phenyl group that can stabilize the intermediate 7 through di spersion of the positi ve charge.

Ch lorin at ion of the compound Ib was carried out in a similar way. But in thi s case two products 4 and 5 were formed in a rati o of I : 1.6. Two fraction s were iso lated by fractional crysta llizati on. Fract ion I (Rr 0.64) was obtained in about 31 % yield. Its IH NMR and 13C NMR data (Table I) are consistent wi th the rearrangement dichloride adduct 4. Fraction 2 (Rr

+ CJ,

• R = C.II, b R = n-Pr

4

69% Racemic IllL'\1urc

Scht' lII (, I 3 1%

1M + 0,

Schtlll t II

Table 1-I.1C NMR (20 MHz) data or Ihe dich loride 4

Ott A a h di e b a

9 ~r - j /-CI-I2 CH2 CII]

c ~O

Type of Signal T ype or Signal carbon (8, ppm) carbon ((S, pplll)

a 10.93 57.5lJ b 21.05 " () :l.4~

~

e 38 .50 h 66. 12 d 4 1.7 1 157.25 e 52.79 1 5~U)O

0.48) was obtained in about 69% yield. Its 'H NMR and 13C NMR data (Table II) correspond to the cis­dichloride structure 5 (Scheme J).

The above reaction is stereoselec ti ve and cis­dichloride adduct is the major product. Formati on of cis-dichloride 5 and the rearrangement adduct 4 can bf' explained by the proposed mechani sm shown in

MALLAKPOUR el al.: STEREOSELECTIVE CHLORINATION OF HETEROCYCLIC ALKENES 779

4

Table II-DC NMR (20 M Hz) data of the dichloride 5

Type of carbon

a b c d

5

Signal (8, ppm)

10.67 20.99 32.02 41.60

Type of carbon

e I' g

Signal (8, ppm)

59.42 64.92 157.66

Scheme III. Formation of the adduct 4 can be explained in terms of the initial formation o( a zwitterion 8 or the intimate ionpair 9, followed by bond migrat ion to form the chlorocarbocation 12. This intermediate can stabi I ize it se l f via strong overlapping between elida- lone pair of the nitrogen atom and empty orbital of the carbocation 12. Such interaction seeins to be extremely strong which

prevents the cr attack from enda-s ide . Thus, cr will

CI

Scheme m

+ 0,

• R = C.H, b R = n-I'r

co.

1l Isomerization

III

AY ° LN // "- R

R ::: It-P,· 13

80%

98%

ottO !l R N~N,/' + J--{

o

Scheme IV

14 T \\Q racellIe 11'iXtlD'"es

20%

attack only from the exa-side and produce only one racemic mixture. 01) the other hand the zwitterion 8 or the intimate ionpair 9 can undergo isomerization to the chloronium ion 10 which by a neighbouring group effect produces 11 and finally the cis-d ic hloride 5. Possibly, this adduct is also generated directl y from the intermediates 8 and 9 . This exp lains the ex tra formation of 5 over 4 .

Chlorination of compound 2a was carried ou t with excess chlorine in carbon tetrachloride ((/ Scheme IV) . The reaction was monitored by TLC. Two fractions were isolated by chromatography. Fract ion I (Rr 0.55) was obtained in about 2 % yield , and was not identified . Fraction 2 (Rr 0.30) was obtained in about

780 INDIAN 1. C HEM. SEC B, JULY 1999

Table III-I3C NMR (20 MH z) data of Irolls- dichloride 13

Type o f Signal T ype o f Signal carbon (0, ppm) carbon (0, ppm)

a 17.69 " 125.64 e

b 23 . 11 h 128.3 1 e 51 .34 129. 11 d 55 .25 J 13 U 9 e 60.70 k 15 1.33

63.84 153.32

98% yield . Its IH NMR and L1C NMR data (ef Table III) are consistent with the trans-dichl oride structure 13. Formation of 13 can be ex plained in terms of the chl oronium ion intermediate and subsequent (fllti ­

attack by cr. Chlorination of 2a is more stereoselective than

bromin ati on '>. Thi s can be attributed to the smaller size of cr which makes it eas ier t.o attack from the an.ti- face.

Chlorin at ion of 2b was carried out in a si milar way (Scheme IV). The reac ti on was monitored by TLC and I H NM R techniques. TLC showed two spots, whereas J.

1C NMR spectrum of the crude product ex hibited 6 signal s for carbonyl groups, indi cating formati on of three unsymmetric products. The crude product was subjected to chromatography. But, on ly two frac ti ons were eluted from the column . Fracli on I with Rr 0.60 was obtained in about 20% yield. Its J.

1C

NMR gave 22 signal s at 8 10.92, 17 .63,2 1.02,29.70, 3 1.40,4 1.40,47.76,49 .73,50.54,50.86,53.91,54.68, 55 .04, 58.57, 59.08, 60.50, 6 1.28, 6 1.65 , 152.30, 152.05, 153.90 and 154.20 ppm which are . in agreement with two racemic mi xtures of 14 (di astereomers). All attempts to reso lve thi s racemic mi xture fail ed. The IH NMR spectrum of thi s frac ti on product al so showed peaks which are consistent with a mixture of two products 14. Fraction 2, with Rr 0.35 was obtained in about 80% yield. Its IH NMR and J.

1C NMR data were in agreement with the tral/S­dichloride 15. 13C NMR spectrum of 15 showed peaks at 8 10.89, 17.36, 20.91 , 23.05, 40 .95 , 51.39, 54.84, 60.98, 63 .63, 152.71 and 154.43 ppm.

Formation of the trans-dichloride IS can be explained via a chloronium ion intermediate, but the formation of the rearrangement products 14 cann ot be explained by this type of intermediate . Therefore, an intermediate like 16 which can resu lt from a zwitterion or an intimate ion-pair bond mi grati on will be proposed. This ion can be stabili zed to some extent by the interaction with the lone pair of nitrogen atom. This interacti on is weaker than that In the intermediate 12, due to less ri g idit y of the intermediate 16. Therefore, CI' can preferabl y attack from exo-s ide to less extent. Attack of CI ' from e.w ­side leads to the formati on of the major racemic mi xture and its attack from elldo-side produces the other minor racemic mixture. The J.

1C NM R and I H NMR spectra also confirmed thi s.

Experimental Section Materials and equipmcnts . Reage nts were

purchased from Flu ka Chemi cal Co., Ald ri ch Chemi cal Co. and Ri edel-dehaell AG . Melting poin ts were taken on a Gallenh amp me lt in g point appa ratLi s and are uncorrected.

Proton nuclear magneti c resonance ( IH NM R, 90 MH z) spectra were reco rded on a Va rian EM-390 instrument. Multipli cit ies or pro ton resonances are designated as singlet (s), doublet (d). tri plet (t).

quartet (q), sextet (se) , mUltiplet ( Ill ) and broad (br). Tetramethylsilane (TMS) was used as internal reference. Carbon-1 3 spectra we re recorded 0 11 a Bruker instrument operati ng at 20 MH z.

Thin layer chromatography (TLC) on commercial plates of silica gel 60 F25~ 011 aluminium was Ll sed to monitor the progress of the reac ti ons. Colu mn chromatography was carri ed OLit using sili ca gel 60 (Ri edel-dehaen AG). JR spectra were reco rded on a Shimadzu 435 TR spectrophotometer. Spectra of so lids were recorded using KBr pe ll ets (v""" in Clll'\

Elemental analyses were carried OLit at the Research Institute of Petroleum Industry, Tehran, lR Iran .

Reaction of compound la with chlorine. Into a 500 mL two-necked round-bott ommed fl ask, which was equipped with a magnetic stirrer and an inlet

MALLAKPOUR et al.: STEREOSELECTIVE CHLORINA I'lVN OF i-i c.':::i~OC !' C' L; '= ..\ :... "r::NES 78 1

tube, compound la ( 1.00 g, 4.14x I 0" mole) and 250 mL of carbon tetrachl oride were added . Freshly generated chlorine gas (from HCI and potassium permanganate) was bubbled th rough the solution under stirring for 12 hr. The resultant white precIpitate ( 1.1 9g, 92%) was filtered and recrysta lli zed from toluene to give white need les of 3,

mp 2 10-2 11 °C; IR(KBr): 3050(w), 3000(w), 1790(m), 1710(s,br), I 590(w), 1500(m), 1450(w), 1400(s), 1300(w), 1235(s), 11 90(w), 11 40(s), 1090(w), 1060(s), 1040(w), I 020(w), 940(w), 920(w), 850(m), 796(m), 760(m), 745(111), 700(111), 640(w), 620(m) cm· l

; 'H NMR (CDCIJ): 8 1.87 (dd , I H, 11= 11 .37 Hz, 12=unreso lved), 2.57 (dd, IH , 1 1=11.79 Hz, 12=unreso lved), 4.50 (2H, 1=3.37 Hz), 4.70 (m, 2H), 7.45 (s , 5H). Anal. Ca lcd for CI JH IICI 2NJ0 2: C, 50.10; H , 3.55; N, 13.46. Fou nd: C, 50.60; H, 3.80; N, 13.50%.

Reaction of compound Ib with chlorine. Into a 250 mL two-necked rou nd-botto mmed flas k, were placed compound Ib (2 .00 g, 9.65x I0·' mole) and 175 mL of carbon tetrachl oride. Freshl y generated ch lorine gas was bubbled through the so luti on under stirring for 48 hr. The so lvent was removed by evaporat ion under reduced pressure to leave 2.68 g ( 100%) of a viscous o il , which was triturated with hexane. Fractional crystalli zat ion fro m II-hexane gave white crys ta ls of 4 (0.79g, 31 %), mp 108-1 09 °C; IR(KBr): 2950(m), 1780(m) , 1700(s,br), 1440(5), 14 10(s), I 380(w), 11 80(m), 1060(m), 1020(w), 995(w) , 920(w), 870(m), 8 10(w), 770(m), 720(w), 610(w), cm· l

; 'H NMR (C DC IJ): 80.9 1 (t, 3H, 1=7.50 Hz), 1.70 (se, 2H), 2.70 (d, 2H, 1=9.0 Hz), 3.49 (t, 2H, 1=7.5 Hz), 4 .01 (s,br, IH), 4.25 (t, IH , 1=9.0Hz), .4.60 (s,br, 2H). Anal. Ca\cd fo r C IOH 13CI 2N,0 2: C, 43.18 ; H, 4 .71 ; N, 15 . 10. Found: C, 43.00; H, 5 .30 ; N, 14.60%. The filtrate was concentrated to g ive 1.55g of white crystal s of 5 , mp 83-84 °C; IR(KBr): 2950(m), 2850(w), I 780(m), 1700(s,br), I 440(s) , 1410(5), 11 80(m), 1060(m), 995(w), 9 1 5(w) , 870(w), 770(m), 720(w), 620(w) , cm· l

; 'H NMR (COCh): 8 0.93 (t, 3H, 1=7.50 Hz), 1.46-1 .96 (m, 3H, sextet with doublet are overlapped), 2.51 (d , IH, 1=12.0 Hz), 3.51 (t,2H, 1=7.5 Hz) , 4.49 (s, 2H), 4.65 (s, 2H). Anal. Ca\cd. For C IOH I,ChN,0 2: C, 43.18; H, 4.71; N, 15.10%. Found: C, 42.70; H , 4 .80; N, 14.90.

Chlorination of compound 2a . Compound 2a (1.15g, 4 .5x I 0" mole) and carbon tetrachloride (250 mL) were placed into a two-necked rouned-bottomed fl ask, and freshly generated chl orine gas was bubbled

through the solution under stirring for 12 hr. A white precipitate (0.75 g) was fo rmed whi ch was filt ered . The filtrate was concentrated to leave 0.5 8g of a so li d, (total 90%). These so lid s were combined and chromatographed over silica gel using ethyl acetate- ' carbon tetrachl oride (20: 80) as e luent. Frac tion I yielded 0.03g (2.0%) of a wh ite solid whi ch was not identified. Fract ion 2 yie lded 1.30 g (98 %) of a wh ite so lid 13 which was recrysta lli zed from acetone to g ive white crysta ls o f 13, mp 188-1 89 0C; IR (KB r): 3030(w), 2950(w), 1760(111), 17 10(s.br) , 1590(w), 1490(m), 1450(w), 1405(s ,br), 1330(w), I 290(I11,br), 1250(w) , 11 60(w), 11 40(w) , 11 20(111), 1080(w), 1030(w), 1020(w), 980(w) , 9 10(w), 880(w). 840(m), 8 10(w), 790(w) , 770(m), 740( m), 685(w), 640(w), 6 10(w), 590(w) , 560(w) CIll ·

I; ' H NM R (COCl 1): 8 1.76-2.60 (m, 4H), 4.23-4.50 ( 111 , 2H), 4 .60 (s, br, 2H), 7.5 (s, 5H). Ana l. Calce!. for C' 4H ' 1C I2 .10 2: C, 5 1.54; H, 4.0 I ; N, 12.90%. Fou nd: C. 52.00; H. 4 .00; N,12.90%.

Chlorination of compound 2b. Compound 2b (0 .76g, 3.4xlO·J mole) was chlorinated in a similar way . The reaction mi xture was chromatographed over silica gel using ethyl acetate-carbon tetrach lori de (20:80) as el uent. Fraction I yie lded 0 .20 g (20 %) of 14 as a colourless oil ; IR (KBr): 2900(111) , 2850(w), 1765(m, br), 1700(s, br), 1575(m, br), 1440(s), 1410(s), I 380(w), 1330(w), 1240(111, br), 1350(w), 1060(w), 980(w), 940(w) , 880(w) , 845(m). 830(w) , 750(m, br) , 640(w), 590(w), C I11·

I; I H NM R (COC\.1):

8 1.00 (t, 3H, 1=7.5Hz), 1.53-2.90 ( Ill, 6H), 3.50-4.00 (m, 3H), 4.33-5.10 (m, 3H). Fracti on 2, yie lded 0.80 g (80%) of 15 as a pa le ye ll ow so lie! , mp 54-56 °C; IR(KBr): 2950(111), 2900(w), 1760(s), 1700(s,br), 1560(w), 1440(s), ' 141 0(s) , 1380(m), 1340(111), 1250(m), I 220(m, br), 11 65(w), 11 20(w), 1060(w), 975(w), 940(w) , 880(w), 840(w), 8 15(w), 770(s , br), 640(w), 590(w) , 540(w) CI11·

I; 'H NMR (COCU: 8 0.95 (t, 3H, 1=7 .50 Hz), 1.73 (se, 2H) , 1.90-2.63 (m, 4H, overlapped with sextet), 3.55 (t, 2H. J=7 .S Hz), 4.36 (s, 2H), 4 .50 (s, br, 2H).

Acknowledgement The authors wish to express the ir gratitude to the

Isfahan University of Technology, Isfahan , for financial grant.

References I (a) Schimd G H & Garratt 0 G, in: The chell/isfI".\' of dOllh le

bonded f llllctional groups, edited by S Pal ai (Wil ey. New York) 1977, supp l A, part 2 , chapt. 9.

782 INDIAN J. C HEM. SEC B, JULY 1999

(b) Garralt D G , Ryan M D & Beaulieu P L, j Org Chem, 45, 1980,839. (c) Vyunov K A & Ginak A I, Rllss Chem Rev, 50, 1981, 151 . (d) De1a Mare P B D & Botton R, in: Electrol'hilic additioll to unsatllrated systelll, 2nd edn (Elsevier, New York), 1982, pp 136-197. • (e) Brown R S, Slebocka-Ti1k H, Buschek J M & Kopecky K R, j Am Chem Soc, 106, 1984,45 15. (I) Cadogen JIG, Cameron D K, Gosney I, Highcak R M & New1ands S F, j Chem Soc Chelll COIII/IIIIIl , 1985, 1751 . (g) Bellucci G, Bianchini R & Ambroselti R, j Alii Chelll Soc, 107, 1985,2464. (h) Bellucci G, Chiappc C & Marioni F, j Alii Chelll Soc, 109, 1987,5 15. (i) Shmaryahu H, Modechai L & Drora, j Am Chelll Soc, 109, 1987, 5149.

. . . U) Bellucci G, Bianchini R, Chi appc C & Marioni . .I Org Chelll , 55 , 1990,4094.

2 Fahey R C & Schneider H J . .1 Alii G elll Soc . <)0. 1968. 4429.

3 Cristo1 S J, Stormitz F R & Rowcy P S . .I Alii Clll:1II Soc. 78. 1956.4939.

4 Vander Li nde J & Havinga E. Reel Trap Chi,li . X4 , 1965. 1047.

5 De1a Mare P B & Koeni gsbcrgcr R, .I Alii Chelll Soc, 87 , 1965,2172.

6 Bach R D & Henncike H F, .1 Alii Gelll Soc. 92. 1970.5589.

7 Pout sma M L, j Alii Chelll Soc, 87, 1965. 42X5.

8 Norman ROC & Thomas C B . .1 Chl'11I 50c 8 . 1967. 59X.

9 Mall akpour S E & Zolligo1c M A. Illdiall .I Chelll . 34B. 1995 . 302.