J. Org. Chem. 1980,45,4649-4652
4649
Reactions of Terminal Alkynes with Iodine in Methanol Victor L. Heasley,* Dale F. Shellhamer, Lynn E. Heasley, and David B. Yaeger Department
of
Chemistry, Point Loma Collage, Sun Diego, California 92106
Gene E. Heasley Department of Chemistry, Bethany Nazarene College, Bethany, Oklahoma 73008
Received December 27, 1979 Terminal alkynes 1-hexyne (l),tert-butylacetylene (2), and phenylacetylene (3) react with iodine in methanol to give only 1,2-diiodoalkenes, If the reactions are carried out in the presence of silver nitrate, however, diiodo ketones (RC(0)CHIJ and substitution products ( R C d I ) are formed along with the diiodoalkenes. Under similar conditions, 3 produces the intermediate ketal (RC(OCH3)&HIZ),the substitution product, and the diiodide. An ionic mechanism is proposed for the silver-assisted reaction, and a molecule-induced homolytic radical mechanism is suggested for the unassisted reaction.
Recently, we became interested in the reaction of alkynes with iodine in methanol. In particular, we wished to determine the direction of opening of the intermediate iodonium ion by the solvent, providing such reactions occurred. Earlier studies' had shown that trans-diiodoacetylene can be synthesized by the reaction of iodine with acetylene in alcohol, and there was no report of solvent incorporation. It was our feeling, however, that small amounts of products derived from the solvent could easily have gone undetected. From our previous experience with the bromination of 1-hexyne in methanol,2 we assumed that the regiochemistry, if solvent incorporation occurred, would be indicated by the ratio of diiodo ketone to diiodo aldehyde. These carbonyl compounds would form via the intermediate iodomethoxyalkenes which should be more reactive than the starting alkyne and, therefore, react to give an acetal or ketal which would tie hydrolyzed to the corresponding aldehydes or ketones.
Results We observed that 1.-hexyne (I), tert-butylacetylene (2), and phenylacetylene (3) reacted with iodine in methanol to give only 1,2-diiod.oalkanes (4a-c). Not more than a RCGCH
+
cn
12
OH
iI
1 R-C=C
U
/"
0
mere trace, if any, of 1,l-diiodoketones (5a-c) were observed in the NMR analysis of the reaction mixture, and no intermediate ketals (sa-c) or acetals, were detected. This result stands in sharp contrast to chlorination3 and b r ~ m i n a t i o nof ~ ,1-hexyne ~ in methanol in which solvent incorporation was a major reaction. These data raised the question of whether the iodination reactions were occurring by radical (molecule-induced) or (1)R.M.Noyes, R. G . Dickenson, and V. Schomaker, J.Am. Chem. 67, 1319 (i945). (2) V. L. Heasley, D. F. Shellhamer, J. A. Iskikian, D. L. Street, and G.E. Heasley, J. Org. Chena., 43, 3139 (1978). (3)J. J. Verbanc and G . F. Hennion, J. Am. Chem. Soc., 60, 1711 (1938). ' (4) It has recently been reported that the ketal can be isolated as the major product from bromination of 1-hexyne in methanol [S. Uemura, H. O W ,M. Okano, S. Sawada, A. Okada, and K. Kuwabara, Bull. SOC. Chem. Jpn., 51, 1911 (1978)l.
I
R--&CHI~
R&HI~
5a, R = n-butyl b, R = tert-butyl c, R = phenyl
OCH3
6a, R = n-butyl b, R = tert-butyl c, R = phenyl
ionic mechanisms (see Scheme I). An ionic mechanism would require an ion pair (7) in which the positive ion is reactive toward iodide but not methanol. In a recent study on the stereochemistry of several 1,2-diiodoalkenes, prepared by the reactions of iodine with alkynes, it was assumed that iodine and alkynes react by an ionic mechanism, but no proof was provided for the concl~sion.~ At this point in our research, we decided to investigate the effect of added silver nitrate on the reaction of iodine with the alkynes in methanol. Conceivably, silver ion would assist an ionic reaction, and this would imply that the unassisted reaction of iodine with the alkynes in methanol was proceeding by a radical mechanism. When silver nitrate was added to methanol solutions of 1-hexyne (1) and tert-butylacetylene (2) containing iodine, yellow silver iodide immediately began to settle from the reaction solution. Analysis showed the products found in eq 1. R C S H 12' *Oo3> 5ab t 4ab
+
(1)
The results for the reactions of 1 and 2 with iodine in methanol and silver nitrate are summarized in Table I. Diiodo ketones 5ab are clearly solvent-incorporation products formed by hydrolysis of the intermediate ketals (6a,b). Small amounts of ketal 6a were actually observed RCECH
-I 12, A q " b
RC=CHI
3CH3 I2
I
OCH,
I I
n o
R-C-CHI2 OCH3
6a.b R-
SOC.,
0022-3263/80/l945-4649$01.00/0
RCSI
8a, R = n-butyl b, R = tert-butyl
CH30H
I ' 4a, R = n-butyl b, R = tert-butyl c, R = phenyl
OCH3
I1
i;T
C -CHI2
5a,b
in the NMR spectrum of the product when the hydrolysis was not complete. (5)R. A. Hollins and M. P. A. Campos, J.Org. Chem., 44,3931(1979).
0 1980 American Chemical Society
Heasley et al.
4650 J. Org. Chem., VoE. 45, No. 23, 1980 Scheme I
2RCGCH
+
1.2
1
-
I
1
radical mechanism:
RC-CH 2RCzCHI
,*‘
-AgI
4a-c
fI
mechanism:
RCSCH
+
I;!
-
f- RC=CH ion pair
7
,
CH30H
RC=CH
i
I
OCH3
Table I. Reaction of I, with Alkynes in CH,OH Assisted b y AgNO, r a t i o of p r o d u c t s , %
alkyne
1 2
diiodoketone
31 46
monoiodide
diiodide
% yield
46 46
23
89 73
8
In the case of phenylacetylene (3), the ketal (6c), but not the diiodo ketone (5c),was formed under our normal reaction and isolation conditions. Subsequent hydrolysis C G C H
3
i ,CHjOH
9 L
ionic
-
- R+C=CH,NO3 ,’
Iz,CHjOH,AqN03
I
OCH,
6c ( 1 7 % )
@Lcmcl + 4c 8e
of the reaction product with concentrated hydrochloric acid did produce the ketone (5c) as indicated by NMR and IR analyses. Rapid formation of iodine suggested that the ketone (5c) was quite unstable under the hydrolysis conditions. We were able to isolate diiodo ketones 5a,b from the rest of the reaction products by column chromatography over Florisil. This procedure may offer the best method for making most of the diiodo ketones. Many years ago, Fuson and co-workers6 reported the synthesis of 5b from the hindered ketone pinacolone and a solution of sodium poiodite, but apparently attempts by them and others to prepare the diiodo derivatives of less hindered ketones were unsuccessful. Discussion
Iodo ketones 5a,b and ketal 6c are clearly the products of ionic reactions and suggest that the silver-assisted reactions of 1,2, and 3 with Iz in methanol are occurring by an ionic mechanism. On the basis of our previous investigatiorq2 we suggest that ion pair 7 (Scheme I) is an unsymmetrically bridged iodonium ion (9) for these reactions although our data does not distinguish between a bridged and open ion.a (6) R. Johnson and R. C. Fuson, J . Am. Chem. SOC., 57,919 (1935). (7) D. F. Shellhamer, V. L. Heasley, L. E. Heasley, G. E. Heasley, and J. Sabine, “Addition of Iodine Monochloride to 1-Hexeneand 1-Hexyne”, paper presented at the 177th National Meeting of the American Chemical Society, Honolulu, HI, Apr 4,1979, Abstract No. 299.
+
5a,b
+ 6c +
Sa-d
What is the mechanism of the reactions of alkynes 1,2, and 3 with iodine in methanol without silver? On the basis of the products from the silver-assisted reactions, we conclude that the reaction in carbon tetrachloride and the unassisted reaction in methanol are occurring by a molecule-induced radical mechanism as outlined in Scheme I.9J0 We base our proposal of a radical mechanism on the following considerations. (a) The formation and reaction of radicals in a polar solvent such as methanol are not completely unexpected. For example, we have observed and reported that bromine adds to 1-hexyne by a radical mechanism in acetic acid.2 Also, the Fenton reagent involves formation and reaction of the hydroxyl radical in aqueous solution. (b) We find it hard to believe that an intermediate such as 7, even if tightly bridged, should react exclusively with I-, with no opening by methanol, the nucleophile being present in overwhelming abundance. In the reaction of 1-hexyne with bromine in methanol,2 the solvent incorporation product (attack by methanol) is 60% of the product. Although iodide should be somewhat more nucleophilic in methanol than bromide, exclusive attack by iodide, as compared to 40% by bromide, would not be predicted. Furthermore, we have established that the solvent incorporation product is the major product in the reaction of 1-hexene with iodine in methanol.’ It doesn’t seem logical that the saturated iodonium ion in the case of 1hexene sould be opened readily by methanol, but not the unsaturated iodonium ion from 1-hexyne.” (c) We felt that if the reactions of the alkynes with iodine in methanol were occurring by an ionic mechanism the rate should increase significantly in going from a nonpolar solvent, carbon tetrachloride, to a polar solvent, methanol. We determined that the ratio of the reaction times to identical (8) We cannot rule out the possibility that the products are formed by an alternate mechanism as outlined below:
Furthermore, 8a-c may be formed by the following reactions: RC=CH
4+
RC=CAg
12
4 1
RC=CI
(9) Unfortunately, all attempts to confirm a radical mechanism by the use of radical inhibitors failed. Oxygen did not retard the speed of the reactions. There is no reason, however, to except oxygen to be an effective inhibitor in reactions involving iodine atoms. Oxygen is an effective inhibitor of radical reactions involving molecular C1, [see J. L. Poutsma and R. L. Hinman, J. Am. Chem. SOC.,86,3807 (19641,and later papers], but it is ineffective in retarding radical reactions involving bromine atoms [see V. L. Heasley and S. K. Taylor, J. Org. Chem.,34,2779 (1969); D. F. Shellhamer, V. L. Heasley, J. E. Foster, J. K. Luttrull, and G. E. Heasley, ibid.,43, 2652 (1978)]. In fact, oxygen has been shown to accelerate certain reactions involving iodine atoms [see M. K. Eberhardt, Tetrahedron,21, 1383 (1965)l. The common radical inhibitors isoamyl were ineffective because they nitrite and 2,6-di-tert-butyl-4-methylphenol reacted with the iodine. (10) On the basis of our evidence, we are convinced that the reactions reported by Hollins and Campos (ref 5) also occurred by a radical mechanism. (11)A reviewer suggested that the increased solvent incorporation in the silver-assisted reactions may occur because AgCreduces the level of I-, giving methanol an opportunity to compete.
Reactions of Terminal Alkynes with Iodine
percent completion for 1-hexyne (1) and iodine in methanol compared to that in carbon tetrachloride is only 2. This small change in reaction times is in line with a radical reaction, not an ionic reaction. In support of this conclusion, it has recently been shown12 that the rates of addition of chlorine to acrylic acid are increased 50 times for a change in dielectric constant of the solvent from 3.9 t o 18.2. In our case the change i n the dielectric constant is f r o m 2.2 to 32. (d) Substituent effects m a y be used to distinguish between ti radical and ionic mechanism i n the reaction of iodine with alkynes i n methanol. According to studies on the bromination and chlorination of 1-hexyne (1) and 3-hexyne ( l o ) , o n e would anticipate that if the reaction of iodine with the alkynes is occurring by an ionic mechanism the reaction of 10 should be considerably faster than that of 1. There are two reports on the relative rates of ionic addition of bromine to 1-hexyne (1) and 3-hexyne (lo), and the latter is reported to be 3013a n d 1314times more reactive. A recent studylS on the ionic chlorination of 1 and 10 indicates that 10 is 340 times more reactive t h a n 1.
But, w h a t should one anticipate for the relative rates of radical additions tcl 1-hexyne (1) and 3-hexyne (lo)? As far as w e can determine, studies of rates of addition of radicals to alkynes have n o t been made. However, data have been published on the relative rates of addition of alkoxy radicals to alk.enes,16and these data m a y serve as a model for alkynes. S u b s t i t u e n t effects for radical additions to alkenes appear to be small. For example, the relative rates for 1-butene a n d trans-2-butene are 1:1.04. We determined the reaction times to identical percent completion for 1-hexyne (1) and 3-hexyne (10) with iodine i n methanol a n d obtained the relative reactivities 1:1.25. This small s u b s t i t u e n t effect lends support to a radical mechanism i n the reaction of alkynes with iodine i n methanol.
Experimental Section Materials. The alkynes were obtained from Farchan Corporation and were used wit,hout further purification. All NMR and IR spectra were then taken in CC14 with Me4Si as an internal standard. Reaction of Alkynes with Iodine in Methanol. T o 12.0 mmol of the alkynes in 11.7 mL of methanol at room temperature was added 2.4 mmol of iodine. 1 and iodine were 35% reacted in 1 h. 2 reacted somewhat more slowly than 1. The 1,Zdiiodoalkenes were identified as the sole products from the reactions of alkynes 1 and 2 with iodine by NMR and VPC analyses. The reaction niixtures were worked up in four different ways and gave identical results: (a) anelyzed directly by NMR at 50% completion (determined by iodometric titration); (b) allowed to go to 50% completion, added to aqueous bisulfite to remove the excess iodine, extracted with CC,, and analyzed; (c) allowed to go to 50% coinpletion, extraded from dilute aqueous HCl (to hydrolyze any ketal), and analyzed without removing the iodine; (d) carried to completion (still slightly red), extraded from water, and analyzed. All of these products showed only the vinyl proton (4a-c) and no ketal (6a-c) or ketone (5a-c) in the NMR spectra. VPC analyses cclnfvmed the absence of monoiodoalkynes by comparison to the retention times of the authentic compounds. We are suggesting that 4a,b have the trans geometry since the diiodide from acetylene and phenylacetylene,6 formed under similar circumstances, were shown to be trans isomers. (12) R. M. Subramanian and R. Ganesan, J. Org. Chem., 45, 1162 (1980). (13) J. A. Pincock and EL. Yates, Can. J . Chem., 48, 3332 (1970). (14) G. H. Schmid, A. blodro, and K. Yates, J. Org. Chem., 45, 665 (1980). (15) K. Yates and T. A. Go, J. Org. Chem., 45, 2385 (1980). (16) “Free Radicals”, Vol 11, J. Kochi, Ed., Wiley, New York, 1973, p 694. \ - - - - ,
J. Org. Chem., Vol. 45, No. 23, 1980 4651 trans-1,2-Diiodostyrene (4c) was established as the product from the reaction of 3 with iodine as follows. The reaction was allowed to proceed until most of the iodine was consumed. The reaction mixture was added to aqueous bisulfite and was extracted with carbon tetrachloride. The solvent and excess 3 were removed under vacuum to leave a liquid which solidified in the refrigerator. The solid was recrystallized from methanol and gave the melting point (76 “C) and NMR spectrum reported recently5 for trans1,2-diiodostyrene. (The vinyl proton occurred at 7.23 ppm rather than at 7.13 ppm as reportedas) The yields were obtained by NMR on the reaction mixtures resulting from aqueous workup using methylene chloride (1,2dichloroethane for 3) as an internal standard: 4a from 1, 88%; 4b from 2, 75%; 4c from 3,85%. 3-Hexyne (10) reacted with iodine in methanol to give only 3,4-diiodo-3-hexene in 99% yield. Reaction of Alkynes with Iodine in Carbon Tetrachloride. The reaction was carried out as described for methanol. Products were isolated by removal of solvent on a rotary evaporator. The reactions could be stopped a t any point by shaking the reaction mixture with aqueous sodium bisulfite and removal of solvent and unreacted alkyne. The speed of the reaction can be greatly increased by shining a sunlamp on the reaction flask. In fact, the simplest procedure for obtaining 4a-c and 10 is to use the sunlamp procedure and remove the solvent. The resulting diiodoalkenes are nearly pure. Determination of Relative Reaction Times. The relative reaction times for 1 in carbon tetrachloride and methanol and for 1and 10 in methanol were determined as follows. The alkyne and iodine, in the solvent of choice, were mixed instantly. An aliquot was withdrawn immediately after mixing and titrated iodometrically to determine the concentration of iodine. Subsequently, aliquots were analyzed at recorded time intervals until the reactions were approximately 40% complete. Then, elapsed times to identical percent completions were converted into relative reaction times. In the case of 1 and 10 in methanol, elapsed times were plotted against percent completion for both alkynes to give satisfactory curves. From the curves, we established that the relative reaction times remained constant across the course of the reaction. Reaction of Alkynes with Iodine in Methanol Assisted by Silver Nitrate. T o a vigorously stirred solution of 12.2 mmol of the alkyne and 2.40 mmol of iodine in 11.7 mL of methanol was added 2.40 mmol of solid silver nitrate. Silver iodide immediately began to settle from solution. The reaction was essentially complete in a few minutes although the iodine solution persisted for about 1 h. The reaction mixture was stirred until the iodine color was gone. The silver iodide was removed by centrifugation and washed with methanol. The two solutions were combined following recentrifugation. The methanol solution was added to water (1.5 times the volume of methanol), and the organic products were isolated by extraction with carbon tetrachloride. In the case of alkynes 1 and 2 the product ratios (reported in Table I) were obtained by NMR analyses. Ratios of the NMR integrations (per proton) of the following protons were obtained and converted to percentages. For 1: the vinyl proton (6.80 ppm), for 4a; the 3 methylene protons (3.00 ppm) for 8a (the latter integration was obtained by subtracting the 3 methylene proton integration for 4a-bo at 3.00 ppm-from the total 3 methylene proton integration); the methine proton (5.40 ppm) for 5a. For 2: the vinyl proton (7.20 ppm) for 4b; the methyl protons (1.21 ppm) for 8b; the methine proton (5.90 ppm’) for 5b. The yields were obtained from the above integrations and the integrations of the internal standard methylene chloride. For alkyne 3, the yield of ketal 6c was obtained from the methine integration (5.45 ppm) and the integration of the internal standard methylene chloride. Both 4c and 8c were established in the reaction mixture by NMR (following recrystallization from methanol) and VPC analyses, respectively, but individual yields were not obtained. The overall yield (96% } of the reaction was determined by comparing the total integration of the aromatic region, minus aromatic absorption due to unreacted 3, to the internal standard methylene chloride. VPC analysis was used to confirm that 8a and 8c are products in the reaction of 1 and 3, respectively, with iodine in methanol and silver nitrate. Their retention times (min) are 8a (1.3) and
4652 J. Org. Chem., Vol. 45, No. 23, 1980
Heasley et al.
Sc (9.8) under the following conditions: a 4 ft x 0.25 in. glass the presence of 6c in the reaction mixture was based on NMR column, packed with 2.5% SE-30 a t 60 "C. analysis and on the fact that it could be hydrolyzed to the corWe confirmed that diiodides 4a-c did not react with the excess responding ketone 6c. silver nitrate. The integration ratio of 6:l for the methoxymethyl hydrogens Diiodides 4ab a n d Diiodide of 10. The structures of 4ab and (3.28 ppm, s , 6 H) to the methine hydrogen (5.45 ppm, s, 1 H), the diiodide of 10 were established by NMR. Elemental analyses in part confirmed the structure of this compound. (The chemical were not obtained on either compound because of instability. The shifta of the methoxy methyl hydrogens and the methine hycompounds slowly liberated iodine upon standing. drogen, respectively, for the ketal of phenyl dibromomethyl ketone 4a was purified by recrystallization from ethanol a t -78 OC. are' 3.27 and 5.91 ppm; for the analogous dichloro ketal, they are1' It structure was established by the lH NMR spectrum (CC,) [6 2.72 and 5.85-5.66 ppm.) 0.99 (t, J = 6.6 Hz, 3 H), 1.2-1.8 (m, 4 H), 2.53 (t, J = 6.6 Hz, Monoiodoalkynes 8a-c. These compounds were synthesized 2 H), 6.8 (t, J = 0.7 Hz, 1 H)] and by the 13C NMR spectrum by the procedure described below and their structures were (CDClJ [6 13.9, 21.1, 29.9, 44.1, 79.2, 104.2 ppm]. confirmed by comparison of physical properties with those re4b was identified by its 'H NMR spectrum [6 1.21 (s,9 H), 7.20 ported in the literature. General Synthesis Procedure. T o 50 mL of methanol was (s, 1 H)1. The diiodide of 10 was identified by its 'H NMR spectrum [6 added 0.5 g (21.7 mmol) of sodium metal, followed by 19.6 mmol 1.1 (t, J = 6.8 Hz, 6 H), 2.7 (4,J = 6.8 Hz, 4 H)]. of alkyne. Iodine (19.6 mmol) was added slowly to the solution Diiodo Ketones 5a-c. The structures of 5a-c were established of the sodium salt. after being stirred for about a 0.5 h, the by NMR and IR analyses and by reference to a previous report. solution which still contained a residue of iodine was added to Elemental analyses were not obtained for 5a,c because of their aqueous sodium bisulfite. The monoiodoalkynes were extracted decomposition during and following isolation. into methylene chloride, and the solvent was removed on a rotary 5a was identified by its NMR and IR spectra; NMR 6 3.00 (t, evaporator. Distillation gave yields of approximately 45 % . J = 6.5 Hz, 2 H), 5.4 (s,1 H) (other proton absorptions are mixed 8a: bp 80 "c (25 mm); nD251.5143 [lit.1gbp 75 OC (20 mm), with those of 4a and 8a at -0.95 ppm and 1.10-1.80 ppm); IR nDz5 1.51501. 8b: bp 58 "C (28 mm) [lit.20bp 50-51 "C (22 mm)]. 1715 cm-' (C=O). Note that the chemical shift for the methine 812: bp 98 "C (1.2 mm); nDB 1.6608 [lit.21bp 82-83 "C (1.7 mm), proton of 5a is similar to that of 5b and other alkyl dichloromethyl ketones (5.8.55.78 pprn)l7and n-butyl dibromomethyl ketone (5.67 nDZ6 1.65911. ppm).' 5b was prepared by unambiguous synthesis (identical melting Acknowledgment. Support for this work was provided points) according to the procedure of Fuson and Johnson6 and b y the donors of the Petroleum Research Fund, a d m i n gave the following NMR and IR spectra: NMR 6 1.3 (s,9 H), 5.9 istered b y the American Chemical Society, the duPont (s, 1 H); IR 1725 cm-' (C=O). Company, the Research Associates of Point Loma College, 5c was identified by the chemical shift of the methine proton and the Catalysts of Bethany Nazarene College. We thank a t 6.70 ppm (6.64 ppm has been reported for phenyl dichloroDr. John Wright, University of California, San Diego, for methyl ketone17)and by its IR spectrum: 1680 cm-' (M). Aryl obtaining the carbon-13 NMR spectra. conjugated ketones are reportedla at 1700-1680 cm-' (C=O). Diiodo Ketals 6a,c. The presence of trace amounts of 6a in Registry No. 1,693-02-7;2,917-92-0; 3,536-74-3; 4a, 74966-64-6; the reaction mixture was based on peaks in the NMR spectrum 4b, 74966-65-7; 4c, 16141-16-5; Sa, 74966-66-8; 5b, 74966-67-9; 5c, for the methoxymethyl hydrogens (3.29 ppm) and the methine 74966-68-0; 6a, 74966-69-1; 6b, 74966-70-4; 6c, 74966-71-5; 8a, hydrogen (5.32 pprn). The following chemical shifta are reported4 1119-67-1;8b, 23700-63-2;8c, 932-88-7; 10,928-49-4; methanol, 67for the methoxy methyl hydrogens and methine hydrogens, re56-1; iodine, 7553-56-2; 3,4-diiodo-3-hexene,74966-72-6. spectively, of the ketal of n-butyl dibromomethyl ketone: 3.27 and 5.70 ppm. 6c was not isolated from the reaction mixture because of an(19) T. H. Vaughn and J. A. Nieuwland, J . Am. Chem. SOC.,55,2150 ticipated instability; hence, elemental analyses were not obtained. (1933). (20) T. B. Grindley, K. F. Johnson, A. R. Katritzky, H. J. Keogh, C. (17) S. F. Reed, J . Org. Chem., 30, 2195 (1965). Thirkettle, R. D. Topson, J. Chem. SOC.,Perkins Trans. 2, 282 (1974). (18) "Spectroscopic Methods in Organic Chemistry", D. H. Williams (21) M. C. Verploegh, L. Donk, H. J. T. Bos, and W. Drenth, Red. and I. Fleming, Eds., McGraw-Hill, New York, 1966, p 62. Trao. Chim. Pays-Bas, 90, 765 (1971). ~~
