June 5, 1960
ALKYLATION O F 2-
[CONTRIBUTION FROM
?"E
2945
AND 4-ALKYLPYRIDINES
I P A ~ I E FHIGH F PRESSURE A U D CATALYTIC LABORATORY. DEPARTMEUT OF CHEMISTRY, N O R T H W E S I E UNIVERSII EN Y , EVANSTON, ILL1
Relative Side-Chain Ethylation of 2- and 4-Alkylpyridine~l~~ BY
BRUNONOTAR13 AiYD HERMAN PINES RECEIVED NOVEMBER 13, 1959
The competitive side-chain ethylation reactions of various pairs of 2- and 4-alkylpyridines were investigated. T h e results obtained indicate t h a t in t h e majority of cases the rate of ethylation is a function of the acidity of alkylpyridines. The major component of t h e ethylated material was in each case derived from t h e more acidic starting compound. 4Alkylpyridines undergo ethylation more easily than the correspondiiig 2-alkylpyridines. The ethylation reaction is hindered by the presence in the side chain of an isobutyl group, The competitive ethylation reactions indicate t h a t solvation of carbanions by the substituted pyridines may play an important role in the ethylation reaction. Certain apparent abnormalities in the ethylation reactions are discussed.
Introduction I t was previously shown that alkylpyridines containing a t least one hydrogen atom on the a-carbon atom of the alkyl side chain can undergo side-chain alkylation with ethylene1,4s5or propylene'^^ in the presence of sodium catalyst. I n order to gain a TABLE I COMPETITIVE ETIITLATIONS O F 2-ALKYLPYRIDINES
Expt
2-Alkylpyridines used 22CsHnNR CsHaNR' R = R' =
1
-C
-c-c
2
-cc
-c
3
-cc
4
-C
Maxi- Extent mum of press., reacn., atm. %
150
40
20
150
35
15
-ccc cc
140
29
0
-C
153
/"
Mole ratio R:R'
5.5
TABLE I1 COMPETITIVE ETHYLATIONS OF ALKYLPY PYRIDINES
>25
\C
/
C
\
C
5
Temp OC.
better understanding of the mechanism of alkylation, the relative rates of ethylation of various alkylpyridines were determined by means of competitive reactions similar to those used in the study of alkylbenzenes.6 2- and 4-alkylpyridines having methyl, ethyl, isopropyl, n-propyl, sec-butyl, isobutyl and methylisobutyl groups as substituents mere used in the present investigation. The following types of competitive reactions were studied : 1, ethylation of 2-alkylpyridines (Table I) ; 2 , ethylation of 4-alkylpyridines (Table 11); 3, ethylation of isomeric 2- and 4-alkylpyridines (Table 111).
-C
/
\
4-Alkylpyridines used
1'7 Expt.
42
10
>25
C
-cc
4- CsHiS R
10
150
52
15
-ccc
-cc
/c \
144
74
20
0.13(1:7.5)
-c-c
-C
/ \
165
27
27
1.2
144
3
15
1
C
-C
-C-C
C
/ \
150
35
30
7
i
150
35
9
8.5
8
150
35
20
6.5
-c-c
-ccc
160
31
35
1.9
13
-c/c
-C
145
85
19
2.8
150
51
30
( 1 ) I?rper S I X of thc scrie, "Rahe c,italy,cd paper X \ ' l I l , kec If. Pine5 and I3 Notari, 'l'rrrs
19
141
30
15
8.3
156
'XJ
18 16
145
30
10
-cc
-C
\ 15
150
\
cc
14
C
C
12
C
-
0
-C-C
15 lla
6
-c
Mole r5tio R!R
C
11
/"
R =
Maxi- Extent 4mum of CsHnNR' T e m p , , press,, reacn., R' = 'C. iatm. %
\
C
-CCC
-cc
13.5
Reactions." Ilgr 82, 220!l
C ' 16
\
i l!ltjOl.
1'7
-cc
--c
JOITRKAI.,
12) T h i , researrh IVB auppurtcrl 111- a (:rant Iron, the Petrulcorn Research F u n d administered by the American Chemical Society. Grateful acknowledgment is hereby made t o the donors of t h e fund. ( 3 ) Petroleum Research Fund Postdoctoral Fellow, 1958-lQ5Y On leave of absence from E n t e Nazic~naleIdrocarburi, San Donato 2lilanese. %Tilano, Italy ( 1 1 11 P i n e s a n d I ) . \ V u n d c ~ l i ~ ~ 'l'rrrr h . J O ~ ~ K N A I 81, ,, 2 3 ~ 8f I ! j > X ) , i i i 1,: Pron't 31111 I; S r h u r i d p r , . i ; . r l i P h u v ) ; ~289, , , 99 ( l U 5 l j ) .
/
C C
-C
cc -CC
\
C
3
2946
BRUNONOTARIAND HERMAN PINES TABLE I11
COMPETITIVE E T H Y L A T I O N O F I S O M E R I C
2-
A N D 4-.kLKI’L-
PYRIDINES
Expt.
18 19 20 21
2- and 4Alkylpyridines CjHcPiR,R =
-C
-cc -cc /c -C \
22
-C
\
Temp., OC.
Alaximiim press.. atm.
150 134 110
38 67 77
15 20 20
3.5 4 6.1
150
31
21
6.7
150
46
19
r
Extent o f ream., Mole ratio 70 &:2-
C
Vol. 82
The competitive reactions show that the 4-alkylpyridines undergo ethylation much more easily than the corresponding 2-isomers; for the picolines the ratio of 4- to 2- was 3.5:1 and for the sec-butylpyridines the ratio was 7:l (Table 111). The temperature has an effect on the ratio of the ethylated products, lower temperature favoring the formation of reaction products from the more acidic compounds (expt. 19 vs. 20, Table 111).
Discussion The mechanism proposed for the addition reaction to ethylene is
I
cc Ill
In the study of the relative rates of side-chain ethylation in aromatic hydrocarbons it was found that the substitution of a benzylic hydrogen by an alkyl group greatly influences the rate of ethylation. With such a substitution two factors were changed simultaneously-the acidity of the alkylbenzene and the steric requirements of the intermediate benzylic carbanions participating in the reaction. In the pyridine series, barring solvation effects, it should therefore be possible to separate these two factors. It was observed by us that 4alkylpyridines are more acidic than the corresponding 2-isomers; their steric requirements for ethylation should, however, be the same. For this reason i t was thought possible to determine the effect of alkylpyridine acidity on the side-chain ethylation reaction. Results The experimental results are summarized in Tables I 111. The structure of the ethylated product from each of the listed alkylpyridines resulted from the replacement of a hydrogen atom on the a-carbon of the alkyl group by an ethyl group. In carrying out the experiments, equimolar ratios of the different pairs of alkylpyridines were used and the reaction was planned in such a way as to permit in most cases only about 20% of the alkylpyridines to undergo ethylation. This was necessary in order not to disturb to any considerable extent the ratio of the original alkylpyridines subjected to ethylation. From Table I it is seen that the extent of ethylation of 2-picoline is over five times as great as that for 2-ethylpyridine (expt. 1). The ratio of ethylation for 2-ethyl- and 2-isopropylpyridine as compared with its next higher homolog is much higher: 17:l to >25:1 (expt. 2, 3, and 4). I n the 4-alkylpyridine series the ratio of 4-picoline to 4-ethylpyridine is 1:7.5 (Table 11, expt. 10) which is the reverse of what was found in the 2series. The ratio of ethylation of 4-ethyl- as compared with 4-propylpyridines and that of 4-isopropyl- as compared with 4-sec-butylpyridine is of the order of 1.2:1 to 2.3:l (expt. 11-13). The ratio is, however, greatly increased (8.3:l to 16:l) when an alkylpyridine is compared with its higher homolog containing an isobutyl group in the side chain (Gpt. 14-16, Table 11).
The initiation step is here not considered since, as soon as the steady state is reached, it no longer influences the reaction. The path of the ethylation reaction depends on the relative values of the rate constants and upon the pressure of ethylene.’ The mechanism of ethylation of alkylpyridine is very similar to that the inforof a l k y l b e n ~ e n e s . For ~ ~ ~that ~ ~ ~reason ~ ination regarding the ethylation of alkylbenzenes could be used in elucidating the mechanism of alkylpyridines alkylation. I t has been reportedg that (-)-2-phenylpentane reacts with ethylene a t elevated pressure to form optically inactive 3-methyl-3-phenylhexane. The recovered 2-phenylpentane had the same optical activity as the starting material. This would indicate that metalation is the rate-determining step and that the addition to ethylene is a relatively fast subsequent reaction. Had the rate-determining step been the addition of carbanions to ethylene, then the carbanions present would haVe a chance to racemize the starting material by prototropic transfer. It has been shown’O that carbanions undergo racemization readily. In light of the above findings the rate of formation of ethylated alkylpyridines should be a function of the rate of metalation. In many instances this was found to be the case. In expt. 2-4 i t was found that the more acidic alkylpyridines” give the major amounts of the ethylated material. The effect of the acidity of alkylpyridines on the rate of ethylation was also demonstrated in competitive reactions between the isomeric 2- and 4(7) H. Pines, J. A. Vesely and V. N. Ipatieff, THISJ O U R N A L , 77, 554 (1955). (8) H. Pines and V. Mark, ibid., 78, 421G (1956). (9) H. H a r t , ibid., 78, 2G19 (1950). (10) R. L. Letsinger, i b i d . , 73,4842 (1959). (11) T h e relative acidity of alkylpyridines W L S not reported. I t is fair, however, t o assume t h a t t h e relative acidities of t h e alkylpyridines follow the same pattern as t h a t of alkylbenzenes.” 112) I T . H a r t and R . E. Crocker. T H I S TouRNAL, 82, 418 (1960).
June 5 , 1960
ALKYLATIONOF 2-
AND 4-ALKYLPYRIDINES
2947
alkylpyridines. The 4-alkylpyridines, being more 111),a much greater molar ratio of the correspondacidic underwent ethylation more readily (Table ing ethylated product results than would be expected on the basis of the assumed acidities of the 111). The effect of acidity on the rate of ethylation was respective compounds.l 4 The above observation could be accounted for if further indicated by competitive reactions in which 2- and 4-ethylpyridine, respectively, were the steric effects involved in the addition of carethylated in the presence of ethylbenzene (Table banions to ethylene are considered. The ethyla117). As expected13 only a trace of sec-butyl- tion reaction could be visualized as an approach benzene was formed when 2- and none when the of the carbanion to the plane of the ethylene molecule so as to polarize the a-electron system and then more acidic 4-ethylpyridine was used. Metalation, however, is not always the rate- form the final sp3-hybrid. Inspection of molecdetermining steps ; kinetic studies had revealed that a t lower pressures the pressure of ethylene may determine the rate of ethylation. The competitive ethylation carried out with 2alkylpyridines (Table I) show surprising results. The ratios of ethylated products obtained from 2ethyl- vs. 2-isopropyl and vs. n-propyl- and from 2-isopropyl- vs. 2-sec-butylpyridine were over 17 to 1. These ratios are much higher than those obtained from the corresponding competitive ethylation reactions of 4-alkylpyridines (Table 11) and of alkylbenzenes6 If the acidity of the compounds undergoing ethylation were the rate-determining ular models shows that under these conditions factor, then the ratios of the ethylated products ob- there will be steric hindrance to the approach to tained from 2-alkylpyridines should have values the ethylene molecule when the side-chain contains intermediate between those obtained €or the cor- @-methylgroup. This effect would be expected to responding 4-alkylpyridines and alkylbenzenes. increase with the increase in the number of @I t is tentatively proposed that the solvation of the methyl groups. carbanions might be responsible for the observed In the cases of toluene vs. ethylbenzenes and of results. If the nitrogen of the pyridine nucleus is 4-methyl- vs. 4-ethylpyridine (expt. 11, Table 11) involved in the solvation, either in the solvated the acidity cannot be the only controlling factor, carbanion and/or in the solvating molecule, then since the ethyl derivatives react faster. It may be the alkyl group in the 2-position will interfere with that, owing to a greater loss of resonance energy in the solvation. The carbanion with the smaller the activation process of the primary carbanion, side chain will be more effectively solvated, its the free energy difference between the transition concentration increased, and its ethylated product states is smaller than that between the carbanions. favored. This would fall in line with the gradual This effect could more than compensate for the decrease in reaction ratio observed with increasing effect of acidity and therefore favors the ethylation size of the alkyl group. Preliminary experiments of the ethyl derivatives. indicate that when competitive reactions are performed in the presence of a third compound with Experimental Part good solvating power, e.g., tetrahydrofuran, a The ethylation reactions were carried out in a 100-ml. lower ratio is obtained. capacity agitated autoclave, Magne-Dash,lc which was TABLE IV COMPETITIVE ETHYLATION OF ALKYLPYRIDINES AND ALKYL
Starting material lixpt.
L\NJ
A
4 +
B
BENZENES Extent of reacn., Temp..
h4aximum press., atm.
hfole ratio A:B
70
O C .
20
146
69
>25"
30
150
79
256
f No reaction product from ethylbenzene detectable. Only a trace of sec-butylbenzene was found in t h e reaction mixture.
When 4-alkylpyridines are compared with higher homologs containing an isobutyl group in the side chain (e.g., iso- and n-propyl- vs. isobutyl- or secbutyl- vs. sec-isoamylpyridine, expt. 14-16, Table (13) Ethylpyridines are much more acidic t h a n ethylbenzene since only t h e former undergo metalation by sodium amide in liquid ammonia.
charged with 0.2-0.5 mole of each alkylpyridine, 0.3-0.5 g. (0.013-0.026 g. a t . ) of sodium and 0.05 g. of anthracene. The autoclave was sealed and after flushing with nitrogen i t was charged with about 18-23 a t m . of ethylene and heated t o the desired temperature, generally t o 150" unless otherwise indicated. When this was reached stirring was begun. After 0.5-1.5 hours the desired amount of reaction occurred as judged by pressure drop. The stirring was then stopped and the autoclave was removed from the heating jacket and allowed to cool. After the pressure was released, a few ml. of methanol was added to the reaction mixture in order to decompose the organosodium compounds. The crude reaction mixture was then analyzed by vapor phase chromatography1' on a 20-foot column packed with 40y0 of monohydroxyethyltrihydroxypropylethylenedi(14) T h e relative acidities c.g. of isopropyl- and isobutylbenzene were not measured. Experimental d a t a reported in t h e literature,12'ls however, leads one t o expect not too great a difference in t h e acidities of these two compounds since t h e inductive effect of one isopropyl groups should be comparable t o t h e inductive effect of two methyl groups. Similar reasons could be applied t o the relative acidities of 4-isopropyl- and 4-isobutylpyridine. (15) D. Bryce-Smith, V. Gold and D. P. N. Satchell, J . Chem. SOL,
2743 (1954). (16) Autoclave Engineers, Inc., Erie, Pa.
(17) Podbielniak, Inc., Chicago, 111.
amine'8 on Chromo~orb.~gThe retention tixries of some alkylpyridines on this substrate have been determinedlo and it was observed t h a t the values of 2- and 4-isomers differ greatly, the 4-isomers having longer retention times. I t is interesting to note that 2-ethylpyridine has a smaller retention time than 4-picoline. This could be ascribed to the hindrance t o solvation of the 2-substituted pyridines on the (18) Visco Products Co , Inc , Houston, Texas (IS) Johns-Manville Corporation. (20) A W. Decora and G. V Dinneen, Paper presented before t h e Analytical Division, American Chemical Society Meeting, September, 1958, Chicago, Ill.
polar solvent. .I complete separation of the stdrtitig xnaterial and the reaction product was in such cases achieved. The column was kept at 150". Helium was used as a carrier gas. I n the case of 4-alkylpyridines homologs, a shorter column-about 10 feet-could be used, since the separatiori is quite large; for the lower 2-alkylpyridine homologs, an additional 10-foot column improved the separation. The pressure of the carrier gas was changed from 10 to 30 Ib./sq. inch according to the increase in length of the column.
Acknowledgment.-The authors wish to thank N r . Ed. 11. Lewicki for technical assistance. Evazsros. ILL
[CONTRIBUTION FROM THE DEPARTMENT O F CHEMISTRY O F THE POLYTECHNIC I N b l l r L 1 E U F BROOKL\l.zi]
Diaryliodonium Salts. XIV. Reactions of Organometallic Compounds with Iodosobenzene Dichlorides and with Iodonium Salts1s2 BY F. MARSHALL BERINGER JOSEPH IV. DEHX,JR.,
AND
MURRAY LVINICOL
RECEIVED XOVEMBER 30, 1959 At low temperatures ar>-llithium coinpounds react with aryliodoso dichlorides in ether, tetrahydrofuran or tolucllc t i 1 give 20-50Y0 of diaryliodonium salts. More aryllithium compound or arylmagnesiurn halide converts the iodoniurn salt to a triaryliodine, from which the iodoiiiuni salt can be recovered in good yield by cleavage with acid A triarjliodine or a n alkyldiaryliodine allowed t o warm to 0" or above in ether gives products formed by decomposition to iodo compounds and free radicals, which may react with each other or with solvent.
Introduction.-Three steps may be considered in the reactions of organometallic compounds (RM) with iodine(II1) chlorides.
benzene and iodobenzene and with phenylmagnesium bromide gave biphenyl, iodobenzene arid a trace of a diphenyliodonium salt. The appearance of ethylbenzene, biphenyl and R M f IClp ----f RIClz + hlCl (A) iodobenzene suggests the further reaction of the R M f RICL --+ RJC1 MCl Grignard reagent with the iodonium salt formed (B) in the initial reaction. Examples of reaction C R M f RJC1 +RjI + MC1 (C) are the formation a t low temperature of triphenylReaction X is exemplified by the formation of iodineg,l0from diphenyliodonium iodide and phenyltruns-2-chlorovinyliodoso dichloride from the cor- lithium and of phenyl-2,2'-biphenylyliodine1from responding mercuric chloride by treatment with 2,2'-biphenylyliodonium iodide and phenyllithium. iodine t r i ~ h l o r i d e . ~There are few examples of re- Both trisubstituted iodines are yellow. The latter action A alone, as in most cases it is followed by cyclic trisubstituted iodine was relatively stable to reaction B t o give an iodonium salt; e.g., bis- 100", while triphenyliodine decomposed above 0' (trans-2-chlorovinyl)-mercury with iodine tri- to give, as one product, biphenyl. chloride gave bis-(trans-2-chlorovinyl)-iodonium In 1953, i t mas reported'? from these laboratories chloride4 while both diphenylmercury and phenyl- that ethereal methylrnagnesium iodide, cthylstannic chloride with iodine trichloride gave di- magnesium bromide. phenylmagnesium broiiiide phenyliodonium ~ h l o r i d e . ~ and phenyllithium a t 0' or above gave with diReaction B has been run with organometallic phenyliodonium bromide toluene (59%), ethylcompounds of m e r c ~ r y ,silver,7 ~ . ~ tin6 and magne- benzene (3770) and biphenyl (33 and sium.8 Reactions with phenylstannic chloride6 At t h a t time it was thought t h a t these pr were convenient and successful while those with probably arose from nucleophilic attack of the Grignard reagentss gave iodoniurn salts in only organometallic compound on the I-carbon of the trace amounts. For example, iodosobenzene di- diphenyliodonium ion. The alternative route of chloride with ethylmagnesium bromide gave ethyl- formation via trisubstituted iodines was not explicitly considered. (1) This paper is taken from the M.S.thesis of Murray R'inicov and The first aim of the present work was to iiivestithe P h . D . dissertation of Joseph W. Ilehn, J r , and was presented in gate the synthesis of diaryliodoniutii salts froiii imrt a t the h-ew York City Meeting of the American Chemical Society i n September. 1{1.57 (Abstracts o f Papers, 11. :1GP). aryliodoso dichlorides a n d organolithiuni or nlagtlc( 2 ) Preceding paper: F. hl. Reringer and I. I,illien, 'l'111sI O U R N A L , siuin coinpounds a t low temperatures. The secontl aiiii was to investigate. i u r t h t r the products o f t h c ssiicinte I'rufesstrr. Yxle Unircriity, l ! l . X - l!jcj!l. reaction of diphenv1iodr)niLuii chloride ill cthcr i 4 ) A . N. Kesmeyanov, Bull. n c i i c i . s l i 1 - R..Y S . , ( : i m s c S c i iiiiii., 2,'jY (1Y431; C. A , , 40, 2122 (1946). with Grignard reagents.
+
( 5 ) R . K. Freidlina and A. N. A-esmeyantiv, C o i n p l . y e l i d . , o c l i d . s o . I' R . S . S . , 2 9 , 567 ( l Y 4 0 ) ; C. A , , 35, 3614 (1941). (6) C. Willgerodt, H K , 3 0 , 56 (1807); 3 1 , 915 (18!>8). ( 7 ) C Willgerodt, ihi!/, 28, 2107 f l 8 ! ) > ) ; .i 'l'hielc : ~ n dH.I l ; l a k h , .'I j l j l , 369, I :< I ' I < l [ I ! l J 1% I I l l ? p \ > ~ ~ l l l .I l , l ' l l r i i i S'ili , 119, I l ' i i , l ' l 2 l l .
t'
(II)G. Wittig and 51.Rieber, A X K ,662, 187 (1!)4!1). (10) G. Wittig and K , Clauss, ibhl., 578, 136 (1933). (11) K . Clauss, C h e w 1 3 ~ ; ,. 88, !?G8 f l < l G ) . ( 1 2 ) I?. R l 13rriiiurr. .4. H i i ~ . r l r v ,11 l~rt.xler, 1; 11. (>in(llw:in11 c I iiiiil,L.iii 'I.HI\ I O I , K \ > I , 7 5 , l 7 i i h f I
