William G. Young University of Caliiornla LOS Angeles
Unexpected Rearrangement and Lack of Rearrangement in Allylic Systems
I
have been fortunate to be associated with a large number of exceptional graduate students, postdoctoral fellows and staff members working in a field of chemistry which regularly developed unusual and stimulating results. Since this good fortune has also led to the NS-SAMA award, it is most appropriate for me to describe some of the expected and ~rnexpectedrearrangements and lack of rearrangements which we have encountered in our work on allylic systems. I gratefully acknowledge the many unsung heroes whose excellent experimental work I shall discuss. Early work in the UCLA laboratories showed that each of the two allylic alcohols (I) a-methylallyl alcohol and (11) r-methylallyl alcohol gave similar mixtures of the allylic bromides (111) and (IV). During isolation of (111) and (IV) by low temperature fractional distillation, it was discovered that these compounds rapidly rearranged to an equilibrium mixture unless great care was exercised. This revealed the necessity of developing controlled experiments which would prevent rearrangement of both the st,arting materials and final products when dealing with certain allylic systems. Even under controlled conditions both alcohols (I) and (11) gave similar but different mixtures of bromides (111) and (IV). This led to the postulation that two competitive reactions H H H HaC-C-CrCH
+
HRr
H H H3C-C=CCOH H H I1
+
HBr
-
H H H Hd-C-C=CH
H H HIC-C=C-CBr H H IV
were involved, namely a bimolecular reaction, SN2, of bromide ion with the conjugate acids (Ia) and (IIa) of each alcohol without rearrangement, and an ionic reaction, SN1, involving the formation of a common carbonium ion intermediate which gave the same mixture of bromides from either alcohol. (See Fig. 1.) If the major reaction involved the carboninm ion intermediate (V), it follolr-s that in the ahsence of bromide ion the action uf sulfuric acid in water with either alcohol (I) or (11) should produce the ion (V) which could react with all nucleophilic or oxygencontaining species in the reaction medium. When Thk IRE2 Scientific Apparatus ~ a k &A.ssoeiation A.ward in Chemical Education was uresented to William G. Youne. Vice Chancellor of the u n i v e i i t y of California, Lo8 ~ngeles,% the 141st Meeting of the ACS, Washington, D. C., March, 1962. The award address published here was a feature of the banquet meeting of the Division of Chemical Education held a t Howard University on March 22.
either alcohol was treated with 6M acid at room temperature, a mixture of at least six products mas formed according t,o Figure 2. The reaction of each alcohol (1) and (11) with either of the two positive positions on the carbonium ion(V) accounts for the formation of the three ethers (VI), (VII), and (VIII). H H H HaC4--C=CH
SNZ ---t
+ Br-
H H H HG-C-C=CH
I
Br
YSN1
~a
111
Br-/'
IIa
IV
Figure 1.
Further work under controlled conditions led to the conclusion that in less polar solvents such as acetone or alcohol, the primary or secondary allylic chlorides usually react with ions by a bimolecular (SK2)mechanism to give products without rearrangement. \\bile in polar solvents such as water or acetic acid the chlorides react to produce mixtures of products which arise from the ionic (Sd)mechanism or by competition between mechanisms SNIand S N ~(See . Fig. 3.) H H H8C-C=C-C-CI H H
+ OAe-
H H H HX-C-C=C-H
+
I
Cl -.
SNZ
acetone
HOAo A
sw1
H H H3C4=C-C-OAc H H (100%)
H H H.C-C=C-C-OAc H H
(55%)
H H H&-C-C=C-H
(45%)
H
t
OAc Figure
3.
Abnormal Bimolecular Displacements
Another reaction of interest which was first found in our lahorat,ories is the so-called "abnormal bimolecular displacement, reaction" of allylic halides. Figure 4 shows several possible types of bimolecular displacements. Type (B) was predicted by us and by English chemists many years ago, but no bonafide example was found for ten years. This reaction involves a nucleoVolume 39, Number 9, September 1962
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455
H H H H H8C-C=C-C-0-C-C=C-CH, H H
H H H H H HsC-C=C-GO-C-C=C-HI 1 H CHa VII
H
VI
dH3 VIII
I
CHa
2
7
2
H H H H H2C=C-C-0-C-C=CH1
H H H HaC-C4-C-OH H
+H,O
H H H H,C-C-C=CH
L
I
- H30
H n H HG-C-GCH + H
OH
I
H+
IIa Figure 2.
philic attack on the y-carbon of the allylic system with the simultaneous shift of the double bond and removal of a halide ion. The first example found in our laboratories was announced simultaneously with a report from England which claimed that the reaction
I Normal Type (A) Figure 4.
Abnormal Type (B)
Possible types of bimoleculm dirplocement
\
I
HN-R I
Cyclic Type (C)
reactions.
was theoretically impossible. Since several examples had been found in our laboratory at UCLA and elsewhere, this latter claim must have been erroneous. At least three conditions must be met before a react,ion can be classified as an example of abnormal bimolecular substit,ution: (1) The rate of the reaction must be proportional to the concentrat,ion of both the nucleophilic reagent and the allylic compound heing at,tacked. (2) The reaction must give isolable amount,^ of abnormal silbst,itution products. (3) It must be demonstrated that neither the starting material nor the normal substitution product undergoes rearrangement under the conditions of the reaction. These conditions have been demonstrated in the reaction of a-methylallyl chloride with diethylamine, dimethylamine, trimethylamine, and thiourea. Figure 5 shows t,hat a-nlethylallyl chloride gives completely abnormal or rearranged product when treated with diet,hylamine while its allylic primary isomer, y-methylallyl chloride, gives only normal product with no rearrangement. In this case the abnormal position of the allyl system is hindered and the normal position is easily attacked. Consequently the SNZ1 process cannot compete effectively. 456
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Journol o f Chemical Education
Another interesting displacement reaction is that involving thionyl chloride n-ith allylic alcohols. The first step involves the formation of an allylic chlorosulfinate and hydrogen chloride. Several possible paths are available to produce the final products. These are shown in Figure 6. Pat,h 1 (Sd) should lead to retention of optical structure without rearrangement; path 2 (SNil) should give 10070 rearrangement; path 3 ( S d ) should give inversion of optical structure with no
Figure 5
rearrangement. Actually, in the absence of a solvent, mixtures of isomeric chlorides are always obtained in the reaction of thionyl chloride and allylic alcohols. We have found, however, that the Swi' mechanism (path 2) may he made very dominant by the use of a dilute ether solution of the alcohol where the liberat,ed hydrogen chloride is rendered inactive. Under these conditions ?-methyl allyl alcohol yields 100% a-methylallyl chloride and a-methylallyl alcohol yields 100% y-methylallyl chloride as shown in Table 1. The presence of excess HCI or chloride ion produced by triethylamine allows the SN2reaction to become dominant
.~
\/ 1 0
Figure 6.
2
abnormal
H H H HaCC-C=CH CI
+ SO? Sh.!'
in the case of the primary alcohol, but only competitive with the &if reaction when the secondary alcohol is used. We have recently found that the trifluoromethyl grollp has a very profound influence on the thionyl chloride reaction. The chlorosulfinate (IX) from the primary alcohol and the chlorosulfinate (X) from the secondary alcohol shown in Figure 7 are very st,able as
spread or difference in composition of the products obtained from the two allylic isomers. As the nucleophilic power of the solvent decreases and the ionizing power increases, we see that the spread in composition disappears. This observation caused us to consider the possibility that the difference in composition of the products obtained from the two allylic isomers might be the result of competition between the first order reaction, SN1,and a second order reaction, SN2, involving nucleophilic attack by the solvent. Consequently, a detailed study was begun on the effectof nucleophilic character and ionizing power of the solvent on the rate of solvolysis, in the presence of ethanol, methanol, 80% ethanol Table 2.
Effect of Solvent on Spread in Composition of I Products from Allylic Isomers
1
0 IX Figure 7.
shown by stability to vapor phase chromatography and lack of sulfur dioxide evolution. As a consequence the SNi reaction leading to rearrangement does not occur readily even a t high temperatures. The isomers (1x1 and (X) show a great difference in reactivity to the SN2 reaction. Chlorosulfinate (IX), gives primary chloride with great speed in the presence of chloride ion which is produced when amine is added, but chlorosulfinate (X) is completely inert to S N under ~ the same conditions. The corresponding methyl chlorosulfinares undergo both the S N and ~ the SNilreactions rrith great rapidity. Table 1 Add
To
POH
SOCL
Oi;
SCI
%
PC1
eth-r --
-
100
0
90
10
0
100
0
100
68
32
and water, acetic acid and formic acid, respectively. Early kinetic studies on the solvolysis of a,a and y,ydimethylallyl chlorides in acetic acid produced evidence that these reactions can be highly complex. The starting material a,a-dimethylallyl chloride not only solvolyzed rapidly to give mixtures of such esters as would he expected from the production of a carbonium ion, but it also rearranged into its allylic isomer the 7,y-dimethylallyl chloride faster than it solvolyzed. By the time the reaction was 30% complete the rate of solvolysis was the same as that of the pure y,y-dmethylallyl chloride, showing that the starting material had been completely rearranged. Subsequently, i t was shown by kinetic studies and analysis that both allylic isomers are solvolyzing a t the same time the isomerization reaction is occurring. The rates of all three reactions were determined as shown in Figure 8. Where KT is
ether
POH
SOCL
SOCI?
POH
SOH
SOClr
HCI
ether
smine
ether ether
SOH
SOCll
A
smine
1
Solvolysis Reactions
We next turn our attention to solvolysis reactions of allylic chlorides, since conditions designed to give first order reactions producing the carbonium ion showed that the two allyl isomers do not always produce exactly the same mixture of products. Table 2 records the spread in composition of products obtained when the two allylic isomers are separately allowed to react with each solvent. It is seen that a powerful electrophilic agent such as silver ion aids in the production of the carbonium ion and thus decreases the
acetate mixtures Figure 8.
the rate of solvolysis of a,a-dimethylallyl chloride, K p is the rate of solvolysis of y,y-dimethylallyl chloride and Ki is the rate of isomerization of the a,a-dimethylallyl chloride. The fact that the rate of rearrangement was unaffected by the concentration of the chloride ion eliminated the previous accepted possibility that the isomerization involved a dissociated carbonium ion accompanied by a so-called "mass law effect." Volume 39, Number 9, September 1962
/
457
Instead it was postulated that the reaction involved the formation of an undissociated ion pair with the isomerization resulting from the phenomenon now called "internal return." The discovery of "internal return" rearrangement during solvolysis led us to approach the problem anew by comparing the products of two very fast reactions involving carbonium-ion intermediates, which are less likely to involve "internal return," namely the silver-ion catalyzed solvolysis of allylic chlorides and the decomposition of the diazonium salts of the related allylic amines. The results of these comparisons in water are shown in Table 3. The composition of the mixture of allylic alcohols was the same regardless of whether the starting material was the primary or tertiary halide or amine indicating the forma%I of a true common carbonium ion intermediate in hoth reactions. Table 3.
Isomer
Solvolysis and Deamination in Water
Solvent
% P'OH
The results obtained in acetic acid, as summarized in Table 4 came to us as a surprise. To be sure, we had found, as expected, that both pairs of isomeric allylic chlorides would give the same mixture of esters when allowed to react with silver acetate in this solvent. However, the corresponding diazonium salts gave less rearrangement than would be expected from the resonating carhonium ion. The unexpected results could be explained if a competing reaction occurred in acetic acid which did not involve the resonating carbonium ion and which gave no rearrangement of the allylic system. Table 4 shows the amount of this unknown reaction "U" needed to explain the results. The following proposals have been considered for "U." (1) The formation of a diazo compound by the loss of a proton followed by reaction with acetic acid without rearrangement.
(2). A bimolecular (SN2)reaction of acetate ion,to give a Walden inversion with no rearrangement.
(3). The formation of a diazoacetate which decomposes by a cyclic &if) process to give retention of optical structure with no rearrangement. H H H H3C-C-C=CH I
+
OAc
-
N,+
H H H HsC-C-C=CH
&>03-c~. N-0
(4). The formation of a "hot carbouium" ion xhose formation does not require a distribution of charge and which reacts with predominant racemization but no rearrangement.
A series of experiments eliminated possibilities (I), (2), (31, and confirmed the existence of (4) as the cause of the unexpected results in acetic acid. Table 4.
Solvolysir and Deamination in Acetic Acid c:
Acetate from Starting Agt rnnt,erial
%s
70p
Acetate from HOKO %s 76 p
s-Ci 44 56 67 p.CI 40 60 21 t-CI 45 55 40 p'-CI 45 55 22 p = H,C-CH=CH-CH?-: p' = HaC-C(CHI)=CH-CH,-;
tion lhy
Starting nmtne
path
(I:)
s-NH, 4:3 pNH? 50 DO L-NH9 10 i8 p'-NHI 50 s = HsC-CH-CH=CH. t = CH1-C(CHI)-CH=CHI RR
79
New Procedures
This mechanism would require that deuterium would be found in the final ester when deutero-acetic acid was used. Actually no deuterium was found in the product thus ruling out possibility 1. 458 / Journal of Chemical Education
Finally we will consider new procedures which enable us to follow accurately the composition of the reaction mixture a t any time during a solvolysis reaction of allylir compounds in contrast to previous work which studied only the composition of final products of the reartion. With the advent of vapor phase chromatography, it became practical to quench the solrolysis reaction at given intervals of time and look for evidence of rearrangement of starting materials as well as to study the nature and composition of final products. We chose the silver-catalyzed solvolysis of czs-and trans-y-methylallyl chloride and a-methylallyl chloride in water using very dilute silver nitrate. The nitrate ion was chosen since it has poor nucleophilic properties and therefore was less likely to become involved in the reaction products. Vapor phase chromatography enabled us to consider the cis-trans isomerism in this
allylic system for the first time. For example, in Figure 9 you will see that the cis-carboninm ion CC+, and the trans-carbonium ion, TCf, have double bond character between carbons 1 and 2 and carbons 2 and 3. This should prevent rotation and preserve the cis-or transstructure when they react a t carbon 1 to give the primary isomer. From Figure 9 it may be concluded that the ion pairs involving the carbonium ions (CC+) and TC+) coming from each of the chlorides may collapse by internal return to give either original chloride or rearranged chloride except for the restriction that the cis-carbonium ion (CC+) would be expected to give only the cis-primary chloride, CPCI, and the transcarbonium ion, TC+ would give the trans-primary chloride; either could give secondary chloride. One other phenomenon which was not expected but which actually was found is the combination of the carbonium ions with nitrate ions to give the primary nitrate (p-NOa) and secondary nitrate (s-NOa) followed by the solvolysis of these nitrates as time progressed. Table .5 summarizes the experimental details obtained in the hydrolysis of a-methylallyl chloride using dilute silver ion as a catalyst. I n Table 5 lines 1, 2, and 3 give the percentage composition of the reaction mixture a t the various times given in line 0. It will be noted that the ROH builds up as RCI decreases. In addition R-NO3 is formed in considerable amounts but a t the end hoth the chlorides and nitrates have reacted to leave only a mixture of allylic alcohols. Lines 4 and 51give the percentage composition of the alcohol mixture in terms of the two allylic alcohols p-OH and s-OH a t any given time. This mixture is approximately onethird primary alcohol and two-thirds secondary alcohol
\c/
NC/
Time (minutes)
0
0.5
2.0
4 0
6.0
8.0
14.0
Table 6. Solvolysis of Cis-Crotyl Chloride in O.09OM Aqueous Silver Nitrate Solution without Added Calcium Carbonate
Time (minutes)
0
0.5
1 R-OH 3.50 96.5 2 R-Cl 3 R-NOa ... 4 v-OH 50)
s-C1 pN01 s-NOa Transp-OH
7 8 9 10
0.6
... . ..
2.0
2.0
4.0
6 0
8.0
12.0
19 4 59 4 80.3 88.9 94.6 79.5 3 6 . 1 13.5 5.82 0 8 1 1 2 4.55 6.22 2 4.58 4 0 . 5 4 9 . 0 4 8 . 8 4 9 . 2 50.6
1.10 2 . 9 3.8 49.3 60.6 70.0 507 3 9 . 4 30.0 4.73 7 . 2 2 10.2
I 77.6 22.4 10.7
1l/-" 90.8 9.2 14.3
of total a-OH
b
CH,
H / \NOz \H secondary nitrate
Table 5. Solvolysis of a-Methylallyl Chloride in 0.090M Aqueous Silver Nitrate Solution without Added Calcium Carbonate
\C/
/I
\\CH,
H CI CHn
\
/
/
C=C
\
H
serondrtry chloride
\
H CH&I Trans-primary chloride
H&
H
\ C=C/ /
H
C-c
/e3 .\ H\ H' CHg
/ \
H NO, Primary nitrate
/
Trans-carbonium ion
/H
/C=C ' c H m
H Trans-primary hydroxide
H
CH3
H
/
/"="\ CH,CI CH, Cis-primary chloride
c=.c/ / @ .\
\
\
H
CH?
Cis-carhonium ion
\/ CHs
CHI
\
*
CH, H
H
\c/ ,I
6~
CH
\\
H CH,
H' Secondary alcohol
\
/
H
/C=C CHs \cH,OH. Cis-primary alcohol
Figure 9.
Volume 39, Number 9, September 1962
/
459
during the course of the reaction. The primary alcohol arising from the hydrolysis of the secondary chloride is almost entirely trans-alcohol. This indicates that the trans-carbonium ion (TC+)is formed selectively when chloride ion is removed from the secondary chloride. From lines 6 and 7 you will see that rearrangement of the secondary chloride is very fast and that even after only two minutes 20% of the chloride mixture has rearranged to primary chloride. The results of the solvolysis of the cis-primary chloride listed in Table 6 are very interesting when compared to those ohtained from the secondary chloride. For example, the amount of nitrate ester (line 3) formed as a by-product is only about one-third that ohtained from the secondary chloride. Second, the ratio of primary alcohol to secondary alcohol is 1:l compared to
460
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Journal o f Chemical Education
1:2. Third, the amount of rearranged chloride (line 7) is very small at all times compared to that found with the secondary chloride. Fourth, the amount of transprimary alcohol (line 10) obtained from the cis-primary chloride is so small that it verifies the prediction that the cis-carbonium ion (CC+) holds its configuration. The trans-primary alcohol which is formed can he accounted for by hydrolysis of the secondary chloride ohtained by rearrangement of the cis-primary chloride. Summary
Bimolecular reactions of allylic compounds in nonpolar solvents are usually predictable and controllable while reactions in polar solvents which lead to carhonium ions are unpredictable and complicated.
