Sulfonyl Transfer to Nucleophiles - American Chemical Society

27 Sulfonyl Transfer to Nucleophiles J. F. King, S. Skonieczny, K. C. Khemani, and J. D. Lock

Downloaded by SUNY STONY BROOK on September 16, 2014 | http://pubs.acs.org Publication Date: July 1, 1987 | doi: 10.1021/ba-1987-0215.ch027

University of Western Ontario, London, Ontario N6A 5B7, Canada

Sulfonyl-transfer mechanisms are briefly reviewed, and two recent studies described in greater detail. (1) From comparison of the la beled CH SO from the reaction of CH SO Cl with (CH ) N in a buffered D O-organic medium with that from the products of the reactions of CH SO N (CH ) FSO and BrCH SO under similar conditions, part of the reaction with (CH ) N (~40%) was found to occur by net direct displacement of Cl- by (CH ) N, with most of the remainder by elimination of HCl to give sulfene. (2) Hydrolysis of 2hydroxyethanesulfonyl chloride is shown to proceed largely by way of β-sultone, which reacts with water or added nucleophiles (Nu-) to give HOCH CH SO and NuCH CH SO , respectively; the pos sibility of sulfur-oxygen cleavage of β-sultone by Cl- is discussed. 3

3-

3

2

3

3

2

+

3

2

3 3

3-

2

3

3

2

2

3-

2

2

2-

3

3

3-

S U L F O N Y L TRANSFER TO NUCLEOPHILES may be illustrated by such reac

tions as (1) sulfonyl chloride hydrolysis (RS0 C1 + H 0 — R S 0 H + HCl), (2) esterification of an alcohol or phenol ( R S 0 X + R ' O H — R S 0 O R ' + HX), (3) synthesis of sulfonamides ( R S 0 X + 2 R ' N H — R S 0 N R ' + R ' N H + X " ) , (4) desulfonation of an episulfone (the final stage of the Ramberg-Backlund reaction) (episulfone 4- O H " —• C H = C H + H S 0 ~ ) , (5) the sulfonamide-aminosulfone rearrangement [ C H N H R S 0 A r —• (R'Li) 0 - R N H C H S O A r ] , and (6) arene transsulfonylation [ A r S 0 C H + A r ' H — ( H ) A r H + A r ' S 0 C H ] . Most of these reactions have been wellknown for many years, but efforts to elucidate the mechanism of these processes are, however, much more recent and by no means complete. In this chapter, we shall briefly outline current knowledge of the mechanisms of some of these reactions and then present a progress report on two specific topics currently under study in our laboratory. 2

2

3

2

2

2

2

2

2

2

2

2

6

6

4

2

3

5

2

2

2

3

+

2

3

The older work was summarized by Vizgert (i), and aspects of the more recent studies up to about 1978 were critically reviewed by Kice (2). Some topics in sulfonyl transfer are not discussed here: intramolecular sulfonyl transfers with sulfonic esters (3, 4), episulfone cleavage (5), the sul0065-2393/87/0215-0385$06.00/0 © 1987 American Chemical Society

In Nucleophilicity; Harris, J., et al.; Advances in Chemistry; American Chemical Society: Washington, DC, 1987.

386

NUCLEOPHILICITY

fonamide-aminosulfone rearrangement (6-8), and arene transsulfonylation (9). The earliest mechanistic studies of sulfonyl transfer were concerned primarily with solvolysis in alcoholic or aqueous media and were invariably interpreted in terms of a direct displacement process (J, 2): χδΌ

I

RS0 X + R O H

RS0 OR' + H X

r—se

2

2


-Ο -Η

R"

A much discussed question arising in the direct displacement process concerns the timing of bond formation and breakage, that is, whether I (or a similar species) corresponds to a transition state or intermediate. A good case for a two-step process proceeding via a pentacoordinated intermediate has been put by Kice (2) and supported by the isolation of hypervalent analogues by Perkins and Martin (10). Williams and co-workers (IJ, 12), however, argue that in the particular case of displacement of aryloxide from arenesulfonic ester with hydroxide, their evidence is in better agreement with a one-step mechanism. Such uncatalyzed solvolytic processes are synthetically unimportant; as a procedure for making esters, for example, the reaction is usually highly inefficient because of the tendency of these esters to alkylate an alcohol about as fast as the sulfonyl chloride sulfonylates an alcohol, and so by the time the starting material is consumed, extensive further reaction of the product will have occurred. On the other hand, the promotion of esterification by tertiary amines is a routine synthetic procedure with both arenesulfonyl and alkanesulfonyl species. For the reaction of arenesulfonyl chlorides with pyridine bases, Rogne (13, 14) concluded that the amines function as nucleophilic catalysts, for example, II. ROH +

ArS0 X + C H N 2

5

• [ArS0 N C H X ]

5

2

5

• ArS0 OR + H X

5

2

II When the aryl group is replaced by a 1-alkenyl (e.g., vinyl) grouping, nucleophilic catalysis of a different kind is observed (15): +

CH =CHS0 C1 + C H N — [ C H N C H C H = S0 ] + C l " 2

2

5

5

5

5

2

2

III


27. KING ET AL.

387

Sulfonyl Transfer to Nucleophiles +

+

[ C H N C H C H = S0 ] + ROH — C H N C H C H S 0 O R 5

5

2

2

5

5

2

2

2

IV

III

CH =CHS0 OR 2

+

2

C H NH 5

+

5


V In this case, the nucleophile attacks the vinylogous carbon to form the cationic sulfene III, which on subsequent reaction gives either the betylate (IV, R = alkyl or aryl group) or the simple overall substitution product (V). With alkanesulfonyl halides bearing an α-hydrogen, however, the nor mal attack of a tertiary amine is evidently at the α-hydrogen with elimination to form the sulfene (VI). The key piece of evidence was the observation, in our laboratory (16) and that of Truce (17), of the monodeuterated product (VII) in the presence of the deuterated reagent (e.g., ROD). +

R C H S 0 X + ( C H C H ) N — [RCH = S0 ] + ( C H C H ) N H X " 2

2

3

2

3

2

3

2

3

VI [ R C H = S 0 ] + R O D —* R C H D S 0 O R ' 2

2

VII These experiments, however, were interpreted by the two groups some what differently (18, 19). Truce and Campbell (19) noted that under their conditions [ C H S 0 C 1 in benzene at room temperature with 1.3 equiv of ( C H C H ) N and 1.2 equiv of C H O D ] typically about half of the product was monodeuterated (with the rest undeuterated); these researchers sug gested that the monodeuterated material arose from the sulfene (VI) and the u n d e u t e r a t e d p r o d u c t from the s u l f o n y l a m m o n i u m salt, C H S 0 N ( C H C H ) C l " (VIII), which was formed both (1) by direct displacement of chloride ion by triethylamine and (2) from the sulfene (VI), which "collapses with the triethylammonium chloride produced" (19). Our conditions (using a large excess of R O D , often as the solvent) led to a large proportion (usually >90%) of the monodeuterated product (VII), and our view was that most of the product (>90%) was formed directly from the sulfene (VI) with much of the undeuterated material being formed by trap ping of the sulfene with return of the protium originally on the sulfonyl chloride (and which had been removed in forming the sulfene). Truce and Campbell regarded this latter process as unlikely, citing control experiments in which no exchange was observed between C H O D and preformed crystalline triethylammonium chloride in benzene. In our opinion, however, the possibility of protonation in the sulfene trapping process or of H - D exchange with R O D prior to precipitation is not ruled out by the control studies. Truce and Campbell explained their results by invoking participa3

3

2

2

3

3

+

3

2

2

3

3

3


388

NUCLEOPHILICITY


tion of triethylammonium ion in an unprecedented reaction (with sulfene); our simple notion that the same species is involved in proton transfer or exchange seems much more attractive to us. This chapter describes subsequent experiments to clarify the mecha nism of reactions of alkanesulfonyl chlorides and related compounds with water, alcohols, and aromatic amines. In the course of these studies, we also noted a third-order term in the rate law and further work on this led to the observation of hydrogen-deuterium multiexchange with small tertiary amines. These results prompted further study, which has proceeded gradu ally over a number of years. The current state of this work is described. Mechanism of Reaction of Methanesulfonyl Chloride and Anhydride with Trialkylamines and Water or Alcohols: Multiexchange of Hydrogen with Small Amines Reaction of methanesulfonyl chloride with excess D 0 and trimethylamine in 1,2-dimethoxyethane ( D M E ) gave a mixture of isotopically labeled methanesulfonate salts of the following composition (20, 21): C H S 0 " , 1.8%; C H D S 0 " , 25.6%; C H D S 0 " , 24.7%; and C D S 0 " , 48.0%. Rather more C D product was obtained with quinuclidine or l,4-diaza[2.2.2]bicyclooctane (DABCO), although successive replacement in the trimethylamine of the methyl groups by ethyl reduced the proportion of C D and C H D products until with triethylamine the product consisted of 9.6% C H , 89.8% C H D , and 0.5% C H D materials. A reasonable route to these products is shown in Scheme I. In accord with this, we found a number of years ago that sulfonylammonium salts, for example, C H S 0 N ( C H ) F S 0 ~ , give a larger proportion of the C D product than the sulfonyl chloride under the same conditions (22). To make a quantitative assignment of the relative importance of the competing pathways in Scheme I, especially of the ratio k lk , we devised a buffered aqueous-organic medium [ K C 0 - K D C 0 in D 0 - D M E - M e C N (62:7:10) adjusted to the specific p H with DC1] (1) in which reagents and products were soluble and (2) that maintained pseudofirst-order reaction conditions. The reactions of a series of tertiary amines with methanesulfonyl chloride and with the corresponding sulfonyl-ammonium fluorosulfate were carried out, and though in principle the rate constant ratios of all of the competing reactions in Scheme I can be derived from the combined product compositions from the sulfonyl chloride and the sulfonylammonium salt, in practice the complexity of the mechanism and the limited accuracy of the data lead to considerable uncertainty in values so obtained (23). 2

3

2

3

2

3

3

3

3

3

3

2

3

2

2

+

3

2

3

3

3

3

2

Y

2

3

3

2

To generate sulfene without any possibility of simultaneous formation of the sulfonylammonium salt, we turned to the "abnormal route" to sulfene (17), specifically that from bromomethanesulfinate anion, B r C H S 0 ~ . This reaction, though not ideal because of complication by a competing displace2


2

Sulfonyl Transfer to Nucleophiles


27. KING ET AL.


389

390

NUCLEOPHILICITY

ment of Br by ( C H ) N to give ( C H ) N C H S 0 - (25), is believed, nonethe less, to form methanesulfonate anion only by way of sulfene; the C H S 0 so obtained shows a small but clearly observable proportion of the C D product (see Table I). Simple comparison of the products from the sulfonyl chloride with those of the sulfonylammonium salt the bromomethanesulfinate salts would lead to the conclusion that k ~ fc in the reaction of C H S 0 C 1 . This result was placed on a more quantitative basis by deriving analytical ex pressions relating products to rate constant ratios for a simplified scheme in which proton uptake from the medium was neglected. The parameters so derived were then used in a computer-simulated version of the full scheme, and these parameters were allowed to vary systematically so as to generate a minimum value for the squares of the differences between the found and simulated percentages of the labeled products. In this way, a set of param eters (listed in Table II) was obtained which provided the simulated values shown in Table I. The agreement of the found and simulated numbers is well 3

3

3

3

2

2

_

3

3

3


2

2

3

2

Table I. Experimental and Simulated Values for the Percentages of the Labeled Methanesulfonate Anions CH

CH D

3

+

CH S0 N (CH ) 3

2

3

3

3

FSO3-

2

2

CH S0 OS0 CH 3

2

2

CD

2

3

3

b

1

Found" Simulated Found" Simulated} Found* Simulated Found" Simulated

BrCH S0 ~ CH S0 C1 2

CHD

2

b

Substrate

3

1

1

4

4

8

8

88

88

8 8 21

8 8 20

79 47 12

79 46 12

2 3 6

2 5 8

11 42 62

11 41 60

N O T E : T h e reaction was carried out by addition of the substrate (4-5 mmol) in C H C N (10 m L ) to a solution of trimethylamine (80 mmol) in D 0 ( - 6 2 m L ) plus D M E (7 m L ) with K C 0 - K D C 0 buffer (1 M) adjusted to p H 10.2 with DC1, at 25 ° C . 3

2

2

3

3

e x p e r i m e n t a l value from mass or

1 3

C - N M R spectra.

^Obtained by computer simulation using parameters initially calculated from analytical ex pressions derived from a simplified scheme (ignoring k and k terms) and then modified fitting (least squares) to a computer simulation of the full reaction scheme. Values for k /k , kjk k /k , and k^/k^ were obtained in this way from the sulfonylammonium salt and bro momethanesulfinate results; these parameters were held constant while k^ and k/ki were optimized for the reactions of the sulfonyl chloride and anhydride. 5

8

l2

n

4

ly

4

within experimental uncertainty and is therefore consistent with the mecha nism in Scheme I. Though high accuracy is not claimed for the parameters so obtained, the values in Table II (which include also those for experiments with diethylmethylamine) show a satisfying consistency. For example, as expected from simple considerations of steric accessibility, for the tri methylamine reaction k^k is larger and both tyk and k /k are smaller than those for diethylmethylamine. Interestingly, direct attack on sulfur is the major initial reaction of the anhydride (—70% of the total) with direct sulfene formation contributing only a minor part (—11%). Very recent experiments at x

7

6

l0


27. KING ET AL.


391

Table II. Optimized Parameters for Hydrolyses of Methanesulfonyl Chloride and Methanesulfonic Anhydride 0

Reaction

tyk

7

CH S0 C1 + (CH ) N CH S0 C1 + ( C H C H ) N C H C H S 0 O S 0 C H + (CH ) N 3

2

3

3

2

3

3

2

2

2

2

3

3

0.1 0.004 1.8

0.77 0.46 6.5

3

3

3

0.013 0.02 0.013

5.9 28. 5.9

0.029 0.33 0.029

N O T E : T h e parameters were determined as described in footnote b of Table I. A l l k values except k are pseudo-first-order rate constants and therefore all ratios refer to the specific concentrations used. 6

"Reaction conditions as described in the note of Table I except for the ( C H C H ) N C H , which was carried out at p H 10.7.


3

2

2

experiment with

3

lower p H raise the interesting possibility of significant reversal of the forma tion of the sulfonylammonium chloride. In this event, the various k^jk ratios as found in this work may not reflect simply the relative rates of reaction of the base at sulfur versus hydrogen but may well require more complex interpretation; further work is in progress. We have not prepared C H S 0 N ( C H C H ) X ~ and therefore cannot determine k lk for triethylamine in the same way. Extrapolating from the diethylmethylamine results indicates that the nucleophilic catalysis route would only be a minor, but not necessarily negligible, pathway. Because we saw no sign of C D S 0 ~ with triethylamine, we may conclude that the sulfonylammonium salt, if formed, goes to the sulfene, that is, k /k is fairly large. We also have carried out a parallel series of experiments with C H O D in organic solvents such as benzene and methylene chloride and find a very similar pattern, but limitations of space preclude further description here. Returning to the Truce-Campbell scheme, our more recent work, including that using pure sulfonylammonium salts as starting materials, indicates that some reactions ascribed by these authors to C H S 0 C 1 and C H S 0 N ( C H C H ) do not occur. We suggest that the most likely mecha nism for the reaction of methanesulfonyl chloride with triethylamine and D 0 or C H O D is one proceeding almost entirely via sulfene that has been formed largely (at least 80%) by a direct elimination. In the light of our previous observation that ethanesulfonyl c h l o r i d e gave only 13% C H C D S 0 " with D A B C O - D 0 , apparently the direct elimination process is the normal route for the reaction between a typical tertiary amine and most alkanesulfonyl chlorides bearing an α-hydrogen. One final note concerning Truce and Campbells mechanism. Their proposal apparently arose from a belief that the hydrogen removed from the sulfonyl chloride ( C H S 0 C 1 in this case) could not become incorporated in the C H S 0 group of the C H S 0 O C H product. The following experiment Y

+

3

2

2

3

2

3

x

3

3

6

l0

3

3

+

3

2

3

2

2

3

3

3

2

3

2

3

3

2

2

3

2

3


2

392

NUCLEOPHILICITY

shows, however, that such an exchange can take place. Reaction of an equimolar mixture of C H S 0 C 1 and C H C D S 0 C 1 (the latter compound being much more reactive) with triethylamine and excess methanol in ben zene gave methyl methanesulfonate containing —12% of C H D S 0 O C H ; clearly, some of the hydrogen from one sulfonyl chloride is capable of appearing in the product derived from the other sulfonyl chloride. 3

2

6

5

2

2

2


Hydrolysis of 2-Hydroxyethanesulfonyl

2

3

Chloride

We recently reported (26) on the synthesis and some aspects of the reactivity of 2-hydroxyethanesulfonyl chloride (9) (Scheme II). Our early experiments gave not only the expected 2-hydroxyethanesulfonate anion (XI) but also other materials as well: the reaction in water yielded (except at the lowest initial concentrations) a clearly detectable amount of 2-chloroethanesulfonate (XII), which increased with addition of chloride ion to the reaction mixture. When the reaction was promoted by a tertiary amine, the major product was the betaine (XIII). These products are conveniently accounted for by assum ing that β-sultone (X) is formed in the major path from IX as in Scheme II. βSultone itself (1,2-oxathietane 2,2-dioxide, X) is unknown though simple substituted β-sultones were first shown to be formed as rather fragile species on careful sulfonation of olefins by Bordwell and co-workers (27-29). Those β-sultones with electron-withdrawing groups on position 4 of the ring may be made by the formal cyclization of sulfene with the appropriate carbonyl precursor (e.g., chloral) and are stable, readily isolable materials (for a summary of the literature, see reference 30). The reactivity of β-sultones lacking electron-withdrawing groups, however, would appear to increase with diminishing substitution, and X would be expected to be very reactive indeed. Hence, more insight into its chemistry might well be obtained from a study of the reactions of IX than by possibly fruitless attempts at isolation.

H0CH CH S0 C1 2

2

2

IX

y X

ci-

H 0 2

R N 3

•

HOCH CH S0 2

2

XI

3

C1CH CH S0 2

2

XII

3

+

R N CH CH S0 3

2

2

XHI

Scheme II


3

27.

393


KING ET AL.

The rates of hydrolysis were conveniently measured in water maintained at constant ionic strength (0.3 M , with NaC10 ) at 25.0 °C by the pH-stat technique as described elsewhere (15). These data gave the pH-rate profile shown in Figure 1 and which is described by the rate law k = 2AO X 10" + (5.38 Χ 10 ) [OH~]. The product of the reaction under kinetic conditions (c = 1 0 - 1 0 M) was almost entirely XI with small amounts (—2-5%) of XII. Addition of sodium chloride to the reaction mixture led to more XII. In the presence of sodium thiocyanate IX gave a mixture of XI and N S C C H C H S 0 - (XIV) with the concentration dependence shown (for reactions at two different p H values) in Figure 2. In addition, fc was found to be independent of the thiocyanate concentration; that finding is, of course, the classic rate-product criterion for the presence of an intermediate formed in a rate-determining reaction and consumed in a fast step. From the fact that each of the lines in Figure 2 tends to approach a constant limiting value, we conclude that in both the uncatalyzed and hydroxide-induced processes another route, in addition to the reaction proceeding by way of the inter mediate that reacts with thiocyanate, exists that is unaffected by thiocyanate. The reaction in the presence of added chloride ion showed two further features of interest: (1) a small but unmistakable rate suppression (see Figure 3 and the dashed curve in Figure 1) and (b) an informative pH-product ratio profile (Figure 4). These observations led to the mechanism shown in Scheme III (A and Β indicate acid and base, respectively.) 4

ohsd

4

6

_ 3

- 5

0

2

2

3


obsd

-50

1

0

i 1

2

PH

3

Figure 1. pH-Rate profile for hydrolysis of 2-hydroxyethanesulfonyl chloride (IX) in water at 25.0 °C.; circles (Q) refer to reaction in a medium maintained at ionic strength 0.3 M with NaCl0 ; squares (•) refer to the reaction in 1 M NaCl (no NaCl0 ). 4

4


394

NUCLEOPHILICITY

[NCSCHgCHgSOâ] [HOCH2CH S03 Downloaded by SUNY STONY BROOK on September 16, 2014 | http://pubs.acs.org Publication Date: July 1, 1987 | doi: 10.1021/ba-1987-0215.ch027

2

[SC Ν"] Figure 2. Variation in the ratio of 2-thiocyanoethanesulfonate to 2hydroxyethanesulfonate (XTV:XI) with concentration of thiocyanate anion in the hydrolysis of 2-hydroxyethanesulfonyl chloride; circles (O) refer to the reaction at pH 3.50, squares (\J) to the reaction at pH 6.00.

1

Ο

0.02 0.04 0.06 008

010

0.12

[cr] Figure 3. Variation in the pseudo-first-order rate constant for the reaction of 2-hydroxyethanesulfonyl chloride (IX) with aqueous sodium chloride solution (pH 5.00 and ionic strength was 0.3 M with NaCl0 , 25.0 °C). 4


27.

395


KING ET AL.


ΡΗ

Figure 4. pH-product ratio (14:11) profile for the hydrolysis of 2-hydroxyethanesulfonyl chloride (IX) in the presence of NaCl (1 M) at 25.0 °C.

k + fc , [OH-] 4

4 B

*! + Jfc [OH-]

Q—S0

1B

) C H m a

k

+

.

|C|

_

k + ^[OH-]

2

1_J

][H

\ ,

3

+

U

, ,

H

HOCH^SO,-

M C I " ] + * , [C1-][H+] 5

NCS—CH^CH S0 2

A

C1CH CH S0 -

3

2

XIV

2

3

XII Scheme III

Observation of the reaction course by ^ - N M R spectrometry showed no sign of any intermediates; we therefore applied the steady-state assumption and obtained the following expressions: =

°

Φι + *ι,„[ΟΗ-]) + (α + k [C\-]lk 2

bsd

3

« + MCl-]/* +

where a = 1 + k [H }/k 3A

3

2 A

3

4

4

+

3

+ * [H ][Cl-]/* 2 A

3

+

+ k [OH-]/k 3B

+ fc , [H+][Cl-]/fc ) (fc + fc ,,[OH-])

3

+ k [C\-]lk + k [H ][C\-]/k 5

3

5A

and

3

+

M [c\-}k + k-JC\-}[H }lk [XII] = [XI] be + (k + Jt .„[OH-]) {(fc . + fcj [Cl-][H ]/

Sulfonyl Transfer to Nucleophiles - American Chemical Society

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