Unexpected distinction in reactivity of pentafluorobenzenesulfonyl halides toward organolithiums and organomagnesium halides

1 Introduction

The nucleophilic substitution of halogen atoms X in RSO₂X is one of the typical reactions of this class of organosulfur derivatives [1], [2]. While O- and N-nucleophiles convert RSO₂X to the corresponding sulfonates and sulfonamides, organolithiums and organomagnesium halides (C-nucleophiles) give two types of products. The reaction of aryllithium or arylmagnesium halides with arenesulfonyl fluorides leads to the formation of diarylsulfones [3], [4], [5] (Scheme 1, route a). When the nucleophile is AlkM, aryl(alkyl)sulfones are the minor admixture and major products are 1,1-bis(arylsulfonyl)alkanes [6], [7], [8], [9] (Scheme 1, route b). Similar reactions occur between methanesulfonyl fluoride or phenylmethanesulfonyl fluoride and phenyllithium, although with the less basic PhMgBr, only the substitution of fluorine atom occurs [10] (Scheme 1, routes c and d). At low temperatures, sulfones were obtained in high yield [5] (Scheme 1, route e).

Scheme 1:

Typical reactions of organosulfonyl fluorides with C-nucleophiles.

Reactions of arenesulfonyl chlorides with alkyl- and arylmagnesium bromide give mainly the corresponding sulfones, but the processes are often complicated by partial reduction of ArSO₂Cl to ArSO₂H; formation of sulfoxides, sulfides, biaryls and alkyl or aryl chlorides; and so on. It should be noted that these data are very old and the compositions of products were not analyzed completely [11], [12], [13]. In all these cases, aryl moieties in ArSO₂X were phenyl, tolyl, xylyl or naphthyl, whereas the effect of electron-withdrawing substituent(s) in aryl moiety on the reaction pathways was not investigated.

In search of the convenient synthetic routes to (arylsulfonyl)polyfluoroarenes and (alkylsulfonyl)polyfluoroarenes, we explored the interaction of C₆F₅SO₂X with some organometallic compounds. Our expectations were based on the facts of the easy substitution of chlorine atom in C₆F₅SO₂Cl by O- and N-nucleophiles and formation of organyl pentafluorobenzenesulfonates [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25] and pentafluorobenzenesulfonamides [22], [26], [27], [28], [29], [30], respectively. Pentafluorobenzenesulfonyl fluoride was the less promising reactant: the strong electron-withdrawing effect of five fluorine atoms and SO₂F group caused the substitution of fluorine atom at C-4 carbon atom, while fluorine atom bonded to sulfur remained intact. For example, C₆F₅SO₂F reacts with piperidine in ether to yield 4-piperidinotetrafluorobenzenesulfonyl fluoride [31]. The related substitution occurs with other N-nucleophiles such as aniline [32] and hexamethyldisilazane [33]. The latter forms 4-aminotetrafluorobenzenesulfonyl fluoride and NH(4-C₆F₄SO₂F)₂. The interaction of sodium thiosulfate and C₆F₅SO₂F in DMF led to S(4-C₆F₄SO₂F)₂ [34].

In fact, pentafluorobenzenesulfonyl halides displayed the unpredictable reactivity toward these C-nucleophiles. Herein we present results of reactions of C₆F₅SO₂X (X=F, Cl, Br) with some organolithiums and organomagnesium halides.

2 Results and discussion

To avoid or minimize secondary processes, all reactions were performed in excess of C₆F₅SO₂X.

We found that the reaction of pentafluorobenzenesulfonyl chloride (1) with selected C-nucleophiles is completely different from the reaction with by O- and N-nucleophiles, and C₆F₅SO₂R was not formed. Thus, pentafluorobenzene (2) was the only polyfluoroaromatic product derived from 1 and PhMgBr in ether. Similarly, a mixture of pentafluorobenzene, bromopentafluorobenzene (3) (ratio 27:1) and decafluorodiphenyldisulfide (4) (trace) was obtained from 1 and BuMgBr (Scheme 2) (here and below only polyfluoroaromatic products are presented on schemes).

Scheme 2:

Reaction of C₆F₅SO₂Cl with organomagnesium bromides.

The slow addition of MeLi (contained LiI) in ether to 1 and subsequent hydrolysis gave 2, chloropentafluorobenzene (5) and iodopentafluorobenzene (6) in the ratio of 5:1:2 (¹⁹F NMR). The expected C₆F₅SO₂CH₃ was not detected (Scheme 3).

Scheme 3:

Reaction of C₆F₅SO₂Cl with MeLi in the presence of LiI.

Products 2 and 5 (2:1) were produced from 1 and BuLi. In addition, minor amounts of butylpentafluorobenzene (7) and 1-(1-ethoxyethyl)pentafluorobenzene (8) were detected by ¹⁹F NMR and GS-MC analysis, whereas C₆F₅SO₂Bu was not found (Scheme 4).

Scheme 4:

Reaction of C₆F₅SO₂Cl with BuLi.

When pentafluorobenzenesulfonyl bromide (9) was combined with PhMgBr in ether, the major product was pentafluorobenzene. Unexpectedly, a significant amount of decafluorodiphenyldisulfide was also formed (ratio of 2 to 4=4:1), while 3 and C₆F₅SO₂Ph were absent (Scheme 5).

Scheme 5:

Reaction of C₆F₅SO₂Br with phenylmagnesium bromide.

In contrast to C₆F₅SO₂Cl and C₆F₅SO₂Br, pentafluorobenzenesulfonyl fluoride (10) was converted to C₆F₅SO₂R using organolithiums or organomagnesium halides although this process is accompanied by parallel reactions. For instance, the addition of PhMgBr to 10 in ether at 25°C and subsequent hydrolysis gave (phenylsulfonyl)pentafluorobenzene (11) and, presumably, a few 1-phenylsulfonyl-2-phenyltetrafluorobenzene (12) (ratio 8:1). Under the same conditions, the reaction of 10 with BuMgCl gave two main products, (butylsulfonyl)pentafluorobenzene (13) and 4-butyltetrafluorobenzenesulfonyl fluoride (14) (ratio 1:1) (Scheme 6).

Scheme 6:

Reaction of C₆F₅SO₂F with organomagnesium halides.

The action of MeLi on 10 also caused the substitution of fluorine bonded to sulfur by a methyl group and the formation of (methylsulfonyl)pentafluorobenzene (15). Unlike the above processes, the main by-products are bis(pentafluorophenylsulfonyl)methane (16) and 4-(pentafluorophenylsulfonylmethyl)tetrafluorobenzenesulfonyl fluoride (17). They were formed because of the hydrogen abstraction from 15 by MeLi (Lewis base) and subsequent attack of 10 at the sulfur atom and carbon atom C-4, respectively, by the carboanion C₆F₅SO₂CH₂⁻ (molar ratio of 15:16:17=5:6:1) (Scheme 7).

Scheme 7:

Reaction of C₆F₅SO₂F with MeLi.

Comparing the reactivity of C₆F₅SO₂F with C₆F₅SO₂Cl and C₆F₅SO₂Br reveals the following distinctions. Under the action of RMgX, pentafluorobenzenesulfonyl fluoride underwent the substitution of fluorine atom bonded to sulfur as well as of fluorine bonded to carbon atom of pentafluorophenyl moiety. The other C-nucleophile, C₆F₅SO₂CH₂⁻, generated by hydride abstraction from the methyl group of 15 by methyllithium reacted with 10 in a similar manner. In contrast, reactions of pentafluorobenzenesulfonyl chloride (bromide) led to the other type of products. Taking into account the easy substitution of chlorine in C₆F₅SO₂Cl with O- and N-nucleophiles, this reaction route was quite unexpected.

The investigation of reaction mechanisms was out of the framework of this paper, but we would like to make some suggestions. The analysis of products indicated the radical nature of processes. Thus, the reaction of C₆F₅SO₂Cl with highly nucleophilic RLi always leads to C₆F₅H and C₆F₅Cl (Schemes 3 and 4). The latter product as well as C₆F₅Br was not found in reactions with the less nucleophilic RMgBr. Probably, the first process proceeds via the addition of RLi and subsequent homolytic dissociation of S–Cl and then C–S bonds. The abstraction of hydrogen atom by pentafluorophenyl radical from solvent gives C₆F₅H, and recombination with chlorine atom results in C₆F₅Cl (Scheme 8, route a). Alternatively, the redox process can be a source of pentafluorophenyl radical from C₆F₅SO₂X (X=Cl, Br) and RMgBr (Scheme 8, route b).

Scheme 8:

Proposed routes of decomposition of C₆F₅SO₂X (X=Cl, Br) under the action of C-nucleophiles.

The other remarkable peculiarity is the formation of C₆F₅I from C₆F₅SO₂Cl and MeLi that contains LiI (Scheme 3) and the absence of C₆F₅I in the reaction of C₆F₅SO₂F (Scheme 7). It should be noted that the closely related replacement of the SO₂Cl group by hydrogen and iodine atoms was observed in the reaction of 1 with NaI in MeCN at room temperature [35] (Scheme 9).

Scheme 9:

Experimental data and the proposed route of formation of C₆F₅I from C₆F₅SO₂Cl and NaI in acetonitrile [35].

Following the author of [35], we concluded that the formation of C₆F₅I in our case also proceeded via a similar redox mechanism.

3 Conclusions

1. Under the action of organolithiums or organomagnesium halides, pentafluorobenzenesulfonyl chloride (bromide) mainly forms C₆F₅H, whereas the substitution of chlorine (bromine) with the organyl rest does not occur. This distinguishes them from ArSO₂Cl with the less electron-withdrawing aryl moieties (phenyl, tolyl, xylyl or naphthyl) which mainly form the corresponding diarylsulfones.

2. In contrast to C₆F₅SO₂X (X=Cl, Br), C₆F₅SO₂F undergoes only the nucleophilic substitution of fluorine in the pentafluorophenyl substituent as well as at the sulfur atom.

3. Increased electron-accepting character of the aryl moiety in arenesulfonyl halide facilitates redox reactions, and decreases the substitution of chlorine (bromine). On the other hand, C₆F₅SO₂F reacts as its non-fluorinated analog (Scheme 1), although the parallel reaction at the C₆F₅ group also occurs.

4 Experimental section

The NMR spectra were recorded on a Bruker Avance 300 (¹H at 300.13 MHz, ¹⁹F at 282.40 MHz) spectrometer. The chemical shifts were referenced to TMS (¹H), CCl₃F [¹⁹F, with C₆F₆ as secondary reference (δ=−162.9 ppm)]. A Hewlett-Packard 1800A (with HP-5MS column) instrument was used for gas chromatography-mass spectrometry (GC-MS) analysis. BuLi (2.4 m solution in hexanes) (Sigma-Aldrich) was used as supplied. Solutions of C₄H₉MgCl, C₄H₉MgBr and C₆H₅MgBr in ether were prepared from chlorobutane, bromobutane and bromobenzene and Mg, respectively. CH₃Li was prepared from methyl iodide and lithium. Ether was distilled over LiAlH₄ and stored over sodium. (Phenylsulfonyl)pentafluorobenzene [36], and pentafluorobenzenesulfonyl halides C₆F₅SO₂F [37], C₆F₅SO₂Cl [38] and C₆F₅SO₂Br [39], [40] were prepared by the reported procedures. The known compounds 13 [36], 15 [21], 2 [12], 3, 5, 6 [41], 4 [42], 8 [43] and 16 [44] were identified by ¹⁹F NMR spectroscopy and GC-MS data. The preparation of 14 will be reported in a forthcoming publication. The constitution of 12 (minor component) was deduced from the ¹H, ¹⁹F NMR spectra and GC-MS data of its mixture with 13. Yields of products were determined by ¹⁹F NMR spectroscopy using C₆H₅F as a quantitative internal reference. For reliable identification, compound 7 was prepared separately by the modified procedure given in [45].