Oxidation chemistry of perfluoroalkyl-segmented thiols, disulfides, thiosulfinates and thiosulfonates

Journal of Fluorine Chemistry 105 (2000) 11±23

Oxidation chemistry of per¯uoroalkyl-segmented thiols, disul®des, thiosul®nates and thiosulfonates The role of the per¯uoroalkyl group in searching out new chemistry$ Dr. Neal O. Brace* Wheaton College, Wheaton, IL 60l87, USA Accepted 6 March 1999

Abstract The oxidation chemistry of per¯uoroalkyl-segmented thiols, RF±R±SH (1), thiosul®nates, RF±R±S(O)S±R±RF (3), thiosulfonates, RF±R± S(O2)S±R±RF (4) and disul®des, RF±R±SS±R±RF (5) (in which RFˆn-C6F13 or n-C8F17 and RˆCH2CH2) is studied herein. Base catalyzed reaction of C6 thiol 1 with hydrogen peroxide gives pure disul®de 5, quantitatively. Other, less suitable methods for the oxidation of thiol 1 are also examined and compared. Selective oxidation of disul®de 5 by peroxy acids in chlorinated solvents gives excellent yields of thiosul®nate 3. Unlike their hydrocarbon analogues, which are unstable to heating or storage, the RF-segmented thiosul®nates 3 are relatively stable, crystalline compounds. Selective oxidation of 3 by sodium metaperiodate gives thiosulfonate 4 in high yield. Side reactions intervene with unfavorable conditions, or when peroxy acetic acid in acetic acid is used as oxidant,. Oxidation of 5 by hydrogen peroxide in low conversion gives 4 and two new compounds, 8 and 9. Compound 8 is n-C6F13S(O)2CH2CH2C6F13 (probably the sul®nate ester and not the sulfone), and 9 is most likely the O,S-sulfenyl sul®nate or, possibly an isomer, the vic-disulfoxide. A free radical chain mechanism is proposed for conversion of 4 (or 9) to 8. Compounds 8 and 9 are stable in solution and are identi®ed by MS/GC. In 3, 4 and 5, the n CH bands correlate with NMR of CH2 at C(1) and C(2) positions, both 1 H and 13 C NMR. The RF-segment in these unique sulfur compounds enhances their utility and modi®es their chemical and physical properties in important and interesting ways. # 2000 Elsevier Science S.A. All rights reserved. Keywords: Per¯uoroalkyl; Segmented; Base-catalyzed oxidation; Chain mechanisms; O,S-sulfenyl sul®nate; Vic-dioxide.

1. Introduction Per¯uoroalkyl-segmented sulfur compounds constitute a class of useful and largely unexplored substances which have a (C3±C12) terminal per¯uoroalkyl (RF) segment and a hydrocarbon spacer linked to a sulfur atom: RF±R±SY, where Y is H, R or a functional group [1±3].1 The RF-segmented thiols (1) [1±4],2 -sul®nic acids (2) [3] and -disul®des (5) [5,6] are known, as are the RF-segmented $ This paper reports work done at Wheaton College while the author was engaged in exploratory research on perfluoroalkyl-derivatives of sulfur. For previous papers by the author on (perfluoroalkyl)alkanethiols, see [1,2]. * Present address: (a) 2881 65th St. N., St. Petersburg, Fl 33710-3254, USA; or (b) 1430 River Ridge Road, River Falls, WI 54022, USA. 1 In this paper, the notation C6 means C6F13, C10 means C10F21, and so on. 2 See [1,2,4] for procedures suitable for the synthesis of RF(CH2)mSH, mˆ2±15, and their conversion to various other compounds.

sulfonic acids (6) [3,7,8]. The purpose of this paper is to describe improved syntheses of disul®des 5 ([RFCH2CH2S]2; RFˆn-C6F13 or n-C8F17) of newly discovered importance [6], and short syntheses of the novel RFsegmented thiosul®nate (3), and thiosulfonate (4) [3]. Compounds 3 and 4 are thoroughly examined and their properties compared with the known alkyl analogues. The unexpected and unusually stable RF-segmented O,S-sulfenyl sul®nate (or bis-alkyl vic-disulfoxide) is described in some detail. The RF±R±SY compounds are unique and relatively rare [3,9,10]. Because of the highly polar, rigid RF-segment, they exhibit ¯uorophilic properties and stronger intramolecular bonds, as compared to hydrocarbons [11]. Adsorbed at surfaces or at interfaces in solution, the long chain RF compounds form aggregates with oriented ¯uorocarbon chains [12]. Remarkably, and of great importance technically, RF-segmented compounds with a hydrocarbon spacer exhibit the unusual surface properties of per¯uorocarbon analogues [3,12]. RF-segmented acids (2) [3] and (6) [3,7,8]

0022-1139/00/$ ± see front matter # 2000 Elsevier Science S.A. All rights reserved. PII: S 0 0 2 2 - 1 1 3 9 ( 0 0 ) 0 0 2 6 1 - X

12

N.O. Brace / Journal of Fluorine Chemistry 105 (2000) 11±23

have both hydrophobic and lipophobic properties, which are exhibited in their surface activity and in their af®nity for ¯uorocarbon materials [3,12].3 Riess discusses the unique properties of RF-substituted compounds of many types, and comprehensively reviews their applications in the biomedical ®eld [12]. Scheme 1. Base catalyzed oxidation of thiol 1 to disulfide 5 by hydrogen peroxide.

2. Results and discussion 2.1. Oxidation of RF-segmented thiol 1 to disulfide 5 Published methods [13,14] for the oxidation of a alkane thiol to the disul®de are unsatisfactory with the RF-segmented thiol 1.4 Iodine works well as oxidant [6,13,14]; however, side product iodide must be recycled for economical and environmental reasons. Dimethyl sulfoxide [14,15] is selective and effective [16], and thiol 1 (C6) with DMSO gives disul®de 5 (C6, 89.8% conversion) in 20 h at 93± 1268C [15]. With HCl/I2 as catalyst [16], thiol 1 (C8) and DMSO give disul®de 5 in 99.7% yield in 70 min at 808C. As X2 (I2 or Br2) oxidizes thiol 1 to disul®de 5, DMSO oxidizes Xÿ back to X2, which carries on the oxidation [16]. However, the disagreeable-smelling and toxic dimethyl sul®de coproduct contaminates 5, and the excess DMSO must be recovered and puri®ed. RFCH2CH2SCN (7, RFˆn-C6F13 or n-C8F17) is prepared from RFCH2CH2I and KSCN [5]); reaction of 7 with KOH in boiling ethanol gives impure 5 (92% yield, C8; or 76% conversion, C6), and dark colored impurities are dif®cult to remove [5]. 2.1.1. Base-catalyzed oxidation of C6 thiol 1 by hydrogen peroxide After some experimentation, we ®nd a novel, ef®cient method that converts thiol 1 to disul®de 5 in excellent yield (Eq. (1)) [13]. A catalytic amount of NaOH (1±2 mol%), the C6 thiol 1 and 1.3 equivalents of the inexpensive H2O2 provide pure C6 disul®de 5, with water as the only sideproduct. 2RF …CH2 †2 SH ‡ H2 O 1

ethanol

!

NaOH; 30ÿ60 C

‰RF …CH2 †2 SŠ2 ‡ H2 O

thiol 1 in ethanol solution. No reaction occurs at 358C in 4 h. An exotherm follows the addition of a little NaOH solution, and disulfide 5 (99.5% conversion) separates from the mixture in a half hour. No attempt is made to exclude the air from the system and some oxidation of thiol 1 by atmospheric oxygen may occur. The available evidence indicates that a free radical chain reaction is responsible for the rapid, exothermic consumption of 1. It is known that alkyl thiols give disulfide radical anions (RSSR ÿ) when photolyzed in alkaline solution, particularly if di-t-butyl peroxide is present [17]. The RSSR ÿ is obtained by coupling of the RS and RSÿ species, and the RSSR ÿ are detected by EPR as diastereomeric conformers [17]. Scheme 1 provides a rationale for the base-catalyzed reaction of peroxide with 1 [13,14]. The HOÿ ion, the HOOÿ anion and the HO radical are the chain carrying species. This mechanism accounts for the absence of sul®nate and sulfonate, which are the typical byproducts observed in base induced air oxidation of thiols [18±20]. In one experiment with C6 thiol 1, an exotherm carries the temperature to 708C, and 1 is converted to 5 (95%) and sodium sul®nate 2 in 2.4% yield. In this instance, some oxidation by air probably occurs. The base-catalyzed reaction of 1 with H2O2 differs from the air oxidation of thiols in the presence of one or more equivalents of NaOH (on thiol) [14,18±20]. Oxidation by atmospheric oxygen of thiols may proceed by the mechanism of Scheme 2 [18±20]. The HO and the HO2ÿ are the chain carrying species. When a large amount of base is present, the air oxidation process involves the thiolate ion,

5

(1) An induction period at 508C of 10±40 min length is followed by an exotherm to 608C. The clear liquid mixture in 1±2 h separates into two layers, from which pure 5 crystallizes. Without a catalytic amount of base, H2O2 does not oxidize 3 Kawamura reports extensively on the effect, in RF(CH2)mSO3H, of chain length and RF group on surface activity and Krafft points [8]. 4 Ohus reviews oxidation of thiols to disulfides by air (with or without alkali), by HOOH with mol amounts of strong base, by a sulfoxide or by other methods [13]. Field gives is a general review of preparation and reactions of disulfides, routes to dialkyl thiosulfinates and thiosulfonates, and useful reactions thereof and it discusses the stability of thiosulfinates [14].

Scheme 2. Anionic oxidation of thiol to disulfide by oxygen diradical with strong base initiation.

N.O. Brace / Journal of Fluorine Chemistry 105 (2000) 11±23

13

Table 1 Peroxy acid oxidation of disulfides (5) to thiosulfinates (3)a solvent

RF CH2 CH2 SSCH2 CH2 RF ‡ Oxidant ! RF CH2 CH2 S…O†SCH2 CH2 RF ‡ RF CH2 CH2 SO2 SCH2 CH2 RF P or B

5

Entry No.

1c 2d 3e 4 5 6f 7

5

C or D

Oxidant

Solvent b

(2)

4

3

RF

Amount (mmol)

Type

M

Amount (mmol)b

Type

Amount (ml)

C6 C6 C6 C6 C8 C8 C8

2.02 13.1 10.0 10.0 2.01 10.4 10.4

P P P P B P P

0.123 0.385 0.100 0.101 0.087 0.168 0.105

3.21 13.1 10.0 10.1 2.28 10.4 10.5

C D D C C C C

25 40 100 100 23 60 100

Time (h)

Temperature (8C)

Yield (%)

3 mp (8C)

NMR (%)

20 18 3 3 0.5, 3 1, 16 1, 21

40 3, 20 3, 20 3, 20 3, 22 2, 16 3, 21

95 100 93 96.8 85 84.4 100

76±82 76±79d 77±82e 79±80 81±85 110±125f 106±122

3, 3, 3, 3, 3, 3, 3,

85; 4, 15 80; 5, 10 77; 5, 23 76.8; 5, 23 95; 5, 5 90; 5, 10 85; 5, 15

a See Section 3 for illustrative procedures; pure disulfide 5, mp 40±18C; thiosulfinate 3, mp 85±868C; and thiosulfonate 4, mp 122±1238C; oxidizing agents are: B, m-chloroperoxybenzoic acid (85%, Aldrich); and P, peroxyacetic acid (FMC Corp., 35.5 wt.%, in acetic acid, contains also 6.8 wt.% of hydrogen peroxide, making a total of 10.67% `active oxygen'); the total active `O' is thus mmol of P‡6.8% of P; solvents used are: C, chloroform and D, dichloromethane. b M is (mmol P/vol. ml) of P alone in the total mixture; mmol is calculated from the amount of P alone. c With P:5ˆ1.59, a higher reaction temperature, and longer reaction time, oxidation of 5 gives 3 and 4. d The 3, 5 mixture melts at 75±798C, clear; 798C (clear)±1058C, decomposes; cooled to 708C, solid; remelts at 73±758C. e The 3, 5 mixture recrystallized in benzene gives 3, mp 85±868C; TLC and NMR show high purity. MS is that of pure 3 (analysis is run after 2 months); after 10 months at 108C in a refrigerator, mp (sinter 798C) 80±828C. f The 3, 5 mixture recrystallized in benzene and acetone gives mp 122±1248C; TLC and NMR shows high purity.

2.2.1. Reaction of 5 with peroxy acid in chlorinated solvents Selective oxidation of disul®des 5 to thiosul®nate 3 by peroxyacetic acid (P, 35% in acetic acid), or by m-CPBA in CHCl3 or CH2Cl2, gives generally an excellent yield of 3 at 3±408C (Table 1; Eq. (2)) [21±24].5 The results are sum-

marized in Table 1. All of the reactions employ equimolar amounts of 5 and oxidant, except entry one. Here an excess of P is used, the reaction time is longer and the temperature higher; and, in this instance only, over oxidation to 15% of 4 occurs. Reactions go well in either chloroform or dichloromethane solution. By contrast, reaction of 5 (C6 or C8) with hydrogen peroxide in acetic acid gives a complex mixture of 3 and 4 with other products, including acids 2 and 6. This subject is taken up in Section 2.4.1. The selectivity of oxidation with a peroxy acid probably derives from the mechanism, discussed in Section 2.2.2. Freeman oxidizes n-propyl disul®de with m-CPBA in dichloromethane at 08C, and the heat-sensitive product is worked up quickly [21]. Unsymmetical disul®des with peroxyacetic acid give the thiosul®nate product with the alkyl groups scrambled [23], and a mixture of different thiosul®nates in solution exchange alkyl groups, but not by a free radical process [23,24].6 Block measures the thermal stability of dialkyl thiosul®nates (t1/2 at 968C), and these values are 7 min for dimethyl thiosul®nate, 40 min for methyl ethanethiosul®nate and 52 min for ndodecyl dodecanethiosul®nate [24]. Surprisingly, the C10 compound is not more stable, relative to the C1 and C2 thiosul®nates. The thiosul®nates 3 are stable to drying or when kept for several months in a refrigerator at 108C (IR, mp unchanged). The thiosul®nates 3 (C6 and C8) may be recrystallized to constant mp, and are detected by TLC. 1 H, 13 C, and

5 Freeman gives a detailed, critical review of all aspects of peroxy acid oxidation reactions of sulfur compounds; mechanisms and products [22].

6 Block gives the preparation and instability of dialkyl thiosulfinates, mass spectra and an extensive study of new chemistry [23].

which is converted to peroxysulfenate, sul®nate and sulfonate ions [19±20]. The reaction is not quantitative and the product mixture has to be puri®ed in some manner [18]. 2.1.2. Oxidation of C8 thiol 1 with hydrogen peroxide in acidic media Thiol 1 (C6) in ethyl acetate solution, hydrogen peroxide (mol H2O2:1ˆ0.50) and HOAc give disul®de 5 at 418C; however, reaction is incomplete in 29 h, and additional H2O2 is added (total mol H2O2:1ˆ0.71). After 96 h, the product is 5 (85.5%) and thiosulfonate 4 (11.4%), 100% yield (GC, NMR). Similarly, thiol 1 (C8) in ethyl acetate solution, with excess of H2O2 and HOAc at ÿ318C gives 5 (100%) in 18 h (mp, IR) [3]. Thus, H2O2 oxidation of thiol 1 to disul®de 5 is non-selective and/or slow under these conditions. The IR, NMR and mass spectrum of 5 are given in Tables 4±6, and in Section 3.2. 2.2. Peroxy acid oxidation of disulfide 5 to S-2(perfluoroalkyl)ethyl 2-(perfluoroalkyl)ethanethiosulfinate (3)

14

N.O. Brace / Journal of Fluorine Chemistry 105 (2000) 11±23

Scheme 3. Activated complex in the peroxyacid oxidation of dialkyl disulfides. 19

F NMR spectral parameters of disul®de 5, thiosul®nate 3 and thiosulfonate 4 are listed in Table 4, and IR data are in Tables 5 and 6. See also Section 2.5. The C6 3 is eluted by capillary GC/MS, but only in mixtures with 4 and 5 through packed columns. However, C6 3 may be injected into the MS sampling system without apparent decomposition. MS (EI) of 3 gives mol ion, m/e 774 (0.04); HSS(O)H, m/e 82 (1.00), base peak; 3 less one F atom, m/e 755 (0.08); C6F13CH2CH2S(O)SH, m/e 428 (0.17), and C6F13CH2CH2S(O)S, m/e 427 (0.46); C6F13CH2CH2S(O), m/e 395 (0.15); and SCH2CH2C6F13, m/e 379 (0.50). A fragment, C4F9CH2CH2S(O)S, m/e 327 (0.20) is probably derived from m/e 427, by expulsion of CF2=CF2 (FW 100). The MS of 3 is of interest in comparison with that of 4 and the new compounds of Section 2.4. The absence of the mol ion of 5 is noteworthy, as Block shows that the disul®de is formed in the sample chamber during the injection of dialkyl thiosul®nates. The disul®de is principally formed by a bimolecular process involving the sulfenic acid [23,24].7 This is another instance of the unusual stability of the segmented 3 vis a vis the dialkyl sul®nates. 2.2.2. Mechanism of peroxyacid oxidation of 5 to 3 Mechanism studies reveal the nature of the activation complex in analogous oxidation reactions [25±29].8 Nucleophilic attack by the sulfur atom (electron pair) on the electrophilic oxygen of the peroxy acid forms the type A complex of Scheme 3 [25±29]. Because of rigidity in the transition state, negative entropies and relatively low activa-

7 Block shows that the stability of dialkyl thioslfinates depends on the absence of a or b-hydrogens in the alkyl groups. Cycloelimination from 4CHC±S(O)±S±CH3 gives RSOH and S=C3 fragments. The RSOH is trapped by reaction with activated alkenes or alkynes [24]. 8 Benassi presents an ab initio study of peroxy acid oxidation of methyl methanethiosulfinate and a critical review of this, and related reactions and mechanisms. Discusses the formation of diasteromeric vic-disulfoxides; the relative stability and energies of transition state structures; the effect of solvents of differing dielectric constants, and the role of protic solvents and acids [25].

tion energies (ca. 10±12 kcal/mol) are observed [25±29], and the ability of peroxy acids to release an electrophilic oxygen of the peroxide group involves overlap control [26]. Peroxy acids are normally 103 (H2O2 with acid catalysis) to 107 (H2O2 without acid catalysis) times more reactive as oxidants than H2O2 or alkyl hydroperoxide [25,28,29].9 This explains the slow oxidation that occurs in the reactions of 5 with H2O2, but not the lack of selectivity. The effect of a large, highly polar and electron withdrawing per¯uoroalkyl group on the rates of formation and of decomposition of complex A is not known. Any inductive effect by the RF group is partially attenuated (but not entirely) by the CH2CH2 spacer (see below for evidence from IR and NMR). However, there is predictably a noticeable steric effect of the segmented RF groups in complex A, which probably affects, and may increase, its rate of fragmentation. 2.3. Oxidation of thiosulfinates 3 to S-2(perfluoroalkyl)ethyl 2(perfluoroalkyl)ethanethiosulfonates (4) 2.3.1. Sodium metaperiodate oxidation Sodium metaperiodate oxidizes the per¯uoroalkyl-segmented thiosul®nates 3 (mol NaIO4:3ˆ1) to the thiosulfonate 4 in excellent yield [30] and there is no over oxidation. A mixture of acetic acid and acetonitrile as solvent, and HCl as catalyst, give best results (Table 2, Eq. (3)). In entry one, pure 3 (C6) gives pure 4 in 89% yield. In entries 2, 3 and 5, the 3 (C6 or C8) contains 10±15 mol% of 5, and the amount of NaIO4 is adjusted to oxidize the 5 to 4 also. Isolated 4 is recovered in high yield and purity. However, in entry 4, a 1,4-dioxane/MeCN mixture is used as solvent, and in the more polar solvent mixture the small excess of NaIO4 apparently converts 3, 4 or 5 to water-soluble products, probably the acids 2 and 6. The yield of isolated 4 falls to 69%. The otherwise high yield and selectivity of product 4 may derive from the unique mechanism of reaction given in Section 2.3.2. The thiosulfonates 4 (C6 and C8) are sharp mp compounds, more easily puri®ed than 3, readily eluted from GC (packed columns) and identi®ed by NMR and MS. MS by Dip/MS method, or MS/EI gives: 4, mol ion, m/e 790 and a fragment, m/e 771 that arises from 4 with loss of F. An impurity of 5 in the sample (GC, 0.65%) appears as the mol ion, m/e 758 (0.015). An interesting fragment, C6F13CH2CH2SO2SCH2, m/e 457 (0.24) indicates that the stability of the thiosulfonate linkage is considerable. In an important pathway, 4 is split to give C6F13CH2CH2SO2 2H‡, m/e 413 (1.00) (the base peak), and C6F13CH2CH2SH‡ m/e 380 (0.96). Both fragments are protonated. In a coincidence with the MS of 3, a major fragment is C4F9CH2CH2S(O)S,

9

Curci reports the effect of solvents of differing dielectric constants, and the role of protic solvents and acids in oxidation with peroxy acids. Kinetic studies suggest an activated complex of the type A [29].

N.O. Brace / Journal of Fluorine Chemistry 105 (2000) 11±23

15

Table 2 Oxidation of thiosulfinates 3 to thiosulfonates 4 by sodium metaperiodate or peroxy acida solvent

RF CH2 CH2 S…O†SCH2 CH2 RF ‡ NaIO4 ! NaIO3 ‡ RF CH2 CH2 SO2 SCH2 CH2 RF ‡ ‰RF CH2 CH2 SŠ2 ‡ RF CH2 CH2 SO2 Na …or P† catalyst

3

Entry No.

1 2c 3d 4e 5f 6g

Thiosulfinate 3 RF

Amount (mmol)

C6 C8 C8 C6 C6 C8

1.097 1.000 1.017 1.00 1.02 0.908

NaIO4 (mmol)

1.093 1.258 1.224 1.14 1.18 P, 1.10

4

solvent

Catalyst

Type

Amount (ml)b

A, A, A D, A, A

7.5 12.5 20 4.6 7.5 20

M M M M

HCl, HCl, HCl, HCl, HCl, HCl,

3 3 3 3 3 3

drops drops drops drops drops drops

(3)

2

5

Time (h)

Temperature (8C)

4 and 5 product mixture, yield

Analysis

Yield (%)

mp (8C)

NMR (%)

GC, TLC (%)

0.75 1.1 1.16 0.83 0.75 19

35 35 32 31 31 35

88.9 95 91 69.3 89.5 72g

114 142 142 114 113 144

4, 4, 4, 4, ± 4,

99 99 no 3 or 5 100 ca. 90; 5, 10

TLC, 100% TLC, 99 GC: 4, 96.3; 5, 1.21

a

See Section 3.6 or 3.7 for details, including work up and analysis of reaction products; the solvents are acetic acid (A), 1,4-dioxane (D) and MeCN (M); the thiosulfinate 3 used is pure substance, mp 82±83.18C; pure C6 4, mp 1148C; pure C8 4, mp 1428C. b The amount of each solvent is given in the order: A, Mˆ7, 5 ml; and similarly in each case. c Thiosulfinate 3 contains 15 mmol of disulfide 5 (Table 1, entry 7); moles NaIO4:3,5ˆ1.26; mp of 4 is 140±1428C; heated to 1728C, gas evolves, and to 2028C, decomposes. d The C8 3 contains 0.10 mmol of C8 5, Table 1, entry 6; moles NaIO4:3,5ˆ1.22; more solvent (HOAc, 12.5 ml, CH3CN, 5 ml.) is used; however, a slurry forms at 328C and 10 drops of NaIO4 solution gives an exotherm to 358C; the slurry clears, but the next 10 mmol of NaIO4 solution causes a yellow color to appear and the 4 to precipitate. e The 3 contains 0.23 mmol of 5 by NMR (Table 1, entry 4); moles NaIO4: 3ˆ1.14; however, dioxane and acetonitrile mixture as solvent causes over oxidation of the 4 and only 69.3% of 4 is recovered, and no 5; water soluble product is formed but not isolated. f The 3 contains 0.23 mmol of 5 by NMR; moles NaIO4:3ˆ1.18. g The 3 (C8) contains 0.10 mmol of 5 (Table 1, entry 6); moles P:3,5ˆ1.2; the total product weight is 0.93 g (95% recovery) dried in vacuo, at 428C; water washing removes 0.21 g. of soluble material (probably sulfinic acid 2 and sulfonic acid 6) that gives excess peaking at d 2.39 in tbe NMR.

m/e 327 (0.99). The parent fragment is missing, but is found in the MS of 3: C6F13CH2CH2S(O)S (m/e 427). A large peak, probably H2CS2‡, m/e 78 (0.75) and another, HSSH, m/e 66 (0.98) are prominent species in the MS of 4. The sample contains 0.56% of 5 by GC, thus 5 is not generated in the MS sample probe. The fragments of 4 are of interest in the formation of 8 in Section 2.4. 2.3.2. Mechanism of periodate oxidation of thiosulfinate 3 to thiosulfonate 4 According to Oae [30], the periodate ion attacks as a nucleophile at the electron poor sulfur of RS(O), instead of the electron-rich sulfenyl RS atom of the thiosul®nate, to give a sulfurane intermediate complex of Scheme 4. The IO4ÿ ion adds on the protonated thiosul®nate (at the site of the greater positive charge), and the complex fragments to the thiosulfonate and HIO3. The effect of the RFCH2CH2 group on the formation and the fragmentation of the intermediate complex is likely to similar to that of the complex A in Scheme 3. 2.3.3. Peroxyacetic acid oxidation Peroxyacetic acid, in a 21 mol% excess (Table 2, entry 6), oxidizes 3 and 5 (C8) mixture to 4 in good yield but not selectively. The solvent is acetic acid. About 20% of the product is the water soluble acid mixture of 2 and 6. Scheme 5 gives a mechanism for peroxy acid oxidation of thiosul®nate, adapted from Freeman [22]. In the ®rst step,

the peroxy acid and the thiosul®nate(I) form a complex A as in Scheme 4, and its breakdown gives a pair of diastereomeric vic-disulfoxides(IIa,b) as the ®rst observable products at ÿ408C, by 1 H and 13 C NMR [21,22]. Evidence for this is the detection of IIa,b, and by spin trapping, of the O,Ssulfenyl sul®nate [RS(O)OSR, Rˆalkyl] (III) derived from IIa,b in Step 2 [31]. Substance II decomposes and rearranges when warmed to ca. ÿ208C to sul®nes, sul®nic acids and thiosul®nates and (I) given in Step 3. The O,S-sulfenyl sul®nate(III) rearranges to the thiosulfonate(IV) in Step 4. Freeman's papers should be consulted for supporting evidence and a more thorough explanation [22].

Scheme 4. Oxidation of thiosulfinate by nucleophilic addition of iodate ion. Reaction intermediate.

16

N.O. Brace / Journal of Fluorine Chemistry 105 (2000) 11±23

Scheme 5. Steps in the peroxyacid oxidation of thiosulfinate. Attack at the sulfenyl sulfur atom to give vic-disulfoxides; rearrangement to O,Ssulfenyl sulfinate. Rearrangement to thiosulfonate.

2.4. The isolation of new sulfinate ester 8 and a new compound 9, either the O,S-sulfenyl sulfinate or the vicdisulfoxide. The probable formation of 8 from 4 or 9 by a free radical chain mechanism In Section 2.2.1, the reaction of 5 and H2O2 in acetic acid solution is discussed, and generally, mixtures of the thiosul®nate 3 with other products are formed in a non-selective manner. In a signi®cantly different approach, the reaction medium is changed to ethyl acetate, in which oxidation reactions are not so fast as in HOAc. The reactants are 30% H2O2, 5 (mol 2.27:1) and HOAc. After 31 h at 27±458C, 5 remains unchanged. After 24 h at 538C, the mixture is sampled (sample A, evaporated and dried at 258C). The reaction mixture is then dried by a large amount of CaSO4 (peroxide is present, KI test). Liquid sample B is taken now, and not evaporated. GC of A and B are run after 1 month at 108C, and the GC/MS after 2 more months at ambient temperature (Table 3).10 Authentic samples of 3, 4 and 5 are also run to con®rm the identity of these substances. Sample B changes composition on standing (A and B are taken from the same reaction mixture). Sample A has 12.66% of 4, and this is 8.52% in sample B, while 8 increases from 1.69% in A to 7.49% in B. At the same

10

Samples are sent to the Analytical Research Laboratory of CibaGeigy Corp., Ardsley, NY. The analytical reports show the actual date on the print out in each case.

Scheme 6. Radical chain reaction for the formation of compound 8 from O,S-sulfinyl sulfenate (9) or the thiosulfonate 4.

time, 5 decreases from 77.1 to 73.76%. The changes in 4, 8 and 9 are nearly the same (in total) as the decrease in 5. Some oxidation of 5 may occur with peroxide in the sample B to give more 9 (or 4), which are converted into 8. Further, interconversion of 4 and 9 is proposed (in the alkyl compounds) by Freeman [22]. The substance 8 (at 11.69 min) is n-C6F13CH2CH2S(O)2CH2CH2C6F13. In GC/MS, the mol ion is m/e 758, and two fragment ions are, m/e 391 (C10H8F13O or C6F13CH2CH2OCH2CH2), and m/e 363 (C8H4F13O or C6F13CH2CH2O), with loss of CH2CH2. These fragments are not in the MS of 5. Cleavage of the m/e 363 fragment from 8 leaves the sul®nyl fragment, n-C6F13S(O) (FW 395), which occurs in the MS of 3. From this evidence, 8 is most likely the 2-(per¯uorohexyl)ethyl 2-(per¯uorohexyl)ethanesul®nate ester and not the sulfone. Scheme 6 gives a mechanism for the formation of 8 from either 4 or 9. In the initiation steps, a free radical, such as HO from H2O2, reacts with either 4 or 9 to displace C6F13CH2CH2SO2 (11) (found in the MS of 4). In propagation steps, 11 loses SO2 to generate RFCH2CH2 (12), and 12, in turn, displaces C6F13CH2CH2S (13) from 4 or 9 to give 8. The new radical C6F13CH2CH2S completes the cycle by reacting with 4 or 9 to give disul®de 5, which is already present in the mixture. Steps 6 and 7, which break the radical chain, give 8 and 5. Precedents for these steps are as follows: (1) Steps 2, 4 and 5 are similar those proposed by Block for a dialkyl thiosul®nate in Scheme 3 of [24]; (2) Step 3, C6F13CH2CH2SO2 !R ‡SO2, is ®rst disclosed by

N.O. Brace / Journal of Fluorine Chemistry 105 (2000) 11±23

17

Table 3 GC of samples A and B from hydrogen peroxidation of disulfide (5, C6) to thiosulfonate (4, C6), and new compounds 8 and 9a EtOAc

RF CH2 CH2 SSCH2 CH2 RF …5; C6† ‡ H2 O2 ! RF CH2 CH2 S…O†OSCH2 CH2 RF …9† ‡ …4† ‡ RF CH2 CH2 S…O†2 CH2 CH2 RF …8†

(4)

HOAc

Entry No.

1 2b 3 4 5b 6 7 8 9

GC retention time (min) Sample

Area (%) A

B

9.50 10.09 11.12 11.69 12.35 12.98 14.30 15.09 16.99

2.00 77.10 1.69 1.69 12.66 2.24 0.18 1.09 0.78

2.77 73.76 1.68 7.49 8.52 2.65 0.28 0.71 0.50

FW

Identity

± 758 ± 758 790 790 ± ± ±

Unknown 5 Unknown 8 4 9 Unknown Unknown Unknown

a Column and conditions: a 6 ft by 2 mm diameter glass column is packed with `OV-3' silicone resin loaded on 80±100 mesh `GC-Q'; the column is heated from 72 to 3008C, at 88C/min, with 25 ml/min of helium flow. b The retention times are the same as pure samples of 4 and 5 run independently; the GC/MS retention times are the same as with authentic samples.

Tiers [32];11 Steps 6 and 7 are often given in radical reactions [17,33]. From MS, substance 9 is an isomer of 4 with mol ion, m/e 790, and is either the O,S-sulfenyl sul®nate, nC6F13CH2CH2S(O)OSCH2CH2C6F13 or, the vic-disulfoxide, n-C6F13CH2CH2S(O)S(O)CH2CH2C6F13. The sul®nate is derived from the disulfoxide [22,25,31]. A fragment, C6F13CH2CH2SO2 (11), m/e 411, could be from either compound, but more probably from the O,S-sulfenyl sul®nate. The vic-disulfoxide should give two sul®nyl fragments, m/e 395, not found [23,24]. Only at ca. ÿ408C is the vic-disulfoxide of a bis-alkyl disul®de or the O,S-sulfenyl sul®nate observed by NMR, and these structures are not eluted by GC [23,25]. It seems unlikely that per¯uoroalkyl-segmented 9 would survive in solution a month at 108C, and longer at 258C. However, the evidence for 9 seems compelling and further investigation of these results appears warranted. 2.4.1. Oxidation of 5 with hydrogen peroxide in acetic acid solution; conversion to 4, 2 and 6 The experiment above is carried out with the same reactants (moles H2O2:5: 2.27), and conditions, except acetic acid is used as solvent. In 1 h at 438C the 5 is substantially converted to 4, and in 4 h, the conversion is 45% to pure 4, and 55% to 3, 5 and a mixture of sul®nic acid 2 (decolorizes KMnO4) and sulfonic acid 6. The acids are converted to sodium salts of 2 and 6 (96% recovery; 43.7% calculated as 6). The pure sodium salt 6 is recrystallized from ethanol and characterized by FAB/MS [3]. Thus, over oxidation occurs in acetic acid solution to give a wide range of products. 11 In hydocarbons, such as n-heptane, the n CH (asym) of CH2 is at 2926 cmÿ1 and the n (sym) CH2 stretching vibration is at 2653 cmÿ1 [34].

2.5. Spectroscopy of segmented perfluoroalkyl sulfur compounds 2.5.1. NMR, mass and IR spectoscopy In NMR, the large RF groups of 3, 4 and 5 reduce the complexity of the 1 H and 13 C NMR spectra. There are few 1 H nuclei in these compounds. Since 13 C NMR chemical shifts of C1 to C4 (Table 4) are distinctly greater than 1 H NMR, identi®cation and determination of amounts of 3, 4 or 5 is more easily done with 13 C NMR. Because of symmetry, 5 has only two sets of different signals, but in 3 and 4, the 13 C resonances of C1 to C4 are unique. The chemical shift for C2 in both 3 and 4 is the greatest in the series. Mass spectra analysis is given in previous sections, and in the Section 3 for 3, 4 and 5 and for 8 and 9. MS of 5 differs in having CF3CF2CF2, CF3CF2 and CF3 fragments, and only a minor amount of the C6F13CH2CH2S, fragment from cleavage of the SS linkage. 2.5.2. IR spectroscopy; correlation of asymmetric and symmetric vibrations of methylene groups with 1H and 13 C NMR [3]. Diagnosis of disulfide 5, thiosulfinate 3 and thiosulfonate 4 The effects of the combined RF and the sulfur functional group on the n CH2 stretching vibrations of 3, 4, and 5 are noteworthy (Table 5). The frequency and intensity of the n CH (asym) and (sym) indicate the position of the a and b CH2 groups, and the strong (ÿI) effects of the RF and the SO2 groups are clearly evident. The n CH2 (asym) of C2 in 3 and 4 (Table 5) are 2980 and 3000 cmÿ1, respectively, and well above 5 at 2845 cmÿ1. These results correlate with the chemical shifts in the NMR of 3 to 5 (Table 4). The n CH2(asym) of C2 in 6 (sulfonic acid) shows the (ÿI) of the SO3 group gives the highest n CH in the series of Table 5.

18

N.O. Brace / Journal of Fluorine Chemistry 105 (2000) 11±23

Table 4 1 H, 13 C, and 1

19

2

F NMR spectra parameters of thiosulfinate 3, thiosulfonate 4 and disulfide 5a 3

4

1

RF CH2 CH2 SSCH2 CH2 RF …5† Entry

Code

2

5 3 4 4

19

F NMR chemical shifts 3 5e 6e

4

4

Chemical shift (d or ppm)b

n

1

1 2 3c 4d

3

RF CH3 CH3 S…O†n SCH2 CH2 RF …3; 4†

± 1 2 2 6

5ÿ3

13

H chemical shift

C chemical shift

d, H1

d, H2

d, H3

d, H4

C1

C2

C3

C4

2.57 2.68 2.65 2.68

2.91 3.42 3.53 3.60

2.91 3.42 3.33 3.40

2.57 2.68 2.65 2.68

30.9 t 24.5 t 25.7 tc 27.05 t

27.7 s 46.1 s 53.7 s 54.65 s

27.7 s 23.3 s 26.1 s 26.65 t

30.9 t 32.5 t 31.7 t 32.65 t

2

1

m m m m

m m t td

10

20

m m tc td 3ÿ50

m m m m

60

CF3 …CF2 †CF2 CF2 CH2 CH2 S…O†SCH2 CH2 CF2 CF2 …CF2 †3 CF3 6, 5.10; 5±3, 46.1±47.1; 2, 47.3; 1, 37.5. 10 , 38.5; 20 , 47.6; 3±50 , 46.1±47.2; 60 , 5.10 CF3(CF2)3CF2CF2CH2CH2S(O)2SCH2CH2CF2CF2(CF2)3CF3 6, 5.28; 5±3, 47.9±46.9; 2, 47.3; 1, 37.1. 10 , 38.1; 20 , 47.6; 3±50 , 46.1±47.2; 60 , 5.28

a

Compounds 3, 4 and 5 are pure substances; NMR spectra are run at the Analytical Research Laboratory, Ciba-Geigy Corp., Ardsley, N.Y. Samples are run in DCCl3 at ambient temperature; the reference substance for 13 C NMR is ``DSS'', 2,2-dimethyldisilylpentane sulfonate. c The C6 compound; the signals at d3.33 and 25.7 ppm show fine splitting; the singlets are broadened. d The C8 compound is run at 1208C; the signals at d3.40, d3.60, d26.65 and d27.05 ppm show fine splitting; the singlet at 54.65 ppm is broadened. e Samples are run in DCCl3; the reference substance for 19 F NMR is CF3COOH; chemical shifts are given downfield and the minus sign is omitted. b

2.5.3. The carbon±fluorine (n CF) and the n S=O frequencies in 3, 4 and 5 identify the compound The well known IR correlation of the n S=O in RS(O)R or RSO3R should not apply to 3, 4, and 5, since the n S=O (sym) in SO2 or S(O) are coincident with the n CF (asym) and (sym) of CF3 and CF2 in per¯uorocarbons [34±36]. For cystine (‡/ÿ)S-oxide (thiosul®nate diastereomers), n S=O is 1060 or 1078 cmÿ1, and in the cystine dioxide (thiosulfonate), the n S=O (sym) of SO2 is 1120 cmÿ1 [37]. The n S=O (sym) of alkyl thiosulfonates range from 1154 to 1144 cmÿ1, and the n SO2 (asym) frequencies are from 1342 to 1331 cmÿ1 [38]. The n CF (asym) of CF3 and CF2 are 1350±1200 cmÿ1, and the n CF(sym) range from 1200 to 1080 cmÿ1 [34±36]. Thus, in 3, n S=O is at 1065 cmÿ1, and in 4, the n S=O (sym) of SO2 is higher, at 1085 cmÿ1. The problem may be resolved with recourse to a method of Bellamy and Williams [40]. The n S=O (asym) and the n S=O (sym)12 frequencies of the group R1R2SO2 are in relation to each other, and the more electronegative the R group, the stronger the S=O bond, and hence, the higher the frequency. For 3, n S=O(asym)/n S=O(sym)ˆ1065/ 1370ˆ0.78, and it is the same (‡/ÿ0.01) for the series 2, 3, 6 and 11. In 4, the n S=O (sym) vibration of SO2 at 1085 cmÿ1 may be coincident with a n CF(sym) vibration. Then, this ratio for 4 is 0.79, consistent with the related compounds. Similar sets of IR vibrations (and others) are found in the spectra of the segmented disul®de 5 and thiocyanate 7, as given in Table 6. Bands at 1365 and 1335 cmÿ1 in 5, and at 1365 and 1320 cmÿ1 in 7 are attributed to the CF3 group [34,36], and the heavy absorption from 1300±1120 cmÿ1 in 12 The n S=O (sym) frequencies are at 1190±1135 cmÿ1 in 97 sulfuryl compounds of different types [38].

5 and 7 is due to CF2 [36]. Sharp bands at 1080 and 1035 cmÿ1 in 5, or at 1100 and 1080 cmÿ1 in 7 are in the region given for n CF(sym) vibrations of the CF3 and the CF2 moieties [36]. Since there is no sulfuryl group in 5 or 7, they must be CF vibrations. The 1065 cmÿ1 band in salt 2, at 1060 cmÿ1 in 3 and in salts 6 and 10 (Table 6), is the n S=O (sym) band, and it is not present in 5 or 7. 2.6. Important uses for the perfluoroalkyl segmented compounds of this study The disul®de 5 (C6 and C8) exhibits superior friction reducing properties on sliding surfaces [6] and this behavior may other uses as well. In unpublished work, the free radical addition of 5 to 1,6-dienes, with cyclization, occurs readily under de®ned conditions [41]. This process affords the bisadducts having two segmented per¯uoroalkyl chains attached to the ring, and such structures are of interest in the ®eld of surface activity and surface modi®cation. Reaction of 3 (C6) with acrylic acid as in [23] gives a crystalline product, with an IR consistent with the expected RFCH2CH2S(O)CH2CH2CO2H. Treating 4 with a strong base or nucleophile affords RFCH2CH2S(O)OH (2) in excellent yield [3]. Many possibilities for new chemistry may be found in the published work on thiosul®nates and thiosulfonates [16,17,22±24]. 3. Experimental section 3.1. Source of materials and physical methods The preparation and properties of segmented thiols 1 are reported [1,2]. Molecular Sieves (mol sieves) are used for

N.O. Brace / Journal of Fluorine Chemistry 105 (2000) 11±23

19

Table 5 Infrared spectra parameters of sodium and tetrabutylammonium sulfinate 2, thiosulfinate 3, thiosulfonate 4, disulfide 5, and sodium sulfonate 6a 1

2

3

4

…5† RF CH2 CH2 SSCH2 CH2 RF Entry No. b

1 2c 3d 4e 5f 6

Compound 5 2 2 3 4 6g

1

2

1

2

3

4

…2; 6† RF CH2 CH2 S…X† salt …3; 4† RF CH2 CH2 S…O†n SCH2 CH2 RF

Asymmetric and symmetric methylene stretching vibrations of listed methylene groups in X, n

Salt

C1 (asym)

C1 (sym)

C2 (asym)

C2 (sym)

C3 (asym)

C3 (sym)

C4 (asym)

C4 (sym)

± O2 O2 O, 1 O, 2 O3

± Na Bu4N ± ± Na

2960 2960 2960 2980 2980 2980

2920 2920 2920 2920 2920 2960

2920 2920 2920 2980 3000 3020

2845 2845 2870 2920 2920 2960

2920 ± ± 2960 2980 ±

2845 ± ± 2920 2920 ±

2960 ± ± 2960 2960 ±

2920 ± ± 2920 2920 ±

a Spectra are run in CCl4 solution or slurry on KBr plates, on a grating spectrophotometer at 258C; the samples used are analytically pure and checked by NMR, TLC and elemental analysis; also by MS in some cases. b The disulfide 5, RFˆC8.; mp 808C; n CH absorptions are: 2960, 2920, 2845 cmÿ1 in a ratio of 2:3:1, approximately. c The compound 2 is RFCH2CH2SO2Na, RFˆC6; n CH absorptions are: 2960, 2920 and 2845 cmÿ1 in a ratio of 3:4:2, approximately. d RFˆC6; see [3]; the compound is RFCH2CH2S(O)OÿBu4N‡, 99.6% pure substance. e The thiosulfinate 3, RFˆC6, recrystallized, mp 85±868C, pure 3, NMR, CHFS; n CH absorptions are: 2980, 2960,and 2920 cmÿ1 in a ratio of 1:1:1, approximately. f The compound 6 is RFCH2CH2SO3Na, RFˆC6 [3]; n CH absorptions are: 3015, 3005, 2980 and 2960 cmÿ1 in a ratio of 1:1:2, approximately; see Table 6 for preparation and complete listing of IR of these compounds. g The thiosulfonate 4, C6; (mp 114±115.58C); n CH absorptions are: 3000, 2980, 2950 and 2920 cmÿ1 in a ratio of 1:1:1:2, approximately; in another pure sample, n CH absorptions 3000, 2980, 2950 and 2920 cmÿ1 are in a ratio of 2:2:1:4, approximately.

Table 6 IR absorption bands for thiosulfinate 3, thiosulfonate 4, disulfide 5 and related compoundsa IR (RFCH2CH2SO2Na, monohydrate, 2, C6; Nujol mull, or CCl4 slurry) IR (3, C6; CCl4 slurry) IR (4, C6; CCl4 slurry)

IR (5, C6 or C8, CCl4) IR RFCH2CH2SO3Na, monohydrate, 6; C6, CCl4 slurry or Nujol mull, on KBr platesd IR RFCH2CH2SCN, 7 (C6), CCl4 slurry on KBr platese IR RFSO2Na; sodium n-perfluorooctanesulfinate 10 (C8, CCl4 slurry on KBr plates)f a

n OH, 3540, 3480; n CH 3020,b 2960, 2920, 2860; d CH 1440, 1420; n SO2 (asym) 1380; n CF (asym) 1300±1250; n CF (sym) 1140,1120, 1095, 1075; n S=O (sym) 1065, 1050, 1020; bands at 970, 910, 820, 810, 780, 750, 730, 700, 685; n C±S 655; n CH2±S, 540 (s); 470 and 390 (vs) cmÿ1 n CH, 2980, 2920; d CH 1440, 1420; n CF (asym) 1360, 1330, 1280±1150; n CF (sym) 1140, 1120; n S=O 1065; bands at 950, 920 (CCl4 820±730) 705; nC±S 640, 600; n CH2±S, 560, 530; 490 and 430 cmÿ1 n CH 3000, 2980, 2960, 2920; d CH 1440, 1410, 1400 (d); n S=O (asym), 1370; n CF (asym) 1320,1300,1250±1200; n CF (asym) 1140, 1120; nS=O (sym) 1085 (vs); bands at 1040 (w), 950 (vs), 920 (CCl4 820±730) 710, 700, 690; n C±S 640; n CH2± S 550 (vs); 490 (vs) cmÿ1c n CH 2960, 2920, 2845; d CH 1440, 1420; n CF (asym) 1365, 1320, 1280±1200; n CF (sym), 1140, 1120, 1080; bands at 1030, 950 (vs), 920, 835, (CCl4 800±730), 790, 760, 750, 740, 710, 700; nC±S 660, 640; n CH2±S 560 and 530 cmÿ1 Bonded n OH, 3600±3200 (vs); n CH 3015, 2980, 2960; d CH 1450, 1430; n SO2 (asym)1370,1360 (d); n CF (asym) 1330±1250; n CF (asym), 1140, 1120, 1095; n S=O (sym), 1070, 1060; bands at 965 and 910; 820 (810±720, CCl4), 780, 750, 730, 710, 700, n C±S 660, 650 (d), 620, 590, n CH2±S 550, 530, 480 and 400 cmÿ1. No n OH; n CH 3010, 2960, 2920, 2845; d CN, 2080; d CH 1440, 1365; n CF (asym) 1300, 1280±1200 (vs); n CF (asym)1140, 1120, 1100, 1080; bands at 1020, 965, 920, 840, (CCl4 800±730), 710; n C±S 645 (d), n CH2±S 560 and 530 cmÿ1 Bonded n OH, 3700±3400; n SO2 (asym) 1380, 1340; n CF (asym)1330±1180; n CF (asym)1150, 1140, 1120, 1090; n SO2 (sym) 1060, 1040 (w); bands at 935 (810± 720, CCl4) 710, 650 and 600 cmÿ1

Assignments are based on correlations of hydrocarbon and fluorocarbon compounds in references [34±40]; see also [3]. This vibration is found in RFCH2CH2SO3Na monohydrate (6) and not in RFCH2CH2SO2H, or in other samples of sodium salt 2; thus, this higher frequency vibration may be derived from impurity of 6 in the sample of 2. c The C6 homologue of 4 has a band at 915 cmÿ1, and one band at 645 cmÿ1; the C8 homologue has no band at 915 cmÿ1 and a doublet centered at 655 cmÿ1. d Sodium sulfonate 6 is prepared from RFCH2CH2I and Na2SO3 as a pure substance and its NMR spectra cannot be distinguished from sodium salt 2 [3]; the identity of 2 and 6 are determined by FAB/MS [3]. e RFCH2CH2SCN (C6) 7 is prepared by phase transfer reaction of RFCH2CH2I and KSCN as a pure substance [5,41]. f RFSO2Na; sodium n-perfluorooctanesulfinate (C8) 10 is prepared from RFI and sodium hydrosulfite [3]; with no CH bonds, the bands at 930 and 710 cmÿ1 are probably derived from CF vibrations [36]. b

20

N.O. Brace / Journal of Fluorine Chemistry 105 (2000) 11±23

drying. Solutions are evaporated (evaporated) by rotary evaporator when possible. However, this often causes too much foaming because of surface activity of salt 2. 1,1,2Trichloro-1,2,2-tri¯uoroethane (`F-113') is used as a solvent. 2,2-Dimethyldisilylpentane sulfonate (DDS) is used as reference in D2O solution for NMR. Elemental analysis, NMR (by Dr. Ronald Rodebaugh) and MS are performed at the Central Research Laboratory, Analytical Research Division of Ciba-Geigy Corporation, Ardsley, NY 10502. MS and GC/Ms are done by spectroscopists Mr. Kenneth Ng and Mr. Charles Shimanski. 3.2. bis-[2(Perfluorohexyl)ethyl] disulfide (5) by oxidation of (C6) thiol 1 with alkaline hydrogen peroxide in ethanol; IR, MS and NMR Thiol 1 (96.4% C6 by GC; 76.95 g, 194.3 mmol), NaOH (1.5 ml, 10% aq. solution; 0.15 g, 3.75 mmol) and ethanol (100 ml, 95%) is stirred by magnet bar at 508C in a constant temperature bath, while hydrogen peroxide (14.11 g, 124 mmol, 30% aq. solution; mol H2O2:1ˆ0.673) is added during 45 min at 47±628C (exotherm). In 10 min an exotherm occurs. The cloudy mixture is stirred for 16 h at 518C, and stands for 48 h at 258C. Water (100 ml) is used to break up and wash the solid 5. Air-dried 5 weighs 74.07 g (100% yield), mp 39±408C (lit. [5,6] 418C). TLC, a single spot. GC: unknowns of 0.762 and 0.210%; 5 (C6) 97.88% and 5 (C8), 1.057%. IR, see Tables 5 and 6. For 1 H NMR and 13 C NMR, see Table 4. MS (EI) gives mol ion‡2, m/ e760 (0.12), mol ion‡1, m/e 759; 5 mol ion, m/e 758 (1.00), also as base ion; 5, less one F atom, m/e 739; C6F13CH2CH2SSCH2, m/e 425 (0.15), 5, less the CH2C6F13 fragment); C6F13CH2CH2S±S, m/e 411 (0.13), 5, less CH2CH2C6F13; C6F13CH2CH2S, m/zˆ378 (0.08);CF3CF2CF2, m/e 169 (0.03); CF3CF2, m/e 119 (0.06); CH2S=S, m/z 78 (0.14); CF3H, m/e 70 (0.32). This last fragment is the next largest to 5, itself. The RF group is fragmented as these data show; however, the cleavage of 5 at the S±S linkage is surprisingly small. 3.3. Disulfide (5) by oxidation of (C6) thiol 1 with alkaline hydrogen peroxide in ethanol. Isolation of sodium 2(perfluorohexyl)ethanesulfinate (C6 2) as by-product As above, thiol 1 (96.4% C6, by GC; 81.14 g, 213. 4 mmol), NaOH (1.5 ml, 10% aq. solution; 0.15 g, 3.75 mmol) and ethanol (100 ml, 95%) is stirred at 508C in a constant temperature bath, while hydrogen peroxide (17.00 g, 134.6 mmol, 15.5 ml of 30% aq. solution; mol peroxide:1ˆ0.6307) is added dropwise. Two immiscible layers form in 40 min, and an exotherm to 708C occurs. In 5 min, at 758C, the ¯ask is cooled and after 10 min, at 358C, heating is resumed. The remaining peroxide is added (10 min) to the clear liquid layers, and stirring is continued for 20 h at 508C. The product mixture is worked up as above.

The solid, dried in air for three days weighs 76.56 g (94.56% yield of 5), mp 38.2±39.08C. The aqueous ®ltrate is evaporated off and deposits white sodium sul®nate 2 (C6), 2.29 g, (5.066 mmol, 2.37% yield, on 1); mp, >1408C. IR: C6 2, identi®ed by FB/MS [3]. Impure salt 2 (0.85 g of shiny ¯akes) is collected from the ®ltrate. 3.4. Non-oxidation of C6 thiol 1 by hydrogen peroxide in ethanol without NaOH. The reaction is catalyzed by added base As above, C6 thiol 1 (21.13 g, 55.6 mmol) and 95% ethanol (25 ml) is stirred at 28±338C, while 30% hydrogen peroxide (3.51 g, 27.8 mmol) is added during 10 min. No exotherm occurs, and two liquid layers form. After 2 or 24 h at 348C, a sample tests positive for peroxide and is acidic. Accordingly, 10 drops of 5% NaOH solution is added at 358C, and an exotherm to 398C occurs. After 24 h, the solid product is washed with water and dried; 19.84 g, mp 37± 388C; yield of 5 is 99.3%. MS: pure 5. 3.5. Oxidation of C6 thiol(1) at 418C to disulfide 5 and thiosulfonate 4 by hydrogen peroxide in acetic acid and ethyl acetate solution Thiol 1 (C6, 76.93 g, 202 mmol) in ethyl acetate (100 ml) containing acetic acid (6.00 g, 100 mmol) is stirred at 418C while 27% hydrogen peroxide (13.17 g, 104 mmol; moles HOOH:1ˆ0.5) is added during 5.5 h. to give a clear, colorless mixture. Thiol (C6) 1 remains unreacted after 5.5 and 29 h. Hydrogen peroxide (1.00 g, 7.9 mmol) is added after 35 h and 53 h, and (3.00 g, 23.7 mmol) after 79 h (total HOOH:1ˆ0.71). Heating is continued until 96 h have elapsed. A sample melts at 43±858C, and is, therefore, a mixture of products. The solvent is stripped by rotary evaporator (1 h, to 558C/12 mm), and the solid±liquid mixture, 76.33 g (ca. 100% recovery), is melted to a liquid, and sampled. GC: C6 5, 85.47%; C6 thiosulfonate 4, 11.43%; and unknown substances of 0.57, 1.28, 0.62 and 0.62%. The 1 H NMR in CDCl3 indicates a ratio of 7 mol of 5 to 4. 3.6. Typical procedure. S-2-(Perfluorohexyl)ethyl 2(perfluorohexyl)ethanethiosulfinate 3 (C6) by oxidation of disulfide 5 with 35% peroxyacetic acid in dichloromethane; MS and NMR (Table 1, entry 4, also 1±3) Disul®de C6 5 (7.62 g, 10.0 mmol) is dissolved in 80 ml of chloroform and cooled to 38C by an ice-salt bath. The slurry is stirred by magnet bar while 35% peroxyacetic acid (1.92 g, 10.10 mmol) in chloroform (20 ml, a cloudy mixture), is added during 45 min at 38C (bath is at 08C). A needle-®tted stopcock is used in the dropping funnel. In a further 15 min the white slurry dissolves and the mixture warms to 228C during 3.5 h. The clear solution is dried over mol seives and a sample is evaporated to C6 3, mp (sinter

N.O. Brace / Journal of Fluorine Chemistry 105 (2000) 11±23

758C) 79±818C. IR (C6 3, CCl4 slurry), Tables 5 and 6. The solution is shaken with 5% NaHCO3, which gives a foamy aqueous layer. The chloroform layer is dried over CaSO4, and stripped (rotary evaporator) at 12 mm pressure and 258C, to give 3, 7.30 g, 97% yield; mp 79±808C (clear liquid melt) when heated rapidly; or mp (sinter 768C) 77± 808C, heated at less than 18C/min. TLC (silica gel plates F254, using dichloromethane/heptane (70/30) as mobile phase, and iodine or chlorine/starch with KI for detection, gives a weak spot for 5, an unknown weak spot and a strong spot for 3. NMR (see below, and Table 4) shows 77% of 3 and 23% of 5. Recrystallized (1.0 g) from benzene solution (15 ml) at 408C. no more than 5 min, cooled to 258C, ®ltered and rinsed with ligroine (bp 60±708C) gives 3; wt, 0.41 g, mp 85±868C; 3, 0.18 g, mp 84±85.58C, and 3, 0.20 g, mp (sinter 838C) 85.0±85.58C. A total 79% recovery of pure 3. For 1 H NMR, 13 C and 19 F NMR, see Table 4. MS (EI) of 3 gives the mol ion of m/e 774 (0.04); HSS(O)H, m/e 82 (1.00), base peak; 3 less one F atom, m/e 755 (0.08); C6F13CH2CH2S(O)SH, m/e 428 (0.17), and C6F13CH2CH2S(O)S, m/e 427 (0.46); C6F13CH2CH2S(O), m/e 395 (0.15); and SCH2CH2C6F13, m/e 379 (0.50). A fragment, C4F9CH2CH2S(O)S, m/e 327 (0.20) is probably derived from m/e 427, by expulsion of CF2=CF2. The base peak or mol ion of 5 does not appear in this spectrum. Anal. Calc. for C16H8F26OS2: C, 24.8; H, 1.0; F, 63.8; S, 8.3. Found: C, 24.5; H, 1.0; F, 62.7; S, 8.5. Found (recrystallized, mp 85± 868C): C, 24.4; H, 1.0; F, 65.3; S,. 8.5. 3.7. Thiosulfinate C8 3 by oxidation of disulfide 5 with 35% peroxyacetic acid in chloroform (Table 1, entries 6, 7) Disul®de 5 (C8, 10.0 g, 10.4 mmol) and chloroform (75 ml) is stirred by a paddle stirrer at 2±58C in an ice-salt bath, while 35% peroxyacetic acid (1.98 g, 10.4 mmol; total `O'ˆ13.2 mmol; 0.104 M) in chloroform (25 ml) is added dropwise during 1.3 h. The white slurry is stirred at 38C for two h, and becomes thicker on warming to 218C for 16 h. The solid 3 is ®ltered, rinsed twice with chloroform, dried in air; the weight is 9.31 g, mp (sinter 1068C) 106± 1228C. NMR, 90% of 3 and 10% of unreacted 5. The ®ltrate is evapd (rotary evaporator) to impure 3, 0.65 g. The ¯ask is cleaned with hot acetone, and evaporated to solid, 0.95 g. Total recovery 100%. A 3.00 g-sample is recrystallized from benzene (60 ml) and acetone (40 ml) at 508C, and the clear solution is quickly cooled to 208C. Pure C8 3, 2.47 g, mp (sinter 1208C) 122±1248C (82.3% recovery) is obtained. NMR shows only 3. For IR see Tables 5 and 6; and for NMR see Table 4. When the reaction above is repeated, using 60 ml of chloroform (peroxy acetic acid, 0.213 M) and stirring by magnet bar, the yield (recovery)of 3 is 84.5.5%; mp (sinter 1088C) 110±1268C. NMR: 85% of 3 and 15% of 5. Part of 3 is lost when the rotary evaporator foamed over. Anal. Calc. for C20H8F34OS2: C, 24.6; H, 0.83; F, 66.3; S, 6.6. Found: C, 24.5; H, 0.9, F, 66.1; S, 6.9.

21

3.8. Typical procedure. Preparation of C6 thiosulfonate 4 by oxidation of thiosulfinate 3 with sodium metaperiodate; Table 2, entry 1; NMR and MS data Thiosul®nate 3 (C6, 0.8498 g; 1.097 mmol, recrystallized, mp 82±83.18C) is dissolved in acetic acid (7.0 ml) at 258C, while stirring with a magnet bar. Acetonitrile (5 ml) and three drops of 12 M HCl (aq.) are added, and the ¯ask is immersed in a constant temperature bath at 308C. A solution of sodium metaperiodate (0.2338 g, 1.093 mmol) in 2.0 ml of water is added in 10 drop portions. The ®rst addition causes the mixture to turn yellow in color and to become too thick to stir. The bath temperature is raised to 35.08C and stirring resumed. Over a 7 min-period, periodate is added three times, and stirring is continued for a half h, to give a yellow, pasty mixture. Water (40 ml) and 5% aqueous sodium bisul®te (aq.) are added and the solid is collected by ®ltration. The solid 4 is dried (air and vacuum oven) at 458C for 18 h, and weighs 0.761 g (87.8% yield); mp 113± 114.58C. GC, 4, 98.6%; 5, 0.44%. More complete 13 C NMR assignments are as follows: C1, 25.7 ppm, t, from long range 19 F coupling; C3, 26.1 ppm s, broadened; C4, 31.7 ppm, t, from long range 19 F coupling; C2 53.7, s, broadened. MS (EI): 4, mol ion plus H, m/e 791 (0.18); 4, mol ion, m/e 790 (0.42); 4 with loss of F, m/e 771 (0.48); 5, mol ion, m/e 758 (0.015); C6F13CH2CH2SO2SCH2, m/e 457 (0.24); C6F13CH2CH2SO2 2H‡, m/e 413 (1.00) the base peak, and C6F13CH2CH2SH‡, m/e 380 (0.99); C4F9CH2CH2S(O)S, m/e 327 (0.99), this is probably derived from m/e 427, with loss of CF2ˆCF2(see Section 3.7); H2CS2‡, m/e 78 (0.75), and HSSH, m/e 66 (0.98). Anal. Calc. for C16H8F26O2S2: C, 24.3; H, 1.0; F, 62.5; S, 8.1. Found: C, 24.4; H, 0.63; F, 64.2; S, 8.5. 3.9. Metaperiodate oxidation of C8 thiosulfinate 3 to thiosulfonate 4 (Table 2, entry 2). NMR data Thiosul®nate 3 (C8, 0.9804 g, 1.00 mmol, mp (sinter 1038C) 106±1228C, contains ca. 10% of 5 (NMR and TLC) is stirred in a constant temperature bath at 328C by magnet bar while acetic acid (12.5 ml) and acetonitrile (5 ml) are added, followed by 10 drops of NaIO4 solution (0.2691 g, 1.258 mmol in 2.00 ml of water) at 328C. An exotherm to 358C occurs, a slight yellow color appears brie¯y, and the slurry becomes homogeneous. During the next 8 min, the remaining NaIO4 solution is added, and 4 begins to precipitate. After stirring the light orange slurry for one h at 338C, water (40 ml) and sodium bisul®te solution (5%, 5 ml) are added. The solid 4 is ®ltered, washed with water and air-dried. After drying in a vacuum oven at 458C for 18 h, the 4 (0.9444 g, 96.3% recovery, 94.8% yield as 4) has mp (sinter 1388C) 140±1428C. When heated further to 1728C some gas evolves, and at 2028C, decomposes. IR, the same as C6 homologue. 1 H NMR and 13 C NMR (taken in C2D2Cl4 solution at 1208C) gives slightly shifted signals relative to the C6F13 homologue in DCCl3 solution (see

22

N.O. Brace / Journal of Fluorine Chemistry 105 (2000) 11±23

Table 4); 5 and the C8 sodium sulfonate 6 are absent. TLC shows no detectable sodium sul®nate 2, no 3 and a trace of 5. The 4 is recrystallized (twice) from acetone, mp 145± 145.28C and mp 145±1468C. Anal. Calc. for C20H8F34O2S2: C, 24.3; H, 0.81; F, 65.2; S, 6.5. Found: C, 24.1; H, 0.8; F, 65.2; S, 6.9. 3.10. Oxidation of thiosulfinate 3 (C8) to thiosulfonate 4 (C8) by peroxyacetic acid in acetic acid solution with HCl catalysis Thiosul®nate 3 (C8, 0.9771 g, 0.903 mmol, contains 0.10 mmol of 5, Table 1, entry 6), acetic acid (20 ml) and hydrochloric acid (three drops, 12 M) is stirred at 358C, while peroxyacetic acid (0.1905 g, 1.10 mmol, 35% solution) is added dropwise during 2 min. There is no change in appearance or a noticeable exotherm. After 3 or 5 h, reaction is incomplete. After 14 h, solvent is evaporated off at 258C (bad foaming on a rotary evaporator), weight of impure 4, 0.93 g (95% mass recovery); mp (sinter 1368C) 138±1448C (cloudy). The 1 H NMR shows excess peaking at d 2.39. After washing with water to remove soluble sul®nic acid 2 and sulfonic acid 6, and air drying, the solid weighs 0.72 g (72% yield), mp (sinter 1428C) 144±1458C (i.e. nearly pure 4); NMR con®rms product identity. There is about 10% of 5 present. 3.11. Oxidation of C6 disulfide 5 to thiosulfonate 4 and isomers by hydrogen peroxide in ethyl acetate solution. Isolation and identification of new compounds 8 and 9 by GC/MS Disul®de 5 (C6) (10.0 g, 13.2 mmol; 0.21 M; mp 39± 418C), ethyl acetate (50 ml) and acetic acid (3.00 g, 50.0 mmol; 0.81 M) is stirred by magnet bar in a constant temperature bath at 418C. Hydrogen peroxide (1.02 g, 30.0 mmol, 3.41 g of 30% aq. solution; 0.49 M; moles H2O2:5ˆ2.27; moles HOAc:H2O2ˆ1.67) is added all at once to give a clear, colorless solution. In 1.5 h at 418C, after 24 h at 278C, and after 5.5 h at 538C, 5 is unchanged (IR, only 5 bands, no 3 or 5; mp 38±398C). In 19 h at 538C, a KI test is positive for peroxide, and a sample A is evaporated off to solid, mp (s 368C) 42±858C; IR shows bands for 5, and for 4, not in 5 at 2980, 2940, 1400 and 490 cmÿ1. The sample A is kept in a closed vial. The reaction mixture is dried by a large amount of CaSO4 (Drierite), the solid CaSO4 washed with ethyl acetate three times, and the combined liquid (54.2 g) kept in a tightly closed bottle. A sample B is removed, and samples A and B, and the product mixture are stored at 108C. The samples are sent away for analysis. GC is run a month later. GC results are listed in Table 3. The amount of 4 and 8 are different in the two samples. Since peroxide remains in sample B, some of 5 is oxidized to the other compounds, and some of 4 is converted to 8, as well. Sample B: peak A, 73.76% of 5; peak B, 7.488% of a new substance 8; peak C, 8.52% of 4; peak D, 2.65% of 9, an

isomer of 4; other unknown substances are present in 0.3± 3% amount. Sample B is also analyzed by capillary GC/MS (EI and CI MS, using isobutane as carrier). Peak A (73.8%) is 5; peak B (7.49%) is C6F13SO2CH2CH2C6F13 (8) by mol ion, m/e 758. The two fragment ions are m/e 391 (C10H8OF13 or C6F13CH2CH2OCH2CH2), and m/e 363 (C8H4OF13 or C6F13CH2CH2O), which result from the loss of CH2CH2 and S, or CH2CH2S. Peak C (8.52%) is 4, mol ion m/e 790; the base peak, m/e 413, C6F13CH2CH2S(O)2 2H. The other major fragments are m/e 771, with loss of F from 4; m/e 726, loss of SO2; m/e 707, from loss of F and SO2; m/e 380, the fragment C6F13CH2CH2SH‡; and, m/e 327, of unknown composition (see also Section 3.9 and [3]). Peak D (2.65%) is 9, an isomer of 4, with m/e 790 as in 4. A fragment, m/e 411 may indicate C6F13CH2CH2SO2‡, from C6F13CH2CH2S(O)OSCH2CH2C6F13 or possibly the vicdisulfoxide, C6F13CH2CH2S(O)S(O)CH2CH2C6F13. 3.12. Oxidation of 2-(perfluorooctyl)ethanethiol 1 to (C8) disulfide 5 with dimethyl sulfoxide [15,16] Thiol 1 (C8; 91.04 g, 183 mmol, 96.5% pure, by GC), dimethylsulfoxide (78.1 g, 1.00 mol), HCl (1.48 ml, 12 molar, 14.2 mmol) and one crystal of iodine in a 500 ml ¯ask is stirred by paddle stirrer under a re¯ux condenser, and heated in a constant temperature bath at 788C. After 17 min, an exotherm carries the temperature to 858C. The cloudy mixture is quickly cooled with cold water. After 10 min at 85±89±808C, the heating bath is returned in place under the ¯ask. After 70 min of total reaction time, the mixture is poured into water (500 ml) and washed twice with water (500 ml) on a Buchner funnel. The white solid 5 (C8) is air dried for 2 days, but retains the garlic odor of (CH3)2S. The solid weighs 87.8 g, 99.7% yield, mp (sinter 788C) 80.5± 81.58C.

References [1] N.O. Brace, J. Fluor. Chem. 69 (1993) 217. [2] N.O Brace, US Patent 3,172,910, March 1965; Chem. Abstr. 63 (1965) 5030. [3] N.O. Brace, J. Fluor. Chem. 102 (2000) 21. [4] W.S. Friedlander, US Patent 3,088,849, May 1963. [5] L. Folletier, J.-P. Lalu, A. Lantz, British Patent 1,384,491 or German Offen. 2,304,000; Chem. Abstr. 80 (1974) 95255. [6] A. Karydas, US Patent 5, 547,594, August 1996. [7] D.K. Ray-Chadhuri, C.P. Iovine, US Patent 3,820,939 (1974); RF(CH2)mSO3H and salts. [8] T. Kawamura, M. Ohshima, E. Kamayama, Nippon Kagaku Kaishi, 3 (1974) 545; Chem. Abstr. 80 (1974) 14323u. [9] N.O. Brace, J. Fluor. Chem. 93 (1999) 1±25; Review, Part I. [10] N.O. Brace, J. Fluor. Chem. 96 (1999) 101±127; Review, Part II. [11] B.E. Smart, in: R.E. Banks, B.E. Smart, J.C. Tatlow (Eds.), Organofluorine Chemistry: Principles and Commercial Applications, Plenum Press, New York, 1994, pp. 57±58. [12] M.P. Krafft, J.G. Riess, Biochemie 80 (1998) 489±514. [13] S. Ohno, S. Oae, in: S. Oae (Ed.), Organic Chemistry of Sulfur, `Thiols', Plenum Press, New York, 1977, Chapter 4, pp. 155±157.

N.O. Brace / Journal of Fluorine Chemistry 105 (2000) 11±23 [14] L. Field, in: S. Oae (Ed.), Organic Chemistry of Sulfur, `Disulfides and Polysulfides', Plenum Press, New York, 1977, Chapter 7, pp. 303±382. [15] S.R. Sandler, W. Karo, Organic Functional Group Preparations, Academic Press, New York, 1968, p. 489. [16] O.G. Lowe, J. Org. Chem. 40 (1975) 2096. [17] M.A. Cremonini, L. Lunazzi, G. Placucci, J. Org. Chem. 58 (1993) 3805. [18] A.A. Oswald, T.J. Wallace, Anionic oxidation of thiols and cooxidation of thiols with olefins, in: N. Kharasch, C.Y. Meyers (Eds.), Organic Sulfur Compounds, Plenum Press, New York, 1977. [19] C.J.M. Stirling, The sulfinic acids and their derivatives, Intl. J. Sulfur Chem., Part B 6 (1977) 277±310. [20] H. Berger, Rec. Trav. Chim. Pays-Bas 82 (1963) 773. [21] F. Freeman, C.N. Angeletakis, J. Am. Chem. Soc. 105 (1983) 4239. [22] F. Freeman, Chem. Rev. 84 (1984) 117±135; vic-Disulfoxides and O,S-sulfenyl sulfinates. [23] E. Block, J. O'Connor, J. Am. Chem. Soc. 96 (1974) 3921. [24] E. Block, J. O'Connor, J. Am. Chem. Soc. 96 (1974) 3929. [25] R. Benassi, L.G. Fiandri, F. Taddei, J. Org. Chem. 62 (1997) 8018± 8023. [26] B. Plesnicar, in: S. Patai (Ed.), The Chemistry of Functional Groups Peroxides, Wiley, New York, 1983 (Chapter 17).

23

[27] R. Curci, J.O. Edwards, in: D. Swern (Ed.), Organic Peroxides, Vol. 1, Wiley, New York, 1970 (Chapter 4). [28] C.G. Overberger, R.W. Cummins, J. Am. Chem. Soc. 75 (1953) 4783. [29] R. Curci, R.A. Di Prete, J.O. Edwards, G. Modena, J. Org. Chem. 35 (1970) 740. [30] Y.H. Kim, T. Takata, S. Oae, Tetrahedron Lett. 26 (1978) 2305. [31] B.G. Gilbert, B. Gill, M.J. Ramsden, Chem. Ind. (London) (1979) 283. [32] G.V.D. Tiers, US Patent 2, 665, 650, 10 December 1960. [33] N.O. Brace, J.E. Van Elswyk, J. Org. Chem. 41 (1976) 766. [34] R.T. Conley, Infrared Spectroscopy, 2nd Edition, Allyn and Bacon, Boston, 1972, pp. 98±99/197±98, p. 207. [35] L.J. Bellamy, The Infrared Spectra of Complex Molecules, 2nd Edition, Wiley, New York, 1958, Chapter 22, pp. 352±356. [36] M. Hauptschein, C.S. Stokes, E.A. Nodiff, J. Am. Chem. Soc. 74 (1952) 4005. [37] W.E. Savidge, J. Eager, J.A. Maclaren, C.M. Roxburgh, Tetrahedron Lett. 44 (1964) 3289. [38] E.A. Robinson, Can. J. Chem. 39 (1961) 247. [39] N. Kharasch, F.A. Billig, Quart. Rep. Sulfur Chem. 1 (1966) 189. [40] L.J. Bellamy, R.J. Williams, J. Chem. Soc. (1957) 863. [41] N.O. Brace, unpublished.