study on the reactions of fluoroalkanesulfonyl azides with n-alkylindoles

Study on the reactions of fluoroalkanesulfonyl azideswith N-alkylindoles

Ping He, Shi-Zheng Zhu*

Key Laboratory of Organofluorine Chemistry, Shanghai Institution of Organic Chemistry,

Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China

Received 21 March 2004; received in revised form 7 June 2004; accepted 8 June 2004

Available online 28 July 2004

Abstract

The reactions of fluoroalkanesulfonyl azides RfSO2N3 1 with N-alkylindoles 2 have been studied in detail. It was found that both solvent

and the amount of the azides seriously affected the product distribution. 1 reacted with an equimolar amount of 2 in ether or 1,4-dioxane

affording 2-(N-substituted-indolinylidene)fluoroalkane sulfonylimines 3 as major product; While, the treatment of 2 with two equivalent of 1

in ethanol afforded N-substituted-2-fluoroalkanesulfonimino-3-diazo-indolines 4 as an unexpected product in good yields. The reaction

mechanism was discussed.

# 2004 Elsevier B.V. All rights reserved.

Keywords: Fluoroalkanesulfonyl azides; N-alkylindoles; Diazo transfer; 1,3-Dipolar cycloaddition; Carbanion process

1. Introduction

As an important nucleus of many alkaloids and pigments,

indole and its derivatives have achieved an increased sig-

nificance in medicinal chemistry in recent years [1]. Due to

its special structural character, investigations of their che-

mical transformation also gained much attention [2]. Among

them, the reactions of sulfonyl azides with indole and its

derivatives were studied extensively. Fusco et al [3] reported

that benzensulfonyl azides added to open chain enamines in

such a fashion that the enamine nitrogen and azide nitrogen

were bonded to the same carbon atom in the product

(Scheme 1).

During the past several years Bailey et al. [4,5] have

reported that the reaction of arylsulfonyl azides with indole

and alkylindoles afforded similar results.

It is well known that replacement of hydrogen by fluorine

in biologically active molecules often yields analogues with

improved reactivity and selectivity due to the unique phy-

sical and chemical properties of fluorine and C–F bond [6].

Per (poly) fluroalkanesulfonyl azides RfSO2N3 1 are more

reactive than other nonfluorinated organic azides due to

the strong electron-withdrawing property of the RfSO2

group. However, their reactions are studied rarely. Recently,

we systematically studied their reactions with electron-

rich olefins such as enamines, silyl enol ethers etc. [7].

As a continuation of our investigation, the reactions of 1with N-alkylindoles have been examined in detail. It

was found that these reactions gave 2-(N-substituted-indo-

linylidene)fluoroalkane sulfonylimines (3), N-substituted-2-

fluoroalkanesulfonimino-3-diazo-indolines (4) and fluor-

oalkanesulfonylamide (5). The distribution of the products

were depended on the reaction conditions such as solvent,

reaction time and molar ratio of the reactants. Herein we

wish to report these results.

2. Results and discussion

The reaction of equimolar fluoroalkanesulfonyl azide 1awith N-methylindole 2a was first investigated. It proceeded

smoothly in anhydrous diethyl ether at room temperature.

TLC analysis showed that the azide 1a disappeared within

one hour and three products with close polarities formed.

After the removal of solvent, the residue was separated and

purified by column chromatography over silica gel using

petroleum ether/ether (4:1) as an eluant. The first compound

3aa was isolated in 76% yield. In addition, an unexpected

product 4aa was also separated in low yield (10%), which

was accompanied by the formation of a small amount of

fluoroalkanesulfonylamide 5a (<3%).

Journal of Fluorine Chemistry 125 (2004) 1529–1536

* Corresponding author. Fax: þ86-21-64166128.

E-mail address: [email protected] (S.-Z. Zhu).

0022-1139/$ – see front matter # 2004 Elsevier B.V. All rights reserved.

doi:10.1016/j.jfluchem.2004.06.003

New products were fully characterized by spectroscopic

and elemental analysis. For instance, the MS spectrum of

3aa showed its strong molecular ion peak at m/z 552. Its 1H

NMR consisits of five peaks at d 7.55 (m), 7.26 (d), 7.11 (d),

4.30 (s), 3.50 (s), which can be assigned to the corresponding

four Ar–H, the two benzylic protons at the 3 position and the

N–CH3, respectively. Meanwhile, a typical strong absorp-

tion at 1552 cm�1 in IR spectrum also confirmed the exis-

tence of C¼N functional group. The mass spectra of 4aa also

showed its molecular ion peak, the mass difference between

3aa and 4aa is 26, which should be assigned to the additional

diazo group (N2). The major fragment ions observed in

spectrum at m/z 235, 207, 159 and 132 could be attributed to

[Mþ-Rf], [Mþ-Rf-N2], [Mþ-RfSO2N] and [Mþ-RfSO2N-N2]

respectively. In its 1H NMR spectrum, the peak of

two benzylic protons at the 3 position was disappeared,

while their 19F NMR was similar to that of 3aa. A strong

absorption at 2153 cm�1 in IR spectrum was found, which is

the typical absorption of C¼Nþ¼N�. Thus, the molecular

structure of compounds 3aa and 4aa was determined as 2-

(N-methyl-indolinylidene)fluoroalkane sulfonylimines and

N-methyl-2-fluoroalkanesulfonimino-3-diazo-indolines,

respectively.

Other azides 1(b–e) reacted with 2 giving similar results.

All these results were summarized in Table 1 (Scheme 2).

Comparing with arylsulfonyl azides, fluoroalkanesulfonyl

azides reacted under milder reaction conditions (room tem-

perature) and shorter reaction time (1–8 h) From Table 1, it

was found that when the azide 1b was used, the yields of 4baor 4bb were increased (Table 1, entries 3 and 4). While in the

case of the reaction of azide 1e with 2a or 2b (entries 8 and

9), the yields of 3ea and 3eb were decreased obviously.

Although the corresponding 4ea and 4eb could not be

isolated due to the very small amount formation, their

formation was confirmed by the TLC analysis. As men-

tioned above, the reaction of 1a with 2a was completed

within 1 h. However, under the same reaction conditions, the

reaction of 1a with N-ethylindole 2b was finished after 4 h

(monitored by TLC). Other azides 1, such as 1b, 1c and 1e,

however, needed longer reaction time to complete their

reactions (4–8 h).

To control the product distribution, some influence factors

were studied in detail. For convenience, the reaction of

fluoroalkanesulfonyl azide 1a and N-methylindole 2a was

chosen as a module reaction. The influence of different

solvents was studied first at room temperature using equi-

molar reactants. The results of solvent effects on the product

distribution were summarized in Table 2.

From Table 2, it is clear that 1,4-dioxane and Et2O are

the suitable solvent for the formation of product 3aa.

Dichloromethane (entry 2) also performed well, but as

there are concerns about using chlorinated solvents on a

certain scale, we decided to carry out optimization of the

reactions between the various fluoroalkanesulfonyl azides

1 and N-alkylindoles 2 with the two solvents mentioned

above. Meanwhile, under the same condition, strong

polar and protonic solvent ethanol gave nearly equal

amount of 3aa, 4aa and 5a (entry 3). Thus, ethanol

was found to be the proper solvent for the formation of

the diazo product 4aa. During our previous study using

Et2O as a solvent, we found that the molar ratio of the two

reactants also affected the product distribution and the

diazo product was obtained as the major product by the

control of the molar ratios. Then different molar ratio of

the two reactants was investigated at room temperature in

ethanol. The whole reaction process was followed by 19F

Scheme 1.

Table 1

Results of the reaction of fluoroalkanesulfonyl azides 1 with N-

alkylindoles 2a

Entry Azides Indoles Time (h) Products and yields (%)b

1 1a 2a 1 3aa (76) 4aa(10) 5a (2)

2 1a 2b 4 3ab (54) 4ab(20) 5a (10)

3 1b 2a 4 3ba (35) 4ba(23) 5b (20)

4 1b 2b 4 3bb (33) 4bb (22) 5b (22)

5 1c 2a 8 3ca (32) 4ca (–)c 5c (30)

6 1c 2b 8 3cb (30) 4cb (12) 5c (28)

7 1d 2a 1 3da (35) 4da(15) 5d (20)

8 1e 2a 8 3ea (27) 4ea (–)c 5e (25)

9 1e 2b 8 3eb (26) 4eb (–)c 5e (26)

a 1:2 ¼ 1:1, Reaction carried out in ether at room temperature.b Isolated yield.c Not isolated as pure product due to the very small amount.

Scheme 2.

1530 P. He, S.-Z. Zhu / Journal of Fluorine Chemistry 125 (2004) 1529–1536

NMR and the corresponding results were summarized in

Table 3.

It is evident that with the increase of 1, the proportion of

3aa decreased from 36 to 5%, while the product 4aaincreased from 32 to 44% (Table 3, entries 1–4). To our

surprise, by applying prolonged reaction time (4 h), the

product 3aa was disappeared and the product 4aa can be

selectively formed (entries 2 and 5). From these results, we

could assume that the products 4 and 5 were formed during

the same process and they might be formed from the

transformation of product 3, which also can be deduced

from the TLC analysis. This point was confirmed during the

following studies.

Until now, the reaction conditions for the formation of the

product 3 or 4 were optimized. Some typical results of the

formation of 3 and 4 were selected and summarized in

Table 4.

From the Table 4, it was found that the treatment RfSO2N3

1 with an equimolar amount of 2 in 1,4-dioxane at room

temperature gave 3 as major products. Meanwhile, by mix-

ing two equimolar amount of 1 with 2 in ethanol at room

temperature, the major products 4 were obtained in moder-

ate to good yields within 2–8 h. Compared with the reaction

carried out in Et2O (See Table 1), the yields of 4 were

improved obviously.

To the best of our knowledge, the transfer of the diazo

group from arylsulfonyl azides to an active methylene

compound has been known for quite some time. Nearly

all of the reported examples have involved the transfer of

diazo group from sulfonyl azides generally under basic

reaction condition [8,9]. However, during the reactions of

fluoroalkanesulfonyl azides 1 and N-alkylindoles 2 the diazo

transfer reaction to an amidine occurred smoothly in the

Table 2

Solvent effects on the product distribution in the reaction of 1a with 2a.

Entry Solvent T (8C) Time (h) Products and yields(%)a

3aa 4aa 5a

1 Et2O 20 1 87 10 3

2 CH2Cl2 20 4 88 9 3

3 C2H5OH 20 0.5 36 32 32

4 1,4-dioxane 20 4 93 6 1

5 CH3CN 20 4 81 8 11

a Determined by 19F NMR.

Table 3

Effect of the molar ratio of reactants on the products distribution in the

reaction of 1a with 2a.

Entry Molar ratio Time (h) Products and yields (%)a

1a/2a 3aa 4aa 5a

1 1 0.5 36 32 32

2 1.5 0.5 20 37 43

3 2 0.5 16 39 45

4 3 0.5 5 44 52

5 1.5 4 0 49 51

6 2 4 0 45 55

7 3 4 0 44 56

a Determined by 19F NMR.

Table 4

Typical results of the reaction of fluoroalkanesulfonyl azides 1 with N-

alkylindoles 2 in different reaction conditions.

Entry Azides R in 2 Condition Product Yield

(%)a

Sol. Molar ratio (1/2) Time(h)

1 1a 2a 1,4-dioxane 1 1 3aa 73

2 1a 2b 1,4-dioxane 1 4 3ab 60

3 1b 2a Et2O 1 4 3ba 35

4 1b 2b Et2O 1 4 3bb 33

5 1c 2a 1,4-dioxane 1 8 3ca 63

6 1c 2b 1,4-dioxane 1 8 3cb 51

7 1d 2a 1,4-dioxane 1 1 3da 70

8 1d 2b 1,4-dioxane 1 1 3db 76

9 1a 2a Ethanol 2 2 4aa 81

10 1a 2b Ethanol 2 2 4ab 90

11 1a 2b Et2O 2 4 4ab 46

12 1b 2a Ethanol 2 8 4ba 52

13 1b 2b Ethanol 2 8 4bb 89

14 1b 2b Et2O 2 8 4bb 84

15 1c 2a Ethanol 2 8 4ca 59

16 1c 2b Ethanol 2 8 4cb 52

17 1d 2a Ethanol 2 2 4da 67

18 1d 2b Ethanol 2 2 4db 89

a Isolated yield based on 2.

Scheme 3.

P. He, S.-Z. Zhu / Journal of Fluorine Chemistry 125 (2004) 1529–1536 1531

absence of base. The products 4 were yellowish stable solid

which is different from the hydro-carbon analogues obtained

from the reaction of arylsulfonyl azides with indoles studied

by Harmon et al [10]. They found that the corresponding

diazo compounds 8 were light sensitive and difficult to

isolate in a pure form, but could be treated with PPh3

affording stable crystalline triphenylphosphine derivatives

9. In addition, the diazo transfer product 8 was not obtained

under the same conditions using 1,4-dioxane as a solvent

instead of ethanol, i.e., the 2-substituted compounds 6 were

the major products and abnormal 3-substituted compounds 7were the minor products in 1,4-dioxane (Scheme 3).

During their studies on the reaction of sulfonyl azides

with indoles, an amino–imino type of tautomeric equili-

brium could be easily observed from the NMR spectra of 6 in

DMSO-d6. However, in our case, the products 3 could be

dissolved in DMSO-d6 solution as well as in CDCl3. Their

NMR spectra showed that no corresponding amino tautomer

existed, but the imino tautomers were the sole type ones

(Scheme 4). These results are opposite to those reported by

Bailey et al [11] in the case of 1,3-dimethylindole and are

amenable to those reported by Harmon et al [12]. They

found that in general electron-withdrawing substituents on

the benzenesulfonamido group reduce the percentage of

amino tautomer in solution. Thus, the strong electron-with-

drawing ability of the fluorine-containing group perhaps can

be used to explain why only the imino tautomers were found

in their NMR spectra.

In our previous study on the fluoroalkanesulfonyl azides

1, the nitrene RfSO2N: formed thermally at 110 8C. There-

fore in above reactions the nitrene intermediates were not

involved. In the reactions of azides 1 with N-alkylindoles 2,

the triazoline A should be formed first via 1,3-dipolar

cycloaddition process. When the triazoline ring carries an

electron-withdrawing group at the 1-position, it is very

labile. Thus, it is considered that the triazolines A were

not isolated, as it decomposed immediately into amidines 3by an elimination of N2 gas and 1,2-H shift. Since the

transfer of diazo group from sulfonyl azides was supposed

to involve a carbanion as the reactive species, the formation

of diazo compounds 4 may be explained well. The formed

amidines 3 could be further reacted with 1 to form product 4and fluoroalkanesulfonamide 5. That is to say, the amidines

3 are considered to be the key intermediates for the forma-

tion of 4 (Scheme 5).

This mechanism was further substantiated by the reac-

tion of amidine 3ba with another equimolar amount of 1bto give diazo compound 4ba in 82% yield. Meanwhile, we

also obtained the compound 4ca by the treatment of

equimolar of 3ca with 1a under the same condition with

excellent yield up to 92%, which could not be isolated

from the product obtained from the reaction of 1c and 2ain Et2O due to the very small amount of formation (Table 1,

entry 5). In addition to 4ca, the formation of another

product IRfSO2NH2 5a confirmed the mechanism again

(Scheme 6).

Scheme 4.

Scheme 5.

Scheme 6.


3. Conclusions

In summary, the reactions of fluoroalkanesulfonyl azides

and N-alkylindoles under mild reaction condition were

studied in detail. By control of the reactant molar ratio,

2-(N-substituted-indolinylidene) fluoroalkane sulfonyli-

mines 3 and N-substituted-2-fluoroalkanesulfonimino-3-

diazo-indolines 4 were obtained selectively in 1,4-dioxane

or ethanol in moderate to good yields, respectively. The

obtained products are important synthons in many synth-

esis processes, their chemical transformations are under

way.

4. Experimental

Melting points were measured in Temp-Melt apparatus

and were uncorrected. 1H and 19F NMR spectra were

recorded in CDCl3 (unless mentioned in text), Bruker

AM-300 instruments with Me4Si and CFCl3 (with upfield

negative) as the internal and external standards, respectively.

IR spectra were obtained with a Nicolet AV-360 spectro-

photometer. Lower resolution mass spectrum or high resolu-

tion mass spectra (HRMS) were obtained on a Finnigan GC-

MS 4021 or a Finnigan MAT-8430 instrument using the

electron impact ionization technique (70 eV), respectively.

Elemental analyses were performed by this Institute. All

solvents were purified before use. Fluoroalkanesulfonyl

azides 1 and N-substituted indoles 2 were prepared accord-

ing to literature [13,14].

4.1. Typical procedure for the preparation of

2-(N-substituted-indolinylidene)

fluoroalkanesulfonylimines 3

To a 10 mL round-bottom flask containing N-substituted

indoles 2a (2.0 equiv.) in 2 mL 1,4-dioxane or anhydrous

ether was added slowly fluoroalkanesulfonyl azides 1a(2.0 equiv.) at room temperature within 2 min. Then the

mixture was continuously stirred at room temperature

within 1 h until TLC analysis shown the reaction finished.

The solvent was evaporated and the residue was chroma-

tographed on a silica column using petroleum ether/diethyl

ether (4:1) as eluant to give pure product 3aa as a white

solid.

4.1.1. 2-(N-methyl-indolinylidene)-(50-Iodo-30-oxa-octafluoropentyl)-sulfonyl imines (3aa)

Mp 79–80 8C. FT-IR (nmax, cm�1): 1576, 1554 (s, C¼N),

1499, 1334, 1177 and 1135. 1H NMR d (ppm): 7.80–7.10

(m, 4H, ArH), 4.30 (s, 2H, CH2), 3.50 (s, 3H, CH3). 19F

NMR d (ppm): �65.2 (t, 2F, ICF2), �81.7 (t, 2F, CF2O),

�85.8 (m, 2F, OCF2), �117.3 (s, 2F, SCF2). MS m/z (ion,

%): 552 (Mþ, 49), 425 (Mþ-I, 8), 227 (IC2F4þ, 6), 209 (Mþ-

Rf, 78), 177 (ICF2þ, 6), 145 (Mþ-RfSO2, 98), 118 (Mþ-

RfSO2-HCN, 100). Anal. Calcd. for C13H9F8IN2O3S: C,

28.26; H, 1.63; N, 5.07%; Found: C, 28.20; H, 1.64; N,

5.00%.

4.1.2. 2-(N-methyl-indolinylidene)-(50-Chloro-30-oxa-octafluoropentyl)-sulfonyl imines (3ba)

Mp 129–130 8C. FT-IR (nmax, cm�1): 1580 (s, C¼N),

1384, 1313, 1200, 1167. 1H NMR d (ppm): 7.42–7.12 (m,

4H, ArH), 4.30 (s, 2H, CH2), 3.50 (s, 3H, CH3). 19F NMR d(ppm): �73.7 (s, 2F, ClCF2), �81.2 (t, 2F, CF2O), �86.7 (t,

2F, OCF2), �116.8 (s, 2F, SCF2). MS m/z (ion, %): 462/460

(Mþ, 13/34), 425 (Mþ-Cl, 8), 209 (Mþ-Rf, 69), 145 (Mþ-

RfSO2, 91), 135 (ClC2F4þ, 7), 118 (Mþ-RfSO2-HCN, 100).

Anal. Calcd. for C13H9ClF8N2O3S: C, 33.91; H, 1.96; N,

6.09%; Found: C, 33.76; H, 1.96; N, 5.86%.

4.1.3. 2-(N-methyl-indolinylidene)-(10,10,20,20,40,40,50,50-Octafluoro-30-oxa-pentyl) sulfonyl imines (3ca)


1338, 1199, 1180. 1H NMR d (ppm): 7.46–7.10 (m, 4H,

ArH), 5.88 (t�t, J ¼ 52.5 Hz, 3 Hz, 1H, HCF2), 4.31 (s, 2H,

CH2), 3.51 (s, 3H, CH3). 19F NMR d (ppm): �81.2 (t, 2F,

CF2O), �88.8 (s, 2F, OCF2), �117.3 (s, 2F, CF2S), �137.6

(d, J ¼ 53 Hz, 2F, HCF2). MS m/z (ion, %): 426 (Mþ, 34),

209 (Mþ-Rf, 45), 177 (ICF2þ, 6), 145 (Mþ-RfSO2, 75), 118

(Mþ-RfSO2-HCN, 100), 101 (HC2F4þ, 14). Anal. Calcd. for

C13H10F8N2O3S: C, 36.62; H, 2.35; N, 6.57%; Found: C,

36.62; H, 2.54; N, 6.31%.

4.1.4. 2-(N-ethyl-indolinylidene)-(50-Iodo-30-oxa-octafluoropentyl)-sulfonylimines (3ab)

Mp 88–90 8C. FT-IR (nmax, cm�1): 2988, 1552 (s, C¼N),

1494, 1331, 1290, 1143, 1089. 1H NMR d (ppm): 7.40–

7.12 (m, 4H, ArH), 4.29 (s, 2H, CH2), 4.04 (q, J ¼ 7.2 Hz,

2H, CH2CH3), 1.36 (t, J ¼ 7.2 Hz, 3H, CH2CH3). 1H NMR

(DMSO-d6) d (ppm): 7.52–7.24 (m, 4H, ArH), 4.34 (s, 2H,

CH2), 4.03 (q, J ¼ 7.2 Hz, 2H, CH2CH3), 1.23 (t,

J ¼ 7.2 Hz, 3H, CH2CH3). 19F NMR d (ppm): �64.7 (t,

2F, ICF2), �81.2 (t, 2F, CF2O), �85.4 (m, 2F, OCF2),

�116.6 (s, 2F, CF2S). MS m/z (ion, %): 566 (Mþ, 22),

439 (Mþ-I, 4), 227 (IC2F4þ, 5), 223 (Mþ-Rf, 50), 177

(ICF2þ, 4), 159 (Mþ-RfSO2, 100), 132 (Mþ-RfSO2-HCN,

39). Anal. Calcd. for C14H11F8IN2O3S: C, 29.68; H, 1.94; N,

4.95%; Found: C, 29.70; H, 1.94; N, 4.92%.

4.1.5. 2-(N-ethyl-indolinylidene)-(50-Chloro-30-oxa-octafluoropentyl)-sulfonyl imines (3bb)


1372, 1317, 1204, 1168. 1H NMR d (ppm): 7.43–7.11 (m,

4H, ArH), 4.29 (s, 2H, CH2), 4.05 (q, J ¼ 7.2 Hz, 2H,

CH2CH3), 1.35 (t, J ¼ 7.2 Hz, 3H, CH2CH3). 19F NMR d(ppm): �74.0 (s, 2F, ClCF2), �81.6 (t, 2F, CF2O), �87.0 (t,

2F, OCF2), �117.0 (s, 2F, CF2). MS m/z (ion, %): 476/474

(Mþ, 9/23), 439 (Mþ-Cl, 5), 223 (Mþ-Rf, 46), 159 (Mþ-

RfSO2, 100), 135 (ClC2F4þ, 27), 80 (Mþ-RfSO2-HCN, 100).

Anal. Calcd. for C14H11ClF8N2O3S: C, 35.41; H, 2.32; N,

5.90%; Found: C, 35.31; H, 2.54; N, 5.89%.


4.1.6. 2-(N-ethyl-indolinylidene)-(10,10,20,20,40,40,50,50-Octafluoro-30-oxa-pentyl)-sulfonylimines (3cb)

Mp 90–92 8C. FT-IR (nmax, cm�1): 1568 (s, C¼N), 1372,

1319, 1166, 1018. 1H NMR d (ppm): 7.44–7.10 (m, 4H,

ArH), 5.88 (t–t, J ¼ 52.8 Hz, 3 Hz, 1H, HCF2), 4.29 (s, 2H,

CH2), 4.04 (q, J ¼ 7.5 Hz, 2H,CH2CH3), 1.36 (t, J ¼ 7.5 Hz,

3H, CH2CH3). 19F NMR d (ppm): �80.9 (t, 2F, CF2O),

�88.6 (t, 2F, OCF2), �116.9 (s, 2F, CF2S), �137.3 (d,

J ¼ 53 Hz, 2F, HCF2). MS m/z (ion, %): 440 (Mþ, 34),

223 (Mþ-Rf, 45), 159 (Mþ-RfSO2N, 100), 132 (Mþ-

RfSO2N-HCN, 43). HRMS for C14H12F8N2O3S Calcd.:

440.04354; Found: 440.04393.

4.1.7. 2-(N-methyl-indolinylidene)-

perfluorobutylsulfonylimines (3da)Mp 171–173 8C. FT-IR (nmax, cm�1): 1581 (s, C¼N),

1504, 1384, 1317, 1163, 1138, 1077. 1H NMR d (ppm):

7.43–7.11 (m, 4H, ArH), 4.31 (s, 2H, CH2), 3.51 (s, 3H,

CH3). 19F NMR d (ppm): �80.7 (t, 3F, CF3), �113.4 (t, 2F,

CF2CF2S), �120.9 (m, 2F, CF2), �125.9 (t, 2F, CF3CF2).

MS m/z (ion, %): 428 (Mþ, 14), 209 (Mþ-Rf, 41), 145 (Mþ-

RfSO2N, 55) 118 (Mþ-RfSO2N-HCN, 100). Anal. Calcd. for


36.70; H, 2.11; N, 6.41%.

4.1.8. 2-(N-ethyl-indolinylidene)-

perfluorobutylsulfonylimines (3db)Mp 48–50 8C. FT-IR (nmax, cm�1): 1569 (s, C¼N), 1374,

1317, 1200, 1140, 1046. 1H NMR d (ppm): 7.44–7.11 (m,

4H, ArH), 4.31 (s, 2H, CH2), 4.06 (q, J ¼ 7.5 Hz, 2H,

CH2CH3), 1.36 (t, J ¼ 7.5 Hz, 3H, CH2CH3). 19F NMR d(ppm): �81.0 (s, 3F, CF3), �113.6 (t, 2F, CF2S), �121.3 (s,

2F, CF2), �126.2 (t, 2F, CF3CF2). MS m/z (ion, %): 442

(Mþ, 13), 223 (Mþ-Rf, 39), 159 (Mþ-RfSO2, 100), 132 (Mþ-

RfSO2-HCN, 43). HRMS for C14H11F9N2O2S Calcd.:

442.03920; Found: 442.03940.

4.1.9. 2-(N-methyl-indolinylidene)-(20-isopropoxylcarbonyl-10-difluoromethyl)

sulfonylimines (3ea)Mp 138–140 8C. FT-IR (nmax, cm�1): 2995, 1763, 1577

(s, C¼N), 1381, 1318, 1156, 1100. 1H NMR d (ppm): 7.44–

7.08 (m, 4H, ArH), 5.26 (m, 1H, CH), 4.30 (s, 2H, CH2),

3.49 (s, 3H, CH3), 1.40 (d, J ¼ 6.3 Hz, 6H, 2CH3). 19F NMR

d (ppm): �109.8 (s, 2F, CF2). MS m/z (ion, %): 346 (Mþ,

32), 304 (Mþ-C3H6, 13), 209 (Mþ-Rf, 93), 145 (Mþ-

RfSO2N, 100), 118 (Mþ-RfSO2N-HCN, 89). 43 (C3H7þ,

15). Anal. Calcd. for C14H16F2N2O4S: C, 48.55; H, 4.62; N,

8.09%; Found: C, 48.48; H, 4.56; N, 8.18%.

4.1.10. 2-(N-methyl-indolinylidene)-(20-isopropoxylcarbonyl-10-difluoromethyl)

sulfonylimines (3eb)Mp 120–122 8C. FT-IR (nmax, cm�1): 2991, 1765, 1568

(s, C¼N), 1374, 1314, 1159, 1097. 1H NMR d (ppm): 7.42–

7.08 (m, 4H, ArH), 5.25 (m, 1H, CH), 4.29 (s, 2H, CH2),

4.02 (q, J ¼ 7.5 Hz, 2H, CH2CH3), 1.40–1.34 (m, 9H,

3CH3). 19F NMR d (ppm): �109.4 (s, 2F, CF2). MS m/z

(ion, %): 360 (Mþ, 26), 318 (Mþ-C3H6, 7), 223 (Mþ-Rf, 69),

159 (Mþ-RfSO2N, 100), 132 (Mþ-RfSO2N-HCN, 32), 43

(C3H7þ, 9). HRMS for C15H18F2N2O4S Calcd.: 360.09498;

Found: 360.09486.

4.2. Typical procedure for the preparation of

N-substituted-2-fluoroalkanesulfonimino-3-

diazo-indolines 4

To a 10 mL round-bottom flask containing N-substituted

indoles 2 (1.0 equiv.) in 2 mL anhydrous ethanol was added

slowly fluoroalkanesulfonyl azides 1 (2.0 equiv) at room

temperature within 2 min. Then the mixture was continu-

ously stirred at r.t. within 1–8 h until TLC analysis shown the

reaction finished. The solvent was evaporated and the resi-

due was chromatographed on a silica column using petro-

leum ether/diethyl ether (4:1) as eluant to give pure product

4 as a yellowish solid.

4.2.1. N-methyl-2-(50-Iodo-30-oxa-octafluoropentyl)-

sulfonimino-3-diazo-indolines (4aa)Mp 90–92 8C. FT-IR (nmax, cm�1): 2147 (s, C¼Nþ¼N�),

1541 (s, C ¼ N), 1386, 1330, 1297, 1218. 1H NMR d (ppm):

7.42–7.26 (m, 4H, ArH), 3.63 (s, 3H, CH3). 19F NMR d(ppm): �65.0 (t, 2F, ICF2), �81.6 (t, 2F, CF2O), �85.8 (m,

2F, OCF2), �116.9 (s, 2F, CF2S). MS m/z (ion, %): 578 (Mþ,

23), 451 (Mþ-I, 2), 235 (Mþ-Rf, 24), 227 (IC2F4þ, 9), 207

(Mþ-Rf-N2, 61), 177 (ICF2þ, 15), 159 (Mþ-RfSO2N, 33),

132 (Mþ-RfSO2N-N2, 100). Anal. Calcd. for C13H7F8I-

N4O3S: C, 26.99; H, 1.21; N, 9.69%; Found: C, 27.27; H,

1.28; N, 9.33%.

4.2.2. N-methyl-2-(50-Chloro-30-oxa-octafluoropentyl)-

sulfonimino-3-diazo-indolines (4ba)Mp 120–121 8C. FT-IR (nmax, cm�1): 2152 (s,

C¼Nþ¼N�), 1544 (s, C¼N), 1387, 1329, 1219, 1128. 1H

NMR d (ppm): 7.42–7.26 (m, 4H, ArH), 3.63 (s, 3H, CH3).19F NMR d (ppm): �73.7 (s, 2F, ClCF2), �81.3 (t, 2F,

CF2O), �86.7 (t, 2F, OCF2), –116.8 (s, 2F, CF2S). MS m/z

(ion, %): 488/486 (Mþ, 11/28), 235 (Mþ-Rf, 28), 207 (Mþ-

Rf-N2, 61), 159 (Mþ-RfSO2N, 32), 135 (ClC2F4þ, 9), 132

(Mþ-RfSO2N-N2, 100). Anal. Calcd. for C13H7ClF8N4O3S:

C, 32.10; H, 1.44; N, 11.52%; Found: C, 31.79; H, 1.68; N,

11.43%.

4.2.3. N-methyl-2-(10,10,20,20,40,40,50,50-Octafluoro-30-oxa-

pentyl)-sulfonimino-3-diazo-indolines (4ca)Mp 114–116 8C. FT-IR (nmax, cm�1): 2153 (s,

C¼Nþ¼N�), 1545 (s, C¼N), 1388, 1329, 1141. 1H NMR

d (ppm): 7.46–7.11 (m, 4H, ArH), 5.88 (t–t, J ¼ 52.2 Hz,

3 Hz, 1H, HCF2), 3.60 (s, 3H, CH3). 19F NMR d (ppm):

�81.3 (t, 2F, CF2O), �88.9 (s, 2F, OCF2), �117.1 (s, 2F,

CF2S), �137.6 (d, J ¼ 53 Hz, 2F, HCF2). MS m/z (ion, %):

452 (Mþ, 26), 235 (Mþ-Rf, 25), 207 (Mþ-Rf-N2, 48), 159


(Mþ-RfSO2N, 33), 132 (Mþ-RfSO2N-N2, 100), 101

(HC2F4þ, 22). Anal. Calcd. for C13H8F8N4O3S: C,

34.51; H, 1.77; N, 12.39%; Found: C, 34.58; H, 1.90; N,

12.41%.

4.2.4. N-ethyl-2-(50-Iodo-30-oxa-octafluoropentyl)-

sulfonimino-3-diazo-indolines (4ab)Mp 85–86 8C. FT-IR (nmax, cm�1): 2130 (s, C¼Nþ¼N�),

1527 (s, C¼N), 1398, 1332, 1291, 1213, 1138. 1H NMR d(ppm): 7.42–7.26 (m, 4H, ArH), 4.18 (q, J ¼ 7.2 Hz,

2H, CH2CH3), 1.36 (t, J ¼ 7.2 Hz, 3H, CH2CH3). 19F

NMR d (ppm): �64.6 (t, 2F, ICF2), �81.3 (t, 2F, CF2O),

�85.4 (m, 2F, OCF2), �116.5 (s, 2F, CF2S). MS m/z (ion,

%): 592 (Mþ, 29), 465 (Mþ-I, 3), 249 (Mþ-Rf, 31), 227

(IC2F4þ, 9), 221 (Mþ-Rf-N2, 93), 177 (ICF2

þ, 24), 146 (Mþ-

RfSO2N-N2, 100). Anal. Calcd. for C14H9F8IN4O3S: C,

28.38; H, 1.52; N, 9.46%; Found: C, 28.50; H, 1.62; N,

9.17%.

4.2.5. N-ethyl-2-(50-Chloro-30-oxa-octafluoropentyl)-

sulfonimino-3-diazo-indolines (4bb)Mp 70–72 8C. FT-IR (nmax, cm�1): 2964, 2155 (s,

C¼Nþ¼N�), 1531 (s, C¼N), 1401, 1329, 1175, 1135. 1H

NMR d (ppm): 7.41–7.26 (m, 4H, ArH), 4.18 (q, J ¼ 7.2 Hz,

2H, CH2CH3), 1.36 (t, J ¼ 7.2 Hz, 3H, CH2CH3). 19F NMR

d (ppm): �73.7 (s, 2F, ClCF2), �81.3 (t, 2F, CF2O), �86.7

(t, 2F, OCF2), �116.6 (s, 2F, CF2S). MS m/z (ion, %): 502/

500 (Mþ, 7/19), 249 (Mþ-Rf, 21), 221 (Mþ-Rf-N2, 54), 146

(Mþ-RfSO2N-N2, 100). Anal. Calcd. for C14H9ClF8N4O3S:

C, 33.57; H, 1.80; N, 11.19%; Found: C, 33.63; H, 1.95; N,

11.31%.

4.2.6. N-ethyl-2-(10,10,20,20,40,40,50,50-Octafluoro-30-oxa-pentyl)-sulfonimino-3-diazo-indolines (4cb)

Mp 86–88 8C. FT-IR (nmax, cm�1): 2134 (s, C¼Nþ¼N�),

1533 (s, C¼N), 1397, 1322, 1210, 1138, 1059. 1H NMR d(ppm): 7.42–7.25 (m, 4H, ArH), 5.88 (t–t, J ¼ 52.5 Hz,

3 Hz, 1H, HCF2), 4.17 (q, J ¼ 7.5 Hz, 2H, CH2CH3),

1.36 (t, J ¼ 7.5 Hz, 3H, CH2 CH3). 19F NMR d (ppm):

�81.0 (t, 2F, CF2O), �88.6 (m, 2F, OCF2), �116.6 (s, 2F,

CF2S), �137.3 (d, J ¼ 52.5 Hz, 2F, HCF2,). MS m/z (ion,

%): 466 (Mþ, 24), 249 (Mþ-Rf, 21), 221 (Mþ-Rf-N2, 47),

146 (Mþ-RfSO2N-N2, 100). HRMS for C14H10F8N4O3S

Cal: 446.03404; Found: 446.03532.

4.2.7. N-methyl-2-perfluorobutylsulfonimino-3-

diazo-indolines (4da)Mp 140–142 8C. FT-IR (nmax, cm�1): 2138 (s,

C¼Nþ¼N�), 1562 (s, C¼N), 1435, 1392, 1307, 1218,

1137. 1H NMR d (ppm): 7.41–7.26 (m, 4H, ArH), 3.64

(s, 3H, CH3). 19F NMR d (ppm): �80.9 (t, 3F, CF3), �113.4

(t, 2F, CF2S), �121.3 (s, 2F, CF2), �126.2 (t, 2F, CF3CF2).

MS m/z (ion, %): 235 (Mþ-Rf, 14), 207 (Mþ-Rf-N2, 23), 159

(Mþ-RfSO2N, 37), 132 (Mþ-RfSO2N-N2, 100). Anal. Calcd.

for C13H7F9N4O2S: C, 34.36; H, 1.54; N, 12.33%; Found: C,

34.28; H, 1.60; N, 12.37%.

4.2.8. N-ethyl-2-perfluorobutylsulfonimino-3-

diazo-indolines (4da)Mp 58–60 8C. FT-IR (nmax, cm�1): 2981, 2143 (s,

C¼Nþ¼N�), 1522 (s, C¼N), 1460, 1395, 1333, 1216,

1165, 1061. 1H NMR d (ppm): 7.41–7.26 (m, 4H, ArH),

4.19 (q, J ¼ 7.2 Hz, 2H, CH2CH3), 1.37 (t, J ¼ 7.2 Hz, 3H,

CH2CH3). 19F NMR d (ppm): �81.0 (t, 3F, CF3), �113.4 (t,

2F, CF2S), �121.3 (s, 2F, CF2), �126.2 (t, 2F, CF3CF2). MS

m/z (ion, %): 468 (Mþ, 43), 249 (Mþ-Rf, 32), 221 (Mþ-Rf-

N2, 46), 146 (Mþ-RfSO2N-N2, 100). Anal. Calcd. for


35.86; H, 1.86; N, 12.08%.

Acknowledgements

The authors thank the National Natural Science Founda-

tion of China (Nos. 20032010, 20372077) and Innovation

Foundation of Chinese Academy of Science for financial

support.

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study on the reactions of fluoroalkanesulfonyl azides with n-alkylindoles

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