# Quantification of the Nucleophilicities of 3-X-Thiophenes: Highlighting the Hyperortho Correlation

W. Gabsi, T. Boubaker, R. Goumont

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W. Gabsi, T. Boubaker, R. Goumont. Quantification of the Nucleophilicities of 3-X-Thiophenes: Highlighting the Hyperortho Correlation. Journal of Chemistry, 2020, 2020, pp.2164759. 10.1155/2020/2164759. hal-03119318

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Research Article

# Quantification of the Nucleophilicities of 3-X-Thiophenes:
## Highlighting the Hyperortho Correlation

W. Gabsi<fnref n="1" />,<fnref n="2" />, T. Boubaker,<fnref n="2" /> and R. Goumont<fnref n="3" />

Correspondence should be addressed to W. Gabsi; wgabsi@ju.edu.sa

Received 22 January 2020; Accepted 18 February 2020; Published 19 March 2020

Academic Editor: Anton Kokalj

Copyright © 2020 W. Gabsi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Kinetics studies for the coupling reactions of the 3-X-thiophene **1a-c** (X = CH₃, H and Br) with the electrophiles **2a** and **3a-c** have been investigated in acetonitrile at 20°C. The second-order rate constants have been employed to determine the nucleophilicity parameters N and s of the thiophene **1** according to the Mayr equation log k (20°C) = s (E + N). The nucleophilic-specific parameters N and s quantified in this work have been derived and compared with the reactivity of other C nucleophiles. Based on the linear correlations log k₁ = f(E) and log k₁ = f(σₚ⁺), we have shown that the mechanism of interactions occurs by a unique process: electrophilic heteroaromatic substitution of an α-carbon position of substituted 3-X-thiophenes **1** known hyperortho correlation.

**1. Introduction**

Nowadays, it has been shown that five-membered rings are very useful for various applications such as phosphor materials [1] and semiconductors [2–4]. As an example, the use of thiophene dicarboxylic acids has made it possible to prepare organometallic nanoarchitectures having very interesting optoelectronic properties [5].

The study of the reactivity of some mono- and bis-substituted thiophenes has attracted the attention of researchers because of their ability to react according to different processes and largely dependent on the substituent [6–8]. Indeed, Mayr and coworkers [6] showed that benzhydrylium ions react very easily with 3-methoxythiophene to form C-substituted derivatives in acetonitrile, which further confuses the idea that the position of α-carbon of aminothiophenes has a high potential for nucleophilic carbon reactivity [9]. In this regard, to provide more information concerning the behavior of these types of heterocycles, we report, in this paper, on the results of a kinetic investigation of the α-carbon reactivity of the 3-X-thiophenes **1a-c** with a series of superelectrophiles **2a** and **3a-c** in acetonitrile.

**2. Experimental Section**

**2.1. Materials.** 3-X-thiophene **1** used in this study (Aldrich products) was of the highest quality commercially available. The electrophiles **2** and **3** have been synthesized by the team of Professor Régis GOUONT at the Versailles laboratory. Acetonitrile (for HPLC, ≥99.9%) was available of the highest quality and used without further purification.

**2.2. Rate Measurements.** Kinetic measurements were performed using a conventional spectrophotometer (Shimadzu UV-visible model 1650) equipped with a thermoelectrically temperature controlled cell holder (model TCC-240 A) which was maintained at 20 ± 0.1°C.

All the reactions were carried out at 20°C under pseudo-first-order conditions with a thiophene concentration of approximately 5 × 10⁻<fnref n="3" /> mol·dm⁻<fnref n="3" /> and oxygen-nucleophile concentrations in the range 1 × 10⁻<fnref n="1" />–1 mol·dm⁻<fnref n="3" />. The pseudo-first-order rate constants, kobsd, measured were found to be reproducible to ±3–5%. Concentrations and the measured rate constants, kobsd, for the individual kinetic experiments values, are given in Tables S1–S3 in Supplementary Material.

<footnote n="1">¹Chemistry Department, College of Sciences and Arts, Jouf University, Algrayat, Saudi Arabia</footnote>

<footnote n="2">²Laboratory CHPNR, Faculty of Sciences of Monastir, University of Monastir, Avenue of the Environment, 5019 Monastir, Tunisia</footnote>

<footnote n="3">³Lavoisier Institute of Versailles, UMR 8180, University of Versailles, 45, United States Avenue, 78035 Versailles Cedex, France</footnote>
<figure><img src="image_2.png" /><figcaption>SCHEME 1</figcaption></figure>

<figure><img src="image_3.png" /><figcaption>SCHEME 2</figcaption></figure>

<figure><img src="image_4.png" /><figcaption>FIGURE 1: UV-visible spectrum of thiophene 1c and the progressive evolution of the formation of the product 4C in acetonitrile at 20°C with [1c] = 1 mol·L⁻¹ and [2a] = 5.10⁻⁵ mol·L⁻¹.</figcaption></figure>

**2.3. Supporting Information Available.** Tables S1–S3: kinetic data for reactions of thiophenes **1** with 4,6-dinitrotrazolopyridine **2a** and benzofuroxane **3a-c** in an aqueous solution at 20°C.

Table S4: physical data for the formation of σ-adducts **4A-C** and **5A-I** derived from the reaction of 3-X-substituted thiophenes **1a-c** with the electrophiles **2a** and **3a-c**.

<figure><img src="image_5.png" /><figcaption>FIGURE 2</figcaption></figure>

Figures S1-S2: UV-visible spectrum of thiophenes **1a** and **1b** and the progressive evolution of the formation of the product **4A** and **4B**.

## 3. Results and Discussion

**3.1. Kinetic Investigation.** The evolution of the kinetic constants of the coupling reaction between 3-X-thiophene **1a-c** and the various electrophiles **2a** (Scheme 1) and **3a-c** (Scheme 2) requires a preliminary study by UV-visible spectrophotometry to determine the wavelengths of these reagents and their σ-adducts **4** and **5**. The addition of a solution of 3-X-substituted thiophene **1a-c** on electrophiles **2a** and **3a-c** in acetonitrile gives rise to absorbents **4A-C** and
<figure><img src="image_6.png" /><figcaption>SCHEME 3</figcaption></figure>

<table><caption>TABLE 1: Second-order rate constants ($k_1$/M⁻¹·s⁻¹) and electrophilicity parameters (E) of the reactions of 3-X-thiophene 1 with the electrophiles **2a** and **3a-c** in acetonitrile at 20°C.</caption><thead><tr><th>Electrophile</th><th>E<sup>a</sup></th><th>Nucleophile</th><th>k<sub>1</sub> (M<sup>-1</sup>s<sup>-1</sup>)</th></tr></thead><tbody><tr><td rowspan="4">O<sub>2</sub>N-C(=N)-N=N-N<sub>2</sub><br>NO<sub>2</sub><br>2a</td><td rowspan="4">-4.58</td><td><b>1a</b></td><td>4.08 × 10<sup>-3</sup></td></tr><tr><td><b>1b</b></td><td>1.28 × 10<sup>-3</sup></td></tr><tr><td><b>1c</b></td><td>3.41 × 10<sup>-4</sup></td></tr><tr><td><b>1a</b></td><td>2.67 × 10<sup>-3</sup></td></tr><tr><td rowspan="2">F<sub>3</sub>CO<sub>2</sub>S-C(=N)-N=N-N<sub>2</sub><br>NO<sub>2</sub><br>3a</td><td rowspan="2">-4.74</td><td><b>1b</b></td><td>7.18 × 10<sup>-4</sup></td></tr><tr><td><b>1c</b></td><td>2.22 × 10<sup>-4</sup></td></tr><tr><td rowspan="3">O<sub>2</sub>N-C(=N)-N=N-N<sub>2</sub><br>NO<sub>2</sub><br>3b</td><td rowspan="3">-5.06</td><td><b>1a</b></td><td>1.23 × 10<sup>-3</sup></td></tr><tr><td><b>1b</b></td><td>3.39 × 10<sup>-4</sup></td></tr><tr><td><b>1c</b></td><td>1.08 × 10<sup>-4</sup></td></tr><tr><td rowspan="3">O<sub>2</sub>N-C(=N)-N=N-N<sub>2</sub><br>CN<br>3c</td><td rowspan="3">-6.41</td><td><b>1a</b></td><td>4.10 × 10<sup>-5</sup></td></tr><tr><td><b>1b</b></td><td>1.35 × 10<sup>-5</sup></td></tr><tr><td><b>1c</b></td><td>4.36 × 10<sup>-6</sup></td></tr></tbody></table>

**5A-I** adducts at wavelengths between 405 and 487 nm. A typical experiment is illustrated in Figure 1. The spectral data for the σ-adducts **4** and **5** considered in this work (the absorption maxima and the corresponding molar extinction coefficients in acetonitrile) are collated in Table S4.

A comparison of these values of $\lambda_{max}$ makes it possible to obtain information on the structure of the various adducts. Indeed, the spectra of all the adducts **4** A-C and **5** D-I have a very high absorption maximum up to 465–487 nm. These high wavelengths translate a strong delocalization of the

<figure><img src="image_7.png" /><figcaption>FIGURE 3: Plots of log $k_1$ versus E for the reactivity of thiophenes **1a-c** with the reference electrophiles **2a** and **3a-c** in acetonitrile at 20°C (the identity of points is given in Table 1).</figcaption></figure>

negative charge on the Z group (NO₂ or CN) of the carbocyclic. In this respect, it should also be noted that the strong electro-deficient character of the carbocycles of electrophiles **2a**, **3b**, and **3c** is known to promote the formation of the σ-anionic complexes [10–14].

The analysis in Table S4 reveals that the σ-adducts **5A-C** show an absorption maximum around 410 nm. This hypochromic effect observed with respect to the σ-complexes resulting from the coupling reaction between the electrophiles **2a**, **3b**, and **3c** with thiophenes **1a-c** suggests that a very high negative charge density is preferentially localized on the carbon bearing the SO₂CF₃ group (Figure 2).

It is interesting to note that electrophiles **2a** and **3a-c** showed negligible absorption at the absorbance wavelengths $\lambda_{max}$ of the σ-adducts considered in this work (Figures 1, S1,

<footnote><sup>a</sup>Ref [7].</footnote>
<table><caption>TABLE 2: Second-order rate constants $k_1$ (M⁻¹·s⁻¹) and selectivity parameters (ρ and pKₐ) of the reactions of 3-X-thiophene **1** with the electrophiles **2a** and **3a-c**.</caption><thead><tr><th rowspan="2">Thiophene</th><th rowspan="2">N/s</th><th rowspan="2">σ<sup>+b</sup></th><th colspan="4">k<sub>1</sub> (M<sup>-1</sup>s<sup>-1</sup>)</th></tr><tr><th>2a</th><th>3a</th><th>3b</th><th>3c</th></tr></thead><tbody><tr><td>1a H</td><td>2.38/1.09</td><td>-0.31</td><td>4.08 × 10<sup>-3</sup></td><td>2.76 × 10<sup>-3</sup></td><td>1.23 × 10<sup>-3</sup></td><td>4.10 × 10<sup>-5</sup></td></tr><tr><td>1b</td><td>1.79/1.06</td><td>0.00</td><td>1.28 × 10<sup>-3</sup></td><td>7.18 × 10<sup>-4</sup></td><td>3.39 × 10<sup>-4</sup></td><td>1.35 × 10<sup>-5</sup></td></tr><tr><td>1c</td><td>1.20/1.03</td><td>0.15</td><td>3.41 × 10<sup>-4</sup></td><td>2.22 × 10<sup>-4</sup></td><td>1.08 × 10<sup>-4</sup></td><td>4.36 × 10<sup>-6</sup></td></tr><tr><td>ρ</td><td></td><td></td><td>-2.23</td><td>-2.27</td><td>-2.22</td><td>-2.03</td></tr><tr><td>pK<sub>a</sub></td><td></td><td></td><td>0.30</td><td>2.95</td><td>3.75</td><td>5.86</td></tr></tbody></table>

<sup>b</sup>Ref [18].

and S2). This observation made possible the kinetic study of the coupling reaction of thiophenes **1a-c** with the various electrophiles **2a** and **3a-c** in acetonitrile.

Theoretically, the reactions proceed according to Scheme 3 and the bimolecular rate constant $k_1$ is related to the formation of the zwitterionic intermediate **IZ**⁺ while the monomolecular rate constants $k_{-1}$ and $k_2$ are associated with the decomposition processes of the intermediate **IZ**⁺ with, respectively, a return to the starting reagents or rearomatization of the thiophenic entity. So, as can be seen, the proposed mechanism is the result of an electrophilic aromatic substitution of the α-carbon position of the thiophenes **1a-c** with formation of a zwitterionic intermediate **IZ**⁺. The various adducts are the result of a two-step S<sub>E</sub>Ar process of the addition-elimination type.

The graphs Ln (A<sub>e</sub> - A) as a function of time measured for a given interaction are linear (R² > 0.9998). From the slope of these lines, the constants k<sub>obsd</sub> were easily determined as follows:

$$ \mathrm{Ln}(A_e - A) = -k_{\mathrm{obsd}}t + \mathrm{Ln}(A_e - A_o). \quad (1) $$

The straight lines k<sub>obsd</sub> as a function of the concentration of thiophenes **1a-c** have proved to be linear and are characterized by a zero origin ordinate.

It follows that the nucleophilic attack of the various thiophenes **1a-c** on the position 7 of the electrophiles **2a** and **3a-c** studied is then the determining step of the coupling reaction, which implies

$$ k_{\text{obsd}} = k_1 [3 - X - \text{thiophene}]. \quad (2) $$

The values of the relative bimolecular rate constants $k_1$ for each electrophile studied are grouped in Table 1.

## 3.2. Nucleophilicities of Thiophenes **1a-C**.
Based on the values measured in acetonitrile at 20°C of the bimolecular rate constants $k_1$ associated with the coupling reaction between thiophenes **1a-c** and electrophiles **2a** and **3a-c** which are grouped in Table 1 with the values of the

parameters E of the various electrophiles **2a** and **3a-c** reported in the literature [7], the plots log k<sub>1</sub>/s as a function of the parameter E could be constructed. The situation is illustrated in Figure 3.

As can be seen, satisfactory lines of equal slope or near unity have been obtained in accordance with Mayr's rearanged equation (equation (3) [15–17]). The values of the parameters N and s relative to each 3-X-substituted thiophene **1a-c** could thus be determined graphically.

$$ \frac{\log k_1}{s} = E + N. \quad (3) $$

In light of the values of N grouped in Table 2, we have undertaken to compare the reactivity of our thiophenes **1a-c** with that of other nucleophiles. Figure 4 reveals that the N parameters for 3-X-substituted thiophenes **1a-c** are located on over a reactivity range of nearly 3 orders of magnitude. As can be seen, the reactivity of the most reactive thiophene **1d** (N = 3.96) [19] is approximately 13 units above the reactivity of tetraethylsilane **6** (N = -6.50) [20] and tris-p-tolylmethane **7** (N = -8.80) [20], but it remains significantly lower (25 units) than that of the 2-phenylpropionitrile anion **8** (N = 28.95) [21] considered to be the nucleophile more reactive encrypted to date. Another important observation is that the nucleophilic reactivity of the pyrroles **9a** and **9b** [22] and the furans **10a** and **10b** [6] is higher than that of the thiophene series **1a-c**. Moreover, the nucleophilicity of the thiophenes **1e** and **1d** is at the level of that of the indoles **11b** and **11c** [23]. Regarding the nucleophilicity of the three less-reactive thiophenes **1a-c**, we find that their ranking on the universal scale N of Mayr is about 4 units higher than that of naphthalenes **12** and **13** [20].

## 3.3. Effect of Substituents on Reactivity.
The analysis of Table 2 clearly shows that the bimolecular rate constant $k_1$ associated with the coupling reaction of thiophenes **1a-c** with the superelectrophiles **2a** and **3a-c** is very sensitive to the nature of the substituent X located in position
<figure><img src="image_8.png" /><figcaption>FIGURE 4: Ranking the carbon reactivity of the 3-X-substituted thiophene 1 on the Mayr N universal N scale.</figcaption></figure>

C-3 of the thiophenes **1a-c**. Indeed, the constant $k_1$ decreases regularly when X=CH₃, the most electro-donor substituent, and changes to X=Br, the most electro-attracting substituent.

This behavior is well illustrated in Figure 5, where the logarithm of the rate constant $k_1$ is a function of the Hammett constant $\sigma^+$, reported in the literature, of the various X substituents [24].

It is interesting to note that obtaining such correlations means the same reaction mechanism despite the variation of the substituent and confirms that the addition step of

thiophenes **1a-c** on electrophiles **2a** and **3a-c** is the decisive stage of the reaction.

The negative values of the reaction constants $\rho$ deduced from the slopes of the lines $\log k_1 = f(\sigma^+)$, as shown in Table 2, indicate a development of a positive charge on the thiophenic entity in the transition state that means a decrease in electron density on the C-2 carbon atom of thiophene (Figure 6). It is noted that the more the substituent X is an electron donor, the more this charge is positive, and therefore the corresponding transition state is stabilized, which confirms the decrease in $k_1$ observed
<figure><img src="image_9.png" /><figcaption>FIGURE 5: Hammett correlations: influence of the nature of the substituent X on the constant $k_1$ relating to the coupling reaction of thiophenes 1a-c with electrophiles 2a and 3a-c in acetonitrile at 20°C.</figcaption></figure>

<figure><img src="image_10.png" /><figcaption>FIGURE 6: Proposed transitional state structures for σ-adducts 4 and 5 in acetonitrile.</figcaption></figure>

when passing from 3-methylthiophene 1a to 3-bromo-thiophene 1c.

It is interesting to note that the low values of $\rho$ obtained can also be interpreted in terms of a large delocalization of the negative charge in the carbocyclic of electrophiles 2a and 3a-c. In addition, our values ($-2.23 < \rho < -2.03$) are similar to the values measured by several authors [18, 25–29]. El Guesmi and coworkers have shown that the aromatic nucleophilic substitution reactivity of triflone 2,4,6-tris (trifluoromethanesulfonyl) anisole with various anilines in acetonitrile at 15°C is characterized by a value of $\rho$ equal to –1.80 [25].

Moreover, the existence of linear correlations $\log k_1 = f(\sigma_p^+)$ and result of the study of the variation of the reactivity according to the structural variations of the nucleophilic pattern (thiophene) exhibits the phenomenon known as “Hyper-Ortho Correlation” [10, 30]. Currently, such a

situation has never been encountered in the context of five-membered heterocycles.

However, $\log k = f(\sigma_p)$ correlations were obtained in thiophenic series, but in these cases, the reactivity variations were made from structural variations in the electrophilic motif [18, 30]. In this regard, we note that Spinelli and coworkers were the first to identify a hyperortho effect in the case of the coupling reaction of various thiophenes such as 2-bromo-3-X-5-nitrothiophene with piperidine in methanol [31].

### 3.4. Reactivity-Acidity Relationship.
A comparison of electrophilic reactivity can be made using the linear free-energy relation similar to that proposed by Brönsted [32, 33]. The relation 4 relates the reactivity *k* to the thermodynamic acidity of the electrophile $pK_a$. The
<figure><img src="image_11.png" /><figcaption>FIGURE 7: Bronsted nonlinear correlations: influence of electrophilic acidity 2a and 3a-c on bimolecular rate constants, k₁, related to the coupling reaction of the thiophene 1a-c with the electrophiles 2a and 3a-c in acetonitrile at 20°C.</figcaption></figure>

constants A measure the reactivity of the family of electrophiles, and $\alpha_{El}$ is the sensitivity of the reaction to the variations of acidity of the electrophile. As can be seen, an

<figure><img src="image_12.png" /><figcaption>FIGURE 8: Brönsted linear correlations for the coupling reaction of the thiophenes 1a-c with the electrophiles 3a-c in acetonitrile at 20°C.</figcaption></figure>

<table><caption>TABLE 3: Nucleophilicity parameters N of 3-X-substituted thiophenes in acetonitrile at 20°C.</caption><thead><tr><th></th><th>σ<sup>+</sup></th><th>N</th><th>Reference</th></tr></thead><tbody><tr><td>OCH<sub>3</sub></td><td>-0.78</td><td>3.06</td><td>[6]</td></tr><tr><td>OC<sub>2</sub>H<sub>5</sub></td><td>-0.81</td><td>3.69</td><td>[16]</td></tr><tr><td>CH<sub>3</sub></td><td>-0.31</td><td>2.38</td><td>This work</td></tr><tr><td>H</td><td>0.00</td><td>1.79</td><td>This work</td></tr><tr><td>Br</td><td>0.15</td><td>1.20</td><td>This work</td></tr><tr><td>NH<sub>2</sub></td><td>-1.30</td><td>4.62</td><td>Estimated</td></tr><tr><td>CF<sub>3</sub></td><td>0.61</td><td>0.23</td><td>Estimated</td></tr><tr><td>CN</td><td>0.66</td><td>0.13</td><td>Estimated</td></tr><tr><td>NO<sub>2</sub></td><td>0.79</td><td>-0.17</td><td>Estimated</td></tr></tbody></table>

examination of Figure 7 leaves no doubt that the Brönsted type graphs for the three thiophenes 1a-c have a curvilinear appearance:

$$ \log k = A + \alpha_{El}pK_a. \quad (4) $$

However, at $pK_a > 3$, the three electrophiles 3a-c define a linear Brönsted correlation according to equation (4). The slope values deduced from the linear straight lines in Figure 8 ($\alpha_{El}^{1a} = -0.64$, $\alpha_{El}^{1b} = -0.61$, $\alpha_{El}^{1c} = -0.60$) suggest that the formation of the carbon-carbon and thus the transfer of the charge of the nucleophile (thiophene) to the electrophile (benzofuraxanes 3a-c) is almost 60% carried out in the state of transition.

Numerous electrophilic substitution studies exist in the literature in which the variations in reactivity have been studied from structural variations in the nucleophilic motif [34, 35]. Challis and coworkers, for example, investigated the reaction of 4,6-dinitrobenzofuraxane 3b with 5-X substituted indoles 11 [34]. In these systems, the Brönsted-type straight lines associated with the reactivity changes are characterized by a slope of $\beta_{nuc}$-type since these changes are the structural variations of the nucleophile. However, in the present work, the $\alpha_{El}$ values reveal the structural variations of the electrophile and we have not found in the literature values of the same type that we could compare to our system.

On the other hand, it remains that our values of $\alpha_{El}$ obtained are in good agreement with a polar heteroaromatic electrophile substitution mechanism [36, 37].

### 3.5. Effect of Substituent X on the Nucleophilicity N.
The aim of this part is to verify if the C-2 carbon nucleophilicity of the 3-X-substituted thiophenes measured by the parameter N is dependent on the electronic effect of the substituent X in position 3. In this context, we have grouped in Table 3 the values of the parameter N of the thiophenes 1a-c quantified in this work as well as that of 3-methoxythiophene 1d reported by Berionni and coworkers [6] and the constants of Hammett $\sigma$ of various groups used in this study [24].

As can be seen, Figure 9 shows that a satisfactory linear line is obtained by carrying the values of N as a function of
<figure><img src="image_13.png" /><figcaption>FIGURE 9: Correlation N = f(σ⁺) of a series of 3-X-substituted thiophenes in acetonitrile at 20°C.</figcaption></figure>

Hammett constants σ. Equation (5) describes this linear dependence:

$$ 
\begin{aligned}
N &= 1.65 - 2.28 \cdot \sigma^{+}, \\
R^{2} &= 0.9663.
\end{aligned} 
\quad (5) 
$$

We note that obtaining the correlation (5) informs us about the exceptional α-carbon nucleophilic reactivity of 3-X-substituted thiophenes. Also, it can be used for a direct estimation of N values that are not easily measurable.

## 4. Conclusion

According to the free-energy relationship log k = s (N + E), the nucleophile-specific parameters N and s of 3-X-thiophenes 1 have been evaluated and compared with the reactivity of other C-nucleophiles in acetonitrile. On the other hand, the satisfactory Hammett correlations (log k₁ vs. σ⁻) obtained confirms that a 3-X substituent exerts an effect on the 2-position of the same type as that exerted from the 5-position: hyperortho correlations.

## Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

## Conflicts of Interest

The authors confirm that this article content has no conflicts of interest.

## Acknowledgments

The authors acknowledge the Ministry of Higher Education and Scientific Research in Tunisia for their financial support during the research. They also thank Lavoisier Institute of Versailles, France, for their helpful reception to achieve this work.

## Supplementary Materials

This is the UV-visible spectrum and the kinetics data of each thiophene 1a-c. Tables S1-S3: kinetics data for reactions of thiophene 1 with 4,6-dinitrotetrazolopyridine 2a and benzofuroxane 3a-c in aqueous solution at 20°C. Table S4: physical data for the formation of σ-adducts 4A-C and 5A-I derived from the reaction of 3-X-substituted thiophenes 1a-c with the electrophiles 2a and 3a-c. Figures S1-S2: UV-visible spectrum of thiophenes 1a and 1b and the progressive evolution of the formation of the products 4A and 4B. (Supplementary Materials)

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