Novel Synthesis of Substituted 2-Trifluoromethyl and 2-Perfluoroalkyl N-Arylpyridinium Compounds—Mechanistic Insights

Abstract

We report a new one-pot synthesis of 2-trifluoromethylated/2-perfluoroalkylated N-aryl-substituted pyridiniums, 5,6,7,8-tetrahydroquinoliniums and 6,7,8,9-tetrahydro-5H-cyclohepta[b]-pyridinium compounds starting from an activated β-dicarbonyl analogue (here a perfluoro-alkylated gem-iodoacetoxy derivative), an aromatic amine and a (cyclic or acyclic) ketone. The key step of this multicomponent reaction, involves the formation of a 3-perfluoroalkyl-N,N’-diaryl-1,5-diazapentadiene intermediate, various examples of which were isolated and characterized for the first time, together with investigation of their reactivity. We propose a mechanism involving a concurrent inverse electron demand Diels-Alder or Aza-Robinson cascade cyclisation, followed by a bis-de-anilino-elimination. Noteworthy, a meta-methoxy substituent on the aniline directs the reaction towards a 2-perfluoroalkyl-7-methoxyquinoline, resulting from the direct cyclization of the diazapentadiene intermediate, instead of pyridinium formation. This is the first evidence of synthesis of pyridinium derivatives from activated β-dicarbonyls, ketones, and an aromatic amine, the structures of which (both reactants and products) being analogous to species involved in biological systems, especially upon neurodegenerative diseases such as Parkinson’s. Beyond suggesting chemical/biochemical analogies, we thus hope to outline new research directions for understanding the mechanism of in vivo formation of pyridiniums, hence possible pharmaceutical strategies to better monitor, control or prevent it.

1. Introduction

Compounds containing a pyridinium moiety are important in natural product chemistry [1,2,3,4] and in organic synthesis [5,6,7]. The presence of various substituents, either on the pyridine ring or at the nitrogen atom of the ring, make these important scaffolds versatile compounds used in various areas, ranging from pharmaceutical to industrial chemical applications.

Pyridinium compounds are generally employed as acylating agents [8], phase transfer catalysts [9], dyes [1] and cationic surfactants [9]. 1-Alkylpyridinium derivatives which are liquid at rt., so-called ionic liquids, are potential new solvents for synthesis and catalysis [5]. Pyridinium compounds have been also used to achieve asymmetric and regioselective synthesis by additions of Grignard reagent [10]. Moreover, pyridinium compounds are widely applied as synthetic building blocks to obtain substituted pyridines, dihydropyridines or piperidines [11]. Other N-methyl-pyridinium derivatives have been investigated as new materials, for example, to allow ionic bonding necessary for molecular packing in self-organized solids [12].

On the other hand, quaternary pyridinium derivatives are unsaturated heterocyclic surfactants, generally known for their germicidal properties with a wide range of antimicrobial activity [13,14,15], as well as against some pathogenic species of fungi and protozoa [16].

Also, it was reported that quaternary ammonium compounds react with cell walls and have a direct or indirect lethal effect on the cell [17]. Related quaternary pyridinium derivatives have been tested for anticancer [18], and anti-malarial activity [19,20], and as cholinesterase inhibitors for the treatment of Alzheimer’s disease [21,22,23].

Moreover, pyridinium ions have been incorporated in drug candidates to improve their water solubility [24,25,26]. Otherwise, the use of pyridinium ions bearing lipophilic groups has been shown to improve their accumulation in mitochondria to scavenge or detect radicals generated there [27,28].

Recently, pyridinium amphiphiles were shown to generate promising transfection systems for gene therapy [29,30,31,32]. Several supramolecular pyridinium containing complexes proved to be extremely efficient nucleic acid delivery systems, displaying excellent serum stability and tissue penetration [30,32].

The association of pyridinium derivatives with the appearance of Parkinson’s disease, led to a search for pyridinium analogs as possible endogenous or exogenous neurotoxins critical to this neurodegeneration [33]. For example, 1-methyl-4-phenylpyridinium (MPP+) 1 is the most popular molecule used to induce Parkinsonism in vivo (Scheme 1) [34,35,36]. More recently, pyridinium furosemide (PF) 2, has been also used as a model in helping to identify specific events of Parkinson’s disease [37].

Besides, pyridinium containing compounds are used as herbicides [38,39], drugs [13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32], and as intermediates in the synthesis of many heterocyclic compounds [1,2,3,4,5,6,7,11] and are considered as possible exogenous neurotoxins [40,41,42]. However, several lines of evidence suggest that pyridinium derivatives may be formed under endogenous conditions [43], for example during the Maillard reaction between proteins and carbonyl compounds [43,44,45].

Synthesis of Pyridinium Compounds—A Short Literature Survey

The best-known method for the synthesis of N-(hetero)arylpyridinium salts is the Zincke amine exchange reaction [46,47,48,49,50], which requires a two-step procedure (Scheme 2): First a pyridine 3 is reacted with 1-chloro-2,4-dinitrobenzene (4, X = Cl) to give an N-(2,4-dinitrophenyl)pyridinium chloride 5. This highly electrophilic compound 5 is then reacted with an (hetero)arylamine to give a new N-(hetero)arylpyridinium salt 6 with elimination of 2,4-dinitroaniline [46,47,48,49,50]. This reaction will work best if R is an electron-donor substituent.

Besides, several synthetic routes to N-alkylpyridinium compounds 7 are known, but the most commonly used method is the Menschutkin reaction, an SN₂ reaction of a pyridine derivative 3 with an alkyl halide or sulfonate (R’-X) (Scheme 2) [51,52]. This reaction is favored by electron-donor substituents R on the pyridine ring. Moreover, pyridinium salts 6 and 7 are also synthesized from the ring transformation reaction of pyrylium derivatives 8 with primary alkyl or (hetero)arylamines (Scheme 2) [53,54].

Pyridinium compounds may also be synthesized by the Chichibabine reaction [55,56,57,58] based on the [2+2+1+1] approach, involving an acid-mediated reaction between three equivalents of an enolisable aldehyde 9 and one equivalent of amine 10. Typically, three products can be isolated from this reaction (Scheme 3); a major product, 1,2,3,5-tetrasubstituted pyridinium 12, which is formed via the auto-oxidation of the product 1,2,3,5-dihydropyridinium 11, and a minor product 1,3,5-trisubstituted pyridinium derivative 13. However, the Chichibabine reaction requires harsh conditions, give low yields with numerous difficult to separate side products [57,58].

In previous articles [59,60,61,62,63,64,65] we have reported the synthesis of various perfluoroalkylated quinoline derivatives, by reacting perfluoroalkylated gem-iodoacyloxy derivatives 14 with substituted anilines 15. Later we observed that the presence of a ketone in the medium leads to the formation of arylpyridiniums instead of quinolines; what suggested an interesting alternative to published synthetic methods, and led us to design a new and efficient synthesis of substituted 2-trifluoromethyl and 2-perfluoroalkyl-N-arylpyridinium derivatives 17–19 under mild reaction conditions and with very good yields. Mechanistic studies addressing possible intermolecular cycloaddition reactions are detailed, underlying possible chemical/biochemical mechanistic analogies in relation to the formation of pyridinium derivatives under biological conditions.

2. Results and Discussion

2.1. Synthesis

We report the reaction of 1-acetoxy-2-(perfluoroalkyl)-1-iodo-ethane 14–14” and various anilines 15a-n in the presence of acetone 16t (R₁ = CH₃, R₂ = H), leading to the formation of 2-trifluoromethyl and 2-perfluoroalkyl-6-methyl-N-arylpyridinium derivatives 17a–n’ in fair to excellent yields (50–90%) (Scheme 4,

Table 1. Reaction conditions and conversions for the synthesis of substituted 2-trifluoromethyl-/2-perfluoroalkyl-N-arylpyridinium compounds 17a–n’, using acetone 16t as reactant.

Entry	14		15		Time	Pyridiniums 17	Conv.
		RF		R	(h)		[%]a
1	14	C5F11	15a	H	4	17a	95
2	14’	CF3	15a	H	4	17a’	95
3	14’’	C3F7	15a	H	4	17a’’	95
4	14	C5F11	15b	o-Me	6	17b	80
5	14	C5F11	15c	m-Me	4	17c	85
6	14	C5F11	15d	p-Me	4	17d	88
7	14’	CF3	15d	p-Me	4	17d’	88
8	14	C5F11	15e	o-Et	6	17e	75
9	14	C5F11	15f	m-Et	4	17f	80
10	14	C5F11	15g	p-Et	4	17g	83
11	14’	CF3	15g	p-Et	4	17g’	85
12	14	C5F11	15h	o-Cl	12	17h	65
13	14	C5F11	15i	m-Cl	6	17i	75
14	14	C5F11	15j	p-Cl	6	17j	83
15	14	C5F11	15k	o-OMe	6	17k	75
16	14	C5F11	15l	p-OMe	4	17l	78
17	14	C5F11	15m	o-CO2H	12	17m	50
18	14’	CF3	15m	o-CO2H	12	17m’	52
19	14	C5F11	15n	p-CO2H	12	17n	60
20	14’	CF3	15n	p-CO2H	12	17n’	62

^a Determined by ¹⁹F-NMR analysis; NMR yield based on consumed 14 and formed 17.

). This reaction was then exemplified using two cyclic ketones, namely cyclohexanone 16u and cycloheptanone 16v, both of which reacted smoothly to give the corresponding 2-trifluoromethyl-/2-perfluoroalkyl-N-(R-phenyl)-5,6,7,8-tetrahydroquinoliniums 18a–n (R₁-R₂ = -(CH₂)₄-;

Table 2. Reaction conditions and conversions for the preparation of substituted 2-trifluoromethyl-/2-perfluoroalkyl-N-(R-phenyl)-5,6,7,8-tetrahydroquinoliniums 18a–n, using cyclohexanone 16u as reactant.

Entry	14		15		Time	Pyridiniums 18	Conv.
		RF		R	(h)		[%]a
1	14	C5F11	15a	H	4	18a	85
2	14’	CF3	15a	H	4	18a’	88
3	14	C5F11	15b	o-Me	6	18b	85
4	14	C5F11	15c	m-Me	4	18c	85
5	14	C5F11	15d	p-Me	4	18d	85
6	14	C5F11	15g	p-Et	4	18g	86
7	14	C5F11	15i	m-Cl	6	18i	78
8	14	C5F11	15l	p-OMe	6	18l	90
9	14	C5F11	15m	o-CO2H	12	18m	75
10	14	C5F11	15n	p-CO2H	12	18n	75

^a Determined by ¹⁹F-NMR analysis; NMR yield based on consumed 14 and formed 18.

) in good to excellent yields (75–90%) and 2-trifluoromethyl-/2-perfluoroalkyl-N-(R-phenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridiniums 19a–m (R₁–R₂ = -(CH₂)₅-;

Table 3. Reaction conditions and conversions for the preparation of 2-trifluoromethyl-/2-perfluoroalkyl-N-(R-phenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridiniums 19a–m, using cyclo-heptanone 16v as reactant.

Entry	14		15		Time	Pyridiniums 19	Conv.
		RF		R	(h)		[%]a
1	14	C5F11	15a	H	4	19a	85
2	14	C5F11	15c	m-Me	4	19c	83
3	14	C5F11	15d	p-Me	4	19d	85
4	14	C5F11	15f	m-Et	4	19f	88
5	14	C5F11	15g	p-Et	4	19g	85
6	14	C5F11	15i	m-Cl	4	19i	70
7	14	C5F11	15j	p-Cl	4	19j	78
8	14	C5F11	15k	o-OMe	6	19k	72
9	14	C5F11	15l	p-OMe	4	19l	88
10	14	C5F11	15m	o-CO2H	12	19m	70

^a Determined by ¹⁹F-NMR analysis; NMR yield based on consumed 14 and formed 19.

), respectively. All reactions proceeded with good to very good yields (70–90%).

The numbering scheme for the investigated examples in compound series 17–19, is the following: (i) the numbers 17–19 denote the compound series depending on the reacting ketone 16t–v; (ii) the letter a–n denotes the aryl substituent inherited from the aniline substrate 15; (iii) the appended ’ or ” denotes the perfluoroalkyl chain R_F from perfluoroalkyl substrate 14: R_F = C₅F₁₁ (14), CF₃ (14’) or C₃F₇ (14”) respectively. For instance, 17a is obtained from 15a and 14, or 17n’ is obtained from 15n and 14’.

Thorough screening of reactants stoichiometries and reaction conditions (monitoring by TLC and ¹⁹F-NMR spectroscopy), allowed us to identify optimized conditions giving the best overall yields: namely one equivalent of gem-iodoacetate 14–14”, three equivalents of arylamine 15a–o and 1.2 equivalents of ketone 16t–v in refluxing anhydrous dichloromethane. Reactions were typically completed within 4–12 h. A straightforward work-up allowed the isolation of pyridinium products 17–19, through: (i) filtering off the excess anilinium salts that precipitated at the end of the reaction, then (ii) precipitating the product from the filtrate by addition of an appropriate solvent. Further purification of 17–19 was carried out by final precipitation from dichloromethane-ether mixture, pure 2-perfluoroalkyl-N-arylpyridinium iodides 17–19 being isolated as amorphous solids.

2.2. Structure Determination of N-Arylpyridiniums 17–19

Structural assignments were accomplished without ambiguity by ¹H-, ¹³C- and ¹⁹F-NMR as well as 2D ¹H-¹H (COSY) and ¹H-¹³C (HETCOR) NMR correlations. As an example, the NMR spectra of 6-methyl-2-perfluoropentyl-1-phenylpyridinium 17a (R = R₂ = H, R₁ = CH₃, R_F = C₅F₁₁) (Figure 1) are typical and will be described in details: the ¹H- and ¹³C-NMR spectra contain six and ten distinct resonances, respectively (see 1D ¹H and ¹³C-NMR in Supplementary Materials).

In its ¹H-NMR spectrum, the singlet at δ_H 2.6 ppm (3H) is readily assigned to the methyl group which show a cross peak with the ¹³C resonance at δ_C 25 ppm in the ¹H-¹³C HETCOR chart. Noticeably, upon shaking the samples dissolved in CDCl₃ with one droplet of D₂O, the methyl resonance of 17a readily disappears from the ¹H spectrum, denoting a rapid H/D exchange which is explained by the acidic character of the protons on alkyl substituents of the pyridinium ring.

¹H resonances corresponding to the N-phenyl moiety, are divided into two groups: first a 3H multiplet is observed at δ_H 7.5–7.6 ppm corresponding to the H_m and H_p on the meta- and para- positions. Then, a slightly deshielded doublet resonance at δ_H 7.7 ppm corresponds to the two H_o protons at ortho- positions. On the HETCOR chart, the meta- and para-hydrogens resonances show cross peaks with ¹³C resonances at δ_C 130.5 and 132.5 ppm, while the ortho- proton resonance also show a clear cross peak with the ¹³C resonance at δ_C 126.7 ppm.

Besides, the most deshielded resonances at δ_H 8.3, 8.7 and 9.1 ppm, were assigned to the three vicinal hydrogen atoms on the pyridinium nucleus (H3, H4 and H5) (Figure 1 and 1D ¹H-NMR in Supporting Information). This can be confirmed in the ¹H-¹H COSY chart where clear cross peaks between those three resonances at δ_H 8.3, 8.7 and 9.1 ppm are observed. Moreover, those resonances exhibit ³J_H–H couplings constants of ca. 8–8.1 Hz characteristic of aromatic hydrogens.

Among them, the most deshielded resonance (δ_H 9.1 ppm) is a triplet signal, thus corresponding to H4, due to vicinal couplings with two neighboring protons H3/H5 the resonances of which indeed appear as two doublets at δ_H 8.3 and 8.7 ppm, which correlate with ¹³C resonances at δ_C 128.8 and 136.2 ppm respectively on the HETCOR chart. The final assignment between H3 and H5 was made on basis of the presence of a 2.5 Hz triplet coupling on the 128.8-ppm ¹³C resonance explained as a ³J_CFcoupling with fluorine nuclei on the vicinal CF₂ group; thus both signals δ_H 8.3 ppm and δ_C 128.8 ppm belong to the H3/C3 position of the pyridinium ring, while the δ_H 8.7 ppm and δ_C 136.2 ppm corresponds to H5/C5.

Three additional ¹³C resonances in the aromatic shift range, correspond to quaternary carbons (invisible on DEPT spectra): the signal at δ_C 140.8 ppm appearing as a large triplet denotes a strong coupling with fluorine nuclei of vicinal CF₂ group (²J_CF = 26.3 Hz), thus can nonambiguously be attributed to carbon C2. Besides, on basis of a higher deshielding by the pyridinium ring, the two other resonances at δ_C 163.8 and 137.8 ppm, were assigned to the carbon C6 and the ipso carbon of the N-phenyl, respectively (Figure 1).

Interestingly, we also observed a large deshielding of the ¹⁹F-NMR resonance of the α-CF₂ directly attached to the pyridinium ring, probably because of the high electron-withdrawing effect of the adjacent positively charged nitrogen atom. This was similarly observed on the whole series of perfluoroalkyl-substituted pyridiniums 17–19.

2.3. The m-Anisidine Case

A notable exception to the above synthesis results, was observed however with a meta-methoxy substitution on substrate 15o (m-anisidine) where the only observed and isolated product was the corresponding 2-perfluoroalkyl- or 2-trifluoromethyl-7-methoxyquinolines 20o (R_F = C₅F₁₁) or 20o’ (R_F = CF₃) in 80–90% yields (Scheme 5 and

Table 4. Reaction conditions and conversions obtained for the formation of substituted 2-perfluoropentyl-/2-trifluoromethyl-7-methoxyquinolines (20o–o’), starting from m-anisidine 15o, with or without ketone 16t–v.

Entry	14		16	Time	Conv.	Quinolines 20
		RF		(h)	[%]a
1	14	C5F11	16t	12	85	20o
2	14	C5F11	16u	12	80
3	14	C5F11	16v	12	82
4	14	C5F11	-	12	86
5	14’	CF3	16t	12	90	20o’
6	14’	CF3	-	12	92

^a Determined by ¹⁹F-NMR analysis; NMR yield based on consumed 14 and formed 19.

); while the ketone 16 was recovered at the end of the reaction (isolated and identified by NMR and mass spectrometry). In the absence of ketone 16 (namely upon reacting 14/14’ with three equivalents of 15o under identical conditions) the same result was observed with similar yields of 20, what is actually consistent with our previous investigations on such reactions [64].

2.4. Reactivity Investigation—Intermediate Isolation

Based on the observed reaction extents and required time for completion according to the substituents (Table 1, Table 2 and Table 3), this series of investigated examples provided preliminary insights on the reactivity of the system, where a primary factor of influence is likely the substitution of aniline 15. For instance, the presence of an electron-withdrawing group on the aromatic ring of 15 resulted in longer reaction times being required to reach completion, as observed e.g., with R = Cl or CO₂H at any o-, m-, p- position (Table 1, entries 12–14, 17–20; Table 2 entries 7, 9, 10; Table 3, entries 6–7, 10). An ortho-substituted aniline 15 also resulted in an extended reaction time, whenever the o-substituent was electron-donating or electron-withdrawing (R = o-Me, o-Et, o-OMe, o-Cl and o-CO₂H; Table 1, entries 4, 8, 12, 15, 17–18; Table 2, entries 3, 9; Table 3, entries 8, 10).

In order to better understand the mechanism of this reaction, its evolution was monitored by ¹⁹F-NMR spectroscopy, carried out on aliquots of the reaction medium diluted in CDCl₃ or DMSO-d₆, then comparing the spectra of reaction mixtures with NMR data of compounds already investigated and characterized in the course of our previous studies on gem-iodoacetoxy related systems [59,60,61,62,63,64,65].

We thus observed that the consumption of the starting 1-acetoxy-1-iodo-2-(perfluoroalkyl)-ethanes 14–14” was accompanied by the formation of an intermediate compound, the latter further disappeared while the final 2-perfluoroalkyl-N-arylpyridinium products 17–19 were gradually formed. Comparison with our previous NMR data provided fair assumption that such intermediate might be an N,N’-diaryl-2-(perfluoroalkyl)-1,5-diazapenta-1,3-diene 21 (Scheme 6), a few examples of which had previously been described by us [59,63,64].

In the absence of ketone 16 as reactant, and upon changing the other reactant stoichiometries to those stated in our previous works [64] namely 1 equiv. 14–14” and 2 equiv. 15 (in DCM at rt: 21a–l,o–o’; or refluxing: 21m–n’), the main reaction product was the intermediate 21, the latter (21a–o’) have been isolated in fair yields then characterized by NMR and mass spectrometry (Scheme 6). All N,N’-diaryl-2-(perfluoroalkyl)-1,5-diazapenta-1,3-dienes 21a–o’ were actually isolated as mixtures of E/Z-stereoisomers, as in our previous works [59,64,65].

2.5. Reactivity of Diazapentadienes 21

We then investigated the reactivity of diazapentadienes intermediates 21a–o’ in the presence of ketones 16a–c, where we noticed that the presence of an additional amount of aniline 15 is necessary to achieve pyridinium 17–19 formation. Thus, upon reacting isolated intermediates 21 with 1.2 equivalents of ketone 16 and one equivalent of arylamine 15 (the same substitution as used in the formation of 21) in the presence of hydrogen iodide in refluxing dichloromethane, the consumption of 21 (monitored by TLC and ¹⁹F-NMR spectroscopy) was accompanied with the formation of the corresponding 2-perfluoroalkyl-N-arylpyridiniums 17–19. Noteworthy from a reactivity/mechanistic viewpoint, to our knowledge this is the first experimental evidence of the formation of arylpyridinium compounds from an N,N’-diaryl-1,5-diazapenta-1,3-diene intermediate.

In the m-methoxy case (substrate 15o), while the derived diazapentadiene intermediate 21o/o’ was formed and isolated under identical conditions and with same yields as other examples a-n, the subsequent reaction of isolated 21o/o’ in the presence of ketone 16 under the same conditions (one equiv. 15o under acidic conditions), formed the 2-perfluoroalkyl-7-methoxyquinolines 20o/o’ as the only products (Scheme 6, lower path), a result actually identical to the reaction of 21o/o’ with 15 in the absence of ketone [64].

Based on required reactant stoichiometry, the mechanism of the reactions may be rationalized as follows (Scheme 7). In a first step, the gem-iodoacetoxy substrate 14/14” reacts with two equivalents of arylamine 15 to form the corresponding diazapentadiene 21, according to our previously reported investigations [64]. Meanwhile, another equivalent of arylamine 15 may condense with ketone 16 through an acid catalyzed, addition-elimination mechanism to give a tautomeric N-phenyl-imino/enamine intermediate 22 (Scheme 7). Then, the resulting intermediates 21 and 22 may react together through two probably competing cyclization cascade mechanisms [66,67,68,69,70]: either: (i) an inverse electron demand Diels-Alder (IEDDA) reaction involving the cycloaddition of the diene 21 and the electron-rich dienophile 22, or (ii) an aza-Robinson annulation-type reaction involving a Michaël addition of enamine 22 to diazapentadienes 21 then subsequent aminal-cyclisation. Both mechanisms could give a bis-anilinotetrahydropyridine (BATHP) intermediate 23. The latter then undergoes a double de-anilino-elimination, thus yielding the corresponding N-arylpyridinium iodides 17–19 (Scheme 7).

2.6. Formation of 2-Perfluoroalkyl-7-Methoxyanilines 20o–o’

The key step of this mechanism is the protonation of 21o and the formation of a conjugated iminium intermediate (Scheme 8). Then Michael addition of m-methoxyaniline 15o gives a cationic bis-anilino intermediate which undergo an intramolecular electrophilic aromatic cyclisation assisted by the electron-donating methoxyl group with subsequent elimination of a m-methoxyaniline. Then a prototropy induced by anilino-group followed by the loss of a proton and a second m-methoxyaniline result in the generation of an aromatic ring and the formation of 2-perfluoroalkyl-7-methoxyanilines 20o–o’.

Conversely in the case of an m-methoxy substituted arylamine, the electron-donation ability of the methoxy- substituent on the N,N’-(3-methoxyphenyl)-2-(perfluoroalkyl)-1,5-diazapentadienes 21o–o’, may promote their direct intramolecular cyclization to 20 (Scheme 8) [59,64], the latter route also taking advantage of an entropically favorable (unimolecular) cyclization over a bimolecular addition of 21o–o’ with 22o.

Indeed, the literature [71] states that electronic and steric effects of substituents have very pronounced influence on both intermolecular Michaël 1,4-additions or Diels-Alder cycloadditions. Many studies show that stereoelectronic requirements for certain intermolecular reaction and the resulting increase in the potential energy for the corresponding transition states, could be so high that intramolecular cyclisation could take place instead [71]. In both cases anyway (either cycloaddition or cyclization), the subsequent elimination of two aniline molecules, may ensure irreversibility, again because of entropic effects.

3. Materials and Methods

3.1. General Methods

All reaction solvents were purchased from commercial suppliers and distilled before use. All synthetic reactions were performed in oven-dried glassware, and their progress was monitored by thin layer chromatography (TLC) using silica gel plates, and by ¹⁹F-NMR spectroscopy of aliquots. Chromatographic column purifications were performed on silica gel (40–63 μm). ¹H, ¹³C, and ¹⁹F-NMR spectra were recorded in either CDCl₃ or DMSO-d₆ solution on an Avance 300 (300 MHz) or an Avance 400 (400 MHz) spectrometer (Bruker, Billerica, MA, USA). Chemical shifts are reported in ppm, using the solvent signal chemical shift as a reference. Abbreviations used in the description of NMR spectra: s: singlet, d: doublet, t: triplet, q: quadruplet, bs: broad signal. Coupling constants (J) are given in Hertz. Mass spectra (either low- or high-resolution) were recorded on a SX102 mass spectrometer (JEOL, Tokyo, Japan) in FAB+ mode, using 3-nitrobenzyl alcohol matrix. Elemental analyses were carried out on a Flash 2000 elemental analyzer (Thermo Finnigan, Waltham, MA, USA).

3.2. General Procedure for the Synthesis 2-Trifluoromethylated and 2-Perfluoroalkylated 6-Methyl-N-(R-Phenyl)Pyridinium Iodides (17a–l), N-(R-Phenyl)-5,6,7,8-Tetrahydroquinolinium Iodides (18a–l) and N-(R-Phenyl)-6,7,8,9-Tetrahydro-5H-Cyclohepta[B]Pyridinium Iodides (19a–l) (All examples except R = CO₂H or R = M-Ome)

To a stirred solution of 1-acetoxy-1-iodo-perfluoroalkylethane compounds 14 (1 equiv.) in anhydrous dichloromethane (10 mL DCM for 1g of 14), was added 3 equiv. of the corresponding substituted aniline 15 and 1.2 equiv. of ketone 16. The mixture was stirred under reflux for the desired time (4–12 h, Table 1, Table 2 and Table 3) until complete consumption of 14 (monitored by TLC eluent petroleum ether/ethyl acetate: 80/20 v/v and ¹⁹F-NMR spectroscopy of aliquots). When the reaction was completed, the mixture was allowed to cool to r.t. then the brown precipitate accumulated during the reaction was separated by vacuum filtration (it was subsequently identified as anilinium salts by NMR and MS). Then ethyl ether was added to the filtrate and the corresponding pyridinium iodides 17a–l, 18a–l, and 19a–l precipitate instantly and were isolated by vacuum filtration as amorphous solids.

2-Perfluoropentyl-6-methyl-N-phenylpyridinium iodide (17a). Aniline 15a (5.24 g, 5.63 × 10⁻² mole) and acetone (16t, 1.65 mL, 1.3 g, 2.25 × 10⁻² mole) were added to a solution of 14 (R_F = C5F11, 10 g, 1.87 × 10⁻² mole) in dry dichloromethane (100 mL). The mixture was stirred for 2 h at reflux to afford 9.55 g of the title product 17a, total yield 90%. ¹H-NMR (400.13 MHz, CDCl₃) δ 2.6 (s, 3H, CH₃), 7.5–7.6 (m, 3H, Ph-H), 7.7 (d, J = 7.1 Hz, 2H, Ph-H), 8.3 (d, J = 8 Hz, 1H, Py-H), 8.7 (d, J = 8 Hz, 1H, Py-H), 9.1 (t, J = 8.1 Hz, 1H, Py-H); ¹H-NMR (400.13 MHz, CDCl₃+D₂O) δ 7.5–7.6 (m, 3H, Ph-H), 7.7 (d, J = 7.2 Hz, 2H, Ph-H), 8.3 (d, J = 8 Hz, 1H, Py-H), 8.7 (d, J = 8.1 Hz, 1H, Py-H), 9.1 (t, J = 8.1 Hz, 1H, Py-H); ¹³C-NMR (100.6 MHz, CDCl₃) δ 25 (s, CH₃), 126.7, 128.8 (t, ³J_CF = 2.5 Hz), 130.4, 132.5, 136.2, 137.8, 140.8 (t, ²J_CF = 26.3 Hz), 148, 163.8; ¹⁹F-NMR (235.3 MHz, CDCl₃) δ −126.5 (m 2F, CF₂-CF₂-CF₂-CF₂-CF₃), −123 (m 2F, CF₂-CF₂-CF₂-CF₂-CF₃), −118 (m 2F, CF₂-CF₂-CF₂-CF₂-CF₃), −102.5 (m 2F, CF₂-CF₂-CF₂-CF₂-CF₃), −81.5 (m 3F, CF₂-CF₂-CF₂-CF₂-CF₃). MS (m/z): 438 ([M − I]⁺, 100). HRMS calcd. for C₁₇H₁₁F₁₁N⁺ 438.0716, found 438.0720. Anal. Calcd. for C₁₇H₁₁F₁₁NI: C, 36.13; H, 1.96; N, 2.48. Found: C, 36.15; H, 1.95; N, 2.46.

2-Trifluoromethyl-6-methyl-N-phenylpyridinium iodide (17a’). Aniline 15a (8.4 g, 9 × 10⁻² mol) and acetone (16t, 2.7 mL, 2 g, 3.61 × 10⁻² mol) were added to a solution of 14’ (R_F = CF3, 10 g, 3 × 10⁻² mol) in dry dichloromethane (100 mL). The mixture was stirred for 2 h at reflux to give 9.9 g of the title product 17a’, total yield 90%. Spectral data: ¹H-NMR (300.13 MHz, CDCl₃) δ 2.6 (s, 3H, CH₃), 7.5–7.6 (m, 3H), 7.8 (d, J = 9 Hz, 2H), 8.5 (dd, J = 9 and 3 Hz, 1H), 8.6 (dd, J = 9 and 3 Hz, 1H), 9 (t, J = 9 Hz, 1H); ¹³C-NMR (75.46 MHz, CDCl₃) δ 24.1 (s, CH₃), 118.6 (q, CF₃, ¹J_CF = 276.9 Hz), 125.6 (q, ³J_CF = 5.2 Hz), 125.7, 130.1, 132.3, 135.1, 136.7, 140.9 (q, C-CF₃, ²J_CF = 35.4 Hz), 148, 162.5; ¹⁹F-NMR (282.4 MHz, CDCl₃) δ −59.8 (s 3F, CF₃). MS (m/z): 238 ([M − I]⁺, 100). HRMS calcd. for C₁₃H₁₁F₃N⁺: 238.0844, found 238.0848. Anal. Calcd. for C₁₃H₁₁F₃NI: C, 42.76; H, 3.04; N, 3.84. Found: C, 42.78; H, 3.05; N, 3.82.

2-Perfluoropropyl-6-methyl-N-phenylpyridinium iodide (17a’’). Aniline 15a (6.45 g, 6.94 × 10⁻² mol) and acetone (16t, 1.6 mL, 2 g, 2.77 × 10⁻² mol) were added to a solution of 14’’ (R_F = C3F7, 10 g, 2.31 × 10⁻² mol) in dry dichloromethane (100 mL). The mixture was stirred for 2 h at reflux, affording 9.69 g of the title product 17a’’, total yield 91%. Spectral data: ¹H-NMR (400.13 MHz, CDCl₃) δ 2.6 (s, 3H, CH₃), 7.5–7.6 (m, 3H), 7.7 (d, J = 7 Hz, 2H), 8.3 (d, J = 8.1 Hz, 1H), 8.8 (d, J = 8 Hz, 1H), 9 (t, J = 8 Hz, 1H); ¹³C-NMR (100.6 MHz, CDCl₃) δ 25.1 (s, CH₃), 126.5, 128.7 (t, ³J_CF = 2.5 Hz), 130.4, 132.2, 136.1, 137.7, 140.9 (t, ²J_CF = 26.5 Hz), 148, 163.7; ¹⁹F-NMR (235.3 MHz, CDCl₃) δ −127 (m 2F, CF₂), −102 (m 2F, CF₂), −80.5 (m 3F, CF₃). MS (m/z): 338 ([M − I]⁺, 100). HRMS calcd. for C₁₅H₁₁F₇N⁺: 338.0780, found 338.0782. Anal. Calcd. for C₁₅H₁₁F₇NI: C, 38.73; H, 2.38; N, 3.01. Found: C, 38.75; H, 2.39; N, 3.04.

2-Perfluoropentyl-6-methyl-N-(2-methylphenyl)pyridinium iodide (17b). 2-Methylaniline (15b, 6 g, 5.63 × 10⁻² mol) and acetone (16t, 1.66 mL, 1.3 g, 2.25 × 10⁻² mol) were added to a solution of 14 (R_F = C₅F_11, 10 g, 1.87 × 10⁻² mol) in dry dichloromethane (100 mL). The mixture was stirred for 4 h at reflux, to give 8.7 g of the title product 17b, total yield 80%. Spectral data: ¹H-NMR (400.13 MHz, CDCl₃) δ 2.5 (s, 3H, CH₃), 2.6 (s, 3H, CH₃), 7.4–7.6 (m, 4H), 7.9 (t, J = 7.2 Hz, 1H), 8.2 (d, J = 8.1 Hz, 1H), 8.9 (d, J = 8.2 Hz, 1H); ¹³C-NMR (100.6 MHz, CDCl₃) δ 20.1 (s, CH₃), 25 (s, CH₃), 127, 128.5 (t, ³J_CF = 2 Hz), 130.5, 131.9, 136.1, 138, 141.1 (t, ²J_CF = 26 Hz), 148, 163.5; ¹⁹F-NMR (282.4 MHz, CDCl₃) δ −125.7 (m 2F, CF₂), −122.1 (m 2F, CF₂), −118.2 (AB system, ²J_FF = 338.8 Hz, 1F, CF₂-CF₂-CF₂), −116 (AB system, ²J_FF = 338.8 Hz, 1F, CF₂-CF₂-CF₂), −108.5 (AB system, ²J_FF = 282.5 Hz, 1F, CF₂-CF₂-CF₂), −98 (AB system, ²J_FF = 282.5 Hz, 1F, CF₂-CF₂-CF₂), −80.6 (m 3F, CF₃). MS (m/z): 452 ([M − I]⁺, 100). HRMS calcd. for C₁₈H₁₃F₁₁N⁺: 452.0872, found 452.0877. Anal. Calcd. for C₁₈H₁₃F₁₁NI: C, 37.33; H, 2.26; N, 2.42. Found: C, 37.35; H, 2.30; N, 2.40.

2-Perfluoropentyl-6-methyl-N-(3-methylphenyl)pyridinium iodide (17c). 3-Methylaniline (15c, 6.34 g, 5.92 × 10⁻² mol) and acetone (16t, 1.75 mL, 1.37 g, 2.36 × 10⁻² mol) were added to a solution of 14 (R_F = C5F11, 0.5 g, 1.97 × 10⁻² mol) in dry dichloromethane (105 mL). The mixture was stirred for 4 h at reflux to give 9.7 g of the title product 17c, total yield 85%. Spectral data: ¹H-NMR (400.13 MHz, CDCl₃) δ 2.6 (s, 3H, CH₃), 2.7 (s, 3H, CH₃), 7.4–7.6 (m, 4H), 8.3 (d, J = 7.2 Hz, 1H), 8.8 (d, J = 8.1 Hz, 1H), 9.2 (t, J = 8.1 Hz, 1H); ¹³C-NMR (100.6 MHz, CDCl₃) δ 22 (s, CH₃), 26 (s, CH₃), 121, 123, 128 (t, ³J_CF = 2 Hz), 130.5, 132, 136.1, 137, 139 (t, ²J_CF = 25 Hz), 145, 148, 161; ¹⁹F-NMR (282.4 MHz, CDCl₃) δ −126 (s 2F, CF₂), −122.4 (s 2F, CF₂), −117.2 (s 2F, CF₂), −103.5 (AB system, ²J_FF = 310.6 Hz, 1F, CF₂-CF₂), −101.1 (AB system, ²J_FF = 310.6 Hz, 1F, CF₂-CF₂), −80.7 (m 3F, CF₃). MS (m/z): 452 ([M − I]⁺, 95). HRMS calcd. for C₁₈H₁₃F₁₁N⁺: 452.0872, found 452.0875. Anal. Calcd. for C₁₈H₁₃F₁₁NI: C, 37.33; H, 2.26; N, 2.42. Found: C, 37.36; H, 2.28; N, 2.40.

2-Perfluoropentyl-6-methyl-N-(4-methylphenyl)pyridinium iodide (17d). 4-Methylaniline (15d, 5.74 g, 5.35 × 10⁻² mol) and acetone (16t, 1.58 mL, 1.24 g, 2.14 × 10⁻² mol) were added to a solution of 14 (R_F = C5F11, 9.5 g, 1.78 × 10⁻² mol) in dry dichloromethane (95 mL). The mixture was stirred for 4 h at reflux to afford 8.79 g of the title product 17d, total yield 85%. Spectral data: ¹H-NMR (400.13 MHz, CDCl₃) δ 2.65 (s, 3H, CH₃), 2.7 (s, 3H, CH₃), 7.4 (d, J = 8 Hz, 2H), 7.7 (d, J = 8 Hz, 2H), 8.3 (d, J = 8.2 Hz, 1H), 8.8 (d, J = 8.3 Hz, 1H), 9 (t, J = 8.2 Hz, 1H); ¹³C-NMR (100.6 MHz, CDCl₃) δ 25 (s, CH₃), 26.1 (s, CH₃), 122.7, 126.5, 127.7 (t, ³J_CF = 1.5 Hz), 129.9, 130, 135.1, 137.8 (t, ²J_CF = 27.2 Hz), 142.5, 146.6, 150.2, 167.5; ¹⁹F-NMR (282.4 MHz, CDCl₃) δ −126 (s 2F, CF₂), −122.4 (s 2F, CF₂), −117.2 (s 2F, CF₂), −101.6 (s, 2F, CF₂-CF₂), −80.7 (m 3F, CF₃). MS (m/z): 452 ([M − I]⁺, 100). HRMS calcd. for C₁₈H₁₃F₁₁N⁺: 452.0872, found 452.0878. Anal. Calcd. for C₁₈H₁₃F₁₁NI: C, 37.33; H, 2.26; N, 2.42. Found: C, 37.37; H, 2.26; N, 2.39.

2-Trifluoromethyl-6-methyl-N-(4-methylphenyl)pyridinium iodide (17d’). 4-Methylaniline (15d, 8.81 g, 8.22 × 10⁻² mol) and acetone (16t, 2.43 mL, 1.9 g, 3.28 × 10⁻² mol) were added to a solution of 14’ (R_F = CF3, 9.1 g, 2.74 × 10⁻² mol) in dry dichloromethane (91 mL). The mixture was stirred for 4 h at reflux to yield 9.14 g of the title product 17d’, total yield 88%. Spectral data: ¹H-NMR (400.13 MHz, CDCl₃) δ 2.6 (s, 3H, CH₃), 2.7 (s, 3H, CH₃), 7.4 (d, J = 8.1 Hz, 2H), 7.7 (d, J = 8 Hz, 2H), 8.3 (d, J = 8 Hz, 1H), 8.7 (d, J = 8.1 Hz, 1H), 9.2 (t, J = 8.1 Hz, 1H); ¹³C-NMR (75.46 MHz, CDCl₃) δ 24.2 (s, CH₃), 25 (s, CH₃), 118.4 (q, CF₃, ¹J_CF = 276.8 Hz), 124.8 (q, ³J_CF = 5 Hz), 122.5, 125.6, 130, 132.3, 140.9 (q, C-CF₃, ²J_CF = 36 Hz), 147.2, 150, 162.5; ¹⁹F-NMR (282.4 MHz, CDCl₃) δ −59.9 (s 3F, CF₃). MS (m/z): 252 ([M − I]⁺, 95). HRMS calcd. for C₁₄H₁₃F₃N⁺: 252.100, found 252.1010. Anal. Calcd. for C₁₄H₁₃F₃NI: C, 44.35; H, 3.46; N, 3.69. Found: C, 44.38; H, 3.47; N, 3.70.

2-Perfluoropentyl-6-methyl-N-(2-ethylphenyl)pyridinium iodide (17e). 2-Ethylaniline (15e, 7 g, 5.8 × 10⁻² mol) and acetone (16t, 1.7 mL, 1.34 g, 2.32 × 10⁻² mol) were added to a solution of 14 (R_F = C₅F₁₁, 10.3 g, 1.93 × 10⁻² mol) in dry dichloromethane (103 mL). The mixture was stirred for 6 h at reflux to produce 8 g of the title product 17e, total yield 70%. Spectral data: ¹H-NMR (400.13 MHz, CDCl₃) δ 1.3 (t, J = 8 Hz, 3H, CH₂-CH₃), 2.6 (q, J = 8 Hz, 2H, CH₂-CH₃), 2.8 (s, 3H, CH₃), 7.4–7.6 (m, 3H), 8 (s, 1H), 8.2 (d, J = 8 Hz, 1H), 8.9 (d, J = 8.1 Hz, 1H); 9.2 (t, J = 8.1 Hz, 1H); ¹³C-NMR (100.6 MHz, CDCl₃) δ 13.2 (s, CH₂-CH₃), 24.3 (s, CH₂-CH₃), 27.1 (s, CH₃), 124.2, 125.9, 127.8 (t, ³J_CF = 2.1 Hz), 129.6, 131, 136.1, 137.5 (t, ²J_CF = 25 Hz), 146.5, 150.1, 167.7; ¹⁹F-NMR (282.4 MHz, CDCl₃) δ −126 (m 2F, CF₂), −122.9 (AB system, ²J_FF = 289.6 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −121.8 (AB system, ²J_FF = 289.6 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −118.7 (AB system, ²J_FF = 300.9 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −115.9 (AB system, ²J_FF = 300.9 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −108.5 (AB system, ²J_FF = 289.6 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −98.8 (AB system, ²J_FF = 289.6 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −80.7 (m 3F, CF₃). MS (m/z): 466 ([M − I]⁺, 95). HRMS calcd. for C₁₉H₁₅F₁₁N⁺: 466.1029, found 466.1033. Anal. Calcd. for C₁₉H₁₅F₁₁NI: C, 38.47; H, 2.55; N, 2.36. Found: C, 38.48; H, 2.56; N, 2.40.

2-Perfluoropentyl-6-methyl-N-(3-ethylphenyl)pyridinium iodide (17f). 3-Ethylaniline (15f, 7.17 g, 5.92 × 10⁻² mol) and acetone (16t, 1.75 mL, 1.37 g, 2.36 × 10⁻² mol) were added to a solution of 14 (R_F = C5F11, 10.5 g, 1.97 × 10⁻² mol) in dry dichloromethane (105 mL). The mixture was stirred for 4 h at reflux to obtain. 9.36 g of the title product 17f, total yield 80%. Spectral data: ¹H-NMR (300.13 MHz, CDCl₃) δ 1.3 (t, J = 8 Hz, 3H, CH₂-CH₃), 2.7 (s, 3H, CH₃), 2.8 (q, J = 8 Hz, 2H, CH₂-CH₃), 7.4–7.7 (m, 4H), 8.4 (d, J = 6.7 Hz, 1H), 8.9 (d, J = 7.1 Hz, 1H), 9.2 (t, J = 7.9 Hz, 1H); ¹³C-NMR (75.46 MHz, CDCl₃) δ 13 (s, CH₂-CH₃), 23 (s, CH₂-CH₃), 27 (s, CH₃), 121.5, 123.5, 127 (t), 128, 130, 134, 135, 139 (t, ²J_CF = 25 Hz), 145, 146, 162; ¹⁹F-NMR (282.4 MHz, CDCl₃) δ −126 (s 2F, CF₂), −122.4 (s 2F, CF₂), −117.2 (s 2F, CF₂), −102.5 (AB system, ²J_FF = 315.5 Hz, 1F, CF₂-CF₂), −101.5 (AB system, ²J_FF = 315.5 Hz, 1F, CF₂-CF₂), −80.7 (m 3F, CF₃). MS (m/z): 466 ([M − I]⁺, 100). HRMS calcd. for C₁₉H₁₅F₁₁N⁺: 466.1029, found 466.1035. Anal. Calcd. for C₁₉H₁₅F₁₁NI: C, 38.47; H, 2.55; N, 2.36. Found: C, 38.49; H, 2.56; N, 2.33.

2-Perfluoropentyl-6-methyl-N-(4-ethylphenyl)pyridinium iodide (17g). 6.9 g of 4-ethylaniline 15g (5.69 × 10⁻² mol) and 1.68 mL or 1.32 g (2.27 × 10⁻² mol) of acetone 16t were added to a solution of 10.1 g (1.89 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 101 mL of dry dichloromethane. The mixture was stirred for 4 h at reflux. 9.34 g of the title product 17g were obtained, total yield 83%. Spectral data: ¹H-NMR (300.13 MHz, CDCl₃) δ 1.3 (t, J = 8 Hz, 3H, CH₂-CH₃), 2.7 (s, 3H, CH₃), 2.8 (q, J = 8 Hz, 2H, CH₂-CH₃), 7.1 (d, J = 8.4 Hz, 2H), 7.7 (d, J = 8.3 Hz, 2H), 8.4 (d, J = 7.5 Hz, 1H), 8.8 (d, J = 7.8 Hz, 1H), 9.1 (t, J = 7.8 Hz, 1H); ¹³C-NMR (75.46 MHz, CDCl₃) δ 13 (s, CH₂-CH₃), 24 (s, CH₂-CH₃), 26.8 (s, CH₃), 113.5, 126.5, 127.5 (t, ³J_CF = 2 Hz), 129.5, 130, 135, 139 (t, ²J_CF = 25 Hz), 147, 159, 162; ¹⁹F-NMR (282.4 MHz, CDCl₃) δ −126.9 (s 2F, CF₂), −123.3 (s 2F, CF₂), −117.3 (s 2F, CF₂), −101.8 (s, 2F, CF₂-CF₂), −80.7 (m 3F, CF₃). MS (m/z): 466 ([M − I]⁺, 100). HRMS calcd. for C₁₉H₁₅F₁₁N⁺: 466.1029, found 466.1030. Anal. Calcd. for C₁₉H₁₅F₁₁NI: C, 38.47; H, 2.55; N, 2.36. Found: C, 38.48; H, 2.56; N, 2.35.

2-Trifluoromethyl-6-methyl-N-(4-ethylphenyl)pyridinium iodide (17g’). 9.85 g of 4-ethylaniline 15g (8.13 × 10⁻² mol) and 2.4 mL or 1.88 g (3.25 × 10⁻² mol) of acetone 16t were added to a solution of 9 g (2.71 × 10⁻² mol) of 14’ (R_F = CF₃) in 90 mL of dry dichloromethane. The mixture was stirred for 4 h at reflux. 9 g of the title product 17g’ were obtained, total yield 85%. Spectral data: ¹H-NMR (400.13 MHz, CDCl₃) δ 1.3 (t, J = 8 Hz, 3H, CH₂-CH₃), 2.7 (s, 3H, CH₃), 2.8 (q, J = 8 Hz, 2H, CH₂-CH₃), 7.1 (d, J = 8 Hz, 2H), 7.7 (d, J = 8 Hz, 2H), 8.2 (d, J = 8 Hz, 1H), 8.7 (d, J = 8 Hz, 1H), 9 (t, J = 8.1 Hz, 1H); ¹³C-NMR (75.46 MHz, CDCl₃) δ 13.2 (s, CH₂-CH₃), 23.9 (s, CH₂-CH₃), 27 (s, CH₃), 118.1 (q, CF₃, ¹J_CF = 277.6 Hz), 125 (q, ³J_CF = 4.8 Hz), 122.4, 125.7, 130.2, 132, 147.2 (q, C-CF₃, ²J_CF = 35.5 Hz), 149.9, 162; ¹⁹F-NMR (282.4 MHz, CDCl₃) δ −58.9 (s 3F, CF₃). MS (m/z): 266 ([M − I]⁺, 100). HRMS calcd. for C₁₅H₁₅F₃N⁺: 266.1157, found 266.1160. Anal. Calcd. for C₁₅H₁₅F₃NI: C, 45.82; H, 3.85; N, 3.56. Found: C, 45.85; H, 3.86; N, 3.52.

2-Perfluoropentyl-6-methyl-N-(2-chlorophenyl)pyridinium iodide (17h). 7.4 g of 2-chloroaniline 15h (5.8 × 10⁻² mol) and 1.7 mL or 1.34 g (2.32 × 10⁻² mol) of acetone 16t were added to a solution of 10.3 g (1.93 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 103 mL of dry dichloromethane. The mixture was stirred for 12 h at reflux. 6.96 g of the title product 17h were obtained, total yield 60%. Spectral data: ¹H-NMR (400.13 MHz, CDCl₃) δ 2.8 (s, 3H, CH₃), 7.7–7.9 (m, 3H), 8.4 (m, 1H), 8.5 (d, J = 8 Hz, 1H), 8.9 (d, J = 8.1 Hz, 1H); 9.4 (t, J = 8 Hz, 1H); ¹³C-NMR (100.6 MHz, CDCl₃) δ 24.2 (s, CH₃), 128.5, 129.1, 130.1, 130.8, 133.8, 135, 136.2, 140.5 (t, ²J_CF = 24.1 Hz), 148.8, 163.8; ¹⁹F-NMR (282.4 MHz, CDCl₃) δ −126.5 (AB system, ²J_FF = 289 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −125.7 (AB system, ²J_FF = 289 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −122.9 (AB system, ²J_FF = 289.6 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −121.6 (AB system, ²J_FF = 289.6 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −118.7 (AB system, ²J_FF = 299.5 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −115.9 (AB system, ²J_FF = 299.5 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −108.2 (AB system, ²J_FF = 288.6 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −98.8 (AB system, ²J_FF = 288.6 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −80.7 (m 3F, CF₃). MS (m/z): 472 ([M − I]⁺, 90). HRMS calcd. for C₁₇H₁₀ClF₁₁N⁺: 472.0326, found 472.0329. Anal. Calcd. for C₁₇H₁₀ClF₁₁NI: C, 34.05; H, 1.68; N, 2.34. Found: C, 34.08; H, 1.67; N, 2.33.

2-Perfluoropentyl-6-methyl-N-(3-chlorophenyl)pyridinium iodide (17i). 7.55 g of 3-chloroaniline 15i (5.92 × 10⁻² mol) and 1.75 mL or 1.37 g (2.36 × 10⁻² mol) of acetone 16t were added to a solution of 10.5 g (1.97 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 105 mL of dry dichloromethane. The mixture was stirred for 6 h at reflux. 8.28 g of the title product 17i were obtained, total yield 70%. Spectral data: ¹H-NMR (400.13 MHz, CDCl₃) δ 2.7 (s, 3H, CH₃), 7.3 (s, 1H), 7.4–7.6 (m, 2H), 7.7 (m, 1H), 8.3 (d, J = 8 Hz, 1H), 8.5 (d, J = 8 Hz, 1H), 8.8 (t, J = 8 Hz, 1H); ¹³C-NMR (100.6 MHz, CDCl₃) δ 27.3 (s, CH₃), 127.9, 129.6, 131.4, 134.1, 135.5, 138.5 (t, ²J_CF = 25 Hz), 141.1, 150.6, 166.4; ¹⁹F-NMR (282.4 MHz, CDCl₃) δ −121.5 (s 2F, CF₂), −117.5 (s 2F, CF₂), −112.7 (s 2F, CF₂), −97.4 (AB system, ²J_FF = 105.3 Hz, 1F, CF₂-CF₂), −97.1 (AB system, ²J_FF = 105.3 Hz, 1F, CF₂-CF₂), −75.9 (m 3F, CF₃). MS (m/z): 472 ([M − I]⁺, 90). HRMS calcd. for C₁₇H₁₀ClF₁₁N⁺: 472.0326, found 472.0330. Anal. Calcd. for C₁₇H₁₀ClF₁₁NI: C, 34.05; H, 1.68; N, 2.34. Found: C, 34.11; H, 1.65; N, 2.36.

2-Perfluoropentyl-6-methyl-N-(4-chlorophenyl)pyridinium iodide (17j). 7.19 g of 4-chloroaniline 15j (5.63 × 10⁻² mol) and 1.66 mL or 1.3 g (2.25 × 10⁻² mol) of acetone 16t were added to a solution of 10 g (1.87 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 100 mL of dry dichloromethane. The mixture was stirred for 6 h at reflux. 9.58 g of the title product 17j were obtained, total yield 85%. Spectral data: ¹H-NMR (300.13 MHz, CDCl₃) δ 2.5 (s, 3H, CH₃), 7.9 (d, J = 8 Hz, 2H), 8.2 (d, J = 8.1 Hz, 2H), 8.6 (d, J = 8 Hz, 1H), 8.8 (d, J = 7.9 Hz, 1H), 9 (t, J = 7.9 Hz, 1H); ¹³C-NMR (75.46 MHz, CDCl₃) δ 26 (s, CH₃), 113.2, 126, 127.4 (t, ³J_CF = 2.2 Hz), 130.2, 136, 139.2 (t, ²J_CF = 24.8 Hz), 147.2, 158, 162.3; ¹⁹F-NMR (282.4 MHz, CDCl₃) δ −125.8 (s 2F, CF₂), −122.3 (s 2F, CF₂), −117.7 (s 2F, CF₂), −101.8 (s, 2F, CF₂-CF₂), −80.2 (m 3F, CF₃); MS (m/z): 472 ([M − I]⁺, 90). HRMS calcd. for C₁₇H₁₀ClF₁₁N⁺: 472.0326, found 472.0324. Anal. Calcd. for C₁₇H₁₀ClF₁₁NI: C, 34.05; H, 1.68; N, 2.34. Found: C, 34.10; H, 1.68; N, 2.35.

2-Perfluoropentyl-6-methyl-N-(2-methoxyphenyl)pyridinium iodide (17k). 6.8 g of 2-methoxyaniline 15k (5.52 × 10⁻² mol) and 1.63 mL or 1.28 g (2.21 × 10⁻² mol) of acetone 16t were added to a solution of 9.8 g (1.84 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 98 mL of dry dichloromethane. The mixture was stirred for 6 h at reflux. 7.67 g of the title product 17k were obtained, total yield 70%. Spectral data: ¹H-NMR (300.13 MHz, CDCl₃) δ 2.8 (s, 3H, CH₃), 3.7 (s, 3H, OCH₃), 7.1 (d, J = 8.3 Hz, 1H), 7.2 (t, J = 7.6 Hz, 1H), 7.7 (t, J = 8.8 Hz, 1H), 8 (m, 1H), 8.3 (d, J = 8.1 Hz, 1H), 8.8 (d, J = 8.2 Hz, 1H), 9 (d, J = 8.2 Hz, 1H); ¹³C-NMR (75.46 MHz, CDCl₃) δ 22.2 (s, CH₃), 54 (s, OCH₃), 113.1, 128.5, 129.1, 130.8, 133.7, 136.2, 139.9 (t, ²J_CF = 25 Hz), 147, 160, 162.2; ¹⁹F-NMR (282.4 MHz, CDCl₃) δ −126.5 (AB system, ²J_FF = 295 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −125.5 (AB system, ²J_FF = 295 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −122.9 (AB system, ²J_FF = 289 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −121.5 (AB system, ²J_FF = 289 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −119 (AB system, ²J_FF = 288 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −116.5 (AB system, ²J_FF = 288 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −107 (AB system, ²J_FF = 282.5 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −99.5 (AB system, ²J_FF = 282.5 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −80.69 (m 3F, CF₃). MS (m/z): 468 ([M − I]⁺, 100). HRMS calcd. for C₁₈H₁₃F₁₁NO⁺: 468.0821, found 468.0827. Anal. Calcd. for C₁₈H₁₃F₁₁INO: C, 36.32; H, 2.20; N, 2.35. Found: C, 36.35; H, 2.21; N, 2.34.

2-Perfluoropentyl-6-methyl-N-(4-methoxyphenyl)pyridinium iodide (17l). 6.94 g of 4-methoxyaniline 15l (5.63 × 10⁻² mol) and 1.66 mL or 1.3 g (2.25 × 10⁻² mol) of acetone 16t were added to a solution of 10 g (1.87 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 100 mL of dry dichloromethane. The mixture was stirred for 4 h at reflux. 9.62 g of the title product 17l were obtained, total yield 86%. Spectral data: ¹H-NMR (300.13 MHz, CDCl₃) δ 2.7 (s, 3H, CH₃), 3.9 (s, 3H, OCH₃), 7.2 (d, J = 8.5 Hz, 2H), 7.7 (d, J = 8.4 Hz, 2H), 8.4 (d, J = 7.5 Hz, 1H), 8.8 (d, J = 7.8 Hz, 1H), 9.1 (t, J = 7.8 Hz, 1H); ¹³C-NMR (75.46 MHz, CDCl₃) δ 22.3 (s, CH₃), 54.2 (s, OCH₃), 113, 128.7 (t, ³J_CF = 2 Hz), 129.4, 130.5, 133, 136.1, 140 (t, ²J_CF = 25 Hz), 147, 160.2, 162.5; ¹⁹F-NMR (282.4 MHz, CDCl₃) δ −126.1 (s 2F, CF₂), −122.3 (s 2F, CF₂), −117.1 (s 2F, CF₂), −101.8 (s, 2F, CF₂-CF₂), −80.7 (m 3F, CF₃). MS (m/z): 468 ([M − I]⁺, 100). HRMS calcd. for C₁₈H₁₃F₁₁NO⁺: 468.0821, found 468.0830. Anal. Calcd. for C₁₈H₁₃F₁₁INO: C, 36.32; H, 2.20; N, 2.35. Found: C, 36.39; H, 2.21; N, 2.38.

2-Perfluoropentyl-N-(phenyl)-5,6,7,8-tetrahydroquinolinium iodide (18a). 5.24 g of aniline 15a (5.63 × 10⁻² mole) and 2.21 g (2.25 × 10⁻² mole) of cyclohexanone 16u were added to a solution of 10 g (1.87 × 10⁻² mole) of 14 (R_F = C₅F₁₁) in 50 mL of dry dichloromethane. The mixture was stirred for 4 h at reflux. 10 g of the title product 18a were obtained, total yield 88%. Spectral data: ¹H-NMR (300.13 MHz, CDCl₃) δ 2 (m, 4H), 2.7 (m, 2H), 3.3 (m, 2H), 7.5–7.6 (m, 3H), 7.7 (d, J = 7.1 Hz, 2H), 8.2 (d, J = 8.1 Hz, 1H), 8.7 (d, J = 8.2 Hz, 1H); ¹³C-NMR (75.46MHz, CDCl₃) δ 19.5, 21, 29.5, 31.2, 115, 125.1, 127, 128.1, 129.2, 139 (t, ²J_CF = 27 Hz), 146, 148.1, 163.1; ¹⁹F-NMR (235.3 MHz, CDCl₃) δ −126.2 (m 2F, CF₂), −122.4 (m 2F, CF₂), −117.3 (m 2F, CF₂), −101.8 (m 2F, CF₂), −80.7 (m 3F, CF₃). MS (m/z): 478 ([M − I]⁺, 95). HRMS calcd. for C₂₀H₁₅F₁₁N⁺ 478.1029, found 478.1033. Anal. Calcd. for C₂₀H₁₅F₁₁NI: C, 39.69; H, 2.50; N, 2.31. Found: C, 39.72; H, 2.51; N, 2.29.

2-Trifluoromethyl-N-(phenyl)-5,6,7,8-tetrahydroquinolinium iodide (18a’). 7.14 g of aniline 15a (7.68 × 10⁻² mol) and 3 g (3.07 × 10⁻² mol) of cyclohexanone 16u were added to a solution of 8.5 g (2.56 × 10⁻² mol) of 14’ (R_F = CF₃) in 85 mL of dry dichloromethane. The mixture was stirred for 4 h at reflux. 9.23 g of the title product 18a’ were obtained, total yield 89%. ¹H-NMR (300.13 MHz, CDCl₃) δ 1.9 (m, 4H, CH₂, cyclohexyl group), 2.6 (m, 2H, CH₂, cyclohexyl group), 3.3 (m, 2H, CH₂, cyclohexyl group), 7.5–7.6 (m, 3H, Ph-H), 7.8 (d, J = 7.5 Hz, 2H, Ph-H), 8.2 (d, J = 8 Hz, 1H, Py-H), 8.8 (d, J = 8.1 Hz, 1H, Py-H); ¹³C-NMR (75.46 MHz, CDCl₃) δ 19.8, 21, 29.6, 32.2, 115, 118.6 (q, CF₃, ¹J_CF = 282.5 Hz), 125.2, 127.1, 128.8, 129.2, 139.5, 146.4, 148.5 (q, C-CF₃, ²J_CF = 34.5 Hz), 163; ¹⁹F-NMR (282.4 MHz, DMSO-d₆) δ −59.8 (s 3F, CF₃). MS (m/z): 278 ([M − I]⁺, 95). HRMS calcd. for C₁₆H₁₅F₃N⁺: 278.1157, found 278.1160. Anal. Calcd. for C₁₆H₁₅F₃NI: C, 47.43; H, 3.73; N, 3.46. Found: C, 47.45; H, 3.74; N, 3.44.

2-Perfluoropentyl-N-(2-methylphenyl)-5,6,7,8-tetrahydroquinolinium iodide (18b). 5.86 g of 2-methylaniline 15b (5.46 × 10⁻² mol) and 2.14 g (2.18 × 10⁻² mol) of cyclohexanone 16u were added to a solution of 9.7 g (1.82 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 97 mL of dry dichloromethane. The mixture was stirred for 6 h at reflux. 8.12 g of the title product 18b were obtained, total yield 72%. Spectral data: ¹H-NMR (300.13 MHz, CDCl₃) δ 1.8 (bs, 2H), 1.9 (s, 3H, CH₃), 2.1 (m, 3H), 2.9 (m, 1H), 3.3 (m, 1H), 3.4 (m, 1H), 7.3–7.5 (m, 3 H), 8 (t, J = 7.2 Hz, 1H), 8.2 (d, J = 8.1 Hz, 1H), 8.8 (d, J = 8.1 Hz, 1H); ¹³C-NMR (75.46MHz, CDCl₃) δ 19.9, 21, 26, 29.5, 32.1, 115.2, 126.5, 127.8, 128, 129.5, 136.5, 138 (t, ²J_CF = 24.2 Hz), 148.1, 150.5, 161.1, 163; ¹⁹F-NMR (282.4 MHz, DMSO-d₆) δ −126.3 (AB system, ²J_FF = 285.6 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −125.4 (AB system, ²J_FF = 285.6 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −123.1 (AB system, ²J_FF = 310 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −121.7 (AB system, ²J_FF = 310 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −118.7 (AB system, ²J_FF = 299.6 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −117.6 (AB system, ²J_FF = 299.6 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −107.1 (AB system, ²J_FF = 290.5 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −98.2 (AB system, ²J_FF = 290.5 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −80.2 (m 3F, CF₃). MS (m/z): 492 ([M − I]⁺, 100). HRMS calcd. for C₂₁H₁₇F₁₁N⁺: 492.1185, found 492.1190. Anal. Calcd. for C₂₁H₁₇F₁₁NI: C, 40.73; H, 2.77; N, 2.26. Found: C, 40.75; H, 2.76; N, 2.25.

2-Perfluoropentyl-N-(3-methylphenyl)-5,6,7,8-tetrahydroquinolinium iodide (18c). 6.4 g of 3-methylaniline 15c (5.97 × 10⁻² mol) and 2.34 g (2.39 × 10⁻² mol) of cyclohexanone 16u were added to a solution of 10.6 g (1.99 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 53 mL of dry dichloromethane. The mixture was stirred for 4 h at reflux. 10.2 g of the title product 18c were obtained, total yield 83%. Spectral data: ¹H-NMR (300.13 MHz, CDCl₃) δ 1.7 (m, 2H), 1.9 (m, 2H), 2.1 (s, 3H, CH₃), 2.9 (m, 2H), 3.5 (m, 2H), 7.5 (s, 1H), 7.6 (m, 3H), 8.2 (d, J = 8.1 Hz, 1H), 8.7 (d, J = 8.1 Hz, 1H); ¹³C-NMR (75.46MHz, CDCl₃) δ 19.8, 21.1, 26.3, 29.5, 31, 117.2, 126.1, 127.8, 128.1, 129.2, 136.8, 138.5 (t, ²J_CF = 25.8 Hz), 148.2, 150.5, 163.1; ¹⁹F-NMR (235.3 MHz, CDCl₃) δ −126.1 (m 2F, CF₂), −122 (m 2F, CF₂), −117 (m 2F, CF₂), −103.1 (AB system, ²J_FF = 275.6 Hz, 1F, CF₂-CF₂), −101.2 (AB system, ²J_FF = 275.6 Hz, 1F, CF₂-CF₂), −80.1 (m 3F, CF₃). MS (m/z): 492 ([M − I]⁺, 100). HRMS calcd. for C₂₁H₁₇F₁₁N⁺: 492.1185, found 492.1187. Anal. Calcd. for C₂₁H₁₇F₁₁NI: C, 40.73; H, 2.77; N, 2.26. Found: C, 40.76; H, 2.77; N, 2.27.

2-Perfluoropentyl-N-(4-methylphenyl)-5,6,7,8-tetrahydroquinolinium iodide (18d). 5.74 g of 4-methylaniline 15d (5.35 × 10⁻² mol) and 2.1 g (2.14 × 10⁻² mol) of cyclohexanone 16u were added to a solution of 9.5 g (1.78 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 95 mL of dry dichloromethane. The mixture was stirred for 4 h at reflux. 8.84 g of the title product 18d were obtained, total yield 80%. Spectral data: ¹H-NMR (300.13 MHz, CDCl₃) δ 1.9 (m, 4H), 2 (s, 3H, CH₃), 2.5 (m, 2H), 3.4 (m, 2H), 7.4 (d, J = 8 Hz, 2H), 7.7 (d, J = 8.1 Hz, 2H), 8.2 (d, J = 8.1 Hz, 1H), 8.7 (d, J = 8.1 Hz, 1H); ¹³C-NMR (75.46MHz, CDCl₃) δ 19.5, 21, 26.2, 29.5, 31.2, 116.2, 125.1, 127, 128.1, 129.2, 135.1, 137.8 (t, ²J_CF = 26 Hz), 146, 148.1, 150, 163.1; ¹⁹F-NMR (235.3 MHz, CDCl₃) δ −126 (m 2F, CF₂), −122.5 (m 2F, CF₂), −117.5 (m 2F, CF₂), −101.2 (m 2F, CF₂), −80.6 (m 3F, CF₃). MS (m/z): 492 ([M − I]⁺, 100). HRMS calcd. for C₂₁H₁₇F₁₁N⁺: 492.1185, found 492.1189. Anal. Calcd. for C₂₁H₁₇F₁₁NI: C, 40.73; H, 2.77; N, 2.26. Found: C, 40.75; H, 2.78; N, 2.25.

2-Perfluoropentyl-N-(4-ethylphenyl)-5,6,7,8-tetrahydroquinolinium iodide (18g). 7.24 g of 4-ethylaniline 15g (5.97 × 10⁻² mol) and 2.34 g (2.39 × 10⁻² mol) of cyclohexanone 16u were added to a solution of 10.6 g (1.99 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 106 mL of dry dichloromethane. The mixture was stirred for 4 h at reflux. 10.72 g of the title product 18g were obtained, total yield 85%. Spectral data: ¹H-NMR (300.13 MHz, CDCl₃) δ 1.3 (t, J = 8 Hz, 3H, CH₂-CH₃), 1.9 (m, 4H), 2.6 (m, 2H), 2.8 (q, J = 8 Hz, 2H, CH₂-CH₃), 3.3 (m, 2H), 7.1 (d, J = 8.2 Hz, 2H), 7.7 (d, J = 8.3 Hz, 2H), 8.2 (d, J = 8.1 Hz, 1H), 8.6 (d, J = 8.1 Hz, 1H); ¹³C-NMR (75.46MHz, CDCl₃) δ 13.1, 19.5, 21, 24.1, 29.5, 31.2, 113.2, 126.1, 127, 129.6, 129.8, 135.1, 138.8 (t, ²J_CF = 26.2 Hz), 148.1, 152, 162.9; ¹⁹F-NMR (235.3 MHz, CDCl₃) δ −126.9 (m 2F, CF₂), −123.5 (m 2F, CF₂), −117.5 (m 2F, CF₂), −101.8 (m 2F, CF₂), −80.6 (m 3F, CF₃). MS (m/z): 506 ([M − I]⁺, 95). HRMS calcd. for C₂₂H₁₉F₁₁N⁺: 506.1342, found 506.1346. Anal. Calcd. for C₂₂H₁₉F₁₁NI: C, 41.72; H, 3.02; N, 2.21. Found: C, 41.75; H, 3.04; N, 2.19.

2-Perfluoropentyl-N-(3-chlorophenyl)-5,6,7,8-tetrahydroquinolinium iodide (18i). 7.33 g of 3-chloroaniline 15i (5.75 × 10⁻² mol) and 2.25 g (2.3 × 10⁻² mol) of cyclohexanone 16u were added to a solution of 10.2 g (1.91 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 102 mL of dry dichloromethane. The mixture was stirred for 4 h at reflux. 9.32 g of the title product 18i were obtained, total yield 76%. Spectral data: ¹H-NMR (300.13 MHz, CDCl₃) δ 1.7 (m, 2H), 1.9 (m, 2H), 2.9 (m, 2H), 3.5 (m, 2H), 7.4 (s, 1H), 7.5–7.6 (m, 2H), 7.7 (m, 1H), 8.2 (d, J = 8 Hz, 1H), 8.7 (d, J = 8 Hz, 1H); ¹³C-NMR (75.46MHz, CDCl₃) δ 19.6, 21, 26, 29.5, 31.5, 118.2, 127.1, 127.8, 128.1, 130.1, 137.8, 138.8 (t, ²J_CF = 24.8 Hz), 147.2, 150.6, 165.6; ¹⁹F-NMR (235.3 MHz, CDCl₃) δ −125.6 (m 2F, CF₂), −117.6 (m 2F, CF₂), −113.5 (m 2F, CF₂), −97.9 (AB system, ²J_FF = 150.2 Hz, 1F, CF₂-CF₂), −98.2 (AB system, ²J_FF = 150.2 Hz, 1F, CF₂-CF₂), −79.1 (m 3F, CF₃). MS (m/z): 512 ([M − I]⁺, 90). HRMS calcd. for C₂₀H₁₄F₁₁NCl⁺: 512.0639, found 512.0643. Anal. Calcd. for C₂₀H₁₄F₁₁NICl: C, 37.55; H, 2.21; N, 2.19. Found: C, 37.58; H, 2.22; N, 2.17.

2-Perfluoropentyl-N-(4-methoxyphenyl)-5,6,7,8-tetrahydroquinolinium iodide (18l). 7.36 g of 4-anisidine 15l (5.97 × 10⁻² mol) and 2.34 g (2.39 × 10⁻² mol) of cyclohexanone 16u were added to a solution of 10.6 g (1.99 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 106 mL of dry dichloromethane. The mixture was stirred for 4 h at reflux. 11.39 g of the title product 18l were obtained, total yield 90%. Spectral data: ¹H-NMR (300.13 MHz, CDCl₃) δ 2 (m, 4H), 2.7 (m, 2H), 3.3 (m, 2H), 3.9 (s, 3H, OCH₃), 7.1 (d, J = 8.8 Hz, 2H), 7.7 (d, J = 8.6 Hz, 2H), 8.2 (d, J = 8.1 Hz, 1H), 8.8 (d, J = 8.2 Hz, 1H); ¹³C-NMR (75.46MHz, CDCl₃) δ 20.1, 22, 29, 31.1, 56, 117, 125, 127, 128.2, 129.9, 139.5 (t, ²J_CF = 27.2 Hz), 146.2, 148.1, 162, 164.5; ¹⁹F-NMR (235.3 MHz, CDCl₃) δ −126.9 (m 2F, CF₂), −123.5 (m 2F, CF₂), −117.5 (m 2F, CF₂), −101.7 (m 2F, CF₂), −80.75 (m 3F, CF₃). MS (m/z): 508 ([M − I]⁺, 100). HRMS calcd. for C₂₁H₁₇F₁₁NO⁺: 508.1134, found 508.1138. Anal. Calcd. for C₂₁H₁₇F₁₁NIO: C, 39.70; H, 2.70; N, 2.20. Found: C, 39.72; H, 2.71; N, 2.19.

2-Perfluoropentyl-N-(phenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridinium (19a). 5.24 g of aniline 15a (5.63 × 10⁻² mole) and 2.52 g (2.25 × 10⁻² mole) of cycloheptanone 16v were added to a solution of 10 g (1.87 × 10⁻² mole) of 14 (R_F = C₅F₁₁) in 100 mL of dry dichloromethane. The mixture was stirred for 4 h at reflux. 9.54 g of the title product 19a were obtained, total yield 82%. ¹H-NMR (300.13 MHz, CDCl₃) δ 1.7 (m, 2H, CH₂, cycloheptyl group), 1.9 (m, 4H, CH₂, cycloheptyl group), 3.1 (m, 2H, CH₂, cycloheptyl group), 3.4 (m, 2H, CH₂, cycloheptyl group), 7.5–7.7 (m, 5H, Ph-H), 8.2 (d, J = 8.2 Hz, 1H, Py-H), 8.9 (d, J = 8 Hz, 1H, Py-H); ¹³C-NMR (75.46MHz, CDCl₃) δ 24, 25.3, 30.7, 33.9, 35.4, 124.2, 125.9, 127.7, 129.6, 131.5, 137.7 (t, ²J_CF = 27.1 Hz), 146.8, 150.3, 167.4; ¹⁹F-NMR (282.4 MHz, CDCl₃) δ −126 (m 2F, CF₂-CF₂ CF₂ CF₂-CF₃), −122.4 (m 2F, CF₂-CF₂-CF₂-CF₂-CF₃), −117.3 (m 2F, CF₂-CF₂-CF₂-CF₂-CF₃), −101.6 (m 2F, CF₂-CF₂-CF₂-CF₂-CF₃), −80.7 (m 3F, CF₂-CF₂-CF₂ CF₂-CF₃). MS (m/z): 492 ([M − I]⁺, 95). HRMS calcd. for C₂₁H₁₇F₁₁N⁺ 492.1185, found 492.1190. Anal. Calcd. for C₂₁H₁₇F₁₁NI: C, 40.73; H, 2.77; N, 2.26. Found: C, 40.75; H, 2.78; N, 2.25.

2-Perfluoropentyl-N-(3-methylphenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridinium (19c). 5.92 g of 3-methylaniline 15c (5.52 × 10⁻² mol) and 2.47 g (2.21 × 10⁻² mol) of cycloheptanone 16v were added to a solution of 9.8 g (1.84 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 98 mL of dry dichloromethane. The mixture was stirred for 4 h at reflux. 9.68 g of the title product 19c were obtained, total yield 83%. Spectral data: ¹H-NMR (300.13 MHz, CDCl₃) δ 1.7 (m, 2H), 1.9 (m, 4H), 2.45 (s, 3H, CH₃), 3 (d, J = 8 Hz, 2H), 3.4 (m, 2H), 7.4 (m, 2H), 7.6 (m, 2H), 8.2 (d, J = 8.4 Hz, 1H), 8.9 (d, J = 8 Hz, 1H); ¹³C-NMR (75.46MHz, CDCl₃) δ 20.7, 21.5, 24.3, 25.3, 30.7, 33.9, 35.7, 122.5, 126.2, 127.7, 129.5, 131, 137.6 (t, ²J_CF = 27 Hz), 146.6, 150.2, 167.8; ¹⁹F-NMR (235.3 MHz, CDCl₃) δ −126 (m 2F, CF₂), −122.5 (m 2F, CF₂), −117 (m 2F, CF₂), −101.7 (m 2F, CF₂), −80.7 (m 3F, CF₃). MS (m/z): 506 ([M − I]⁺, 95). HRMS calcd. for C₂₂H₁₉F₁₁N⁺: 506.1342, found 506.1346. Anal. Calcd. for C₂₂H₁₉F₁₁NI: C, 41.72; H, 3.02; N, 2.21. Found: C, 41.75; H, 3.06; N, 2.19.

2-Perfluoropentyl-N-(4-methylphenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridinium (19d). 6.34 g of 4-methylaniline 15d (5.92 × 10⁻² mol) and 2.65 g (2.36 × 10⁻² mol) of cycloheptanone 16v were added to a solution of 10.5 g (1.97 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 105 mL of dry dichloromethane. The mixture was stirred for 4 h at reflux. 10.62 g of the title product 19d were obtained, total yield 85%. Spectral data: ¹H-NMR (300.13 MHz, CDCl₃) δ 1.6 (m, 2H), 1.9 (m, 4H), 2.4 (s, 3H, CH₃), 3 (m, 2H), 3.3 (m, 2H), 7.3 (d, J = 8 Hz, 2H), 7.6 (d, J = 8 Hz, 2H), 8.2 (d, J = 8.4 Hz, 1H), 8.8 (d, J = 8.4 Hz, 1H); ¹³C-NMR (75.46MHz, CDCl₃) δ 20.8, 21.3, 24.2, 25.3, 30.6, 33.9, 35.4, 122.7, 126.6, 127.7, 129.9, 130.2, 135.1, 137.8 (t, ²J_CF = 27.1 Hz), 142.5, 146.6, 150.2, 167.7; ¹⁹F-NMR (235.3 MHz, CDCl₃) δ −126 (m 2F, CF₂), −122.4 (m 2F, CF₂), −117.2 (m 2F, CF₂), −101.6 (m 2F, CF₂), −80.7 (m 3F, CF₃). MS (m/z): 506 ([M − I]⁺, 95). HRMS calcd. for C₂₂H₁₉F₁₁N⁺: 506.1342, found 506.1348. Anal. Calcd. for C₂₂H₁₉F₁₁NI: C, 41.72; H, 3.02; N, 2.21. Found: C, 41.76; H, 3.05; N, 2.23.

2-Perfluoropentyl-N-(3-ethylphenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridinium (19f). 6.69 g of 3-ethylaniline 15f (5.52 × 10⁻² mol) and 2.47 g (2.21 × 10⁻² mol) of cycloheptanone 16v were added to a solution of 9.8 g (1.84 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 98 mL of dry dichloromethane. The mixture was stirred for 4 h at reflux. 10.5 g of the title product 19f were obtained, total yield 88%. Spectral data: ¹H-NMR (300.13 MHz, CDCl₃) δ 1.2 (t, J = 8 Hz, 3H, CH₂-CH₃), 1.6 (s, 2H), 1.9 (m, 4H), 2.7 (q, J = 8 Hz, 2H, CH₂-CH₃), 3 (m, 2H), 3.3 (m, 2H), 7.5 (m, 3 H), 7.6 (m, 1H), 8.2 (d, J = 8.4 Hz, 1H), 8.9 (d, J = 8 Hz, 1H); ¹³C-NMR (75.46MHz, CDCl₃) δ 15.1, 24.3, 25.4, 28.4, 30.6, 33.9, 35.4, 124.1, 125.9, 127.7, 129.6, 131.5, 137.6 (t, ²J_CF = 26.7 Hz), 146.7, 150.2, 167.4; ¹⁹F-NMR (235.3 MHz, CDCl₃) δ −126 (m 2F, CF₂), −122.4 (m 2F, CF₂), −117.2 (m 2F, CF₂), −102.2 (AB system, ²J_FF = 263.3 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −101.1 (AB system, ²J_FF = 263.3 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −80.7 (m 3F, CF₃). MS (m/z): 520 ([M − I]⁺, 100). HRMS calcd. for C₂₃H₂₁F₁₁N⁺: 520.1498, found 520.1501. Anal. Calcd. for C₂₃H₂₁F₁₁NI: C, 42.68; H, 3.27; N, 2.16. Found: C, 42.70; H, 3.28; N, 2.14.

2-Perfluoropentyl-N-(4-ethylphenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridinium (19g). 6.96 g of 4-ethylaniline 15g (5.75 × 10⁻² mol) and 2.58 g (2.3 × 10⁻² mol) of cycloheptanone 16v were added to a solution of 10.2 g (1.91 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 102 mL of dry dichloromethane. The mixture was stirred for 4 h at reflux. 10.3 g of the title product 19g were obtained, total yield 83%. Spectral data: ¹H-NMR (300.13 MHz, CDCl₃) δ 1.3 (t, J = 7.6 Hz, 3H, CH₂-CH₃), 1.6 (s, 2H), 1.8 (m, 4H), 2.71 (q, J = 7.6 Hz, 2H, CH₂-CH₃), 3 (m, 2H), 3.4 (m, 2H), 7.3 (d, J = 8.4 Hz, 2H), 7.6 (d, J = 8.4 Hz, 2H), 8.1 (d, J = 8 Hz, 1H), 8.8 (d, J = 8 Hz, 1H); ¹³C-NMR (75.46MHz, CDCl₃) δ 14.9, 24.2, 25.3, 28.5, 30.6, 33.9, 35.4, 126.7, 127.7, 128.9, 135.2, 137.8 (t, ²J_CF = 27.1 Hz), 146.6, 148.6, 150.2, 167.7; ¹⁹F-NMR (235.3 MHz, CDCl₃) δ −126.1 (m 2F, CF₂), −122.5 (m 2F, CF₂), −117.2 (m 2F, CF₂), −101.6 (m 2F, CF₂), −80.8 (m 3F, CF₃). MS (m/z): 520 ([M − I]⁺, 100). HRMS calcd. for C₂₃H₂₁F₁₁N⁺: 520.1498, found 520.1499. Anal. Calcd. for C₂₃H₂₁F₁₁NI: C, 42.68; H, 3.27; N, 2.16. Found: C, 42.69; H, 3.29; N, 2.15.

2-Perfluoropentyl-N-(3-chlorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridinium (19i). 6.4 g of 3-chloroaniline 15i (5.01 × 10⁻² mol) and 2.25 g (2.10⁻² mol) of cycloheptanone 16v were added to a solution of 8.9 g (1.67 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 89 mL of dry dichloromethane. The mixture was stirred for 4 h at reflux. 7.65 g of the title product 19i were obtained, total yield 70%. Spectral data: ¹H-NMR (300.13 MHz, CDCl₃) δ 1.6–2.2 (m, 6H), 3.1 (m, 2H), 3.4 (s, 2H), 7.6 (t, J = 8.1 Hz, 1H), 7.7 (d, J = 8.2 Hz, 1H), 7.9 (s, 1H), 8.1 (d, J = 7.9 Hz, 1H), 8.3 (d, J = 8.1 Hz, 1H), 8.9 (d, J = 8.2 Hz, 1H); ¹³C-NMR (75.46MHz, CDCl₃) δ 24.1, 25.2, 30.7, 34, 34.3, 35.5, 127.9, 128.5, 129.8, 136.1, 137.7 (t, ²J_CF = 26.8 Hz), 138.5, 146.8, 150.5, 167.7; ¹⁹F-NMR (235.3 MHz, CDCl₃) δ −126 (m 2F, CF₂), −122.4 (m 2F, CF₂), −117.2 (m 2F, CF₂), −101.5 (m 2F, CF₂), −80.7 (m 3F, CF₃). MS (m/z): 526 ([M − I]⁺, 100). HRMS calcd. for C₂₁H₁₆F₁₁NCl⁺: 526.0796, found 526.0799. Anal. Calcd. for C₂₁H₁₆F₁₁NICl: C, 38.58; H, 2.47; N, 2.14. Found: C, 38.61; H, 2.48; N, 2.14.

2-Perfluoropentyl-N-(4-chlorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridinium (19j). 7.26 g of 4-chloroaniline 15j (5.69 × 10⁻² mol) and 2.55 g (2.27 × 10⁻² mol) of cycloheptanone 16v were added to a solution of 10.1 g (1.89 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 101 mL of dry dichloromethane. The mixture was stirred for 4 h at reflux. 9.68 g of the title product 19j were obtained, total yield 78%. Spectral data: ¹H-NMR (300.13 MHz, CDCl₃) δ 1.7 (m, 2H), 1.9 (m, 4H), 3 (m, 2H), 3.3 (m, 2H), 7.5 (d, J = 8.8 Hz, 2H), 7.8 (d, J = 8.8 Hz, 2H), 8.2 (d, J = 8 Hz, 1H), 8.8 (d, J = 8.3 Hz, 1H); ¹³C-NMR (75.46MHz, CDCl₃) δ 24, 25.2, 30.7, 33.9, 34.2, 35.4, 127.9, 128.4, 129.9, 136.1, 137.5 (t, ²J_CF = 26.8 Hz), 138.3, 146.8, 150.5, 167.6; ¹⁹F-NMR (235.3 MHz, CDCl₃) δ −126 (m 2F, CF₂), −122.3 (m 2F, CF₂), −117.3 (m 2F, CF₂), −101.5 (m 2F, CF₂), −80.7 (m 3F, CF₃). MS (m/z): 526 ([M − I]⁺, 100). HRMS calcd. for C₂₁H₁₆F₁₁NCl⁺: 526.0796, found 526.0797. Anal. Calcd. for C₂₁H₁₆F₁₁NICl: C, 38.58; H, 2.47; N, 2.14. Found: C, 38.60; H, 2.47; N, 2.13.

2-Perfluoropentyl-N-(2-methoxyphenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridinium (19k). 6.18 g of 2-anisidine 15k (5.01 × 10⁻² mol) and 2.25 g (2 × 10⁻² mol) of cycloheptanone 16v were added to a solution of 8.9 g (1.67 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 45 mL of dry dichloromethane. The mixture was stirred for 6 h at reflux. 7.6 g of the title product 19k were obtained, total yield 70%. Spectral data: ¹H-NMR (300.13 MHz, CDCl₃) δ 1.5 (m, 1H), 1.7–2 (m, 4H), 2.1 (m, 1H), 2.9 (m,1H), 3.2–3.5 (m, 3H), 3.8 (s, 3H, OCH₃), 7.2 (d, J = 8.3 Hz, 1H), 7.3 (t, J = 7.6 Hz, 1H), 7.7 (t, J = 8.8 Hz, 1H), 8 (s, 1H), 8.3 (d, J = 8.1 Hz, 1H), 9 (d, J = 8.2 Hz, 1H); ¹³C-NMR (75.46MHz, CDCl₃) δ 24, 25.1, 30.7, 34.4, 34.3, 35.6, 127.8, 128.5, 130, 136.1, 137.8 (t, ²J_CF = 26.9 Hz), 138.8, 147, 151.5, 167.5; ¹⁹F-NMR (282.4 MHz, DMSO-d₆) δ −126.5 (AB system, ²J_FF = 284.5 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −125.5 (AB system, ²J_FF = 284.5 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −123 (AB system, ²J_FF = 355.2 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −121.8 (AB system, ²J_FF = 355.2 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −119.1 (AB system, ²J_FF = 380.5 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −116.5 (AB system, ²J_FF = 380.5 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −107.1 (AB system, ²J_FF = 350 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −99.5 (AB system, ²J_FF = 350 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −80.69 (m 3F, CF₃). MS (m/z): 522 ([M − I]⁺, 100). HRMS calcd. for C₂₂H₁₉F₁₁NO⁺: 522.1291, found 522.1297. Anal. Calcd. for C₂₂H₁₉F₁₁NIO: C, 40.70; H, 2.95; N, 2.16. Found: C, 40.73; H, 2.96; N, 2.16.

2-Perfluoropentyl-N-(4-methoxyphenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridinium (19l). 6.66 g of 4-anisidine 15l (5.41 × 10⁻² mol) and 2.42 g (2.16 × 10⁻² mol) of cycloheptanone 16v were added to a solution of 9.6 g (1.8 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 96 mL of dry dichloromethane. The mixture was stirred for 4 h at reflux. 10.31 g of the title product 19l were obtained, total yield 88%. Spectral data: ¹H-NMR (300.13 MHz, CDCl₃) δ 1.7 (m, 2H), 1.9 (m, 4H), 3 (m, 2H), 3.3 (m, 2H), 3.8 (s, 3H, OCH₃), 7 (d, J = 8.8 Hz, 2H), 7.6 (d, J = 8.4 Hz, 2H), 8.1 (d, J = 8.4 Hz, 1H), 8.7 (d, J = 8 Hz, 1H); ¹³C-NMR (75.46MHz, CDCl₃) δ 24.3, 25.3, 30.7, 33.9, 35.5, 55.8, 114.6, 127.6, 128.2, 130, 138.2, 146.5, 150.2, 161.7, 168.2; ¹⁹F-NMR (235.3 MHz, CDCl₃) δ −126 (m 2F, CF₂), −122.3 (m 2F, CF₂), −117.2 (m 2F, CF₂), −101.5 (m 2F, CF₂), −80.7 (m 3F, CF₃). MS (m/z): 522 ([M − I]⁺, 100). HRMS calcd. for C₂₂H₁₉F₁₁NO⁺: 522.1291, found 522.1295. Anal. Calcd. for C₂₂H₁₉F₁₁NIO: C, 40.70; H, 2.95; N, 2.16. Found: C, 40.74; H, 2.95; N, 2.13.

3.3. General Procedure for the Synthesis of 2-Trifluoromethylated and 2-Perfluoroalkylated 6-Methyl-N-(o-/p-Carboxyphenyl)Pyridinium Iodides (17m–n’), N-(O-/P-Carboxyphenyl)-5,6,7,8-Tetrahydroquinolinium Iodides (18m–n) and N-(O-Carboxyphenyl)-6,7,8,9-Tetrahydro-5H-Cyclohepta[b]Pyridinium Iodide (19m)

To a stirred solution of 1-acetoxy-1-iodo-perfluoroalkylethane compounds 14 or 14’ (1 equiv.) in anhydrous dichloromethane (5 mL DCM for 1 g of 14–14’), was added three equiv. of the corresponding aminobenzoic acid 15m–n and 1.2 equiv. of ketone 16t–v. The mixture was stirred under reflux for 12 h (Table 1, Table 2 and Table 3) until complete consumption of 14–14’ (monitored by TLC eluent petroleum ether/ethyl acetate: 80/20 v/v, and ¹⁹F-NMR of aliquots). When the reaction was completed, the mixture was allowed to cool to r.t. then the brown precipitate accumulated during the reaction was separated by vacuum filtration (it was subsequently identified as anilinium salts by NMR and MS). Then a mixture of petroleum ether and ethyl ether (40/60 v/v) was added to the filtrate and the corresponding pyridinium iodides 17m–n’, 18m–n and 19m instantly precipitate and were isolated by vacuum filtration as amorphous solids.

2-Perfluoropentyl-6-methyl-N-(2-carboxyphenyl)pyridinium iodide (17m). 7.34 g of 2-aminobenzoic acid 15m (5.35 × 10⁻² mole) and 1.58 mL or 1.24 g (2.14 × 10⁻² mole) of acetone 16t were added to a solution of 9.5 g (1.78 × 10⁻² mole) of 14 (R_F = C₅F₁₁) in 48 mL of dry dichloromethane. The mixture was stirred for 12 h at reflux. 5.43 g of the title product 17m were obtained, total yield 50%. ¹H-NMR (300.13 MHz, DMSO-d₆) δ 2.4 (s, 3H, CH₃), 7.7–7.9 (m, 3 H), 8.2 (d, J = 8 Hz, 1H), 8.7 (m, 2H), 9 (t, J = 8 Hz, 1H), 13.9 (bs, 1H, CO₂H); ¹³C-NMR (75.46 MHz, DMSO-d₆) δ 22.9 (s, CH₃), 127.9, 128.6, 129.4, 132.8, 133.6, 134.4, 137, 139.7 (t, ²J_CF = 25.1 Hz), 148.2, 163.4, 165.1 (s, CO₂H); ¹⁹F-NMR (282.4 MHz, DMSO-d₆) δ −126.7 (AB system, ²J_FF = 288.7 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −125.7 (AB system, ²J_FF = 288.7 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −122.8 (AB system, ²J_FF = 289 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −121.8 (AB system, ²J_FF = 289 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −119.2 (AB system, ²J_FF = 310.2 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −116.3 (AB system, ²J_FF = 310.2 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −107.5 (AB system, ²J_FF = 282.5 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −99.1 (AB system, ²J_FF = 282.5 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −80.69 (m 3F, CF₃). MS (m/z): 482 ([M − I]⁺, 100). HRMS calcd. for C₁₈H₁₁F₁₁NO₂⁺ 482.0614, found 482.0622. Anal. Calcd. for C₁₈H₁₁F₁₁INO₂: C, 35.49; H, 1.82; N, 2.30. Found: C, 35.51; H, 1.82; N, 2.33.

2-Trifluoromethyl-6-methyl-N-(2-carboxyphenyl)pyridinium iodide (17m’). 11.02 g of 2-aminobenzoic acid 15m (8.04 × 10⁻² mol) and 2.37 mL or 1.86 g (3.21 × 10⁻² mol) of acetone 16t were added to a solution of 8.9 g (2.68 × 10⁻² mol) of 14’ (R_F = CF₃) in 89 mL of dry dichloromethane. The mixture was stirred for 12 h at reflux. 5.7 g of the title product 17m’ were obtained, total yield 52%. Spectral data: ¹H-NMR (300.13 MHz, DMSO-d₆) δ 2.3 (s, 3H, CH₃), 7.7–7.8 (m, 3 H), 8 (d, J = 8.1 Hz, 1H), 8.8 (m, 2H), 9 (t, J = 8 Hz, 1H), 14.2 (bs, 1H, CO₂H); ¹³C-NMR (75.46 MHz, DMSO-d₆) δ 21.9 (s, CH₃), 118.5 (q, CF₃, ¹J_CF = 280.2 Hz), 127.5 (q, ³J_CF = 3.9 Hz), 128, 133.7, 140.2, 140.7, 146, 148.1 (q, C-CF₃, ²J_CF = 36.6 Hz), 163, 167 (s, CO₂H); ¹⁹F-NMR (282.4 MHz, DMSO-d₆) δ −60.3 (s 3F, CF₃). MS (m/z): 282 ([M − I]⁺, 100). HRMS calcd. for C₁₄H₁₁F₃NO₂⁺: 282.0742, found 282.0745. Anal. Calcd. for C₁₄H₁₁F₃INO₂: C, 41.10; H, 2.71; N, 3.42. Found: C, 41.13; H, 2.72; N, 3.40.

2-Perfluoropentyl-6-methyl-N-(4-carboxyphenyl)pyridinium iodide (17n). 8.27 g of 4-aminobenzoic acid 15n (6.03 × 10⁻² mol) and 1.78 mL or 1.39 g (2.41 × 10⁻² mol) of acetone 16t were added to a solution of 10.7 g (2.01 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 107 mL of dry dichloromethane. The mixture was stirred for 12 h at reflux. 7.35 g of the title product 17n were obtained, total yield 60%. ¹H-NMR (300.13 MHz, DMSO-d₆) δ 2.5 (s, 3H, CH₃), 8 (d, J = 8.1 Hz, 2H, Ph-H), 8.3 (d, J = 8.1 Hz, 2H, Ph-H), 8.8 (m, 2H, Py-H), 9 (t, J = 8 Hz, 1H, Py-H), 13.8 (bs, 1H, CO₂H); ¹³C-NMR (75.46 MHz, DMSO-d₆) δ 22.9 (s, CH₃), 127.1, 128.7, 130.5, 133.8, 139.7, 140.7, 146, 147.6, 163.1, 165.9 (s, CO₂H); ¹⁹F-NMR (282.4 MHz, DMSO-d₆) δ −125.8 (s 2F, CF₂-CF₂-CF₂-CF₂-CF₃), −122.3 (s 2F, CF₂-CF₂-CF₂-CF₂-CF₃), −117.7 (s 2F, CF₂-CF₂-CF₂-CF₂-CF₃), −101.8 (s, 2F, CF₂-CF₂-CF₂-CF₂-CF₃), −80.2 (m 3F, CF₂-CF₂-CF₂-CF₂-CF₃). MS (m/z): 482 ([M − I]⁺, 100). HRMS calcd. for C₁₈H₁₁F₁₁NO₂⁺: 482.0614, found 482.0620. Anal. Calcd. for C₁₈H₁₁F₁₁INO₂: C, 35.49; H, 1.82; N, 2.30. Found: C, 35.52; H, 1.83; N, 2.28.

2-Trifluoromethyl-6-methyl-N-(4-carboxyphenyl)pyridinium iodide (17n’).12.63 g of 4-aminobenzoic acid 15n (9.21 × 10⁻² mol) and 2.72 mL or 2.13 g (3.68 × 10⁻² mol) of acetone 16t were added to a solution of 10.2 g (3.07 × 10⁻² mol) of 14’ (R_F = CF₃) in 102 mL of dry dichloromethane. The mixture was stirred for 12 h at reflux. 7.54 g of the title product 17n’ were obtained, total yield 60%. Spectral data: ¹H-NMR (300.13 MHz, DMSO-d₆) δ 2.5 (s, 3H, CH₃), 8.1 (d, J = 8 Hz, 2H), 8.3 (d, J = 8 Hz, 2H), 8.7 (m, 2H), 9.1 (t, J = 8 Hz, 1H), 14 (bs, 1H, CO₂H); ¹³C-NMR (75.46 MHz, DMSO-d₆) δ 22.7 (s, CH₃), 118 (q, CF₃, ¹J_CF = 279 Hz), 127.1 (q, ³J_CF = 4.2 Hz), 128, 130.4, 133.7, 140, 140.7, 146, 147.6 (q, C-CF₃, ²J_CF = 35.5 Hz), 163, 166 (s, CO₂H); ¹⁹F-NMR (282.4 MHz, DMSO-d₆) δ −59.9 (s 3F, CF₃). MS (m/z): 282 ([M − I]⁺, 100). HRMS calcd. for C₁₄H₁₁F₃NO₂⁺: 282.0742, found 282.0747. Anal. Calcd. for C₁₄H₁₁F₃INO₂: C, 41.10; H, 2.71; N, 3.42. Found: C, 41.14; H, 2.70; N, 3.40.

2-Perfluoropentyl-N-(2-carboxyphenyl)-5,6,7,8-tetrahydroquinolinium iodide (18m). 7.88 g of 2-aminobenzoic acid 15m (5.75 × 10⁻² mol) and 2.25 g (2.3 × 10⁻² mole) of cyclohexanone 16u were added to a solution of 10.2 g (1.91 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 51 mL of dry dichloromethane. The mixture was stirred for 12 h at reflux. 8.96 g of the title product 18m were obtained, total yield 72%. ¹H-NMR (300.13 MHz, CDCl₃) δ 1.8 (s, 2H, CH₂, cyclohexyl group), 2 (s, 2H, CH₂, cyclohexyl group), 2.4 (m, 1H, CH₂, cyclohexyl group), 2.7 (m, 1H, CH₂, cyclohexyl group), 3.1 (m, 1H, CH₂, cyclohexyl group), 3.3 (m, 1H, CH₂, cyclohexyl group), 6.9 (bs, 1H, CO₂H), 7.8 (m, 3H, Ph-H), 8.2 (d, J = 7.4 Hz, 1H, Ph-H), 8.4 (d, J = 8.1 Hz, 1H, Py-H), 8.9 (d, J = 8.2 Hz, 1H, Py-H); ¹H-NMR (400.13 MHz, DMSO-d₆) δ 1.6–1.8 (m, 4H, CH₂, cyclohexyl group), 2.3 (m, 1H, CH₂, cyclohexyl group), 2.6 (m, 1H, CH₂, cyclohexyl group), 3.2 (m, 2H, CH₂, cyclohexyl group), 7.8–8 (m, 3H, Ph-H), 8.3 (d, J = 8 Hz, 1H, Ph-H), 8.6 (d, J = 8 Hz, 1H, Py-H), 8.9 (d, J = 8 Hz, 1H, Py-H); ¹³C-NMR (75.46 MHz, CDCl₃) δ 19.9, 21.4, 29.5, 30.5, 126.5, 126.7, 130.6, 132.2, 132.7, 133.2, 136.4, 139.3 (t, ²J_CF = 25 Hz), 144.4, 147.5, 161.6, 165.8 (s, CO₂H); ¹³C-NMR (100.6 MHz, DMSO-d₆) δ 20, 21.4, 29.1, 30.3, 127.2 (t, ³J_CF = 4 Hz, =C-H, Py), 128.5, 132.6, 133, 134.6, 136.6, 137.2, 137.4 (t, ²J_CF = 22.13 Hz, =C-CF₂, Py), 144.7, 148, 162.2, 164.9 (s, CO₂H); ¹⁹F-NMR (282.4 MHz, DMSO-d₆) δ −126.5 (AB system, ²J_FF = 282 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −125.3 (AB system, ²J_FF = 282 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −123 (AB system, ²J_FF = 367 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −121.9 (AB system, ²J_FF = 367 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −118.9 (AB system, ²J_FF = 338 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −117 (AB system, ²J_FF = 338 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −107 (AB system, ²J_FF = 310 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −98.5 (AB system, ²J_FF = 310 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −80.31 (m 3F, CF₃). MS (m/z): 522 ([M − I]⁺, 98). HRMS calcd. for C₂₁H₁₅F₁₁NO₂⁺ 522.0927, found 522.0933. Anal. Calcd. for C₂₁H₁₅F₁₁NIO₂: C, 38.85; H, 2.33; N, 2.16. Found: C, 38.88; H, 2.34; N, 2.15.

2-Perfluoropentyl-N-(4-carboxyphenyl)-5,6,7,8-tetrahydroquinolinium iodide (18n). 8.27 g of 4-aminobenzoic acid 15n (6.03 × 10⁻² mol) and 2.36 g (2.41 × 10⁻² mol) of cyclohexanone 16u were added to a solution of 10.7 g (2.01 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 53.5 mL of dry dichloromethane. The mixture was stirred for 12 h at reflux. 9.14 g of the title product 18n were obtained, total yield 70%. Spectral data: ¹H-NMR (300.13 MHz, CDCl₃) δ 2 (m, 4H), 2.6 (m, 2H), 3.4 (m, 2H), 7.9 (d, J = 8 Hz, 2H), 8.2 (d, J = 8 Hz, 2H), 8.8 (d, J = 8.1 Hz, 1H), 9 (d, J = 8.1 Hz, 1H) 12.9 (bs, 1H, CO₂H); ¹³C-NMR (75.46MHz, CDCl₃) δ 20.8, 21, 29.2, 31.5, 125.5, 127, 128.4, 129.5, 133.7, 139.7 (t, ²J_CF = 24.3 Hz), 146, 147.2, 163.1, 166 (s, CO₂H); ¹⁹F-NMR (235.3 MHz, CDCl₃) δ −125.9 (m 2F, CF₂), −122.5 (m 2F, CF₂), −117.7 (m 2F, CF₂), −101.5 (m 2F, CF₂), −80.4 (m 3F, CF₃). MS (m/z): 522 ([M − I]⁺, 90). HRMS calcd. for C₂₁H₁₅F₁₁NO₂⁺: 522.0927, found 522.0931. Anal. Calcd. for C₂₁H₁₅F₁₁NIO₂: C, 38.85; H, 2.33; N, 2.16. Found: C, 38.89; H, 2.34; N, 2.15.

2-Perfluoropentyl-N-(2-carboxyphenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridinium (19m). 8.35 g of 2-aminobenzoic acid 15m (6.09 × 10⁻² mol) and 2.73 g (2.43 × 10⁻² mole) of cycloheptanone 16v were added to a solution of 10.8 g (2.03 × 10⁻² mole) of 14 (R_F = C₅F₁₁) in 54 mL of dry dichloromethane. The mixture was stirred for 6 h at reflux. 9.15 g of the title product 19m were obtained, total yield 68%. ¹H-NMR (300.13 MHz, CDCl₃) δ 1.4–2 (m, 6H, CH₂, cycloheptyl group), 2.7 (m, 1H, CH₂, cycloheptyl group), 3 (m, 1H, CH₂, cycloheptyl group), 3.3–3.4 (m, 2H, CH₂, cycloheptyl group), 7.7 (bs, 1H, CO₂H), 7.77 (m, 3H, Ar-H), 8.1 (d, J = 8 Hz, 1H, Ar-H), 8.3 (d, J = 8 Hz, 1H, Py-H), 8.9 (d, J = 8 Hz, 1H, Py-H); ¹H-NMR (300.13 MHz, DMSO-d₆) δ 1.4 (m, 1H, CH₂, cycloheptyl group), 1.6–1.9 (m, 5H, CH₂, cycloheptyl group), 2.8 (m, 2H, CH₂, cycloheptyl group), 3.3 (m, 2H, CH₂, cycloheptyl group), 7.9 (m, 2H, Ar-H), 8 (m, 1H, Ar-H), 8.4 (d, J = 6 Hz, 1H, Ar-H), 8.6 (d, J = 6.15 Hz, 1H, Py-H), 8.9 (d, J = 6.18 Hz, 1H, Py-H); ¹³C-NMR (75.46MHz, DMSO-d₆) δ 24, 25.5, 30.4, 33.4, 35.3, 127.2, 127.5, 129.7, 132.2, 132.6, 132.9, 137.1, 138.2 (t, ²J_CF = 20.1 Hz), 147.1, 149.2, 165.1, 166.6; ¹⁹F-NMR (282.4 MHz, DMSO-d₆) δ −126.6 (AB system, ²J_FF = 293.4 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −125.5 (AB system, ²J_FF = 293.4 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −123.4 (AB system, ²J_FF = 297.1 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −122.3 (AB system, ²J_FF = 297.1 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), -119 (AB system, ²J_FF = 300.96 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −116.5 (AB system, ²J_FF = 300.96 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −108.2 (AB system, ²J_FF = 285.9 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −97.9 (AB system, ²J_FF = 285.9 Hz, 1F, CF₂-CF₂-CF₂-CF₂-CF₃), −80.86 (m 3F, CF₃). MS (m/z): 536 ([M − I]⁺, 95). HRMS calcd. for C₂₂H₁₇F₁₁NO₂⁺ 536.1084, found 536.1089. Anal. Calcd. for C₂₂H₁₇F₁₁NIO₂: C, 39.84; H, 2.58; N, 2.11. Found: C, 39.86; H, 2.59; N, 2.10.

3.4. General Procedure for the Synthesis 2-Trifluoromethyl or 2-Perfluoroalkyl-7-Methoxyquinolines 20o–o’

To a stirred solution of 1-acetoxy-1-iodo-perfluoroalkylethane compounds 14 or 14’ (1 equiv.) in anhydrous dichloromethane (10 mL DCM for 1g of 14–14’), was added 3 equiv. of meta-anisidine 15o. The mixture was stirred under reflux for the desired time (12 h, Table 4) until complete consumption of 14–14’ (monitored by TLC eluent petroleum ether/ethyl acetate: 80/20 v/v, and ¹⁹F-NMR of aliquots). When the reaction was completed, the mixture was concentrated under reduced pressure and then stirred with diethyl ether. An excess of petroleum ether was added; the precipitate that had formed was eliminated by vacuum filtration and washed three times with petroleum ether. The filtrate was concentrated in vacuo to give a brown oil. Chromatography over silica gel column (eluent, petroleum ether/ethyl acetate 98/2 v/v) left a yellow oil which was crystallized from methanol/water to give pure samples of the corresponding quinolines 20o–o’.

3.5. General Procedure for the Synthesis 2-Trifluoromethyl or 2-Perfluoroalkyl-7-Methoxyquinolines 20o–o’ in the Presence of Ketones 16t–v

To a stirred solution of 1-acetoxy-1-iodo-perfluoroalkylethane compounds 14 or 14’ (1 equiv.) in anhydrous dichloromethane (10 mL DCM for 1 g of 14–14’), was added three equiv. of meta-anisidine 15o and 1.2 equiv. of ketone 16t–v. The mixture was stirred under reflux for desired time (12 h, Table 4) until complete consumption of 14–14’ (monitored by TLC eluent petroleum ether/ethyl acetate: 80/20 v/v, and ¹⁹F-NMR of aliquots). When the reaction was completed, the mixture was concentrated under reduced pressure and then stirred with a mixture of petroleum ether/ethyl acetate. Chromatography over silica gel column (eluent, petroleum ether/ethyl acetate 98/2 v/v) left a yellow oil which was crystallized from methanol/water to give pure samples of the corresponding quinolines 20o–o’. We were able to isolate unreacted ketones 16t–v from the corresponding reactions (1.2 equivalent) which were identified and characterized by NMR and mass spectroscopy

2-perfluoropentyl-6-methoxyquinoline (20o). 6.25 g of meta-anisidine 15o (5.07 × 10⁻² mol) and 2.03 × 10⁻² mole of the corresponding ketone (1.17 g of acetone 16t or 1.99 g of cyclohexanone 16u or 2.27 g of cylcoheptanone 16v) were added to a solution of 9 g (1.69 × 10⁻² mole) of 14 (R_F = C₅F₁₁) in 90 mL of dry dichloromethane. The mixture was stirred for 12 h at reflux. In the presence of acetone: 6.1 g of 20o (85% yield) and 0.5 g of 16t. Or in the presence of cyclohexanone: 5.9 g of 20o (82% yield) and 1.9 g of 16u. Or in the case of cycloheptanone: 5.9 g of 20o (82% yield) and 2.25 g of 16u were obtained respectively.

Or 6.8 g of meta-anisidine 15o (5.52 × 10⁻² mol) were added to a solution of 9.8 g (1.84 ×10⁻² mol) of 14 (R_F = C₅F₁₁) in 98 mL of dry dichloromethane. The mixture was stirred for 12 h at reflux. 6.6 g (84% yield) of quinoline 20o were obtained respectively. ¹H-NMR (300.13 MHz, CDCl₃) δ 3.8 (s, 3H, OCH₃), 7.5 (d, J = 8.5 Hz, 1H), 7.8 (d, J = 8.6 Hz, 1H), 8 (m, 2H), 8.6 (d, J = 8.6 Hz, 1H); ¹³C-NMR (75.46 MHz, CDCl₃) δ 55.6 (s, OCH₃), 117.6, 126.5, 130.5, 130.7, 135.2, 138.7, 139.8, 146.3, 147.8 (t, ²J_CF = 26 Hz, C-CF₂); ¹⁹F-NMR (282.4 MHz, CDCl₃) δ −126.5 (m 2F, CF₂-CF₂-CF₂-CF₂-CF₃), −122.5 (m 2F, CF₂-CF₂-CF₂-CF₂-CF₃), −122 (m 2F, CF₂-CF₂-CF₂-CF₂-CF₃), −114.5 (m, 2F, CF₂-CF₂-CF₂-CF₂-CF₃), −81.2 (m 3F, CF₂-CF₂-CF₂-CF₂-CF₃). MS (m/z): 428 [M + H]⁺. HRMS m/z [M + H]⁺ calcd. for C₁₅H₉F₁₁NO⁺: 428.0508, found: 428.0510. Anal calcd. for C₁₅H₈F₁₁NO: C, 42.17; H, 1.89; N, 3.28, found: C, 42.19; H, 1.88; N, 3.26.

2-Trifluoromethyl-6-methoxyquinoline (20o’). 10.9 g of 3-anisidine 15o (8.85 × 10⁻² mol) and 2.6 mL or 2 g (3.54 × 10⁻² mol) of acetone 16t were added to a solution of 9.8 g (2.95 × 10⁻² mol) of 14’ (R’_F = C₂F₅) in 98 mL of dry dichloromethane. The mixture was stirred for 12 h at reflux. 5.9 g of the quinoline 20o’ were obtained, total yield 88%. Spectral data: ¹H-NMR (300.13 MHz, CDCl₃) δ 3.8 (s, 3H, OCH₃), 7.6 (d, J = 8.4 Hz, 1H), 7.8 (d, J = 8.5 Hz, 1H), 7.9–8 (m, 2H), 8.5 (d, J = 8.5 Hz, 1H); ¹³C-NMR (75.46 MHz, CDCl₃) δ 55.5 (s, OCH₃), 116.5 (q, ³J_CF = 2.1 Hz, CH-C-CF₃), 122.8 (q, ¹J_CF = 275.6 Hz, CF₃), 128, 128.5, 129.3, 132.1, 136, 139.1, 142.6, 148.5 (q, ²J_CF = 34 Hz, C-CF₃); ¹⁹F-NMR (282.4 MHz, CDCl₃) δ − 67.8 (m 3F, CF₃). MS (m/z): 228 [M + H]⁺. HRMS m/z [M + H]⁺ calcd. for C₁₁H₉F₃NO⁺: 228.0636, found: 228.0643. Anal calcd. for C₁₁H₈F₃NO: C, 58.15; H, 3.55; N, 6.17, found: C, 58.17; H, 3.56; N, 6.15.

3.6. General Procedure for the Preparation and Isolation of 2-Perfluoroalkyl- and 2-Trifluoromethyl-1-(R-phenyl)amino-3-(R-phenyl)iminopropene Intermediates 21a–l (all examples except R = CO₂H or R = m-OMe)

A mixture of one equivalent of gem-iodoacetate compounds 14 or 14’ or 14” and two equivalents of the corresponding anilines 15a–l in dichloromethane (10 mL DCM for 1 g of 14–14”) was stirred at room temperature until disappearance of ¹⁹F-NMR signals corresponding to the starting products 14–14” (2–6 h). At the end of the reaction, a solution of 10% sodium thiosulfate was added to the reaction mixture and the product was extracted three times with ether. The combined extracts were washed several times with aqueous 0.5 M hydrochloric solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a bright yellow oil. Chromatography over silica gel column (eluent: petroleum ether/ethyl acetate 98/2 v/v) yielded the pure compounds 21a–l as yellow liquids.

3-Perfluoropenthyl-1-phenylamino-3-phenyliminopropene (21a). 3.49 g of aniline 15a (3.75 × 10⁻² mol) were added to a solution of 10 g (1.87 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 100 mL of dry dichloromethane. The mixture was stirred for 4 h at room temperature. 8.28 g of the title product 21a were obtained, total yield 90%. ¹H-NMR (300.13 MHz, DMSO-d₆, EEE-21a) δ 5.5 (d, ³J_HH = 13 Hz, 1H, CH=CH-NH), 6.8 (t (AB system), J = 8.7 Hz, 4H_ortho, Ph-H), 6.9 (t, J = 7.4 Hz, 1H_para, Ph-H), 7.1 (t, J = 7.4 Hz, 1H_para, Ph-H), 7.2 (t, J = 8.1 Hz, 2H_meta, Ph-H), 7.4 (t, J = 7.8 Hz, 2H_meta, Ph-H), 7.45 (m, 1H, CH=CH-NH), 9.9 (d, ³J_HNH = 12.8 Hz, CH=CH-NH); ¹H-NMR (300.13 MHz, DMSO-d₆/D₂O, EEE-21a) δ 5.4 (d, ³J_HH = 13 Hz, 1H, CH=CH-NH), 6.7 (d, J = 8.5 Hz, 4H_ortho, Ph-H), 6.9 (t, J = 7.5 Hz, 1H_para, Ph-H), 7.1 (t, J = 7.4 Hz, 1H_para, Ph-H), 7.2 (t, J = 8 Hz, 2H_meta, Ph-H), 7.4 (t, J = 8 Hz, 2H_meta, Ph-H), 7.45 (m, 1H, CH=CH-NH); ¹³C-NMR (75.46 MHz, DMSO-d₆, EEE-21a) δ 91.5, 114.6, 118.5, 122.1, 123.5, 129.1, 129.5, 130, 140.5, 141.5 (t, ³J_CF = 5.4 Hz, CF₂-(C=N)-CH=CH-NH), 149.9, 153.6 (t, ²J_C1F = 22.5 Hz, CF₂-(C=N)-CH=CH-NH); ¹⁹F-NMR (282.4 MHz, DMSO-d₆, EEE-21a) δ −80.2 (t, J = 8.4 Hz, 3F, CF₂-CF₂-CF₂-CF₂-CF₃), −109.5 (t, J = 11 Hz, 2F, CF₂-CF₂-CF₂-CF₂-CF₃), −120.4 (m, 2F, CF₂-CF₂-CF₂-CF₂-CF₃), −121 (q, J = 5.6 Hz, 2F, CF₂-CF₂-CF₂-CF₂-CF₃), −125.8 (t, J = 11.2 Hz, 2F, CF₂-CF₂-CF₂-CF₂-CF₃). MS (m/z): 491 [M + H]⁺. HRMS calcd. for C₂₀H₁₄F₁₁N₂⁺: 491.0981, found: 491.0985; Anal calcd. for C₂₀H₁₃F₁₁N₂: C, 48.99; H, 2.67; N, 5.71, found C, 48.97; H, 2.66; N, 5.74.

3-Trifluoromethyl-1-phenylamino-3-phenyliminopropene (21a’). 3.64 g of aniline 15a (3.91 × 10⁻² mol) were added to a solution of 6.5 g (1.95 × 10⁻² mol) of 14’ (R_F = CF₃) in 65 mL of dry dichloromethane. The mixture was stirred for 3 h at room temperature. 4.65 g of the title product 21a’ were obtained, total yield 82%. ¹H-NMR (300.13 MHz, DMSO-d₆, EEE-21a’) δ 5.5 (d, J = 13.7 Hz, 1H, CH=CH-NH), 6.8 (d, J = 7.5 Hz, 2H), 7 (m, 3H), 7.15 (t, J = 7.4 Hz, 1H), 7.3 (t, J = 7.8 Hz, 2H), 7.4 (t, J = 7.7 Hz, 2H), 7.6 (t, J = 13 Hz, 1H, CH=CH-NH), 9.9 (d, J = 12.3 Hz, 1H, CH=CH-NH); ¹³C-NMR (75.46 MHz, DMSO-d₆, EEE-21a’) δ 90.8, 115.1, 119.4, 120.5 (q, CF₃, ¹J_CF = 279.2 Hz), 122.2, 123.5, 129.1, 129.5, 140.64, 140.8 (q, ³J_CF = 3 Hz, CF₃-(C=N)-CH=CH-NH), 149.5, 153.3 (q, ²J_CF = 30.5 Hz, CF₃-(C=N)-CH=CH-NH); ¹⁹F-NMR (282.4 MHz, DMSO-d₆, EEE-21a’) δ −65.7 (s, 3F). MS (m/z): 291 [M + H]⁺. HRMS calcd. for C₁₆H₁₄F₃N₂⁺: 291.1109, found 291.1110. Anal. Calcd. for C₁₆H₁₃F₃N₂: C, 66.20; H, 4.51; N, 9.65. Found: C, 66.19; H, 4.48; N, 9.55.

3-perfluoropropyl-1-phenylamino-3-phenyliminopropene (21a”). 2.36 g of aniline 15a (2.54 × 10⁻² mol) were added to a solution of 5.5 g (1.27 × 10⁻² mol) of 14” (R_F = C₃F₇) in 55 mL of dry dichloromethane. The mixture was stirred for 3 h at room temperature. 4.22 g of the title product 21a” were obtained, total yield 85%. ¹H-NMR (300.13 MHz, DMSO-d₆, EEE-21a”) δ 5.5 (d, J = 13.5 Hz, 1H, CH=CH-NH), 6.8 (d, J = 7.4 Hz, 2H), 7 (m, 3H), 7.2 (t, J = 7.4 Hz, 1H), 7.3 (t, J = 7.7 Hz, 2H), 7.4 (t, J = 7.7 Hz, 2H), 7.7 (t, J = 13.1 Hz, 1H, CH=CH-NH), 9.9 (d, J = 12.1 Hz, 1H, CH=CH-NH); ¹³C-NMR (75.46 MHz, DMSO-d₆, EEE-21a’’) δ 90.5, 115, 118.5, 122, 123.5, 129.3, 129.7, 130, 140.5, 141 (t, ³J_CF = 5 Hz, CF₂-(C=N)-CH=CH-NH), 150, 153.6 (t, ²J_CF = 21.5 Hz, CF₂-(C=N)-CH=CH-NH); ¹⁹F-NMR (282.4 MHz, DMSO-d₆, EEE-21a”) δ −80.5 (m, 3F), −109.1 (t, J = 11 Hz, 2F), −126 (m, 2F). MS (m/z): 391 [M + H]⁺. HRMS calcd. for C₁₈H₁₄F₇N₂⁺: 391.1045, found: 391.1055; Anal calcd. for C₁₈H₁₃F₇N₂: C, 55.39; H, 3.36; N, 7.18, found C, 55.41; H, 3.35; N, 7.15.

3-perfluoropentyl-1-(2-methylphenylamino)-3-(2-methylphenylimino)-propene (21b). 3.26 g of 2-methylaniline 15b (3.04 × 10⁻² mol) were added to a solution of 8.1 g (1.52 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 81 mL of dry dichloromethane. The mixture was stirred for 6 h at room temperature. 5.52 g of the title product 21b were obtained, total yield 70%. ¹H-NMR (300.13 MHz, DMSO-d₆, EEE-21b) δ 2.1 (s, 3H), 2.3 (s, 3H), 5.6 (d, J = 13.1 Hz, CH=CH-NH), 6.5–7.3 (m, 8H, H_Ar), 7.6 (m, 1H, CH=CH-NH), 9.3 (bs, 1H, CH=CH-NH); ¹³C-NMR (75.46 MHz, DMSO-d₆, EEE-21b) δ 18.8, 18.9, 89, 113.1, 117.7, 121.5, 123.5, 129, 129.3, 130, 140.5, 141.5 (t, ³J_CF = 4.8 Hz, CF₂-(C=N)-CH=CH-NH), 150.1, 153.5 (t, ²J_C1F = 20.5 Hz, CF₂-(C=N)-CH=CH-NH); ¹⁹F-NMR (282.4 MHz, DMSO-d₆, EEE-21b) δ −80.5 (m, 3F), −109 (m, 2F), −120.5 (m, 2F), −121 (m, 2F), −125.5 (m, 2F). MS (m/z): 519 [M + H]⁺. HRMS calcd. for C₂₂H₁₈F₁₁N₂⁺: 519.1294, found: 519.1298; Anal calcd. for C₂₂H₁₇F₁₁N₂: C, 50.97; H, 3.31; N, 5.40, found C, 50.99; H, 3.30; N, 5.37.

3-perfluoropentyl-1-(3-methylphenylamino)-3-(3-methylphenylimino)-propene (21c). 3.22 g of 3-methylaniline 15c (3.10⁻² mol) were added to a solution of 8 g (1.5 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 80 mL of dry dichloromethane. The mixture was stirred for 4 h at room temperature. 6.23 g of the title product 21c were obtained, total yield 80%. ¹H-NMR (300.13 MHz, DMSO-d₆, EEE-21c) δ 2.2 (s, 3H), 2.3 (s, 3H), 5.4 (d, J = 13.6 Hz, 1H, CH=CH-NH), 6.6 (m, 2H), 6.7 (m, 3H), 6.9 (d, J = 7.6 Hz, 1H), 7.1 (m, 1H), 7.2 (t, J = 7.6 Hz, 1H), 7.5 (t, J = 12.5 Hz, 1H, CH=CH-NH), 9.7 (d, J = 12.5 Hz, 1H, CH=CH-NH); ¹³C-NMR (75.46 MHz, DMSO-d₆, EEE-21c) δ 20.5, 20.9, 89, 113.5, 117.5, 121.5, 123.5, 129, 129.5, 130.2, 140, 141.1 (t, ³J_CF = 5.3 Hz, CF₂-(C=N)-CH=CH-NH), 150, 153 (t, ²J_C1F = 21.5 Hz, CF₂-(C=N)-CH=CH-NH); ¹⁹F-NMR (282.4 MHz, DMSO-d₆, EEE-21c) δ −80.5 (m, 3F), −109.6 (m, 2F), −120.2 (m, 2F), −121.5 (m, 2F), −125.5 (m, 2F). MS (m/z): 519 [M + H]⁺. HRMS calcd. for C₂₂H₁₈F₁₁N₂⁺: 519.1294, found: 519.1295; Anal calcd. for C₂₂H₁₇F₁₁N₂: C, 50.97; H, 3.31; N, 5.40, found C, 50.99; H, 3.28; N, 5.38

3-perfluoropentyl-1-(4-methylphenylamino)-3-(4-methylphenylimino)-propene (21d). 3.62 g of 4-methylaniline 15d (3.38 × 10⁻² mol) were added to a solution of 9 g (1.69 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 90 mL of dry dichloromethane. The mixture was stirred for 4 h at room temperature. 7.71 g of the title product 21d were obtained, total yield 88%. ¹H-NMR (300.13 MHz, DMSO-d₆, EEE-21d) δ 2.2 (s, 3H), 2.3 (s, 3H), 5.4 (d, J = 13 Hz, 1H, CH=CH-NH), 6.7 (d, J = 8 Hz, 2H), 6.8 (d, J = 8.2 Hz, 2H), 7.1 (d, J = 8.2 Hz, 2H), 7.2 (d, J = 8 Hz, 2H), 7.5 (t, J = 12.5 Hz, 1H, CH=CH-NH), 9.7 (d, J = 12.4 Hz, 1H, CH=CH-NH); ¹³C-NMR (75.46 MHz, DMSO-d₆, EEE-21d) δ 20.1, 20.4, 90.2, 115.5, 117.5, 122, 124.5, 129.2, 129.5, 140, 141.9 (t, ³J_CF = 3.5 Hz, CF₂-(C=N)-CH=CH-NH), 150.5, 152.9 (t, ²J_C1F = 31.1 Hz, CF₂-(C=N)-CH=CH-NH); ¹⁹F-NMR (282.4 MHz, DMSO-d₆, EEE-21d) δ −80.3 (m, 3F), −109.5 (m, 2F), −120.1 (m, 2F), −121.5 (m, 2F), −125 (m, 2F). MS (m/z): 519 [M + H]⁺. HRMS calcd. for C₂₂H₁₈F₁₁N₂⁺: 519.1294, found: 519.1290; Anal calcd. for C₂₂H₁₇F₁₁N₂: C, 50.97; H, 3.31; N, 5.40, found C, 50.97; H, 3.29; N, 5.42

3-Trifluoromethyl-1-(4-methylphenylamino)-3-(4-methylphenylimino)-propene (21d’). 5.48 g of 4-methylaniline 15d (5.12 × 10⁻² mol) were added to a solution of 8.5 g (2.56 × 10⁻² mol) of 14’ (R_F = CF₃) in 85 mL of dry dichloromethane. The mixture was stirred for 4 h at room temperature. 7 g of the title product 21d’ were obtained, total yield 86%. ¹H-NMR (300.13 MHz, DMSO-d₆, EEE-21d’) δ 2.2 (s, 3H), 2.3 (s, 3H), 5.4 (d, J = 13.8 Hz, 1H, CH=CH-NH), 6.7 (d, J = 8 Hz, 2H), 6.8 (d, J = 8.2 Hz, 2H), 7.1 (d, J = 8.2 Hz, 2H), 7.2 (d, J = 8 Hz, 2H), 7.5 (t, J = 12.9 Hz, 1H, CH=CH-NH), 9.7 (d, J = 12.4 Hz, 1H, CH=CH-NH); ¹³C-NMR (75.46 MHz, DMSO-d₆, EEE-21d’) δ 20.1, 20.3, 90.4, 115, 119.1, 120.6 (q, ¹J_CF = 279.5 Hz, CF₃), 129.1, 129.7, 129.9, 130.8, 131.1, 132.5, 138.2, 140.8 (q, ³J_CF = 3.1 Hz, CF₃-(C=N)-CH=CH-NH), 147, 153.4 (q, ²J_CF = 30.8 Hz, CF₃-(C=N)-CH=CH-NH); ¹⁹F-NMR (282.4 MHz, DMSO-d₆, EEE-21d’) δ −65.7 (s, 3F). MS (m/z): 319 [M + H]⁺. HRMS calcd. for C₁₈H₁₈F₃N₂⁺: 319.1422, found: 319.1425; Anal calcd. for C₁₈H₁₇F₃N₂: C, 67.91; H, 5.38; N, 8.80, found C, 67.95; H, 5.37; N, 8.82.

3-perfluoropentyl-1-(2-ethylphenylamino)-3-(2-ethylphenylimino)-propene (21e). 3.59 g of 2-ethylaniline 15e (2.96 × 10⁻² mol) were added to a solution of 7.9 g (1.48 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 79 mL of dry dichloromethane. The mixture was stirred for 6 h at room temperature. 5.43 g of the title product 21e were obtained, total yield 67%. ¹H-NMR (300.13 MHz, DMSO-d₆, EEE-21e) δ 1.2 (t, J = 8 Hz, 3H, CH₂-CH₃), 1.3 (t, J = 8 Hz, 3H, CH₂-CH₃), 2.5 (q, J = 8 Hz, 2H, CH₂-CH₃), 2.7(q, J = 8 Hz, 2H, CH₂-CH₃), 5.6 (d, J = 12.8 Hz, CH=CH-NH), 6.5–7.3 (m, 8H, H_Ar), 7.5 (m, 1H, CH=CH-NH), 9.1 (bs, 1H, CH=CH-NH); ¹³C-NMR (75.46 MHz, DMSO-d₆, EEE-21e) δ 13.2 (s, CH₂-CH₃), 13.3 (s, CH₂-CH₃), 24.1 (s, CH₂-CH₃), 24.3 (s, CH₂-CH₃), 89, 112.9, 117.5, 121.2, 129.3, 129.4, 130.5, 140.5, 141 (t, ³J_CF = 4.9 Hz, CF₂-(C=N)-CH=CH-NH), 149.9, 153.1 (t, ²J_C1F = 21.5 Hz, CF₂-(C=N)-CH=CH-NH); ¹⁹F-NMR (282.4 MHz, DMSO-d₆, EEE-21e) δ −80.6 (m, 3F), −109.2 (m, 2F), −120.1 (m, 2F), −121.1 (m, 2F), −125 (m, 2F). MS (m/z): 547 [M + H]⁺. HRMS calcd. for C₂₄H₂₂F₁₁N₂⁺: 547.1607, found: 547.1610; Anal calcd. for C₂₄H₂₁F₁₁N₂: C, 52.75; H, 3.87; N, 5.13, found C, 52.76; H, 3.88; N, 5.10.

3-perfluoropentyl-1-(3-ethylphenylamino)-3-(3-ethylphenylimino)-propene (21f). 3.87 g of 3-ethylaniline 15f (3.19 × 10⁻² mol) were added to a solution of 8.5 g (1.59 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 85 mL of dry dichloromethane. The mixture was stirred for 4 h at room temperature. 6.71 g of the title product 21f were obtained, total yield 77%. ¹H-NMR (300.13 MHz, DMSO-d₆, EEE-21f) δ 1.1 (t, J = 8 Hz, 3H, CH₂-CH₃), 1.3 (t, J = 8 Hz, 3H, CH₂-CH₃), 2.6 (q, J = 8 Hz, 2H, CH₂-CH₃), 2.7 (q, J = 8 Hz, 2H, CH₂-CH₃), 5.4 (d, J = 13.1 Hz, 1H, CH=CH-NH), 6.6–6.8 (m, 5H), 6.9 (d, J = 7.5 Hz, 1H), 7.1 (m, 1H), 7.2 (t, J = 7.6 Hz, 1H), 7.5 (t, J = 12.5 Hz, 1H, CH=CH-NH), 9.6 (d, J = 12.8 Hz, 1H, CH=CH-NH); ¹³C-NMR (75.46 MHz, DMSO-d₆, EEE-21f) δ 13.1 (s, CH₂-CH₃), 13.3 (s, CH₂-CH₃), 24 (s, CH₂-CH₃), 24.3 (s, CH₂-CH₃), 90.2, 114.1, 117.8, 122, 123.1, 129, 129.2, 130.2, 140, 141.1 (t, ³J_CF = 5.9 Hz, CF₂-(C=N)-CH=CH-NH), 151.1, 153.5 (t, ²J_C1F = 22.1 Hz, CF₂-(C=N)-CH=CH-NH); ¹⁹F-NMR (282.4 MHz, DMSO-d₆, EEE-21f) δ −81.5 (m, 3F), −109.1 (m, 2F), −120.2 (m, 2F), −121.5 (m, 2F), −126.1 (m, 2F). MS (m/z): 547 [M + H]⁺. HRMS calcd. for C₂₄H₂₂F₁₁N₂⁺: 547.1607, found: 547.1611; Anal calcd. for C₂₄H₂₁F₁₁N₂: C, 52.75; H, 3.87; N, 5.13, found C, 52.78; H, 3.88; N, 5.14.

3-perfluoropentyl-1-(4-ethylphenylamino)-3-(4-ethylphenylimino)-propene (21g). 4 g of 4-ethylaniline 15g (3.3 × 10⁻² mol) were added to a solution of 8.8 g (1.65 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 88 mL of dry dichloromethane. The mixture was stirred for 4 h at room temperature. 7.67 g of the title product 21g were obtained, total yield 85%. ¹H-NMR (300.13 MHz, DMSO-d₆, EEE-21g) δ 1.2 (t, J = 8 Hz, 3H, CH₂-CH₃), 1.3 (t, J = 8 Hz, 3H, CH₂-CH₃), 2.6 (q, J = 8 Hz, 2H, CH₂-CH₃), 2.7 (q, J = 8 Hz, 2H, CH₂-CH₃), 5.6 (d, J = 13.4 Hz, 1H, CH=CH-NH), 6.6 (d, J = 8.1 Hz, 2H), 6.8 (d, J = 8.2 Hz, 2H), 7.1 (d, J = 8.2 Hz, 2H), 7.2 (d, J = 8.1 Hz, 2H), 7.5 (t, J = 12.8 Hz, 1H, CH=CH-NH), 9.6 (d, J = 12.7 Hz, 1H, CH=CH-NH); ¹³C-NMR (75.46 MHz, DMSO-d₆, EEE-21g) δ 13.3 (s, CH₂-CH₃), 13.4 (s, CH₂-CH₃), 24.3 (s, CH₂-CH₃), 24.5 (s, CH₂-CH₃), 90.2, 115.5, 117.5, 123.1, 125.2, 129.1, 129.3, 140.5, 141.9 (t, ³J_CF = 4.2 Hz, CF₂-(C=N)-CH=CH-NH), 151.5, 153.4 (t, ²J_C1F = 32.2 Hz, CF₂-(C=N)-CH=CH-NH); ¹⁹F-NMR (282.4 MHz, DMSO-d₆, EEE-21g) δ −80.7 (m, 3F), −109.5 (m, 2F), −120.7 (m, 2F), −122.4 (m, 2F), −125.8 (m, 2F). MS (m/z): 547 [M + H]⁺. HRMS calcd. for C₂₄H₂₂F₁₁N₂⁺: 547.1607, found: 547.1609; Anal calcd. for C₂₄H₂₁F₁₁N₂: C, 52.75; H, 3.87; N, 5.13, found C, 52.77; H, 3.87; N, 5.14.

3-Trifluoromethyl-1-(4-ethylphenylamino)-3-(4-ethylphenylimino)-propene (21g’). 6.56 g of 4-ethylaniline 15g (5.42 × 10⁻² mol) were added to a solution of 9 g (2.71 × 10⁻² mol) of 14’ (R_F = CF₃) in 90 mL of dry dichloromethane. The mixture was stirred for 4 h at room temperature. 7.97 g of the title product 21g’ were obtained, total yield 85%. ¹H-NMR (300.13 MHz, DMSO-d₆, EEE-21g’) δ 1.2 (t, J = 7.8 Hz, 3H, CH₂-CH₃), 1.3 (t, J = 8 Hz, 3H, CH₂-CH₃), 2.5 (q, J = 7.9 Hz, 2H, CH₂-CH₃), 2.7 (q, J = 8.1 Hz, 2H, CH₂-CH₃), 5.5 (d, J = 13.6 Hz, 1H, CH=CH-NH), 6.7 (d, J = 7.9 Hz, 2H), 6.8 (d, J = 8 Hz, 2H), 7.1 (d, J = 8.1 Hz, 2H), 7.2 (d, J = 8 Hz, 2H), 7.5 (t, J = 12.5 Hz, 1H, CH=CH-NH), 9.6 (d, J = 12.4 Hz, 1H, CH=CH-NH); ¹³C-NMR (75.46 MHz, DMSO-d₆, EEE-21g’) δ 13.3 (s, CH₂-CH₃), 13.4 (s, CH₂-CH₃), 24.3 (s, CH₂-CH₃), 24.5 (s, CH₂-CH₃), 90.6, 116.2, 120.1, 120.5 (q, ¹J_CF = 280.5 Hz, CF₃), 129.7, 129.9, 130.8, 131, 132.5, 138.3, 140.8 (q, ³J_CF = 4.2 Hz, CF₃-(C=N)-CH=CH-NH), 147.5, 153.1 (q, ²J_CF = 29.9 Hz, CF₃-(C=N)-CH=CH-NH); ¹⁹F-NMR (282.4 MHz, DMSO-d₆, EEE-21g’) δ −65.5 (s, 3F). MS (m/z): 347 [M + H]⁺. HRMS calcd. for C₂₀H₂₂F₃N₂⁺: 347.1735, found: 347.1740; Anal calcd. for C₂₀H₂₁F₃N₂: C, 69.35; H, 6.11; N, 8.09, found C, 69.41; H, 6.10; N, 8.11.

3-perfluoropentyl-1-(2-chlorophenylamino)-3-(2-chlorophenylimino)-propene (21h). 4.84 g of 2-chloroaniline 15h (3.79 × 10⁻² mol) were added to a solution of 10.1 g (1.89 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 101 mL of dry dichloromethane. The mixture was stirred for 4 h at room temperature. 6.57 g of the title product 21h were obtained, total yield 62%. ¹H-NMR (300.13 MHz, DMSO-d₆, EEE-21h) δ 5.6 (d, J = 13.8 Hz, 1H, CH=CH-NH), 6.9 (d, J = 7.71 Hz, 1H_Ar), 7.1–7.4 (m, 7H_Ar), 7.5 (d, J = 7.9 Hz, 1H, CH=CH-NH), 9.5 (bs, 1H, CH=CH-NH); ¹³C-NMR (75.46 MHz, DMSO-d₆, EEE-21h) δ 90.1, 114.2, 115.1, 117.1, 121.2, 129.3, 129.4, 130.5, 140.5, 149.9, 153.2 (t, ²J_C1F = 29.8 Hz, CF₂-(C=N)-CH=CH-NH); ¹⁹F-NMR (282.4 MHz, DMSO-d₆, EEE-21h) δ −80.6 (m, 3F), −109.5 (m, 2F), −120.3 (m, 2F), −121.1 (m, 2F), −125 (m, 2F). MS (m/z): 560 [M + H]⁺. HRMS calcd. for C₂₀H₁₂Cl₂F₁₁N₂⁺: 559.0202, found: 559.0210; Anal calcd. for C₂₀H₁₁Cl₂F₁₁N₂: C, 42.96; H, 1.98; N, 5.01, found C, 42.95; H, 1.96; N, 5.10.

3-perfluoropentyl-1-(3-chlorophenylamino)-3-(3-chlorophenylimino)-propene (21i). 4.79 g of 3-chloroaniline 15i (3.75 × 10⁻² mol) were added to a solution of 10 g (1.87 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 100 mL of dry dichloromethane. The mixture was stirred for 4 h at room temperature. 7.35 g of the title product 21i were obtained, total yield 70%. ¹H-NMR (300.13 MHz, DMSO-d₆, EEE-21i) δ 5.6 (d, J = 13.6 Hz, 1H, CH=CH-NH), 6.7–6.9 (m, 6H), 7.2–7.3 (m, 2H), 7.5 (t, J = 13.2 Hz, 1H, CH=CH-NH), 9.7 (d, J = 12.8 Hz, 1H, CH=CH-NH); ¹³C-NMR (75.46 MHz, DMSO-d₆, EEE-21i) δ 90.4, 112.2, 115.1, 116.4, 117.1, 121.4, 129.1, 129.5, 130.6, 141.5, 150.2, 153.2 (t, ²J_C1F = 30.2 Hz, CF₂-(C=N)-CH=CH-NH); ¹⁹F-NMR (282.4 MHz, DMSO-d₆, EEE-21i) δ −80.5 (m, 3F), −109.1 (m, 2F), −120.1 (m, 2F), −121.1 (m, 2F), −125 (m, 2F). MS (m/z): 560 [M + H]⁺. HRMS calcd. for C₂₀H₁₂Cl₂F₁₁N₂⁺: 559.0202, found: 559.0205; Anal calcd. for C₂₀H₁₁Cl₂F₁₁N₂: C, 42.96; H, 1.98; N, 5.01, found C, 42.98; H, 1.97; N, 5.00.

3-perfluoropentyl-1-(4-chlorophenylamino)-3-(4-chlorophenylimino)-propene (21j). 4.6 g of 4-chloroaniline 15j (3.6 × 10⁻² mol) were added to a solution of 9.6 g (1.8 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 96 mL of dry dichloromethane. The mixture was stirred for 4 h at room temperature. 7.76 g of the title product 21j were obtained, total yield 77%. ¹H-NMR (300.13 MHz, DMSO-d₆, EEE-21j) δ 5.4 (d, J = 13.6 Hz, 1H, CH=CH-NH), 6.8 (d, J = 8 Hz, 2H), 7 (d, J = 8.1 Hz, 2H), 7.3 (d, J = 8.2 Hz, 2H), 7.4 (d, J = 8 Hz, 2H), 7.6 (t, J = 13.2 Hz, 1H, CH=CH-NH), 9.8 (d, J = 12.9 Hz, 1H, CH=CH-NH); ¹³C-NMR (75.46 MHz, DMSO-d₆, EEE-21j) δ 90.3, 116.1, 117.5, 123, 125.2, 129.2, 129.3, 140.6, 141.5 (t, ³J_CF = 5.1 Hz, CF₂-(C=N)-CH=CH-NH), 151.6, 153.5 (t, ²J_C1F = 31.1 Hz, CF₂-(C=N)-CH=CH-NH); ¹⁹F-NMR (282.4 MHz, DMSO-d₆, EEE-21j) δ −80.6 (m, 3F), −109.2 (m, 2F), −120.5 (m, 2F), −122.5 (m, 2F), −125.2 (m, 2F). MS (m/z): 560 [M + H]⁺. HRMS calcd. for C₂₀H₁₂Cl₂F₁₁N₂⁺: 559.0202, found: 559.0209; Anal calcd. for C₂₀H₁₁Cl₂F₁₁N₂: C, 42.96; H, 1.98; N, 5.01, found C, 42.99; H, 1.98; N, 5.03.

3-perfluoropentyl-1-(2-methoxyphenylamino)-3-(2-methoxyphenylimino)-propene (21k). 3.93 g of 2-methoxyaniline 15k (3.19 × 10⁻² mol) were added to a solution of 8.5 g (1.59 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 85 mL of dry dichloromethane. The mixture was stirred for 6 h at room temperature. 5.97 g of the title product 21k were obtained, total yield 68%. ¹H-NMR (300.13 MHz, DMSO-d₆, EEE-21k) δ 3.7 (s, 3H, OCH₃), 3.8 (s, 3H, OCH₃), 5.5 (d, J = 12.8 Hz, CH=CH-NH), 6.5–7.4 (m, 8H, H_Ar), 7.5 (m, 1H, CH=CH-NH), 9.1 (bs, 1H, CH=CH-NH); ¹³C-NMR (75.46 MHz, DMSO-d₆, EEE-21k) δ 55.5 (s, OCH₃), 55.6 (s, OCH₃), 89.2, 112.5, 116.9, 120.8, 129.1, 129.2, 130.2, 132.1, 140.6, 141.2 (t, ³J_CF = 4.5 Hz, CF₂-(C=N)-CH=CH-NH), 149.2, 152.9 (t, ²J_C1F = 20.1 Hz, CF₂-(C=N)-CH=CH-NH); ¹⁹F-NMR (282.4 MHz, DMSO-d₆, EEE-21k) δ −80.6 (m, 3F), −109.1 (m, 2F), −120.1 (m, 2F), −121.3 (m, 2F), −125.5 (m, 2F). MS (m/z): 551 [M + H]⁺. HRMS calcd. for C₂₂H₁₈F₁₁N₂O₂⁺: 551.1193, found: 551.1199; Anal calcd. for C₂₂H₁₇F₁₁N₂O₂: C, 48.01; H, 3.11; N, 5.09, found C, 48.08; H, 3.10; N, 5.11.

3-perfluoropentyl-1-(4-methoxyphenylamino)-3-(4-methoxyphenylimino)-propene (21l). 4.25 g of 4-anisidine 15l (3.45 × 10⁻² mol) were added to a solution of 9.2 g (1.72 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 92 mL of dry dichloromethane. The mixture was stirred for 4 h at room temperature. 6.84 g of the title product 21l were obtained, total yield 72%. ¹H-NMR (300.13 MHz, DMSO-d₆, EEE-21l) δ 3.7 (s, 3H, OCH₃), 3.8 (s, 3H, OCH₃), 5.6 (d, J = 13.1 Hz, 1H, CH=CH-NH), 6.6 (d, J = 7.9 Hz, 2H), 6.8 (d, J = 8 Hz, 2H), 7.1 (d, J = 8 Hz, 2H), 7.2 (d, J = 8.1 Hz, 2H), 7.5 (t, J = 12.5 Hz, 1H, CH=CH-NH), 9.4 (d, J = 12.7 Hz, 1H, CH=CH-NH); ¹³C-NMR (75.46 MHz, DMSO-d₆, EEE-21l) δ 55.5 (s, OCH₃), 55.7 (s, OCH₃), 89.8, 114.8, 115.6, 117.52, 123.1, 125, 129, 129.3, 139.8, 141.5 (t, ³J_CF = 3.9 Hz, CF₂-(C=N)-CH=CH-NH), 151.1, 154.2 (t, ²J_C1F = 29.6 Hz, CF₂-(C=N)-CH=CH-NH); ¹⁹F-NMR (282.4 MHz, DMSO-d₆, EEE-21l) δ −80.5 (m, 3F), −109 (m, 2F), −120.3 (m, 2F), −122.2 (m, 2F), −125.5 (m, 2F). MS (m/z): 551 [M + H]⁺. HRMS calcd. for C₂₂H₁₈F₁₁N₂O₂⁺: 551.1193, found: 551.1195; Anal calcd. for C₂₂H₁₇F₁₁N₂O₂: C, 48.01; H, 3.11; N, 5.09, found C, 48.05; H, 3.12; N, 5.08.

3.7. General Procedure for the Isolation of 2-Perfluoropentyl- and 2-Trifluoromethyl-1-((2-/4-)-Carboxy-phenyl)Amino-3-((2-/4-)-Carboxyphenyl)Iminopropene Intermediates 21m–n’

A mixture of one equivalent of gem-iodoacetate compounds 14 or 14’ and two equivalents of the corresponding aminobenzoic acid 15m–n in dichloromethane (10 mL DCM for 1 g of 14–14’) was stirred at reflux until disappearance of ¹⁹F-NMR signals corresponding to the starting products 14–14’ (2–4 h). The reaction mixture was concentrated in vacuo and then diluted with diethyl ether. An excess of petroleum ether was added, and the precipitate that had formed was eliminated by vacuum filtration. The filtrate was concentrated under reduced pressure to give brown oil. Chromatography over silica gel column (eluent, petroleum ether/ethyl acetate 90/10 v/v) then purification over a plate chromatography (eluent petroleum ether/ethyl acetate 70/30 v/v) yielded pure compounds 21m-n’ as yellow amorphous solids.

3-perfluoropentyl-1-(2-carboxyphenylamino)-3-(2-carboxyphenylimino)-propene (21m). 5.15 g of 2-aminobenzoic acid 15m (3.75 × 10⁻² mol) were added to a solution of 10 g (1.87 × 10⁻² mol) of 14 (R_F = C₅F₁₁) in 100 mL of dry dichloromethane. The mixture was stirred for 4 h at reflux. 4.88 g of the title product 21m were obtained after column chromatography, yield 45%. ¹H-NMR (300.13 MHz, DMSO-d₆, EEE-21m) δ 5.7 (d, ³J_HH = 13.7 Hz, CH=CH-NH), 6.9–7.45 (m, 8H, H_Ar), 7.6 (m, 1H, CH=CH-NH), 9.6 (bs, 1H, CH=CH-NH), 14 (bs, 2H, CO₂H); ¹³C-NMR (75.46 MHz, DMSO-d₆, EEE-21m) δ 90.1, 114.5, 115, 118.1, 120.8, 129.1, 129.4, 131.2, 141.5, 150.5, 153.1 (t, ²J_C1F = 25.6 Hz, CF₂-(C=N)-CH=CH-NH), 170.5 (s, CO₂H), 170.7 (s, CO₂H); ¹⁹F-NMR (282.4 MHz, DMSO-d₆, EEE-21m) δ −80.3 (m, 3F), −109.68 (m, 2F), −120.4 (m, 2F), −121.05 (m, 2F), −125.83 (m, 2F). MS (m/z): 579 [M + H]⁺. HRMS calcd. for C₂₂H₁₄F₁₁N₂O₄⁺: 579.0778, found: 579.0783 Anal calcd. for: C₂₂H₁₃F₁₁N₂O₄: C, 45.69; H, 2.27; N, 4.84, found C, 45.72; H, 2.26; N,4.82.

3-Trifluoromethyl-1-(2-carboxyphenylamino)-3-(2-carboxyphenylimino)-propene (21m’). 6.44 g of 2-aminobenzoic acid 15m (4.69 × 10⁻² mol) were added to a solution of 7.8 g (2.34 × 10⁻² mol) of 14’ (R_F = CF₃) in 78 mL of dry dichloromethane. The mixture was stirred for 4 h at reflux. 3.99 g of the title product 21m’ were obtained after column chromatography, yield 45%. ¹H-NMR (300.13 MHz, DMSO-d₆, EEE-21m’) δ 5.7 (d, J = 13.6 Hz, CH=CH-NH), 6.8–7.5 (m, 8H, H_Ar), 7.6 (m, 1H, CH=CH-NH), 9.7 (bs, 1H, CH=CH-NH), 14.1 (bs, 2H, CO₂H); ¹³C-NMR (75.46 MHz, DMSO-d₆, EEE-21m’) δ 91.4, 115.2, 119.5, 121 (q, ¹J_CF = 277.7 Hz, CF₃), 129.2, 129.7, 130.1, 130.8, 131.5, 132.5, 138.1, 140.7 (q, ³J_CF = 2.8 Hz, CF₃-(C=N)-CH=CH-NH), 147.1, 153.5 (q, ²J_CF = 30.1 Hz, CF₃-(C=N)-CH=CH-NH), 170.3 (s, CO₂H), 170.5 (s, CO₂H); ¹⁹F-NMR (282.4 MHz, DMSO-d₆, EEE-21m’) δ −65.6 (s, 3F). MS (m/z): 379 [M + H]⁺. HRMS calcd. for C₁₈H₁₄F₃N₂O₄⁺: 379.0906, found: 379.0911 Anal calcd. for: C₁₈H₁₃F₃N₂O₄: C, 57.15; H, 3.46; N, 7.41, found C, 57.19; H, 3.45; N,7.40.

3-Perfluoropenthyl-1-(4-carboxyphenyl)amino-3-(4-carboxyphenyl)iminopropene (21n). 5.15 g of 4-aminobenzoic acid (3.75 × 10⁻² mole) were added to a solution of 10 g (1.87 × 10⁻² mole) of 14 (R’_F = C₆F₁₃) in 100 mL of dry dichloromethane. The mixture was stirred for 4 h at reflux. 5.21 g of the title product 21n were obtained after column chromatography, yield 48%. ¹H-NMR (300.13 MHz, DMSO-d₆, EEE-21n) δ 5.4 (d, ³J_HH = 12.9 Hz, 1H, CH=CH-NH), 6.8 (d, ³J_HH = 8.1 Hz, 2H, Ar-H), 7 (d, ³J_HH = 8.3 Hz, 2H, Ar-H), 7.3 (d, ³J_HH = 8.3 Hz, 2H, Ar-H), 7.4 (d, ³J_HH = 8.1 Hz, 2H, Ar-H), 7.6 (t (dd), ³J_HH = ³J_HNH = 12.5 Hz, 1H, CH=CH-NH), 9.9 (d, ³J_HNH = 12.2 Hz, CH=CH-NH), 13.5 (bs, 2H, CO₂H); ¹³C-NMR (75.46 MHz, DMSO-d₆, EEE-21n) δ 91, 115.5, 118.5, 121.9, 123.5, 129.2, 129.5, 130.1, 142.5, 141.9 (t, ³J_CF = 4.9 Hz, CF₂-(C=N)-CH=CH-NH), 149.8, 153.8 (t, ²J_C1F = 20.5 Hz, CF₂-(C=N)-CH=CH-NH); 170.1 (s, CO₂H), 170.4 (s, CO₂H); ¹⁹F-NMR (282.4 MHz, DMSO-d₆, EEE-21n) δ −80.5 (m, 3F, CF₂-CF₂-CF₂-CF₂-CF₃), −109.2 (t, J = 11.2 Hz, 2F, CF₂-CF₂-CF₂-CF₂-CF₃), −120.4 (m, 2F, CF₂-CF₂-CF₂-CF₂-CF₃), −121.5 (m, 2F, CF₂-CF₂-CF₂-CF₂-CF₃), −125.5 (m, 2F, CF₂-CF₂-CF₂-CF₂-CF₃). MS (m/z): 579 [M + H]⁺. HRMS calcd. for C₂₂H₁₄F₁₁N₂O₄⁺: 579.0778, found: 579.0782 Anal calcd. for: C₂₂H₁₃F₁₁N₂O₄: C, 45.69; H, 2.27; N, 4.84, found C, 45.71; H, 2.26; N,4.82.

3-Trifluoromethyl-1-(4-carboxyphenylamino)-3-(4-carboxyphenylimino)-propene (21n’). 8.67 g of 4-aminobenzoic acid 15n (6.32 × 10⁻² mol) were added to a solution of 10.5 g (3.16 × 10⁻² mol) of 14 (R_F = CF₃) in 105 mL of dry dichloromethane. The mixture was stirred for 4 h at reflux. 6.57 g of the title product 21n’ were obtained after column chromatography, yield 55%. ¹H-NMR (300.13 MHz, DMSO-d₆, EEE-21n’) δ 5.5 (d, ³J_HH = 13 Hz, 1H, CH=CH-NH), 6.8 (d, J = 8 Hz, 2H), 7.1 (d, J = 8.1 Hz, 2H), 7.3 (d, J = 8 Hz, 2H), 7.4 (d, J = 8.1 Hz, 2H), 7.6 (t, J = J = 12.8 Hz, 1H, CH=CH-NH), 9.8 (d, J = 12.5 Hz, CH=CH-NH), 13.8 (bs, 2H, CO₂H); ¹³C-NMR (75.46 MHz, DMSO-d₆, EEE-21n’) δ 91.1, 115.5, 119.8, 121.5 (q, CF₃, ¹J_CF = 278.2 Hz), 123.1, 123.5, 128.9, 129.2, 140.5, 141.2 (q, ³J_CF = 2.1 Hz, CF₃-(C=N)-CH=CH-NH), 150.2, 153.5 (q, ²J_CF = 27.5 Hz, CF₃-(C=N)-CH=CH-NH), 170 (s, CO₂H), 170.2 (s, CO₂H); ¹⁹F-NMR (282.4 MHz, DMSO-d₆, EEE-21n’) δ −65.5 (s, 3F). MS (m/z): 379 [M + H]⁺. HRMS calcd. for C₁₈H₁₄F₃N₂O₄⁺: 379.0906, found: 379.0910 Anal calcd. for: C₁₈H₁₃F₃N₂O₄: C, 57.15; H, 3.46; N, 7.41, found C, 57.19; H, 3.45; N,7.42.

3.8. General Procedure for the Preparation and Isolation of 2-Perfluoropentyl- and 2-Trifluoromethyl-1-(3-Methoxyphenyl)Amino-3-(3-Methoxyphenyl)Iminopropene Intermediates 21o–o’

A mixture of one equivalent of gem-iodoacetate compounds 14 or 14’ and two equivalents of 3-anisidine 15o in dichloromethane (20 mL DCM for 1 g of 14–14’) was stirred at room temperature. The evolution of the reaction was monitored by TLC (eluent petroleum ether/ethyl acetate: 80/20 v/v), and ¹⁹F-NMR spectroscopy of aliquots. After four h of stirring, a solution of 10% sodium thiosulfate was added to the reaction mixture and the product was extracted three times with ether. The combined extracts were washed two times with saturated sodium bicarbonate solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a yellow oil. Chromatography over silica gel column (eluent: petroleum ether/ethyl acetate 98/2 v/v), then purification over a plate chromatography (eluent petroleum ether/ethyl acetate 85/15 v/v) yielded the pure compounds 21o–o’ as yellow liquids.

3-Perfluoropenthyl-1-(3-methoxyphenyl)amino-3-(3-methoxyphenyl)iminopropene (21o). 3.98 g of 3-anisidine 15o (3.23 × 10⁻² mole) were added to a solution of 8.6 g (1.61 × 10⁻² mole) of 14 (R_F = C₅F₁₁) in 172 mL of dry dichloromethane. 4 g of the title product 21o were obtained after column chromatography, yield 45%. ¹H-NMR (300.13 MHz, DMSO-d₆, EEE-21o) δ 3.7 (s, 3H, OCH₃), 3.8 (s, 3H, OCH₃), 5.4 (d, J = 13.1 Hz, 1H, CH=CH-NH), 6.6–6.9 (m, 6H, Ph-H), 7.1 (t, J = 7.4 Hz, 1H, Ph-H), 7.3 (t, J = 7.4 Hz, 1H, Ph-H), 7.6 (t, J = 12.9 Hz, 1H, CH=CH-NH), 9.6 (d, J = 12.8 Hz, 1H, CH=CH-NH); ¹³C-NMR (75.46 MHz, DMSO-d₆, EEE-21o) δ 55.5 (s, OCH₃), 55.6 (s, OCH₃), 89.5, 113.5, 115.5, 117.5, 121.5, 123.5, 129.1, 129.4, 130.6, 140, 140.8 (t, ³J_CF = 4.2 Hz, CF₂-(C=N)-CH=CH-NH), 150.5, 153.2 (t, ²J_C1F = 26.7 Hz, CF₂-(C=N)-CH=CH-NH); ¹⁹F-NMR (282.4 MHz, DMSO-d₆, EEE-21o) δ −80.5 (m, 3F, CF₂-CF₂-CF₂-CF₂-CF₃), −109.5 (m, 2F, CF₂-CF₂-CF₂-CF₂-CF₃), −120.5 (m, 2F, CF₂-CF₂-CF₂-CF₂-CF₃), −121.3 (m, 2F, CF₂-CF₂-CF₂-CF₂-CF₃), −125.6 (m, 2F, CF₂-CF₂-CF₂-CF₂-CF₃). MS (m/z): 551 [M + H]⁺. HRMS calcd. for C₂₂H₁₈F₁₁N₂O₂⁺: 551.1193, found: 551.1198; Anal calcd. for C₂₂H₁₇F₁₁N₂O₂: C, 48.01; H, 3.11; N, 5.09, found C, 48.03; H, 3.11; N, 5.10.

3-Trifluoromethyl-1-(3-methoxyphenyl)amino-3-(3-methoxyphenyl)iminopropene (21o’). 6.67 g of 3-anisidine 15o (5.42 × 10⁻² mol) were added to a solution of 9 g (2.71 × 10⁻² mol) of 14’ (R_F = CF₃) in 180 mL of dry dichloromethane. 4.55 g of the title product 21o’ were obtained after column chromatography, yield 48%. ¹H-NMR (300.13 MHz, DMSO-d₆, EEE-21o’) δ 3.7 (s, 3H, OCH₃), 3.8 (s, 3H, OCH₃), 5.4 (d, J = 13 Hz, 1H, CH=CH-NH), 6.7–6.9 (m, 6H, Ph-H), 7.1 (t, J = 7.3 Hz, 1H, Ph-H), 7.3 (t, J = 7.4 Hz, 1H, Ph-H), 7.7 (t, J = 12.7 Hz, 1H, CH=CH-NH), 9.6 (d, J = 12.6 Hz, 1H, CH=CH-NH); ¹³C-NMR (75.46 MHz, DMSO-d₆, EEE-21o’) δ 55.5 (s, OCH₃), 55.6 (s, OCH₃), 90.2, 113.1, 115.5, 116.5, 119.4, 120.7 (q, ¹J_CF = 278.7 Hz, CF₃), 123.5, 124.2, 129.6, 138.7, 139.1, 140.5, 141 (q, ³J_CF = 2.8 Hz, CF₃-(C=N)-CH=CH-NH), 149.6, 153.5 (q, ²J_CF = 30.1 Hz, CF₃-(C=N)-CH=CH-NH); ¹⁹F-NMR (282.4 MHz, DMSO-d₆, EEE-21o’) δ −65.6 (s, 3F, CF₃). MS (m/z): 351 [M + H]⁺. HRMS calcd. for C₁₈H₁₈F₃N₂O₂⁺: 351.1320, found: 351.1322; Anal calcd. for C₁₈H₁₇F₃N₂O₂: C, 61.71; H, 4.89; N, 8.00, found C, 61.75; H, 4.88; N, 8.01.

3.9. Reaction of N,N’-Diaryl-2-(Perfluoroalkyl)-1,5-Diazapentadienes 21a–o’ with Anilines 15a–o and Ketones 16t–v: Formation of 2-Trifluoromethyl-/2-Perfluoroalkyl-N-Arylpyridinium Derivatives 17–19 or 2-Trifluoromethyl-/2-Perfluoroalkyl-7-Methoxyquinolines 20o–o’

To a stirred solution of N,N’-diaryl-2-(perfluoroalkyl)-1.5-diazapentadienes 21a–o’ (1 equiv.) in anhydrous dichloromethane (10 mL DCM for 1g of 21), was added one equiv. of the corresponding substituted aniline 15a–o and 1.2 equiv. of ketone 16t–v. The mixture was stirred under reflux for desired time (4–12 h) until complete consumption of 21a–o’ (monitored by TLC eluent petroleum ether/ethyl acetate: 80/20 v/v, and ¹⁹F-NMR of aliquots). When the reaction was completed, the mixture was allowed to cool to r.t. then the brown precipitate accumulated during the reaction was separated by vacuum filtration (it was subsequently identified as anilinium salts by NMR and MS).

Then in the cases of pyridinium iodides 17a–l, 18a–l and 19a–l, ethyl ether was added to the filtrate. However, in the cases of pyridinium iodides 17m–n’, 18m–n and 19m, a mixture of petroleum ether and ethyl ether (40/60 v/v) was added to the corresponding filtrates and the expected pyridiniums 17a–n’, 18a–n and 19a–m precipitate instantly and were isolated by vacuum filtration as amorphous solids.

In the case of 3-anisidine (15o) at the end of the reaction, the mixture was concentrated under reduced pressure and then stirred with diethyl ether. An excess of petroleum ether was added; the precipitate that had formed was eliminated by vacuum filtration and washed three times with petroleum ether. The filtrate was concentrated in vacuo to give a yellow oil. Chromatography over silica gel column (eluent, petroleum ether/ethyl acetate 98/2 v/v) left a yellow oil which was crystallized from methanol/water to give pure samples of the corresponding quinolines 20o–o’. All the isolated pyridiniums 17a–n’, 18a–n, 19a–m and quinolines 20o–o’ were fully characterized and found identical to the previously obtained products.

4. Conclusions

We have developed a new simple and efficient method for the synthesis of substituted 2-trifluoromethyl-/2-perfluoroalkyl-N-arylpyridiniums 17a–n’, 2-trifluoromethyl-/2-perfluoroalkyl-N-(R-phenyl)-5,6,7,8-tetrahydroquinoliniums 18a–n and 2-trifluoromethyl-/2-perfluoroalkyl-N-(R-phenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridiniums 19a–m, starting from perfluoroalkylated gem-iodoacetoxy derivative 14–14”, substituted anilines 15a–o and ketones 16t–v, under mild conditions with good to excellent yields. To our knowledge this is the first synthesis of pyridinium derivatives by a multicomponent reaction involving an activated β-dicarbonyl compound, a ketone, and an aromatic amine.

The reaction is assumed to proceed by a cascade cyclisation mechanism [66,67,68,69,70], either through an inverse electron demand Diels-Alder (IEDDA) cycloaddition, or through an Aza-Robinson cyclisation (Scheme 7), both ways being supported by the isolation and characterization of the intermediate N,N’-diaryl-2-(perfluoroalkyl)-1,5-diazapentadiene 21a–o’, while stereoelectronic effects may account for the preferred intramolecular diazapentadiene cyclization in the case of the m-methoxy substituent, selectively forming the perfluoroalkylated quinoline 20.

Beyond the scope of this work, various literature reports point out such hetero-Diels-Alder reactions as possibly relevant of bio-orthogonal chemistry because of their selectivity, moderate activation energy and ability to proceed under biological conditions, taking in account e.g., the pH and temperature [66,67,68,69,70]. Besides, since pyridinium-containing compounds are considered as possible exogenous neurotoxins, research efforts have also been undertaken to disclose the formation of such compounds under endogenous (biogenic) conditions [33,34,35,36,37,43,44,45]. In this respect, the biological activity of newly synthesized pyridinium compounds 17–19, are currently under evaluation with promising results to be published in future papers.