CZ186798A3 - Nitration of aromatic compounds - Google Patents

Abstract

A method of nitrating electron-deficient carbocyclic or heterocyclic aromatic compounds such as pyridines, diazines and triazines and benzenoid aromatics having electron-withdrawing substituents involves first reacting the aromatic species with a sulphilimine species or with the corresponding N-alkali metal salt thereof to generate an N-(hetero)aryl-S,S-dialkyl, diaryl or alkylarylsulphilimine derivative. This intermediate may then be readily oxidised under relatively mild conditions using a peroxycarboxylic acid such as m-chloroperbenzoic acid, peracetic or peroxytrifluoroacetic acid. Good yields of nitrated products are obtained including some previously unprepared. The novel N-alkali(alkylaryl)sulphilimine reagents are prepared by reacting an alkali metal hydride, an alkali metal hydrogenous base or an alkyl lithium with the corresponding sulphilimine. Preferred salts are the N-lithio types and the preferred sulphilimine is diphenylsulphilimine. Where the salt is used reaction should be in an aprotic solvent but if the sulphilimine per se is the reagent a polar solvent is used.

Description

The invention relates to a method of nitration of aromatic compounds, in particular nitration of electron-deficient heterocyclic and carbocyclic aromatic compounds.

Current state of the art

Typical electron-deficient heterocyclic aromatic compounds are such compounds as pyridines, diazines {especially pyrimidines and pyrazines) and triazines, while electron-deficient carbocyclic aromatic compounds can be described as benzoid aromatic compounds substituted with electron-withdrawing groups. In general, for purposes of the present invention, an electron-deficient aromatic compound is defined as either a heterocyclic or an aromatic compound bearing a leaving group that is typically displaced by nitrogen nucleophiles. Such leaving groups include halogens, nitro groups, alkoxy groups and nitrile groups.

Conventional electrophilic nitration methods based on nitronium ion (Ν0 ₂ ⁺ ) chemistry are widely used in chemical syntheses and are very successful in the nitration of carbocyclic aromatic compounds such as toluene

- and -electron-rich heteroaromatic compounds>--such as -1,2,4-triazolone. For electron-deficient aromatic systems, such as benzenes containing electron-withdrawing groups and heterocyclic azines, diazines, and triazines, methods based on nitronium ion =' chemistry are almost completely ineffective. For example, the nitration of pyridine using potassium nitrate and oleic acid at 350°C yields less than 3% of 3-nitropyridine (R. M. Acheson, An i

1

Introduction to the Chemistry of Heterocyclic Compounds, 3rd ed., p. 237 (Interscience, 1976)).

A number of attempts have been made to overcome these difficulties, including the use of nucleophilic nitrating agents. For example, AgNO ₂ or NaNO ₂ was used to create nitrite ions that replace the halogen from the aromatic nucleus. However, this agent has a number of serious defects. Thus, it is relatively expensive and as a chemical agent is undesirable from an environmental point of view. It also exhibits low specificity in its mode of action, often leading to the formation of nitrite esters rather than nitro compounds.

It is known that nitrated heterocyclic compounds can be prepared by oxidation of dialkylsulfilimines and related phosphinimine intermediates derived from aminoheterocycles (Taylor et al., J. Org. Chem. 47, 552 (1982) and Rakitin et al. Khim. Geterot. Šoed. 153.6 ( 1990) and Coburn et al. 23 (1986) and J. Chem.

However, these procedures are not interesting, since the use of aminoheterocycles requires additional procedures for their preparation, and suitable aminoheterocycles are limited in availability. In the case of the phosphinimines (where furazan is used as the heteroaromatic core) there were difficulties in the oxidation step and it was necessary to use the somewhat unusual oxidizing agent dimethyldioxirane (DMD) to obtain good yields of the nitrated product.

The preparation of some phosphinimine derivatives of heteroaromatic compounds by nucleophilic substitution was described by Tamura et al. (J. Org. Chem. 38, 4324 (1993)) to prepare 1-S,S-diphenylsulfilimino-2,4-nitrobenzene from 2,4-dinitrofluorobenzene. Vlasova et al. (Org. Prep. Proced. Int. 26, 331 (1994)) give some examples of nucleophilic substitution in a heteroaromatic ring as well as 2,4-dichlorobenzene using S,S-diphenylsulfilimine, the reaction being carried out in ···· ** · · * · · ·

dichloromethane. None of these sulfilimine or phosphinimine derivatives were subsequently oxidized to form the corresponding nitro compounds, and in fact in some cases the starting compounds for their formation were nitro compounds (ie the leaving group was a nitro group)..

Vlasova et al. report that mildly activated nitroheterocycles such as 4-methyl- and 4-phenyl-3-nitrofurazan do not react with S,S-diphenylsulfilimine and also that the hydrate

S,S-diphenylsulfilimine (which they obtained as an intermediate in the preparation of the non-hydrated material) does not react with one selected heteroaromatic compound and is therefore a weaker nucleophilic agent than the non-hydrated derivative. Their preferred reaction conditions avoided the use of a hydrate and used a non-polar solvent such as dichloromethane, carbon chloride, and benzene. All these solvents are less environmentally acceptable.

The essence of the invention

The inventors of the present invention, on the other hand, have found that by changing the reaction conditions, especially the choice of the solvent used, a much wider range of nucleophilic aromatic substitution reactions, involving either dialkyl-, diaryl- or mixed alkylarylsulfilimines, becomes possible and that under suitable conditions it can also be with some advantages the hydrated form of these sulfilimines was used. Substituted heteroaromatic compounds, substituted benzenoid aromatic compounds (carbocyclic aromatic compounds) can also be used as starting materials.

A first aspect of the present invention includes a process for the preparation of N-aryl- and N-heteroarylsulfilimine derivatives of electron-deficient carbocyclic and heterocyclic aromatic compounds, which comprises the following steps;

>i * · · 4 4

44

a) reaction of an electron-deficient heterocyclic or carbocyclic aromatic compound with a dialkyl, diaryl or mixed alkylarylsulfilimine in a polar solvent; and

b) isolation of the resulting N-(hetero)aryl-S,S-dialkyl-, diaryl- or alkylarylsulfilimine [or N-aryl-S,S-alkylarylsulfilimine] derivative.

It is particularly advantageous as a sulphiminizing agent

5.5-diphenylsulfilimine, as it is commercially available. Other possible sulfilimines include S-methyl-S-phenyl- and

5.5-dimethylsulfilimine.

A preferred polar solvent is an alcohol or ether, most preferably a low molecular weight alcohol such as ethanol or other lower alcohols having a chain length of 4 carbon atoms or less. The ether may be a cyclic ether such as tetrahydrofuran (THF) or 1,4-dioxane.

Under the circumstances intended for this procedure, separated from the particularly greater activity observed by the inventors of the present invention (for example, less reactive pyridine, pyrimidine and pyrazine heterocycles can successfully react under these conditions), a substantially higher economic utilization of the sulfilimine reagent was achieved. Thus, for example, while the method of Vlasov et al.:·· involves the use of three equivalents of -5,5-diphenylsulfilimine per one equivalent of the aromatic agent, in the post according to the present invention only two equivalents are used, one of which is recovered in in salt form (e.g., halogen salts) and can be reconverted to the diphenylsulfyliraine reagent by treatment with butyllithium. Another advantage is the use of the environmentally acceptable solvents mentioned above.

* «

With the exception of the above-mentioned 1-S,S-diphenylsulfilimino2,4-dinitrobenzene, all N-(hetero)aryl-S,S-diphenylsulfilimine compounds produced in the process of the present invention are novel compounds. They include the following compounds:

6-chloro-2-pyrazinyl-S,S-diphenylsulfilimine, 3-nitro-2-pyridinyl-S,S-diphenylsulfilimine, 4-nitro-3-chlorophenylS, S-diphenylsulfilimine, 2-chloro-3-nitro-4-pyridinylS, S-dif enylsulf iline, 2-pyrazinyl-S, S-dif enylsulf iline,

2-(n-propoxy)-4-chloro-6-(1,3,5-triazinyl)-S,S-diphenylsulfilimine

2.3.5.6-tetrachloro-4-pyridinyl-S,S-difenylsulfiline,

3.4.5.6-tetrachloro-2-pyridinyl-S,S-diphenylsulfiline,

2-(n-propoxy)-4,6-(1,3,5-triazinyl)-bis-S,S-diphenylsulfiline,

2.4- bis-(n-propoxy)-6-(1,3,5-triazinyl)diphenylsulfylylene, 6-chloro-4-pyrimidinyl-S,S-diphenylsulfylylene, 5-nitro-2pyridinyl-S,S -diphenylsulfilimine, 4-chloro-2-pyrimidinylS, S-diphenylsulfilimine, 2,4-dichloropyrimidinylS, S-diphenylsulfilimine, 4,6-dichloropyrimidinylS, S-diphenylsulfilimine, 2,5,6-trichloropyrimidinylS, S- diphenylsulfilimine, 4,5,6-trichloropyrimidinyl5,5-diphenylsulfilimine and 2,3,5,6-tetrahydro-4-pyridinylΞ, S-diphenylsulfilimine, 3,5-dinitro-2-pyridinylS,S-diphenylsulfilimine and 3, 5,6-trifluoro-2-pyridinyl5,5-diphenylsulfilimine. The formulas for these compounds are shown in Figures 1 and 2 under the numbers I to XX.

All of these materials are stable crystalline solids or oils.

The inventors of the present invention have further discovered a completely new class of related reagents which, in addition to substitution with electron-withdrawing groups, enable vicarious substitution of hydrogen on carbocycles and heteroaromatic rings with diarylsulfilimine groups performed under facile conditions. A second aspect of the present invention consists in finding a class of novel reagents ♦ * comprising N-alkali metal salts of S,S-dialkyl-, diaryl- or alkylarylsulfilimines having the general formula XL

where R ¹ and are independently alkyl and/or aryl and M is sodium or potassium. A particularly preferred class of reagents of this type are N-lithium salts, esp

N-lithium-S,S-diphenylsulfilimine.

These new reagents are easily prepared by reacting the corresponding sulfilimine with a 1 to 4 chain alkyllithium, preferably n-butyllithium, an alkali metal hydride such as lithium hydride, sodium hydride or potassium hydride with hydrogen bases containing an alkali metal such as N ,N-di(isopropyl)amides of lithium, sodium or potassium or the corresponding N,N-bis(trimethylsilyl)amides or suitable bases.

When these reagents are used in a process comprising the first aspect of the present invention, an even wider range of reaction products can be obtained. However, in the case of these reagents, it was found that the reaction should be carried out in an aprotic solvent. According to a further process of the present invention, a process for the preparation of N-(heteroaryl)sulfilimine derivatives of carbocyclic aromatic and heteroaromatic compounds with electron deficiency has been found 'including the step ' “ ''' ^T

a) reaction of an electron-deficient carbocyclic or heterocyclic aromatic compound with an N-salt of an alkali metal

S,S-dialkyl-, diaryl- or alkylarylsulfilimine in an aprotic solvent; and

Φ000

0 0

b) isolation of the resulting N-(hetero)aryl-S,S-dialkyl-, diaryl- or alkylarylsulfilimine derivative.

A preferred N-alkali metal salt is an N-lithium sulfilimine salt, and a particularly preferred salt is N-lithium-S,S-diphenylsulfinimine, which is readily available from a commercially available compound

S,S-Diphenylsulfinimine. Although the corresponding sodium-potassium-derived salts would react in a monosulfite manner, their preparation is more difficult than the preparation of the lithium salts and, therefore, involves less desirable reagents from the point of view of practical use.

They are preferably used as aprotic agents

1,4-dioxane, dimethoxyethane, diethylene glycol dimethyl ether (diglyme) or especially tetrahydrofuran.

Yet another aspect of the present invention relates to a process for the nitration of electron-deficient carbocyclic and heterocyclic aromatic compounds, comprising:

a) reaction of an electron-deficient carbocyclic or heterocyclic aromatic compound (as defined herein) with a dialkyl-, diaryl- or alkylarylsulfilimine in a polar solvent or with its corresponding N-lithium salt in an aprotic solvent to form the corresponding N-(hetero)aryl- of an S/S-dialkyl'-, diaryl or alkylarylsulfilimine deriv.

b) treating the product from step (a) with an oxidizing agent to convert the sulfilimine compound into a nitro group, and

c) isolation of the nitrated aromatic compound

4

44· obtained in step (b) .

The reaction of step (a) is described above. In the second, oxidation step, the inventors of the present invention have found, in contrast to earlier work with phosphinimines, that sulfilimine derivatives can be readily oxidized by commercially available oxidizing agents such as m-perchlorobenzoic acid. This results in a more economical and industrially acceptable procedure.

In general, any peroxycarboxylic acid is used, such as various perbenzoic acids, especially m-chloroperbenzoic acid, peracetic acid or peroxytrifluoroacetic acid.

Yields in the first stage, nucleophilic substitution, are typically in the range of 60% to quantitative yields and in the second, oxidation stage, they are in the range of 10 to 63%. In general, even for compounds previously obtained by conventional electrophilic nitrations, the yields are greater according to the present two-step procedure than previously achieved.

It will be appreciated that in addition to the formation of mononitro-substituted aromatic compounds, the ability of the above-mentioned novel N-lithium(alkyl or aryl)sulfilimine reagents to cause approximately vicarious hydride substitution in which a hydrogen atom is substituted ortho- or para- (but especially ortho-) to the already of the present nitro group in the ring, will allow to easily obtain polynitrated heterocyclic and carbocyclic aromatic compounds. These materials may previously have been often difficult or almost impossible to prepare. ····.·

Compounds such as 3,4-dinitrochlorobenzene, 2-chloro-6-nitropyrazine, 4-nitro-2,3,5,6-tetrachloropyridine, 2-nitro-3,4,5,6-tetrachloropyridine and 4-nitro- 2,3,5,6-tetrafluoropyridine and a new compound 2-chloro-3,4dinitropyridine was obtained.

9 9

These polynitro-substituted aromatic compounds are considered important precursors for the preparation of new types of thermally and shock-sensitive explosive materials.

The invention is further described by reference examples, which are only illustrative in nature and do not limit the scope of the invention in any respect. The formulas below correspond to either the starting materials or the nitrocompounds (formulas XXXI to XXXVIII and XXI to XXX) found in Figures 3 and 4.

Examples of embodiments of the invention

Example 1

Preparation of 2-chloro-6-nitropyrazine (XXI) from 2,6-dichloropyrazine (XXXI)

1st degree. S,S-diphenylsulfilimine monohydrate (0.540 g, 2.46 mmol, 2 equiv.) was weighed into a 100 mL three-necked round-bottom flask. THF (tetrahydrofuran, 15 mL) was added to dissolve the sulfilimine compound. THF was purified by distillation.

2,6-Dichloropyrazine (XXXI, 0.183 g, 1.23 mmol, 1 equiv) was added to the solution in the vessel. The central neck of the vessel is equipped with a Liebig cooler, a magnetic stirrer is inserted into the vessel, and the remaining openings are closed with a plug. The contents of the container are stirred and refluxed for 18 hours. This is achieved by using a heated paraffin oil bath. A white precipitate forms during the first hour of reflux. At the end of 18 hours, the container is removed from the oil bath and allowed to cool to room temperature. The white precipitate is separated from the solution by gravity filtration. A salt of diphenyl(aminosulfonium) chloride, a by-product of the formation of N-aryl S,S-diphenylsulfilimine, is detected in the solid by ¹ H nmr spectroscopy and elemental analysis. THF was removed from the filtrate using a rotary evaporator.

The remaining yellow-brown oil is analyzed by nmr and found to be a slightly impure form of the desired product,

2-Chloro-6-S,S-diphenylsulfiliminopyrazine (I, 0.366 g, 95%). Impurities formed by 5% of the starting 2,6-dichloropyrazine are removed by purifying the crude product by flash chromatography. The column is filled with 10 g of Merck Kieselgel 60 for flash chromatography (particle size 0.040 to 0.063 mm) and is eluted under slightly reduced pressure with a mixture of dichloromethane and gasoline (boiling point 40 to 60 °C) in a volume ratio of 1:2 and then with pure dichloromethane . The crude product is dissolved in approximately 1 mL of elution solvent and loaded onto the column using a long pipette. The dichloromethane used is HPLC grade and the gasoline is redistilled before use. The desired product has a retention factor of 0.16 on a thin layer chromatography plate coated with Merck Kieselgel 60 F-254 and elutes in dichloromethane, i.e. Rf = 0.16 (CH2Cl2) · The impurity has a retention factor of 0.50 {CH2Cl2) Data for the first-stage product, 2-chloro-6-S,Sdiphenylsulfyliminopyrazine (I): ¹ H nmr (CDC1 ₃ , 300 MHz) 7, 60 (1H, s, ArH) 7.42 - 7.78 (6H, m, ArH) 7.71 - 7.79 (4H, m,

ArH) 8.10 (1H, s, ArH) where s = singlet, m = multiplet, ArH = proton attached to aryl group, CDCl 3 = deuterated chloroform and a Bruker AC 300 spectrometer was used. EI mass spectrometry; 313, 315 (M ⁺ ,' 4%, 1%) 278 (M-Cl,

1) 204, 206 (M-SPh, 3, 1) 186 (SPh ₂ , 100), 109 (SPh, 17) 92 (M-Cl-SPh 2 , 11) 83 (18), exact mass for a molecule containing ^^ Cl adjusted to 0.1 ppm. Images outside the parentheses indicate the molecular weight of the fragments, and the content in the parentheses indicates the identity of the fragment and its peak intensity in percent.

M indicates the molecular fragment. Mass spectra are obtained using a Krátos Analytical Profile MS and a Shimadtu GC-14A.

2nd degree. The oxidizing agent 3-chloroperoxybenzoic acid (0.198 g, 1.15 mmol, 6 eq.) was weighed into a 100 mL three-necked round-bottom flask. The flask openings were fitted with a stopper, an ice cooler and a thermometer, and a magnetic stirrer was inserted into the flask. 10 ml is added to the container

of HPLC-grade 1,2-dichloroethane and the vessel and its contents are • a a · * · • « • *· · cooled to -5°C using a mixture of salt and ice.

2-Chloro-6-S,S-diphenylsulfinimino-pyrazine (I, 60 mg, 0.19 mmol, 1 eq.) was added to the flask. The contents of the vessel are stirred, the ice bath is removed, the vessel is allowed to warm to room temperature and then placed in a bath of paraffin oil used at the 1st degree. The reaction mixture was refluxed for 2 hours and then allowed to cool. The mixture was washed with two 10 ml portions of 0.5 M aqueous sodium hydroxide solution and then with two portions of distilled water. The reaction mixture is then dried over 5 g of anhydrous magnesium sulfate. The dry reaction mixture is separated from the solid magnesium sulfate by gravity filtration,

The 1,2-dichloroethane was removed on a rotary evaporator to give a brown oil. The oil is purified by flash chromatography on silica gel and eluting with the solvent described in step 1. 2-Chloro-6-nitropyrazine (XXI) is obtained as a yellow oil {0.018 g) in 20% yield; Rf = 0.59 (CH ₂ Cl ₂ ); ^Τ Η nmr (CDCl ₃ , 300 MHz) 8.90 (1H, s), 9.30 (1H, s). An oxidation byproduct, diphenyl sulfone (0.029 g) is also obtained.

Example 2

Preparation of 2,3-dinitropyridine (XXII) from 2-chloro-3-nitropyridine (XXXII)

1st degree. Apparatus as in Example 1 was used. S,S-diphenylsulfilimine monohydrate (0.519 g, 2.37 mmol, 2 equiv) and 20 mL of ethanol were added to a 100 mL three-necked round-bottom flask. 2-Chloro-3-nitropyridine (0.188 g, 1.18 mmol, 1 equiv) was added to the reaction mixture and the mixture was refluxed for 7 h and then allowed to cool. Since the lighter product, diphenyl(aminosulfonium) chloride is soluble in ethanol, it cannot be filtered off at this stage. Instead, ethanol was removed from the reaction mixture on a rotary evaporator to give a dirty yellow solid. This substance is purified by flash chromatography on a column (elution solvent CH ₂ C1 ₂ - gasoline (boiling temperature 40 to 60 °C) in a volume ratio of 3:2, • 4

4444 44 44

444 444

444 · 4444

4 4 4 4 4

4 4 4 4 4

444 444 44 44 gradient up to 100% CH ₂ C1 ₂ )). The desired product is obtained,

2- S,S -diphenylsulfilimino-3-nitropyridine (II) as a crystalline yellow solid in 76% yield (0.290 g); Rf=0.20 (CH ₂ Cl ₂ ); melting point 132 to 134 °C; elemental analysis, found C, 63.42, H, 4.04, N, 12.97, calcd, C 63.14, H, 4.05, N, 12.99; ¹ H nmr (CDCl ₃ , 300 MHz) 6.46 - 6.50 (1H, dd, ArH) 7.45 - 7.48 (6H, m, ArH) 7.88 - 7.91 (4H, m, ArH) 8.06 - 8.08 (1H, dd, ArH) 8.15 - 8.19 (1H, dd, ArH), dd = doublet doublet.; mass spectrometry (El) 323 (M ⁺ , 7%) 293 (M-NO, 1) 258 (3) 214 (M-SPh, 1) 186 (SPh ₂ , 100) 168 (12) 152 (6) 139 ( 11)

109 (SPh, 9) 77 (Ph, 14), exact mass 3.7 ppm.

2nd degree. A vessel containing 3-chloroperoxybenzoic acid (0.224 g, 1.30 mmol, 6 equiv) and 1,2-dichloroethane (10 mL) was cooled in an ice-salt bath to -5 °C as described in Example 1. Add with 2-S,S-diphenylsulfilimino-3-nitropyridine (II, 0.07 g, 0.22 mmol). The mixture was allowed to warm to room temperature, refluxed for 2 hours and then cooled to -10°C. A white precipitate of an oxidation by-product

3-Chlorobenzoic acids are removed from the mixture by gravity filtration. 1,2-Dichloroethane is then removed from the reaction mixture on a rotary evaporator. The desired product, 2,3-dinitropyridine (XXII) is obtained as a yellow oil in 9% yield after purification by flash column chromatography (elution solvent CH ₂ C1 ₂ - gasoline in a volume ratio of 3:4 (melting point 40 to 60 °C), gradient to 100% CH ₂ Č1 ₂ ). The by-product diphenylsulfone is also obtained. Data for 2,3-dinitropyridine: Rf =

0.58 (CH ₂ Cl ₂ ) ,· ^X H nmr (CDCl ₃ , 300 MHz) 7.80 - 7.85 (1H, m. ArH), 8.51 - 8.54 (1H, m, ArH) , 8.77'- 8, 7 9 (1H, m, ArH) F mass spectrometry (El) 169 (M ⁺ , 100) 147 (4) 105 (10) 99 (33) 77 (M-2NO ₂ , 13) exact mass 3.9 PP ^m ·

Example 3

Preparation of l-chloro-3,4-dinitrobenzene (XXIII) from l-chloro-4nitrobenzene (XXXIII) • 4 ··

4· ♦ 4 » a » a • 4

1st degree. A 100 mL round-bottom flask containing a magnetic stir bar, a 20 mL syringe with a Luer needle, and a 5 mL syringe with a Luer needle are dried in an oven for 24 hours at 150 °C. The techniques described in this section are suitable for handling self-igniting materials, i.e. oxygen and hydrogen are excluded. The container is removed from the dryer, the central neck is fitted with a nitrogen washer, and the remaining two necks are fitted with rubber septa. The vessel is purged with nitrogen. S,S-diphenylsulfilimine monohydrate (1.097 g, 5 mmol, 1 eq.) was added to the vessel.

ml syringe is removed from the desiccator and used to add 15 ml anhydrous THF to the beaker. THF was freshly distilled over potassium hydride. The solution in the container is degassed by connecting a long needle to the nitrogen supply and sticking the needle through the rubber septum so that the end of the needle is in the solution. Bubbles of nitrogen are passed through the solution in this manner for 10 minutes. The long needle is then removed. The 5 ml syringe is removed from the desiccator and flushed with nitrogen for 5 minutes. It is then used to add n-butyllithium (4 mL of a 2.5 M solution in hexanes, 10 mmol, 2 eq., a dangerous auto-igniting compound!) dropwise to the stirred solution, which immediately turns yellow, indicating the presence of N-lithium- S,Sdiphenylsulfilimine. The empty 5 ml syringe is placed in a larger beaker with butan-l-ol immediately after use. l-Chloro-4nitrobenzene (XXXIII, 0.788 g, 5 mmol, 1 equiv) was added to the yellow solution by removing one of the septa and the mixture was stirred under nitrogen at room temperature for 24 h. The mixture is then exposed to air and the THF is removed on a rotary evaporator. The crude product is purified by flash chromatography (elution solvent CH2CI2 - gasoline (boiling point 40 to 60 °C) in a volume ratio of 1:2). 1-Chloro-3-S,S-diphenylsulfilimino-4-nitrobenzene (III, 0.34 g) is obtained as a crystalline yellow solid in 19% yield; R f = 0.43 (CH 2 Cl 2 ); elemental analysis, found, C, 60.06, H, 3.57, N, 7.90, calcd, C, 60.58, H, 3.67, N, 7.85; ¹ H nmr (CDC1 ₃ , 300 • φφφφ φ φ φ φ φφφ φφ φφ φ φ ♦ φφφφ φφ φφ φ φ φ φ φφφ

MHz) 6.56 - 6.60 (1Η, dd, ArH), 6.94 - 6.95 (1Η, d, ArH) 7.49 - 7.52 (6Η, m, ArH) 7.69 -7 .73 (1H, d, ArH) 7.83 - 7.88 (4H, m, ArH); mass spectroscopy (El) 356, 358 (M ⁺ , 1%, 0.3%) 186 (SPh ₂ , 100) exact mass, ³⁵ C1, 2.5 ppm.

2nd degree. 3-Chloroperoxybenzoic acid (0.320 g, 1.86 mmol, 6 equiv) and 1,2-dichloroethane (20 mL) were cooled to -5 °C in a 100 mL three-necked flask using an ice-salt bath. 1-Chloro-3-S,S-diphenylsulfylimino-4-nitrobenzene (III, 0.110 g, 0.31 mmol, 1 equiv) was added, the vessel was allowed to warm to room temperature and then refluxed for 2 hours. After cooling, the reaction mixture is washed with two 10 ml portions of 0.5 M aqueous sodium hydroxide solution and then with two 10 ml portions of distilled water and then dried over anhydrous magnesium sulfate (see Example 1}. After removing the magnesium sulfate by gravity filtration, it is removed from the reaction mixture of i,2-dichloroethane on a rotary evaporator. The crude product is purified by flash column chromatography (eluent CH ₂ C1 ₂ - gasoline (boiling point 40 to 60 °C) in a volume ratio of 1:3, gradient to 100% CH ₂ C1 ₂ ) and the desired product 1-chloro-3,4dinitrobenzene (XXIII) is obtained as a pale yellow solid in 32% yield (0.020 g), Rf = 0.79 (CH ₂ C1 ₂ ); ¹ H nmr (CDC13, 300 MHz) 7.69 - 8.18 (3H, ra, ArH); mass spectrometry (El) 202, 204 (M ⁺ , 15%, 5%) 172, 174 (M-NO, 4.1), 156 , 158 (M-NO2, 38.13) 139, 141 (42.14) 128, 130 (8.3) exact mass ³⁵ C1, 5.4 ppm.

Example 4 —preparation·· 2^-ch-l-or---37'4--ďini-tropyri-di-nu-“(-X-X-T-Vj^z-“-2—eh-l-or—3 — nitropyridine (XXXII)

1st degree. A solution of N-lithium-S,S-diphenylsulfilimine (1.23 mmol, 1 equiv) in 15 mL of anhydrous THF was prepared using S,S-diphenylsulfilimine monohydrate (0.270 g, 1.23 mmol, 1 equiv) and n -butyllithium (0.98 ml of a 2.5 M solution in

0000 *

• 00 • Φ

0 0 000 hexanes, 2.46 mmol, 2 eq.), using the method, apparatus, and precautions described in Example 3. 2-Chloro-3-nitropyridine (XXXII, 0.195 g, 1.23 mmol) was added to the solution and the stirred under nitrogen at room temperature for 24 hours.

At the end of this time, the mixture is exposed to air and the THF is removed on a rotary evaporator. The crude product is purified by flash chromatography (eluent CH ₂ C1 ₂ ^_ gasoline (boiling point 40 to 60 °C) in a volume ratio of 1:3, gradient to 100% CH ₂ C1 ₂ ) and the desired product, 2-chloro-3- nitro-4-S,Sdiphenylsulfiliminopyridine (IV), is obtained as a yellow solid in 49% yield; Rf = 0.15 (CH ₂ Cl ₂ ); nmr (CDC1 ₃ , 300 MHz)

6.75 - 6.81 (1H, d, ArH) 7.40 - 7.55 (6H, m, ArH) 7.63 - 7.73 (4H, m, ArH), 7.85 - 7.90 (1H, d, ArH); mass spectrometry (El) 357, 359 (M ⁺ , 5%, 2%) 291 (1) 232 (3)

186 (SPh ₂ , 100) 125 (12) 105 (52) 77 (Ph, 24) exact mass, ³⁵ C1, 4.2 ppm.

2nd degree. 3-Chloroperoxybenzoic acid (0.290 g, 1.68 mmol, 6 equiv) and 1,2-dichloroethane (10 mL) were weighed into a three-necked round-bottom flask and cooled to -5 °C using a salt-ice bath. 2-Chloro-3-nitro-4-S,S-diphenylsulfiliminopyridine (IV, 0.100 g, 0.28 mmol) was added and the flask was allowed to warm to room temperature, refluxed for 2 hours and then cooled to -10 °C, by-products are oxidized with 3-chlorobenzoic acid and precipitated from solution. The precipitate is removed by gravity filtration and 1,2-dichloroethane is removed from the resulting filtrate using a rotary evaporator. The crude product is purified by flash column chromatography (the elution solvent is a mixture of CH ₂ Cl ₂ and gasoline (boiling points 40 to 60 °Cj~in a volume of porner at 1 “T?2*)~)7~The desired' product, 2-chloro- 3,4-Dinitropyridine (XXIV) is obtained as a yellow oil in 9% yield; Rf = 0.54 (CH ₂ Cl ₂ ) nmr (CDCl ₃ , 300 MHz) 8.02 - 8.08 (1H, d, ArH) 8.83 - 8.90 (1H, d, ArH); mass spectrometry (El) 203, 205 (M ⁺ , 39%, 12%) 173 (3) 155 (3) 129 (7) 84 (100) exact mass, ³⁵ C1, 1.7 ppm.

• •·· ·· ·· 4· « · · · ·

444 4 · · · · 4

Example 5

Preparation of 4-nitro-2,3,5,6-tetrachloropyridine (XXV) from pentachloropyridine. (XXXV)

1st degree. S,S-Diphenylsulfinimine (1.08 g, 4.92 mmol, 2 equiv) was weighed into a 100 mL three-necked round-bottom flask.

THF (15 mL) was added to dissolve the solid sulfilimine. Pentachloropyridine (XXXV, 0.618 g, 2.46 mmol, 1 equiv) is added to the solution in the vessel. A water cooler is placed on the central neck and the remaining two holes are closed with a glass plug. A magnetic stirrer is used to stir the solution. The contents of the vessel are stirred and refluxed for 4 hours using heated paraffin oil. At the end of 4 hours, the reaction mixture is cooled to room temperature and the white precipitate of diphenylaminosulfonium chloride formed during the reaction is removed by filtration. This salt is saved for recycling. THF is removed from the filtrate using a rotary evaporator. The white solid remaining after rotary evaporation was purified using flash column chromatography. The column is eluted with a mixture of dichloromethane and gasoline (boiling point 40 to 60 °C) in a volume ratio of 1:4. Two products are obtained. 4-S,S-Diphenylsulfilimino-2,3,5,6-tetrachloropyridine (VII, 0.473, 46%); melting point 143 to 144 °C; Rf = 0.65 (CH ₂ Cl ₂ ); elemental analysis, found C, 48.95, H, 2.18, N, 6.85, C ₁₇ H- _L qN ₂ SC1 ₄ calcd, C, 49.06, H, 2.42, N, 6.73 . δ _Η (CDCl ₃ , 300 MHz) 7.45 - 7.51 (6H, m, ArH) 7.84 - 7.91 (4H, m, ArH); S _c (CDCl-j, 100.6 MHz) 121.6 (G3 of pyridine) 126.2 , 129.9, 131.'9 (ortho; meta ^- a ^- para carbons' - ferriylul*/ ¢0(71^ C*'p±pO'jény ^- k“'sí'řejl'4'S7-6'5-r-l'5-6T8-'-(e27 ^t “

C4 of pyridine).,- M/z (El) 416, 414 (M ⁺ , 4%, 3%) 381 (M-Cl, 1) 307 (M-SPh, 1) 270 (2) 232, 230 (6 , 5) 186 (SPh ₂ , 78), 84 (100) 77 (Ph, 14), exact mass, 4 x ³⁵ C1, 2.7 ppm, ³⁷ C1 + 3 x ³⁵ C1, 3.1 ppm.

2-S,S-diphenylsulfilimine-3,4,5,6-tetrachloropyridine (VIII, • ···

0.181 g, 18%); melting point 175 °C; Rf = 0.80 (CH ₂ Cl ₂ ); elemental analysis found C, 48.99, H, 2.16, N, 6.71,

^c 17 ^H 10 ^N 2 ^scl 4 calculated C, 49.06, H, 2.42, N, 6.73; oh _H (CDC1 ₃ , .300 MHz) 7.49 - 7.52 (6H, m, ArH) 7.81-7.88 (4H, m, ArH); m/z (E1) 414, 416 (M ⁺ , 14 %, 18%) 379 (M-Cl, 1) 339 (M-Ph, 1) , 305, 307 (M-SPh, 18, 23) 186 (SPh ₂ , 100) 109 (SPh, 12) 77 (Ph, 16) exact weight, 4 x ³⁵ C1, 1.6 ppm, ³⁷ C1 + 3 X ³⁵ C1, 1.2 ppm.

2nd degree. The oxidizing agent 3-chloroperoxybenzoic acid (0.497 g, 2.87 mmol, 6 eq.) was weighed into a 100 mL three-necked round-bottom flask. The holes in the flask are closed with a stopper, a water cooler and a thermometer, and a magnetic stirrer is placed in the container. HPLC grade 1,2-dichloroethane (20 mL) was added to the vessel and the contents of the vessel were cooled to -5°C by placing it in a mixture of ice and salt (e.g. sodium chloride). 4-S,S-Diphenylsulfilimino-2,3,5,6-tetrachloropyridine (VII,

0.200g, 0.481. mmol, 1 eq.) is added to the reaction mixture and the mixture is allowed to warm to room temperature. At this point the mixture will turn green. The mixture is then refluxed for 2 hours during which time the color changes from green to yellow. The reaction mixture is cooled to -5 °C and the precipitate of 3-chlorobenzoic acid that appears at this temperature is removed by filtration. 1,2 Dichloroethane is removed from the filtrate using a rotary evaporator and the crude product with Pure flash column chromatography (elution solvent CH ₂ C1 ₂ - gasoline (melting point 40 to 60 °C) ) in a volume ratio of 1:4, gradient up to 1:1 CH ₂ C1 ₂ - gasoline (melting point 40 to 60 °C).

^: 4-Nitro-2,3; 5,6-Tetrachloropyridine (XXV; 0.046 g) is obtained as a yellow oil in 3.7% yield; ~Rf~0 ^_ ;'82'('CH^Cl^j"·;"*' (CHC1 ₃ )/cm ¹ , 1337 (s, NO2 ) 1563 (s, NO2 ); &c <CDC13 , 100.6 MHz) 121.4 (C3 and C5) 147.81 (C2 and C6) 155.1 (C4); m/z (El) 260, 262 (M ⁺ , 9%, 12%) 230, 232 (M-NO, 20, 24) 214, 216 (M-NO 2 , 20, 24) 179, 181 (M-C1 -NO ₂ , 5, 7) 139 (100) exact mass, 4 x ³ ^Cl, 1.9 ppm).

4·44

4« * ···

4-S,S-Diphenylsulfoximino-2,3,5,6-tetrachloropyridine (XXVII) is obtained as a by-product; melting point 158 to 159 °C; Rf - 0.63 (CH ₂ Cl ₂ ); δ _Η (CDCl, 300 MHz) 7.45 - 7.60 (6H, m, ArH) 8.00 - 8.11 (4H, m, ArH); m/z (El) 430., 432 (M, %, 16%) 397 (M-Cl, 2) 305, 30.7 (M-SOPh, 2, 2) 270, 272 (7, 7) 218 (Ph ₂ SON, 13) 202 (12) 186 (SPh ₂ , 13) 154 (20) 125 (SOPh, 100) 109 (SPh, 34) 77 (Ph, 58) exact mass, 4 x ³⁵ C1, 1.4 ppm.

Example 6

Preparation of 2-nitro-3,4,5,6-tetrachloropyridine (XXVI) from pentachloropyridine (XXXV)

1st degree. See the first step of Example 5, where 2-S,S-diphenylsulfilimino-3,4,5,6-pyridine (VIII) is prepared.

2nd degree. Weigh the oxidizing agent 3-chloroperoxybenzoic acid (0.075 g, 0.434 mmol) into a 100 mL three-necked round-bottom flask. The holes in the flask are closed with a glass stopper, a water cooler and a thermometer, and a magnetic stirrer is placed in the vessel. HPLC grade 1,2-dichloroethane (5 mL) was added to the flask and the contents of the flask were cooled to -5 °C by placing it in a mixture of ice and salt. 2-S,S-Diphenylsulfilimino-3,4,5,6-tetrachloropyridine (VIII, 0.030 g, 0.073 mmol) was added to the reaction mixture and the vessel was allowed to warm to room temperature. At this point the mixture will turn blue-green. The mixture is then refluxed for 2 hours during which the color changes from blue to yellow. Towards the end of the reaction, the reaction mixture is cooled to -5 °C and the precipitate of 3-chlorobenzoic acid is removed by filtration, 1,2-Dichloroethane is removed from the filtrate using a rotary evaporator and the crude product is purified by flash column chromatography (elution solvent CH ₂ C1 ₂ - gasoline (melting point 40 to 60 °C) in volume ratio 1:6, gradient up to 1:1 CH ₂ C1 ₂ - gasoline (melting point 40 to 60 °C) 2-Nitro-3,4,5,6 -tetrachloropyridine (XXVI, 0.012 g) is obtained as a caramel-scented yellow oil in 63% yield; Rf =

0.79 (CH ₂ C1 ₂ ) ,- m/z (El) 262, 260 (M ^- , 13%, 12%) 230, 232 (M-NO, 61, 49) 214, 216 (M-N0 ₂ , 94, 75) 181, 179 (M-C1-NO ₂ ,

47), exact mass 4 x ³⁵ Cl, 1.7 ppm.

A white solid, 2-S,S-diphenylsulfoximino-3,4,5,6-tetrachloropyridine (XXVIII), is obtained as a by-product; Rf = 0.68 (CH ₂ Cl ₂ ); δ _Η (CDCl ₃ , 300 MHz), 7.48 - 7.59 (6H, m, ArH)

8.05 - 8.11 (4H, m, ArH); m/z (E1) 430, 432 (M ⁺ , 1%) 353,

355 (M-Ph, 4, 5) 305, 307 (M-SOPh, 2, 1) 202 (Ph ₂ SO, 2) 125 (PhSO, 12) 109 (SPh, 16) 77 (Ph, 20), exact mass, 4 x ³⁵ C1, 1.4 ppm).

Example 7

Preparation of 4-nitro-2,3,5,6-tetrafluoropyridine (XXIX) from pentafluoropyridine (XXXVI)

1st degree. S,S-Di.phenylsulfylene (1.0 g, 4.92 mmol) was weighed into a 100 mL three-necked round-bottom flask. THF (20 mL) was added to dissolve the solid sulfilimine. Pentafluoropyridine (XXXVI, 0.416 g, 2.46 mmol) is added to the solution in the vessel. The reaction mixture is processed in the same way as described for pentachloropyridine (see example 5. l. step above), with the reaction time lasting 6 hours. During flash chromatography, the column is eluted with a mixture of CH ₂ C1 ₂ - gasoline (boiling point 40 to 60 °C) in a volume ratio of 1:2. The product, 4-S,S-diphenylsulfilimino2,3,5,6-tetrafluoropyridine (XVIII) is obtained as a white solid in 84% yield; melting point 87 to 88 °C; Rf = 0.58 (CH ₂ Cl ₂ ); δ _Η (CDCl ₃ , 300 MHz) 7.50 - 7.59 (6H, m, ArH) 7.81 7.88 (4H, m, ArH); 6 _C (CDC1 ₃ , 100.6 MHz), 126.7, 130.0, 132.2 (ortho, meta and para carbons of phenyl) , 135.0, 137.6 <C3 and C5,

2m) , 138.7 (SC Ph) 143.3, 147.5 (C2 & C6, 2m), 144.8 (C4, m) , 5 _f (CDC1 ₃ , 376.4 GHz) , 4.25 ( C3 F & C5 F), 67.15 <C2 F & C6 F) .

• 9

99Φ *· 99 99 9·

Step 2 4-S,S-Diphenylsulfilimino-2,3,5,6-tetrafluoropyridine (XVIII, 0.168 g, 0.481 mmol, 1 equiv) was treated with 3-chloroperoxybenzoic acid (0.497 g, 2.87 mmol) in the same manner as described above (Example 5, 2nd degree) . After warming to room temperature, the mixture turns blue-green. The mixture is then refluxed for 18 hours, during which time the color of the mixture changes from blue to yellow. The mixture containing the product is then processed further as described in Example 5,

2nd stage, with the fact that an isocratic system is used in flash chromatography (a mixture of CH ₂ C1 ₂ and gasoline (boiling point 40 to 60 °C) in a volume ratio of 1:4)). 4-Nitro-2,3,5,6-tetrafluoropyridine (XXIX) is obtained as a yellow oil in 21% yield; R f =

0.88 (CH ₂ Cl ₂ ); V _max (CHC1 ₃ )/cm' ¹ , 1581 (NO ₂ ) 1370 (NO ₂ ); (CDC1 ₃ , 376.4 MHz) 17.9 (F3, F5), 81.3 (F2, F6); m/z (E1) 177 (MF, 3%) 158 (M-2F, 31) 166 (M-NO), 2) 150 (M-NO ₂ , 6).

4-(S,S-diphenylsulfoximino)-2,3,5,6-tetrafluoropyridine was determined as a by-product (16% yield).

Example 8

Preparation of 3,5-dinitro-2~pyridinyl-S,S-diphenylsulfilimine (XIX) from 2-chloro-3,5-dinitropyridine (XXXIV)

To a solution of S,S-diphenylsulfilimine monohydrate (0.947 g, 4.32 mmol) in THF (20 mL) was added 2-chloro-3,5-dinitropyridine (XXXIV, 0.439 g, 2.16 mmol). The mixture immediately turns yellow and is refluxed for 30 minutes. The THF is removed in vacuo, the crude product is purified by flash column chromatography (CH ₂ -C1 ₂ - gasoline 40 to 60 °C in a 1:2 v/v ratio) to give the desired product, 3,5-dinitro-2-pyridinyl-S ,S-diphenylsulfilimine (XIX) as a crystalline yellow solid in quantitative yield; Rf = 0.52 (CH ₂ Cl ₂ ); δ _Η (CDC1 ₃ , 300 MHz) 7.45 - 7.52 (6H, m, ArH) 7.86 - 7.93 (4H, m, ArH) 8.90 8.94 (2H, 2d, ArH) ; m/z (El) 368 (M ⁺ , 12%} 303 (2) 243 (M-SOPh, 10) 213 (M-SOPh-NO, 8) 202 (15) 186 (SPh ₂ , 100) 154 (Ph ₂ , 12) 141 (6) 109 (SPh, 20) 77 (Ph, 22), exact ·· 00 00 *0 mass, 2.2 ppm.

This product forms a useful precursor for the preparation

2.3.5- trinitropyridine.

Example 9

Preparation of 1,2,4-trinitrobenzene (XXIIIB) from 2,4-dinitrophenyl5,5-diphenylsulfilimine

2,4-Dinitrophenyl-S,S-diphenylsulfilimine was prepared according to the method described by Tamura et al. (J. Org. Chem. 38, 4324 (1973)).

2,4-Dinitrophenyl-S,S-diphenylsulfilimine (0.043 g, 0.118 mmol) was added to a solution of 3-chloroperoxybenzoic acid (0.122 g, 0.705 mmol) in 1,2-dichloroethane (5 mL) which had been cooled to -5 ^D C and the mixture is allowed to warm to room temperature and then refluxed for 18 hours. After 4 hours, the color of the mixture changes from green to yellow. At the end of reflux, a sample is taken and the 1,2-dichloroethane is allowed to evaporate in air. Analysis of the crude product by TLC and ¹ H nmr indicates a yield of 1,2,4-trinitrobenzene (XXIIIB) of approximately 20% (based on sulfoximine by-product); Rf = 0.61 (CH ₂ Cl ₂ ); δ _Η (CDCl ₃ , 300 MHz) 8.64 - 8.65 (1H, d, ArH) 8.82 8.83 (1H, d, ArH), third peak obscure.

Example 10

Preparation of 1,2,4-trinitrobenzene (XXIIIB) from 1-fluoro-3,4dinitrobenzene (XXXVIII)

1st degree. To a solution of 1-fluoro-3,4-dinitrobenzene (XXXVIII, 0.014 g, 0.075 mmol) in THF (3 mL) was added two equivalents of diphenylsulfylamine monohydrate (0.033 g, 0.150 mmol) and the mixture was refluxed for 5 hours. The THF is removed in vacuo and the crude product is purified by flash chromatography (Cl^Cljø 40 to 60°C gasoline in a 1:1 v/v ratio). The desired product resulting from substitution at the fluorine position is obtained as a yellow solid (21 mg, 76%); Rf = 0.29 (CH ₂ Cl ₂ ); Č> _H (CDC1 ₃ , 300 MHz) 6.89 - 6.94 (1H, dd, ArH) 7.02 (1H, d, ArH) 7.50 - 7.60 (6H, m, ArH) 7, 71 - 7.78 (4H, m, ArH) 7.92 - 7.95 (1H, d, ArH); m/z (El) 367 (M ⁺ , 6%) 337 (M-NO, 9) 321 (M-NO ₂ , 3) 186 (SPh ₂ , 100) 109 (SPh, 16) 77 (Ph, 22) , exact weight 0.6 ppm. The side product, resulting from substitution of the 3-nitro group, 1-fluoro-3-(S,S-diphenylsulfilimino)-4nitrobenzene is obtained as a yellow solid (6 mg, 22%); Rf = 0.36 (CH ₂ Cl ₂ ); δ _Η (CDC1 ₃ , 300 MHz) 6.27 - 6.35 (1H, ddd, ArH) 6.60 - 6.67 (1H, dd, ArH) 7.45 - 7.52 (6H, m, ArH ) 7.80 - 7.91 (5H, m, dd, ArH).

2nd degree. To a solution of 3-chloroperoxybenzoic acid (0.059 g, 343 mmol) in 1,2-dichloroethane (5 mL) cooled to -5 °C was added 3,4-dinitrobenzyl-1-S,S-diphenylsulfilimine (0.021 g, 0.057 mmol ) and the mixture is refluxed for 2 hours. The solvent is allowed to evaporate in air. Although insufficient material was obtained to detect the products by ¹ H nmr, analysis of the spot at Rf = 0.61 (CH ₂ C1 ₂ ) revealed the presence of 1,2,4-trinitrobenzene (XXIIIB) (analogous to the preparation of 1,2,4 -trinitrobenzene described in example 9).

Example 11

Preparation of l-fluoro-3,4-dinitrobenzene (XXIIIÁ) from l-fluoro-4nitrobenzene (XXXIIIA)

1st degree. To a solution of diphenylsulfilimine monohydrate (1.092 g, 5 mmol) in anhydrous degassed THF (20 mL) was added BuLi (4 mL of a 2.5 M solution in hexane, 10 mmol) with stirring under nitrogen, the mixture turned deep yellow and stirred 30 minutes. Add 1-fluoro-4-nitobenzene (XXXIIIA, 0.530 mL,

I, • Φ · I φ φφφ

0.706 g, 5 mmol) and the mixture was stirred under nitrogen at room temperature for 18 h. The THF is removed in vacuo and the crude product is purified by flash chromatography (CH ₂ C1 ₂ - 40 to 60 °C gasoline v/v 1:7, gradient CH ₂ C1 ₂ - 40 to 60 °C gasoline v/v 1:3) . The desired product, 4-nitrobenzyl-i-fluoro-3-S,S-diphenylsulfilimine, is obtained as a clear yellow oil (0.213 g, 13%); Rf = 0.18-0.31 (CH ₂ Cl ₂ );

δ _Η (CDC1 ₃ , 300 MHz) 6.27 - 6.35 (1H, dd, ArH) 6.60 - 6.67 (1H, dd, ArH) 7.45 - 7.52 (6H, m, ArH ) 7.80 - 7.91 (5H, m, dd, ArH); S _F (CDCl ₃ , 376.5 MHz) 58.1 (m); m/z (E1) 340 (M ⁺ ,

%) 323 (1) 232 (M-SPh, 1) 186 (SPh ₂ , 100) 171 (3) 154 (Ph ₂ , 7) 125 (SOPh, 3) 109 (SPh, 6) 77 (Ph, 10) exact mass, 3.0 ppm.

2nd degree. To a solution of 3-chloroperoxybenzoic acid (0.161 g, 0.935 mmol) in 1,2-dichloroethane (5 mL) cooled to -5 °C was added a solution of 4-nitrobenzyl-1-fluoro-3-Ξ,S-diphenylsulfilimine (0.053 g, 0.156 mmol) in 1,2-dichloroethane (5 mL). The mixture was allowed to warm to room temperature, refluxed for 2 h, and then the 1,2-dichloroethane was removed in vacuo. The crude product is purified by flash column chromatography (CH ₂ C1 ₂ - 40 to 60 °C gasoline in a volume ratio of 1:5, gradient to 100% CH ₂ C1). The desired product, 1-fluoro-3,4-dinitrobenzene (XXIIIA) is obtained as a yellow oil (0.014 g, 48%); Rf = 0.68 (CH ₂ Cl ₂ ); δ _Η (CDCl ₃ , 300 MHz) 7.42 - 7.50 (1H, ddd, ArH) 7.60

- 7.64 (1H, dd, ArH) 8.02 - 8.09 (1H, dd, ArH); m/z (El) 186 (M\ 100%) 156 (M-NO, 1) 140 (M-N0 ₂ , 4) 122 (1) 112 (6) 94 (M-2N0 ₂ , 32) 82 (43 ), exact mass, 7.8 ppm. The side product, 1-fluoro-3-(S,S-diphenylsulfoximino)-4-nitrobenzene is obtained as yellow solid'*(O7l6g,"29Rf = 0.48 (CH ₂ C1 ₂ ); δ _Η (CDC1 ₃ , 300 MHz) 6.57 - 6.63 (1H, ddd, ArH) 7.05

- 7.12 (1H, dd, ArH) 7.45 - 7.53 <6H, m, ArH), 7.80 - 7.86 (1H, dd, ArH) 8.08 - 8.17 (4H, m, ArH); m/z (E1) 356 (M ⁺ ,

100) 337 (MF, 1) 310 (M-N0 ₂ , 2) 259 (2) 218 (Ph ₂ SO ₂ , 5) 202 (SOPh ₂ , 17) 154 (Ph ₂ 30) 141 (10), 125 ( PhSO, 41) 109 (SPh, 45) 77 (Ph, 48), exact mass, 1.3 ppm.

Example 12

Preparation of 2-nitro-3,5,6-trifluoropyridine (XXX) from 2,3,5,6-tetrafluoropyridine (XXXVII)

1st degree. S,S-Diphenylsulfilimine (1.08 g, 4.92 mmol) was weighed into a 100 mL three-necked round-bottom flask. THF (20 mL) was added and then 2,3,5,6-tetrafluoropyridine {XXXVII, 0.372 g, 0.248 mL, 2.46 mmol) was added via syringe. The mixture is refluxed for 4 hours. The white precipitate was removed by filtration and the THF was removed from the filtrate using a rotary evaporator. The crude product is purified by flash column chromatography (the column is eluted with a mixture of dichloromethane and 40 to 60 °C gasoline in a volume ratio of 1:2) The product, 3,5,6-trifluoro-2-pyridinyl-S,S-diphenylsulfinimine (XX) is obtained as a pale yellow solid (0.777 g, 95%); melting point 119 to 121 °C; Rf = 0.48 (CH ₂ Cl ₂ ); elemental analysis, found, C, 61.40, H, 3.12, N, 3.82, ^C 17H ₁₁ N ₂ SF ₃ calcd C, 61.43, H, 3.34, N, 8.43; OH _H (CDCl 3 , 300 MHz) 7.10 - 7.19 (1H, dd, ArH) 7.45 - 7.53 (6H, m, ArH) 7.77 7.81 (4H, m, ArH); Č _c (CDC1 ₃ , 100.6 MHz) 114.1 (C4) 127.5 132.7 (ortho, meta, para carbons in phenyl) 132.9 - 135.8 (C5) 137.6 (SC in Ph ) 143.2 - 145.7 (C6) 145.2 - 147.8 (C3) 148.6 (C2); S _F (CDC1 ₃ , 376.5 MHz) 6.6, 27.2 (F3, F5) 67.4 (F6); m/z (El) 332 (M ⁺ , 25%) 255 M-Ph, 4) 223 (M-SPh, 33) 186 (SPh ₂ , 100) 171 (4) 152 (10) 109 (SPh, 18) 77 (Ph, 37) , exact mass 0.8 ppm.

The oxidizing agent 3-chloroperoxybenzoic acid (0.497 g, 2.87 mmol) was weighed into a 100 mL three-necked round-bottom flask and 1,2-dichloroethane (20 mL) was added. The flask was cooled to -5 °C using an ice-salt bath and 3,5,6-trifluoro-2-pyridinyl-S,S-diphenylsulfilimine (XX, 0.160 g, 0.482 mmol) was added. The mixture is allowed to warm to room temperature (turns blue-green) and then refluxed 3

4444 • 4* 4 • ·*· • «4 hours (turns yellow). The reaction mixture was cooled to -5 °C and the precipitate of 3-chlorobenzoic acid was removed by filtration.

1,2-Dichloroethane is removed from the filtrate using a rotary evaporator and the product is purified by flash column chromatography (eluting with a mixture of dichloromethane and gasoline 40 60 °C in a volume ratio of 1:4. 2-Nitro-3,5,6-trifluoropyridine (XXX ) is obtained as a yellow oil (0.063 g, 74%); Rf = 0.65 (CH ₂ C 1 ₂ ); δ _Η ( _{CDCl 3} , 300 MHz) 7.65 - 7.76 (1H, dd, ArH); _ρ (CDC1 ₃ , 376.5 MHz) 42.1, 45.7, (E3, F5) 79.5 (F6); m/z (E1) 178 (M ⁺ , 5) 159 (MF, 3) 148 (M-NO, 2) 139 (M-2F, 100) 132 (M-NO ₂ , 7), exact mass 2.9 ppm.

Claims (33)

A method of nitration of carbocyclic and heterocyclic aromatic compounds with electron deficiency, comprising the steps of: a) reacting a carbocyclic or hetrocyclic aromatic compound with an electron deficiency having a leaving group, which is usually replaced by nitrogen nucleophiles, with a dilakyl-, diaryl- or alkylarylsulfilimine in a polar solvent of the solvent or its corresponding N-lithium salt in an aprotic solvent to form the corresponding. An N- (hetero) aryl-S, S-dialkyl-, diaryl or alkylarylsulfilimine derivative; b) treating the product of step (a) with an oxidizing agent to convert the sulfilimine compound to a nitro group; and c) isolating the nitrated aromatic compound obtained in step (b). The process according to claim 1, wherein the sulfilimine is diphenylsulfilimine. n is a salt; The process according to claim 1 or 2, wherein the sulfilimine is a phenolithium salt. The process according to any one of claims 1 to 3, wherein the heterocyclic aromatic compound is pyridine, diazine or triazine. 5. The process of claim 4 wherein the diazine is pyrimidine or pyrazine. Process according to any one of claims 1 to 5, characterized in that the oxidizing agent used in step (b) is a peroxycarboxylic acid. Method according to claim 6, characterized in that the peroxycarboxylic acid is perbenzoic acid, in particular m-chloroperbenzoic acid. The process of claim 6, wherein the peroxycarboxylic acid is peracetic acid or peroxytrifluoroacetic acid. The process according to any one of claims 1, 2 and 4 to 8, when dependent on them, characterized in that the polar solvent used in step (a) is an alcohol having a chain length of 4 carbon atoms or less or a cyclic ether. 10. The process of claim 9 wherein the polar solvent is ethanol, 1,4-dioxane, or tetrahydrofuran. The process of claim 3, wherein the aprotic solvent used in step (a) is 1,4-dioxane, dimethoxyethane, diethylene glycol dimethyl ether or tetrahydrofuran. 12. 2-Chloro-3,4-dinitropyridine. 13. A process for the preparation of N-aryl and N-heteroarylsulfilimine derivatives of carbocyclic and heterocyclic aromatic compounds with an electron deficiency, having a leaving group which is usually replaced by nitrogen nucleophiles, characterized in that it comprises the following steps: • 9 9,999 · 9 99 99 9 • 999 9 9 9 9 9 9 · a) reacting the heterocyclic or carbocyclic aromatic compound with an electron deficiency with a dilakyl-, diaryl or mixed alkylarylsulfilimine in a polar solvent; and b) isolating the resulting N- (hetero) aryl-S, S-dialkyl-, diaryl- or alkylarylsulfilimine derivative. 14. The process of claim 13 wherein the sulfilimine is S, S-diphenylsulfilimine. Process according to claim 13 or 14, characterized in that the polar solvent used in step (a) is an alcohol having a chain length of 4 carbon atoms or a smaller or cyclic ether. 16. The process of claim 15 wherein the polar solvent is ethanol, 1,4-dioxane or tetrahydrofuran. The process according to any one of claims 13 to 16, wherein the heterocyclic aromatic compound is pyridine, diazine or triazine. The method of claim 17, wherein the diazine is pyrimidine or pyrazine. 19. A process for the preparation of N- (hetero) arylsulfilimine derivatives of carbocyclic aromatic and heteroaromatic compounds with electron deficiency which is usually replaced by nitrogen nucleophiles, comprising the steps of: a) Heterocyclic or carbocyclic reaction 44 44 4 44 444 444 4 4 4 4 4 4 4 4 4 4 4 · electron-deficient aromatic compounds with an alkali metal N-salt of dilakyl-, diaryl- or mixed alkylarylsulfilimine in a polar solvent, and b) isolating the resulting N- (hetero) aryl-S, S-dialkyl-, diaryl- or alkylarylsulfilimine derivative 20. The method of claim 19 wherein the alkali metal is lithium. · The method of claim 19 or claim 20, wherein the sulfilimine is 5.5- Diphenylsulfilimine. The process according to any one of claims 19, 20 or 21, wherein the aprotic solvent is 1,4-dioxane, dimethoxyethane, diethylene glycol dimethyl ether or tetrahydrofuran. The method of any one of claims 19 to 22, wherein the heterocyclic aromatic compound is pyridine, diazine or triazine. 24. The method of claim 23, wherein the diazine is pyrimidine or pyrazine. 25. Any of the following compounds: 6-chloro-2-pyrazinyl-S, S-diphenylsulfilimine, 3-nitro-2-pyridinyl-S, S-diphenylsulfilimine, 2-nitro-5-chlorophenyl5,5-diphenylsulfilimine, 2-chloro-3-nitro-4-pyridinyl5. 5-diphenylsulfilimine, 2-pyrazinyl-S, S-diphenylsulfilimine, 2- (n-propoxy) -4-chloro-6- (1,3,5-triazinyl-S, S-diphenylsulfilimine) 2.3.5.6-tetrachloro-4-pyridinyl-S, S-diphenylsulfilimine, 3.4.5.6-tetrachloro-2-pyridinyl-S, S-diphenylsulfilimine, 2- (n-propoxy) -4,6- (1,3,5-triazinyl) -bis-S, S-diphenylsulphilimine; »4 · 4 4 4 · 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 2,4-bis- (n-propoxy) -6- (1,3,5-triazinyl) diphenylsulfilimine, 6-chloro-4-pyrimidinyl-S, S-diphenylsulfilimine, 5-nitro-2-pyridinyl-S, S-diphenylsulfilimine, 4 -chloro-2-pyrimidinyl5,5-diphenylsulfilimine, 2,6-dichloro-4-pyrimidinylS, S-diphenylsulfilimine, 4,6-dichloro-2-pyrimidinylS, S-diphenylsulfilimine, 2,5,6-trichloro-4-pyrimidinylS , S-diphenylsulfilimine, 4,5,6-trichloro-2-pyrimidinylS, S-diphenylsulfilimine, 2,3,5,6-tetrafluoro-4-pyridinyl5,5-diphenylsulfilimine, 3,5-dinitro-2-pyridinyl5.5 - diphenylsulphilimine and 3,5,6-trifluoro-2-pyridinyl- ^: Ξ, S-diphenylsulfilimine. 26. The alkali metal N-salt of S, S-dialkyl-, diaryl- or alkylarylsulfilimine. 27. The salt of claim 26 wherein the alkali metal is lithium. The salt of claim 26 or claim 27, wherein the sulfilimine is dimethylsulfilimine. The salt of claim 26 or claim 27, wherein the sulfilimine is diphenylsulfilimine. 30. A process for the preparation of an alkali metal N-salt according to claim 26, comprising reacting the corresponding sulfilimine with a reagent selected from the group consisting of C1 -C4 alkyllithium, alkali metal hydrides and alkali metal nitrogen bases in an aprotic solvent. . 31. The process of claim 30 wherein the reagent is n-butyllithium. ·· φ • φφ 31 32. The method of claim 30, wherein the reagent is lithium, sodium, or magnesium N, N-di (isopropyl) amide or N, N-bis (trimethylsilyl) amide. A process according to any one of claims 30 to 32, wherein the aprotic solvent is 1,4-dioxane, dimethoxyethane, diethylene glycol dimethyl ether or tetrahydrofuran.