GB2308119A - Nitration of aromatic compounds sulphilimines - Google Patents
Nitration of aromatic compounds sulphilimines Download PDFInfo
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- GB2308119A GB2308119A GB9525789A GB9525789A GB2308119A GB 2308119 A GB2308119 A GB 2308119A GB 9525789 A GB9525789 A GB 9525789A GB 9525789 A GB9525789 A GB 9525789A GB 2308119 A GB2308119 A GB 2308119A
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- diphenylsulphilimine
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07C201/06—Preparation of nitro compounds
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- C07C201/06—Preparation of nitro compounds
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- C07C381/00—Compounds containing carbon and sulfur and having functional groups not covered by groups C07C301/00 - C07C337/00
- C07C381/10—Compounds containing sulfur atoms doubly-bound to nitrogen atoms
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/61—Halogen atoms or nitro radicals
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- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
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- C07D239/42—One nitrogen atom
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- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/16—Halogen atoms; Nitro radicals
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- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/20—Nitrogen atoms
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- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/26—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hetero atoms directly attached to ring carbon atoms
- C07D251/40—Nitrogen atoms
- C07D251/42—One nitrogen atom
- C07D251/44—One nitrogen atom with halogen atoms attached to the two other ring carbon atoms
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- C—CHEMISTRY; METALLURGY
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- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/26—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hetero atoms directly attached to ring carbon atoms
- C07D251/40—Nitrogen atoms
- C07D251/42—One nitrogen atom
- C07D251/46—One nitrogen atom with oxygen or sulfur atoms attached to the two other ring carbon atoms
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Description
Nitration of Aromatic Compounds
The present invention relates to a process for the nitration of aromatic compounds and in particular the nitration of both heterocyclic and carbocyclic electron deficient aromatics.
Typical heterocyclic electron deficient aromatics are such substances as pyridines, diazines (especially pyrimidines and pyrazines) and triazines whilst the carbocyclic electron deficient aromatics may be described as being benzenoid aromatics substituted with electron-withdrawing groups. In general, for the purposes of the present invention, an electron-deficient aromatic is defined as either a heterocyclic or carbocyclic aromatic bearing a leaving group which is commonly displaced by nitrogen nucleophiles. Such leaving groups include halogens, nitro groups, alkoxy groups and nitrile groups.
Conventional electrophilic nitration methods based on nitronium ion (NO2+) chemistry are widely used in chemical synthesis and are highly successful in the case of nitration of carbocyclic aromatics such as toluene and with electron-rich heteroaromatics such as 1,2,4-triazolone. With electron-deficient aromatic systems such as benzenes containing electron-withdrawing groups and heterocyclic azines, diazines and triazines, however, methods based on nitronium ion chemistry are almost entirely ineffective. For example nitration of pyridine using potassium nitrate/oleum at 3500C yields less than 3% of 3-nitropyridine (RM Acheson, "An Introduction to the
Chemistry of Heterocyclic Compounds, 3rd. Ed.", p237 (Interscience, 1976)).
A number of strategies have been attempted to overcome these difficulties, including attempts at use of nucleophilic nitrating agents. For example, AgNO2 or
NaNO2 have been used to generate nitrite ions which will displace halogen from the aromatic species. However, this reagent suffers from a number of serious defects.
Thus it is relatively expensive and at the same time environmentally undesirable as a chemical reagent. It also exhibits a lack of specificity in its mode of attack, often yielding predominantly nitrite esters rather than nitro compounds.
It is known that nitroheterocycles may be prepared by oxidation of dialkylsulphilimine and related phosphinimine intermediates derived from aminoheterocycles (Taylor et al, J Org. Chem. 47 552 (1982) and Rakitin et al, Khim.
Geterot. Soed. 1536 (1990); and Coburn et al J Het. Chem. 23 421 (1986) and J Het.
Chem. 26 1883 (1989)). However these processes are not initially attractive since the use of aminoheterocycles requires additional process steps to prepare these and suitable aminoheterocycles are of limited availability. In the case of the phosphinimines (where furazan was used as the heteroaromatic nucleus) difficulties were experienced in the oxidation step and use of the rather exotic oxidant dimethyldioxirane (DMD) was necessary to obtain good yields of the nitro product.
Preparation of some phosphinimine derivatives of heteroaromatics by nucleophilic substitution has been reported and Tamura et al (J. Org. Chem. 38, 4324 (1973)) reported the preparation of 2,4-dinitrophenyl-S,S-diphenylsulphilimine rom 2,4-dinitrofluorobenzene. Vlasova et al (Org. Prep. Proced. Int. 26 331 (1994)) have reported some examples of nucleophilic substitution in heteroaromatics and also with 2,4-dinitrochlorobenzene using S,S-diphenylsulphilimine with the reactions being carried out in dichloromethane. None of these sulphilimine or phosphinimine derivatives was subsequently oxidised to generate the corresponding nitro-compounds and indeed in some cases the starting materials for their generation were nitrocompounds (ie. the departing group was a nitro-substituent).
Vlasova et al commented that mildly activated nitroheterocycles such as 4methyl- and 4-phenyl-3-nitrofUrazan did not react with S,S-diphenylsulphilimine and also that S,S-diphenylsulfilimine hydrate (which they obtained as an intermediate in the preparation of the non-hydrated material) did not react with one of the selected heteroaromatics and was therefore a weaker nucleophile than the non-hydrate. Their preferred reaction conditions thus avoided use of the hydrate and used as solvent non
polar species such as dichloromethane, carbon tetrachloride and benzene. All of these
solvents are less acceptable from an environmental point of view.
The present inventors on the other hand have now found that by variation of
the reaction conditions and in particular by the selection of the solvent which is used, a
much broader range of nucleophilic aromatic substitution reactions involving either
dialkyl-, diaryl- or mixed alkylarylsulphilimines becomes possible and that under
appropriate circumstances the hydrated form of such sulphilimines can also be used
with some advantage. As well as substituted heteroaromatics, substituted benzenoid
aromatics (carbocyclic aromatics) may be used as the starting materials.
Accordingly in a first aspect of the present invention there is provided a method
of preparing N-aryl- and N-heteroarylsulphilimine derivatives of electron-deficient
carbocyclic and heterocyclic aromatics which comprises the steps of:
a) reacting an electron-deficient heterocyclic or carbocyclic aromatic
compound with a dialkyl-, diaryl- or mixed alkylarylsulphilimine in a
polar solvent; and
b) isolating the N-(hetero)aryl-S,S-dialkyl-, diaryl- or
alkylarylsulphilimine [or N-aryl-S,S-alkylarylsulphilimine] derivative
which is formed.
As the sulphilimine reagent S,S-diphenylsulphilimine is particularly preferred since this is a commercially available material. Other possible sulphilimines include Smethyl-S-phenyl- and S,S-dimethylsulphilimine.
Preferably the polar solvent is an alcohol or an ether, most preferably an alcohol of low molecular weight such as ethanol or other lower alcohols with chain length 4 carbon atoms or less. The ether may be a cyclic ether such as tetrahydrofuran (TIFF) or 1,4-dioxane.
Under the circumstances stipulated for this process, apart from the notably greater reactivity which has been observed by the present inventors (for example the less reactive pyridine, pyrimidine and pyrazine heterocycles may be successfully reacted under these conditions), a substantially more economical use of the sulphilimine reagent is achieved. Thus whereas the method of Vlasova et al involves use of three equivalents of S,S-diphenylsulphilimine to one equivalent of aromatic reagent, in the present process only two equivalents are used of which one is recovered in the form of a salt (eg. the halide salt) and may be reconverted to the diphenylsulphilimine reagent by treatment with butyllithium. An additional advantage is the use of environmentally acceptable solvents as noted earlier.
With the exception of the above noted 2,4-dinitrophenyl-S,Sdiphenylsulphilimine, all of the N-(hetero)aryl-S,S-diphenylsulphilimine compounds generated using the process of the present invention are novel materials. This includes the following compounds: 6-chloro-2-pyrazinyl-S,S-diphenylsulphilimine, 3 -nitro-2 - pyridinyl-S,S-diphenylsulphilimine, 2-nitro-5-chlorophenyl-S,S-diphenylsulphilimine, 2-chloro-3-nitro-4-pyndinyl-S,S-diphenylsulphilimine, 2-pyrazinyl-S,Sdiphenylsulphilimine, 2-(n-propoxy)-4-chloro-6-(1,3,5-triazinyl)-S, S- diphenylsulphilimine, 2,3,5,6-tetrachloro-4-pyndinyl-S,S-diphenylsulphilimine, 3,4,5,6 tetrachloro-2-pyridinyl-S,S-diphenylsulphilimine, 2-(n-propoxy)-4,6-(1,3,5-triazinyl)- bis-S,S-diphenylsulphilimine, 2,4-bis-fn-propoxy)-6-( 1,3,5-triazinyl)- diphenylsulphilimine, 6-chloro-4-pyrimidinyl-S,S-diphenylsulphilimine, 5-nitro-2pyridinyl-S,S-diphenylsulphilimine, 4hloro-2-pyrimidinyl-S ,S-diphenylsulphilimine, 2,6-dichloro4-pyrimidinyl-S,S-diphenylsulphilimine, 4,6-dichloro-2-pyrimidinyl-S,Sdiphenylsulphilimine, 2, 5,6-trichloro-4-pyrimidinyl-S,S-diphenylsulphilimine, 4,5,6 trichloro-2-pyrimid inyl-S, S-diphenyisulphil imine and 2,3,5, 6-tetrafluoro4 -pyridinyl- S,S-diphenylsulphilimine. The formulae for these compounds appear respectively as I to XVIII in Figures 1 and 2.
All of these materials are stable crystalline solids or oils.
The present inventors have further provided an entirely novel class of related reagents which, in addition to substitution of electron-withdrawing groups, enable vicarious substitution of the hydrogen on carbocycles and heteroaromatics by diarylsulphilimino groups to proceed under easy conditions. According to a second aspect of the present invention therefore there is provided a class of novel reagents comprising N-alkali metal salts of S,S-dialkyl-, diaryl- or alkylarylsulphilimines having the general formula (XXX):
where R' and R2 are independently alkyl and/or aryl groups and M is lithium, sodium or potassium. A particularly preferred class of reagents of this type are the N-lithio salts and especially N-lithio-S,S-diphenylsulphilimine.
These novel reagents may be readily prepared by reacting the corresponding sulphilimine with alkyl lithiums with chain length 1 to 4 atoms (preferably nbutyllithium), alkali metal hydrides such as lithium, sodium or potassium hydrides, alkali metal nitrogenous bases such as lithium, sodium or potassium N,Ndi(isopropyl)amides or the respective N,N-bis(trimethylsilyl)amides or other suitable base. The reaction is preferably carried out in an aprotic solvent such as 1,4-dioxane, dimethoxyethane, diethyleneglycol dimethyl ether or tetrahydrofuran.
When these reagents are applied to the process which comprises the first aspect of this invention, a yet broader range of reaction products may be obtained. However for these reagents it has been found that the reaction should be carried out in an aprotic solvent. Accordingly in a further aspect of the present invention there is provided a process for the preparation of N-(hetero)arylsulphilimine derivatives of electron-deficient carbocyclic aromatics and heteroaromatics comprising the steps of:
a) reacting an electron-deficient carbocyclic or heterocyclic aromatic
compound with an N-alkali metal salt of an S,S-dialkyl-, diaryl- or
alkylarylsulphilimine in an aprotic solvent, and
b) isolating the N-(hetero)aryl-S,S-dialkyl-, diaryl- or
alkylarylsulphilimine derivative which is formed.
Preferably the N-alkali metal salt used is an N-lithio sulphilimine salt and particularly preferred is N-lithio-S,S-diphenylsulphilimine which is readily derived from the commercially available compound S,S-diphenylsulphilimine. Although the corresponding salts derived from sodium and potassium would react in a similar manner these are likely to be more difficult to prepare than the lithium salts and therefore comprise less desirable reagents from a practical point of view.
As the aprotic solvent 1,4-dioxane, dimethoxyethane, diethyleneglycol dimethylether (diglyme) or most especially tetrahydrofuran are preferred.
In a yet further aspect the present invention provides a process for the nitration of electron-deficient carbocyclic and heterocyclic aromatic compounds which comprises the steps of:
a) reacting an electron-deficient carbocyclic or heterocyclic aromatic
(as hereinbefore defined) with a dialkyl-, diaryl- or
alkylarylsulphilimine in a polar solvent or with the corresponding N
alkali metal salt thereof in an aprotic solvent to generate the
corresponding N-(hetero)aryl-S,S-dialkyl-, diaryl or
alkylarylsulphilimine derivative thereof;
b) treating the product of step (a) with an oxidising agent to convert the
sulphilimino group to a nitro-group; and
c) isolating the nitrated aromatic compound obtained in step (b).
The reaction of step (a) is as previously described. In the second, oxidation, step the inventors have found, in contradistinction to earlier work with phosphinimines, that the sulphilimine derivatives may be readily oxidised with commercially available oxidants such as m-chloroperbenzoic acid. A more economical and potentially industrially-applicable process thus results. In general any peroxycarboxylic acid may be employed such as various aromatic peroxycarboxylic acids (particularly mchloroperbenzoic acid), peracetic acid or peroxytrifluoroacetic acid.
Yields in the first, nucleophilic substitution, step are typically in the range of 60% to quantitative and in the second, oxidation, step in the range of 10 to 50%. In general, even in the case of compounds which have previously been obtainable via conventional electrophilic nitrations, the yields are greater with the present two-step process than have been achieved before.
It will be readily appreciated that in addition to the generation of mono-nitrosubstituted aromatics, the ability of the aforementioned novel N-alkali metal(alkyl/aryl)sulphilimine reagents to bring about vicarious hydride substitution in which a ring hydrogen atom either ortho- or para- (but especially the former) to a nitro-group already present in the ring is substituted, enables polynitro heterocyclic and carbocyclic aromatics to be produced quite readily. Such materials have previously often been either very difficult or indeed 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-nitro2,3,5,6-tetrafluoropyridine have been prepared and additionally the novel compounds 2,3-dinitropyridine and 2-chloro-3,4-dinitropyridine have now been obtained.
Such polynitro-substituted aromatics are regarded as important precursors for the production of new types of thermally- and impact-insensitive high explosives materials.
The invention will now more particularly be described with reference to the following examples. Formulae referenced below which correspond to either starting materials or to nitro compound products (formulae XXXI to XXXVI and XXI to
XXIX) appear respectively on Figures 3 and 4.
Example 1: PreDaration of 2-cbloro-6-nitronvrazine (XXI) from 2*S dichioronyrazine (XXXT).
Ist step. S,S-Diphenylsulphilimine monohydrate (0.540g, 2.46 mmol, 2 equiv.) was weighed out into a 100ml triple-necked round-bottomed flask. TIFF (tetrahydrohiran, 15 ml) was added, causing the sulphilimine to dissolve. The TIFF had been purified by distillation. 2,6-Dichloropyrazine (XXXI, 0.183g, 1.23 mmol, 1 equiv.) was added to the solution in the flask. The central neck of the flask was fitted with a Liebig condenser, a magnetic stirrer bar was placed in the flask and stoppers were placed in the remaining two necks of the flask. The contents of the flask were stirred and refluxed for 18 hr. This was accomplished using a paraffin oil bath heated on a hotplate-stirrer device. During the first hour of reflux a white precipitate appeared. At the end of the 18 hr the flask was lifted out of the oil bath and allowed to cool to room temperature. The white precipitate was separated from the solution by gravity filtration. The white solid was shown by 'H nmr spectroscopy and elemental analysis to be the salt diphenyl(aminosulphonium) chloride, the side product of N-aryl S,S- diphenylsulphilimine formation. The TIFF was removed from the filtrate using a rotary evaporator. A yellow brown oil remained, which was shown by nmr to be a slightly impure form of the desired product 6-chloro-2-pyrazinyl-S,S-diphenylsulphilimine (I, 0.366g, 95%). The impurity, 5% of the starting material 2,6-dichloropyrazine, was removed when the crude product was purified by flash column chromatography.The column was packed with 10g of Merck Kieselgel 60 flash silica (particle size 0.040 0.063mm) and eluted under pressure using small bellows with a 1:2 vol./vol. mixture of dichloromethane and petrol (b.pt. 40-60"C) followed by pure dichloromethane. The crude product was dissolved in approx. lml of the eluting solvent and put onto the column using a long pipette. HPLC grade dichloromethane was used and the petrol had been distilled prior to use. The desired product had a retention factor of 0.16 on a thin layer chromatography plate pre-coated with Merck Kieselgel 60 F-254 and eluted in dichloromethane, i.e. Rf= 0.16 (CH2C12). The impurity had a retention factor of 0.50 (CH2C12).
Data for the product of the first step, 6-chloro-2-pyrazinyl-S,S-diphenylsulphilirnine (I): 1H nmr (CDCl3, 300MHz) 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, CDCl3 = deuterated chloroform and a Bruker AC 300 spectrometer was used. E.I. mass spectrometry; 313,315 (M+, 4%, 1%) 278 (M-CI, 1) 204, 206 (M-SPh, 3, 1)186 (SPh2, 100) 109 (SPh, 17) 92 (M-CI-SPh2, 11) 83 (18), accurate mass for molecule containing 35Cl correct to 0.1 ppm.The figures outside the brackets denote the molecular masses of the fragments seen and the contents of the bracket give the identity of the fragment and the intensity of its peak as a percentage.
M denotes the molecular fragment. The mass spectra were obtained using a Kratos
Analytical Profile MS and a Shimadzu GC-14A.
2nd step. The oxidising agent 3-chloroperoxybenzoic acid (0.1 98g, 1.15 mmol, 6 equiv.) was weighed out into a 100ml triple-necked round-bottomed flask of the type used in the first step. The three necks of the flask were fitted with a stopper, a water condenser and a thermometer respectively, and a magnetic stirrer bar was placed in the flask. 10ml of HPLC grade 1,2-dichloroethane was added to the flask, and the flask and its contents were cooled to -50C using ice-salt mixture. 6-Chloro-2-pyrazinyl-S,Sdiphenylsulphilimine (I, 60mg, 0.19 mmol, 1 equiv.) was added to the flask. The contents of the flask were stirred, the ice bath was removed, the flask was allowed to warm up to room temperature and was then placed in the paraffin oil bath used in the first step. The reaction mixture was refluxed for 2 hr and then allowed to cool.The mixture was washed with two 1 oil portions of 0.5 M aqueous sodium hydroxide followed by two 10ml portions of distilled water. The reaction mixture was then dried over 5g of anhydrous magnesium sulphate. The dry reaction mixture was separated from the solid magnesium sulphate by gravity filtration and then 1 ,2-dichloroethane was removed on a rotary evaporator leaving a brown oil. The oil was purified by flash column chromatography using the type of silica and eluting solvent described in the first step. 2-Chloro-6-nitropyrazine (XXI) was obtained as a yellow oil (0.018g) in 60% yield; Rf-0.59 (CH2CI2); lH nmr (CDC13, 300 MHz) 9.21 (2H, m, ArH). The side-product of oxidation, diphenyl sulphone, was also obtained (0.029g).
Example 2: Preparation of 2dinitronyridine (XXII) from 2-chloro-3 nitronyridine (XXXIT).
Ist step. Apparatus and method as in Example 1. S,S-Diphenylsulphilimine monohydrate (0.519g, 2.37 mmol, 2 equiv.) and 20ml ethanol were added to a 100ml triple-necked round-bottomed flask set up for reflux. 2-Chloro-3-nitropyridine (XXXII, 0.1 88g, 1.18 mmol, 1 equiv.) was added and the reaction mixture was refluxed for 7 hr and then allowed to cool. Since the side-product diphenyl(aminosulphonium) chloride was soluble in ethanol it was not removed by filtration at this stage. Instead, ethanol was removed from the reaction mixture on a rotary evaporator leaving an impure yellow solid.This was purified by flash column chromatography (eluting solvent 3:2 vol./vol. CH2Cl2-petrol (b.pt. 40-60"C), gradient to 100% CH2C12). The desired product, 3-nitro-2-pyridinyl-S,S-diphenylsulphilimine (It) was obtained as a crystalline yellow solid in 76% yield (0.290g); Rf-0.20 (CH2C12); m.pt. 132-1340C; elemental analysis, found C, 63.42, H, 4.04, N, 12.97, requires C, 63.14, H, 4.05, N, 12.99; 'H nmr (CDC13, 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) 8.158.19 (1H, dd, ArH), dd=doublet of doublets; mass spectrometry (EI) 323 (M+, 7%) 293 (M-NO; 1)258 (3) 214 (M-SPh, 1) 186 (SPh2, 100) 168 (12) 152 (6) 139 (11) 109 (SPh, 9) 77 (Ph, 14), accurate mass 3.7ppm.
2nd step. A flask containing 3-chloroperoxybenzoic acid (0.224g, 1.30mmol, 6 equiv.) and 1,2.dichloroethane (lOml) was cooled to -5 C in an ice-salt bath as described in
Example 1. 3-nitro-2-pyridinyl-S,S-diphenylsulphilimine (H, 0.07g, 0.22mmol) was added. The mixture was allowed to warm up to room temperature, reflux for 2 hr and then cooled to -10 C. A white precipitate of the oxidation side-product 3chlorobenzoic acid appeared, and this was removed from the mixture by gravity filtration. 1,2-Dichloroethane was then removed from the reaction mixture on a rotary evaporator. The desired product, 2,3-dinitropyridine (XXII), was obtained as a yellow oil in 9% yield after purification by flash column chromatography (eluting solvent 3:4 vol./vol.CH2Cl2-petrol (b.pt. 40-60"C), gradient to 100% CH2Cl2). The side-product diphenyl sulphone was also obtained. Data for 2,3-dinitropyridine: Ref60.58 (CH2C12); 'H nmr (CDCl3, 300 MHz) 7.80-7.85 (1H, m, ArH) 8.51-8.54 (1H, m, ArH) 8.77-8.79 (1H, m, ArH); mass spectrometry (EI) 169 (M+, 100) 147 (4) 105 (10) 99 (33) 77 (M2NO2, 13) accurate mass, 3.9ppm.
Example 3. Preparation of 1-chloro-3*4-dinitrobenzene (XXTIfl from 1-chloro-4- nitrobenzene (XXXllT).
1st step. A 100ml triple-necked round-bottomed flask containing a magnetic stirrer bar, a 20ml syringe with Luer needle and a 5ml syringe with Luer needle were dried in an oven for 24 hr at 1 500C. The techniques described in this section are appropriate for the handling of pyrophoric materials i.e. oxygen and water are excluded. The flask was removed from the oven, the central neck was fitted with a nitrogen bubbler and the remaining two necks were fitted with rubber septa. The flask was flushed with nitrogen. S,S-diphenylsulphilimine monohydrate (1.097g, Smmol, 1 equiv.) was added to the flask. The 20ml syringe was removed from the oven and used to add 15ml of anhydrous TIFF to the flask.The TIFF had been freshly distilled over calcium hydride.
The solution in the flask was degassed by attaching a long needle to a nitrogen supply and putting the needle through one of the septa so that the end of the needle was in the solution. Bubbles of nitrogen were allowed to pass through the solution in this way for 10 min. The long needle was then removed. The Sml syringe was removed from the oven and flushed with nitrogen for 5 min.It was then used to add n-butyllithium (4ml of a 2.5 M solution in hexanes, 10 mmol, 2 equiv., DANGER pyrophoric compound !) dropwise to the stirred solution which immediately turned yellow, indicating the presence of N-lithio-S,S-diphenylsulphilimine. The empty Sml syringe was placed in a large beaker of butan-1-ol immediately after use. 1-Chloro-4nitrobenzene (XXXm, 0.788g, 5 mmol, 1 equiv.) was added to the yellow solution by briefly removing one of the septa, and the mixture was stirred under nitrogen at room temperature for 24 hr. The mixture was then exposed to the air and the TIFF removed on a rotary evaporator.The crude product was purified by flash column chromatography (eluting solvent 1:2 vol./vol. CH2Cl2-petrol (b.pt. 40-60"C)). 2
Nitro-5-chlorophenyl-S,S-diphenylsulphilimine (m, 0.34g) was obtained as a crystalline yellow solid in 19% yield; Ref60.43 (CH2Cl2); elemental analysis, found, C, 60.06, H, 3.57, N, 7.90, required, C, 60.58, H, 3.67, N, 7.85; 1H nmr (CDCl3, 300MHz) 6.56-6.60 (1H, dd, ArH) 6.94-6.95 (lH, d, ArH) 7.49-7.52 (6H, m, ArH) 7.69-7.73 (1H, d, ArH) 7.83-7.88 (4H, m, ArH); mass spectroscopy (EI) 356, 358 (M4, 1%, 0.3%) 186 (SPh2, 100), accurate mass, 35Cl, 2.5 ppm.
2nd step. 3-Chloroperoxybenzoic acid (0.320g, 1.86mmol, 6 equiv.) and 1,2dichloroethane (20ml) were cooled to -5 C in a 100ml triple-necked flask using an icesalt bath. 2-Nitro-5-chlorophenyl-S,S-diphenylsulphilimine (III, 0.11 Og, 0.31 mmol, 1 equiv.) was added, the flask was allowed to warm up to room temperature and was then refluxed for 2 hr. After cooling, the reaction mixture was washed with two 10 ml portions of 0.5M aqueous sodium hydroxide followed by two 10ml portions of distilled water and then it was dried over anhydrous magnesium sulphate (see Example 1).
After removal of the magnesium sulphate by gravity filtration, 1,2-dichloroethane was removed from the reaction mixture on a rotary evaporator. The crude product was purified by flash column chromatography (eluting solvent 1:3 vol./vol. CH2C12-petrol (b.pt. 40-60"C), gradient to 100% CH2C12) and the desired product, 1-chloro-3,4dinitrobenzene (XXIII), was obtained as a pale yellow solid in 32% yield (0.020g); Ref=0.79 (CH2C12); lH nmr (CDCl3, 300MHz) 7.69-8.18 (3H, m, ArH); mass spectrometry (EI) 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), accurate mass, 35C1, 5.4ppm.
Example 4: Preparation of 2-chloro-3g4-dinitropvridine (XXIV) from 2-chloro-3 nitroDvridine (XXXIV).
1st step. A solution of N-lithio-S,S-diphenylsulphilimine (1.23 mmol, 1 equiv.) in 15ml anhydrous TIFF was prepared using S,S-diphenylsulphilimine monohydrate (0.270g, 1.23 mmol, 1 equiv.) and n-butyllithium (0.98ml of a 2.5 M solution in hexanes, 2.46 mmol, 2 equiv.) using the method, apparatus and precautions described in Example 3.
2-Chloro-3-nitropyridine (XXXIV, 0.195g, 1.23mmol) was added to the solution and it was stirred under nitrogen at room temperature for 24 hr. At the end of this time, the mixture was exposed to the air and the TIFF was removed on a rotary evaporator.
The crude product was purified by flash column chromatography (eluting solvent 1:3 vol./vol. CH2Cl2-petrol (b.pt. 40-60"C), gradient to 100% CH2Cl2) and the desired product, 2-chloro-3-nitro4-pyridinyl-S,S-diphenylsulphilimine (IV), was obtained as a yellow solid in 49% yield; Ref60. 15 (CH2Cl2); lH nmr (CDCl3, 300MHz) 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 (EI) 357,359 (M+, 5%,2%) 291 (1) 232 (3) 186 (SPh2, 100) 125 (12) 105 (52) 77 (Ph, 24), accurate mass, 35Cl, 4.2 ppm.
2nd step. 3-Chloroperoxybenzoic acid (0.290g, 1.68mmol, 6 equiv.) and 1,2dichloroethane (10my) were weighed out into a triple-necked round-bottomed flask and cooled to -5 C using an ice-salt bath. 2-Chloro-3-nitro4-pyridinyl-S,S- diphenylsulphilimine (IV, 0.1 00g, 0.28mmol) was added, the contents of the flask were allowed to warm up to room temperature, refluxed for 2 hr and then cooled to -100C, allowing the side-product of oxidation, 3-chlorobenzoic acid, to precipitate out of solution. The precipitate was removed by gravity filtration and 1,2-dichloroethane was removed from the resulting filtrate using a rotary evaporator.The crude product was purified by flash column chromatography (eluting solvent 1:2 vol./vol. (b.pt. 40 60"C)). The desired product, 2-chloro-3,4-dinitropyridine (XXIV), was obtained as a yellow oil in 9O/O yield; Rf-0.54 (CH2Cl2); 'H nmr (CDCl3, 300MHz) 8.02-8.08 (1H, d,
ArH) 8.83-8.90 (1H, d, ArH); mass spectrometry (EI) 203,205 (M+, 39%,12%) 173 (3)155 (3) 129 (7) 84 (100), accurate mass, 35Cl, 1.7ppm.
Example 5: Preparation of 4-nitr*2*3,5*6-tetrachloropvridine (XXV) from pentachioropyridine (XXXV1.
Ist step. S,S-diphenylsulphilimine (1.08g, 4.92 mmol, 2 equiv.) was weighed into a 100ml triple-necked round-bottomed flask. TIFF (15 ml) was added, causing the solid sulphilimine to dissolve. Pentachloropyridine (XXXV, 0.618g, 2.46 mmol, 1 equiv.) was added to the solution in the flask. The central neck of the flask was fitted with a water condenser, and the remaining two necks fitted with glass stoppers. A magnetic stirrer was used to stir the solution. The contents of the flask was stirred and refluxed for 4 hr, using a paraffin oil bath heated on a hotplate stirrer device. At the end of the 4 hr the reaction mixture was cooled to room temperature and the white precipitate of diphenylaminosulphonium chloride which had appeared during the reaction was removed by filtration.This salt was saved for recycling. TIFF was removed from the filtrate using a rotary evaporator. The white solid which remained after rotary evaporation was purified using flash column chromatography. The column was eluted with a 1:4 vol./vol. mixture of dichloromethane and petrol (b.pt. 40-60 C). Two products were obtained. 2,3,5,6-Tetrachloro-4-pyndinyl-S,S-diphenylsulphilimine (VII, 0.473g, 46%); m.pt. 143-1440C; Rf-0.65 (CH2Cl2); elemental analysis, found, C, 48.95, H, 2.18, N, 6.85, Cl7HloN2SCl4 requires, C,49.06, H, 2.42, N, 6.73; 5H (CDCl3, 300 MHz) 7.45-7.51 (6H, m, ArH) 7.84-7.91 (4H, m, ArH); 8c (CDC13, 100.6 MHz) 121.6 (C3 of pyridine) 126.2, 129.9, 131.9 (ortho, meta andpara phenyl C's) 140.4 (phenyl C attached to sulphur) 145.65, 156.8 (C2, C4 of pyridine);; rn/z (EI) 416, 414 (M+, 4%, 3%) 381 (M-Cl, 1) 307 (M-SPhs 1) 270 (2) 232, 230 (6, 5)186 (SPh2, 78) 84 (100) 77 (Ph, 14), accurate mass, 4 x 35C1, 2.7ppm, 37Cl + 3 x 35C1, 3.1 ppm.
3,4,5,6-Tetrachloro-2-pyridinyl-S,S-diphenylsulphilimine (VIII, 0.181g, 18%); m.pt.
175 C; Rf=0.80 (CH2Cl2); elemental analysis, found, C, 48.99, H, 2.16, N, 6.71, Cl7HloN2SCl4 requires C, 49.06, H, 2.42, N, 6.73; #H (CDCl3, 300 MHz) 7.49-7.52 (6H, m, ArH) 7.81-7.88 (4H, m, ArH); m/z (EI) 414, 416 (M+, 14%, 18%) 379 (M-CI, 1) 339 (M-Ph, 1) 305, 307 (M-SPh, 18, 23) 186 (SPh2,100)109(SPh, 12) 77 (Ph, 16), accurate mass, 4 x 35Cl, 1.6 ppm, 37Cl + 3 x 35Cl, 1.2 ppm.
2nd step. The oxidising agent 3-chloroperoxybenzoic acid (0.497g, 2.87 mmol, 6 equiv.) was weighed out into a 1 00ml triple-necked round-bottomed flask. The three necks of the flask were fitted with a stopper, a water condenser and a thermometer, and a magnetic stirrer bar was placed in the flask. HPLC grade 1,2-dichloroethane (20 ml) was added to the flask and the contents of the flask were cooled to -5 C by suspending the flask in a plastic bowl filled with an ice-salt mixture. 2,3,5,6
Tetrachloro-4-pyridinyl-S,S-diphenylsulphilimine (VII, 0.200g, 0.481 mmol, 1 equiv.) was added to the reaction mixture, and the mixture allowed to warm up to room temperature. At this point the reaction mixture was lime green. It was then refluxed for 2 hr, during which time the colour changed from green to yellow.The reaction mixture was then cooled to -5 C and the precipitate of 3-chlorobenzoic acid which appeared at this temperature was removed by filtration. 1,2-Dichloroethane was removed from the filtrate using a rotary evaporator and the crude product was purified using flash column chromatography (eluting solvent: 1:4 vol./vol. CH2Cl2-petrol (b.pt.
40-60 C), gradient to 1:1 vol./vol. CH2Cl2-petrol (b.pt. 40-60 C). 4-Nitro-2,3,5,6tetrachloropyridine (XXV, 0.046g) was obtained as a yellow oil in 37% yield; Rf=0.82 (CH2Cl2); Vmix (CHCl3)/cm-, 1337 (s, NO2) 1563 (s, NO2); oc (CDC13, 100.6 MHz) 121.4 (C3 and C5) 147.81 (C2 and C6) 155.1 (C4); m/z (EI) 260, 262 (M+, 9%, 12%) 230, 232 (M-NO, 20, 24) 214, 216 (M-NO2, 20, 24) 179, 181 (M-CI-NO2, 5, 7)139 (100), accurate mass, 4 x 35Cl, 1.9 ppm.
4-(S,S-Diphenyisulphoximino)-2,3,5,6-tetrachlornpyridine (XXVII) was obtained as a side product; m.pt. 158-1590C; Ref 0.63 (CH2Cl2); & (CDCl3, 300MHz) 7.45-7.60 (6H, m, ArH) 8.00-8.11 (4H, m, ArH); m/z (EI) 430, 432 (M*, 12%, 16%) 397 (M-C1, 2) 305, 307 (M-SOPh, 2, 2) 270, 272 (7, 7) 218 (Ph2SON, 13) 202 (12)186 (SPh2, 13)154 (20) 125 (SOPh, 100) 109 (SPh, 34) 77 (Ph, 58), accurate mass, 4 x 35C1, 1.4 ppm.
Example 6: Preparation of 2-nitro-3g4,56-tetrachloropyridine (XXVI) from pentachloropyridine (XXXV).
Ist step. See first step of example 5, where 3,4,5,6-tetrachloro-2-pyridinyl-S,Sdiphenylsulphilimine (VIII) was prepared.
2nd step. The oxidising agent 3-chloroperoxybenzoic acid (0.075g, 0.434 mmol) was weighed out into a 100ml triple-necked round-bottomed flask. The three necks of the flask were fitted with a glass stopper, a water condenser and a thermometer. A magnetic stirrer bar was placed in the flask. HPLC grade 1,2-dichloroethane (5 ml) was added to the flask, and the mixture cooled down to -5 C using an ice-salt bath.
3 ,4,5,6-Tetrachloro-2-pyridinyl-S, S-diphenylsulphiiimine (VIII, 0.030g, 0.073 mmol) was added and the flask allowed to warm up to room temperature. At this point the reaction mixture was blue-green. The mixture was refluxed for 2 hr, changing colour from blue to yellow. At the end of the reaction, the mixture was cooled to -5 C, and the precipitate of 3-chlorobenzoic acid was removed by filtration. 1,2-Dichloroethane was removed from the filtrate on a rotary evaporator, and the crude product was purified by flash column chromatography (eluting solvent, 1:6 vol./vol. CH2Cl2- petrol (b.pt. 40-60"C), gradient to 1:1 vol./vol.CH2Cl2-petrol (b.pt. 40-60"C). 2-Nitro3,4,5,6-tetrachloropyridine (XXVI, 0.012g) was obtained as a yellow oil with a caramel odour in 63% yield; Rf- 0.79 (CH2Cl2); m/z (EI) 262,260 (M+, 13%, 12%) 230, 232 (M-NO, 61, 49) 214, 216 (M-NO2, 94,75)181, 179 (M-Cl-NO2, 47), accurate mass, 4 x 35Cl, 1.7 ppm.
A white solid, 2-(S,S-diphenylsulphoximino)-3,4,5,6-tetrachloropyridine (XXVIII) was obtained as a side-product; Ref=0.68 (CH2C12); 5H (CDC13, 300 MHz) 7.48-7.59 (6H, m, ArH) 8.05-8.11 (4H, m, ArH); m/z (EI) 430, 432 (M*, 1%) 353, 355 (M-Ph, 4, 5) 305, 307 (M-SOPh, 2, 1) 202 (Ph2SO, 2)125 (PhSO, 12) 109 (SPh, 16) 77 (Ph, 20), accurate mass, 4 x 35Cl, 1.4 ppm:
Example 7: Preparation of 4-nitro-2g3g5g6-tetrafluoroyvn.dine (XXIX) from pentafluoropyridine (XXXVI).
S,S-diphenylsulphilimine (1.08g, 4.92 mmol) was weighed into a 100ml triple-necked round-bottomed flask. TIFF (20 ml) was added, causing the solid sulphilimine to dissolve. Pentafluoropyridine (XXXVI, 0.416 g, 2.46 mmol) was added to the solution in the flask. The reaction mixture was then treated in a similar manner to that already described for pentachloropyridine (see example 5, Ist step, above), except that the reaction period was 6 hr. During flash chromatography, the column was eluted with a 1:2 vol./vol. CH2Cl2-petrol (b.pt. 40-60"C) mixture.The product, 2,3,5,6 tetrafluoro-4-pyridinyl-S,S-diphenylsulphilimine (XVIII) was obtained as a white solid in 84% yield; m.pt. 87-88"C; Rf=0.58 (CH2C12); 6H (CDC13, 300 MHz) 7.50-7.59 (6H, m, ArH) 7.81-7.88 (4H, m, ArH); 5c (CDC13, 100.6 MHz) 126.7, 130.0, 132.2 (ortho, meta andpara phenyl C's), 135.0, 137.6 (C3 and C5, 2m),138.7 (SC of Ph) 143.3, 145.7 (C2 & C6, 2m), 144.8 (C4, m); OF (CDCl3, 376.4 Mhz) 4.25 (C3 F & C5 F), 67.15 (C2 F & C6 F).
2nd step. 4-S,S-Diphenylsulphilimino-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 a manner similar to that already described above (example 5, 2nd step).
After warming to room temperature, the mixture was blue-green. It was then refluxed for 18 hr, during which time the colour changed from blue to yellow. The product mixture was then treated frirther as described in example 5, 2nd step, except that in the flash chromatography an isocratic system was used (1:4 vol./vol. mixture of CH2C12 and petrol (b.pt. 4000C)). 4-Nitro-2,3,5,6-tetrafluoropyridine (XXIX) was obtained as a yellow oil with a caramel odour (47 mg, 50%); Rf=0.61 (CH2C12); v, (CHCI3)/cm-, 1370 (NO2) 1581 (NO2); 5F (CDCl3, 376.4 MHz) 13.08 (C3 F and C5 F), 70.76 (C2 F and C6 F). Some 4-(S,S-diphenylsulphoximino)-2,3,5,6- tetrafluoropyridine was detected as a.side-product.
Claims (37)
1. A process for the nitration of electron-deficient carbocyclic and heterocyclic aromatic compounds which comprises the steps of:
a) reacting an electron-deficient carbocyclic or heterocyclic aromatic
(as hereinbefore defined) with a dialkyl-, diaryl- or
alkylarylsulphilimine in a polar solvent or with the corresponding N
alkali metal salt thereof in an aprotic solvent to generate the
corresponding N-(hetero)aryl-S,S-dialkyl, diaryl- or
alkylarylsulphilimine derivative thereof;
b) treating the product of step (a) with an oxidising agent to convert the
sulphilimino group to a nitro-group; and
c) isolating the nitrated aromatic compound obtained in step (b).
2. A process according to claim 1 wherein the sulphilimine is a diphenylsulphilimine.
3. A process according to claim 1 or claim 2 wherein the sulphilimine is a lithium salt thereof.
4. A process according to any of claims 1 to 3 wherein the heterocyclic aromatic compound is a pyridine, diazine or triazine.
5. A process according to claim 4 wherein the diazine is a pyrimidine or a pyrazine.
6. A process according to any of claims 1 to 5 wherein the oxidising agent used in step (b) is a peroxycarboxylic acid.
7. A process according to claim 6 wherein the peroxycarboxylic acid is an aromatic peroxycarboxylic acid, particularly m-chloroperbenzoic acid.
8. A process according to claim 6 wherein the peroxycarboxylic acid is peracetic acid or peroxytrifluoroacetic acid.
9. A process according to any of claims 1, 2 and 4 to 8 when dependent thereon, wherein the polar solvent used in step (a) is an alcohol with chain length 4 carbon atoms or less or a cyclic ether.
10. A process according to claim 9 wherein the polar solvent is ethanol, 1,4dioxane or tetrahydrofuran.
11. A process according to any of claims 3 and 4 to 8 when dependent thereon, wherein the aprotic solvent used in step (a) is 1 ,4-dioxane, dimethoxyethane, diethyleneglycol dimethyl ether or tetrahydrofuran.
12. A nitrated carbocyclic or heterocyclic aromatic compound when obtained by a process as claimed in any of claims 1 to 11.
13. 2,3 -dinitropyridine and 2-chloro-3 ,4-dinitropyridine.
14. A process for preparing N-aryl- and N-heteroarylsulphilimine derivatives of electron-deficient carbocyclic and heterocyclic aromatics which comprises the steps of:
a) reacting an electron-deficient heterocyclic or carbocyclic aromatic
compound with a dialkyl-, diaryl- or mixed alkylarylsulphilimine in a
polar solvent; and
b) isolating the N-(hetero)aryl-S,S-dialkyl-, diaryl- or
alkylarylsulphilimine derivative which is formed.
15. A process according to claim 14 wherein the sulphilimine is S,S- diphenylsulphilimine.
16. A process according to claim 14 or claim 15 wherein the polar solvent used in step (a) is an alcohol with chain length 4 carbon atoms or less or a cyclic ether.
17. A process according to claim 16 wherein the polar solvent is ethanol, 1,4dioxane or tetrahydrofuran.
18. A process according to any of claims 14 to 17 wherein the heterocyclic aromatic compound is a pyridine, diazine or triazine.
19. A process according to claim 18 wherein the diazine is a pyrimidine or a pyranne.
20. A N-(hetero)aryl-S,S-dialkyl-, diaryl- or alkylarylsulphilimine compound when produced by the process as claimed in any of claims 14 to 19.
21. A process for the preparation of N-(hetero)arylsulphilimine derivatives of electron-deficient carbocyclic aromatics and heteroaromatics comprising the steps of:
a) reacting an electron-deficient carbocyclic or heterocyclic aromatic
compound with an N-alkali metal salt of an S,S-dialkyl-, diaryl- or
alkylarylsulphilimine in an aprotic solvent, and
b) isolating the N-(hetero)aryl-S,S-dialkyl-, diaryl- or
alkylarylsulphilimine derivative which is formed.
22. A process according to claim 21 wherein the alkali metal is lithium.
23. A process according to claim 21 or claim 22 wherein the sulphilimine is S,S- diphenylsulphilimine.
24. A process according to any of claims 21, 22 or 23 wherein the aprotic solvent is 1 ,4-dioxane, dimethoxyethane, diethyleneglycol dimethyl ether or tetrahydrofuran.
25. A process according to any of claims 21 to 24 wherein the heterocyclic aromatic compound is a pyridine, diazine or triazine.
26. A process according to claim 25 wherein the diazine is a pyrimidine or a pyrazine.
27. A N-(hetero)aryl-S,S-dialkyl-, diaryl- or alkylarylsulphilimine compound when produced by the process as claimed in any of claims 21 to 26.
28. Any one of the compounds: 6-chloro-2-pyrazinyl-S,S-diphenylsulphilimine, 3 nitro-2-pyridinyl-S,S-diphenylsulphilimine, 2-nitro-5-chlorophenyl-S,Sdiphenylsulphilimine, 2-chloro-3-nitro4-pyridinyl-S,S-diphenylsulphilimine, 2 pyrazinyl-S, S-diphenyisulphilimine, 2-(n-propoxy)4-chloro-6-(1,3,5-triazinyl)-S,S- diphenylsulphilimine, 2,3,5,6-tetrachloro4-pyridinyl-S,S-diphenylsulphilimine, 3,4,5,6 tetrachloro-2-pyridinyl-S, S-diphenylsulphilimine, 2-(n-propoxy)-4,6-(1,3,5-triazinyl)- bis-S,S-diphenylsulphilimine, 2,4-bis-(n-propoxy)-6-( 1,3,5-triazinyl)- diphenylsulphilimine, 6-chloro-4-pyrimidinyl-S,S-diphenylsulphilimine, 5-nitro-2pyridinyl-S, S-diphenylsulphilimine, 4-chloro-2-pyrimidinyl-S, S-diphenylsulphilimine, 2,6-dichloro-4-pyrimidinyl-S,S-diphenylsulphilimine, 4,6-dichloro-2-pyrimidinyl-S,Sdiphenylsulphilimine, 2,5 ,6-trichloro4-pyrimidinyl-S,S-diphenylsulphilimine, 4,5,6 trichloro-2-pyrimidinyl-S, 5-diphenylsulphilimine and 2,3,5,6-tetrafluoro-4-pyridinyl- S, S-diphenylsulphilimine.
29. An N-alkali metal salt of an S,S-dialkyl-, diaryl- or alkylarylsulphilimine.
30. A salt according to claim 29 where the alkali metal is lithium.
31. A salt according to claim 29 or claim 30 wherein the sulphilimine is dimethylsulphilimine.
32. A salt according to claim 29 or claim 30 wherein the sulphilimine is diphenylsulphilimine.
33. A method for preparing the N-alkali metal salt of claim 29 which comprises reacting the corresponding sulphilimine with a reagent selected from the group comprising alkyllithiums with chain length 1 to 4 carbon atoms, alkali metal hydrides and alkali metal nitrogenous bases.
34. A method according to claim 33 wherein the reagent is n-butyllithium.
35. A method according to claim 33 wherein the reagent is the N,Ndi(isopropyl)amide or the N,N-bis(trimethylsilyl)amide of lithium, sodium or potassium.
36. A method according to any of claims 33 to 35 wherein the reaction is carried out in an aprotic solvent.
37. A method according to claim 36 wherein the aprotic solvent is 1,4-dioxane, dimethoxyethane, diethyleneglycol dimethyl ether or tetrahydrofuran.
Priority Applications (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB9525789A GB2308119A (en) | 1995-12-16 | 1995-12-16 | Nitration of aromatic compounds sulphilimines |
IL12496096A IL124960A (en) | 1995-12-16 | 1996-12-09 | Nitration of electron deficient carbocyclic and heterocyclic aromatic compounds |
GB9811567A GB2322857B (en) | 1995-12-16 | 1996-12-09 | Nitration of aromatic compounds |
PCT/GB1996/003020 WO1997022590A1 (en) | 1995-12-16 | 1996-12-09 | Nitration of aromatic compounds |
CZ19981867A CZ291529B6 (en) | 1995-12-16 | 1996-12-09 | Process and intermediates for the nitration of carbocyclic and heterocyclic aromatic compounds |
EP96941744A EP1021412A1 (en) | 1995-12-16 | 1996-12-09 | Nitration of aromatic compounds |
CA002240644A CA2240644A1 (en) | 1995-12-16 | 1996-12-09 | Nitration of aromatic compounds |
ZA9610559A ZA9610559B (en) | 1995-12-16 | 1996-12-13 | Nitration of aromatic compounds |
NO982753A NO309524B1 (en) | 1995-12-16 | 1998-06-15 | Nitration of aromatic compounds |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB9525789A GB2308119A (en) | 1995-12-16 | 1995-12-16 | Nitration of aromatic compounds sulphilimines |
Publications (2)
Publication Number | Publication Date |
---|---|
GB9525789D0 GB9525789D0 (en) | 1996-02-14 |
GB2308119A true GB2308119A (en) | 1997-06-18 |
Family
ID=10785573
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB9525789A Withdrawn GB2308119A (en) | 1995-12-16 | 1995-12-16 | Nitration of aromatic compounds sulphilimines |
GB9811567A Expired - Fee Related GB2322857B (en) | 1995-12-16 | 1996-12-09 | Nitration of aromatic compounds |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB9811567A Expired - Fee Related GB2322857B (en) | 1995-12-16 | 1996-12-09 | Nitration of aromatic compounds |
Country Status (8)
Country | Link |
---|---|
EP (1) | EP1021412A1 (en) |
CA (1) | CA2240644A1 (en) |
CZ (1) | CZ291529B6 (en) |
GB (2) | GB2308119A (en) |
IL (1) | IL124960A (en) |
NO (1) | NO309524B1 (en) |
WO (1) | WO1997022590A1 (en) |
ZA (1) | ZA9610559B (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20130008334A1 (en) * | 2010-03-16 | 2013-01-10 | Qinetiq Limited | Mems detonator |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110330432B (en) * | 2019-07-29 | 2022-07-29 | 重庆医药高等专科学校 | Synthetic method of aromatic nitro compound |
-
1995
- 1995-12-16 GB GB9525789A patent/GB2308119A/en not_active Withdrawn
-
1996
- 1996-12-09 GB GB9811567A patent/GB2322857B/en not_active Expired - Fee Related
- 1996-12-09 IL IL12496096A patent/IL124960A/en not_active IP Right Cessation
- 1996-12-09 CZ CZ19981867A patent/CZ291529B6/en not_active IP Right Cessation
- 1996-12-09 EP EP96941744A patent/EP1021412A1/en not_active Withdrawn
- 1996-12-09 CA CA002240644A patent/CA2240644A1/en not_active Abandoned
- 1996-12-09 WO PCT/GB1996/003020 patent/WO1997022590A1/en not_active Application Discontinuation
- 1996-12-13 ZA ZA9610559A patent/ZA9610559B/en unknown
-
1998
- 1998-06-15 NO NO982753A patent/NO309524B1/en unknown
Non-Patent Citations (2)
Title |
---|
CA 113:6241 & J.Org. Chem. (1990), 55(12), 3755-61 * |
CA 66:50516 & Spectrochim. Acta (1967), 23A(1), 89-108 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20130008334A1 (en) * | 2010-03-16 | 2013-01-10 | Qinetiq Limited | Mems detonator |
Also Published As
Publication number | Publication date |
---|---|
GB2322857A (en) | 1998-09-09 |
WO1997022590A1 (en) | 1997-06-26 |
NO982753D0 (en) | 1998-06-15 |
GB2322857B (en) | 2000-03-29 |
GB9811567D0 (en) | 1998-07-29 |
EP1021412A1 (en) | 2000-07-26 |
CZ186798A3 (en) | 1998-10-14 |
IL124960A0 (en) | 1999-01-26 |
CZ291529B6 (en) | 2003-03-12 |
CA2240644A1 (en) | 1997-06-26 |
NO982753L (en) | 1998-08-17 |
NO309524B1 (en) | 2001-02-12 |
ZA9610559B (en) | 1997-06-24 |
IL124960A (en) | 2003-02-12 |
GB9525789D0 (en) | 1996-02-14 |
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