CN103992265B - Two three bromo 1,3-bis-pyridine alkali propane and preparation method thereof, using method, recovery method and application - Google Patents

Two three bromo 1,3-bis-pyridine alkali propane and preparation method thereof, using method, recovery method and application Download PDF

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CN103992265B
CN103992265B CN201410235515.XA CN201410235515A CN103992265B CN 103992265 B CN103992265 B CN 103992265B CN 201410235515 A CN201410235515 A CN 201410235515A CN 103992265 B CN103992265 B CN 103992265B
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lsothiocyanates
propane
bis
bromo
reaction
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CN103992265A (en
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孟歌
童静
师建华
田超
乃比·努斯热提
卜羽思
杨凌飞
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Xian Jiaotong University
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Abstract

Two three bromos 1,3-bis-pyridine alkali propane and preparation method thereof, using method, recovery method and application, by 1,3-bipyridyl bromo propane water dissolution, then add Potassium Bromide, after Potassium Bromide dissolves, add the potassium hydrogen persulfate composite salts aqueous solution again and be made into settled solution, then at-10 DEG C ~ 0 DEG C stirring reaction until separate out solid, isolate solid, obtain two three bromo 1,3-bis-pyridine alkali propane; This product can prepare lsothiocyanates, aromatic series thiocarbamide or Acetanilide.Preparation method's raw material of the present invention is easy to get, mild condition, and reaction process is simple to operate; Two three bromo 1,3-bis-pyridine alkali propane can not only use as brominated reagent, can also use, improve reaction efficiency simultaneously as organic synthesis intermediate, reclaim convenient and can recycle.

Description

Two three bromo 1,3-bis-pyridine alkali propane and preparation method thereof, using method, recovery method and application
Technical field
The invention belongs to organic synthesis reagent field, be specifically related to a kind of two three bromo 1,3-bis-pyridine alkali propane and preparation method thereof, using method, recovery method and application.
Background technology
Traditional bromo method comprises direct bromo or indirect bromo uses elemental bromine.But evaporate very fast under simple substance bromine normal temperature, its steam has strong asphyxiating pungent taste, thus make it use, store and transport very inconvenient.The investigator in organic synthesis field is finding the compound replacing simple substance bromine product to have bromination ability always, as N-bromo-succinimide, and C5H6Br2N2O2.These agent structure belong to organic amide class, and character is insoluble in water, are that the purification difficulty of product increases, and are difficult to reclaim, so a class has excellent water miscible novel brominated reagent---and tribromide just arises at the historic moment.Nineteen twenty-three, after there is single tribromide tetramethyl-tribromide ammonium first, people start to pay close attention to organic tribromide ammonium gradually, have occurred again phenyl tribromide ammonium, cetyl trimethyl tribromide ammonium, tetrabutyl tribromide ammonium, pyridine hydrobromide salt perbromide etc. subsequently.The appearance of these novel agents certainly will to its physico-chemical property, and the aspects such as effect purposes are studied.Originally, OATB uses as brominated reagent, finds that its effect is not only confined to bromo afterwards, and it can also be used for being oxidized, catalyzing and synthesizing heterocycle, catalytic alcohol or phenol, amine, mercaptan, polyvalent alcohol acetylize, protection aldehyde ketone etc.The purposes of lsothiocyanates and derivative thereof is extremely extensive, can be used as the synthetic intermediate of agricultural chemicals and medicine, for the synthesis of polytype heterogeneous ring compound, and these heterogeneous ring compound great majority have biological activity, and agricultural chemicals is used as antibacterial, Insecticides (tech) & Herbicides (tech) etc.; Pharmaceutically for the treatment of the disease such as antisepsis and anti-inflammation and cancer, also to can be used for measuring in peptides and proteins amino-acid sequence and as fluorescein-labelled thing.Very important in synthesizing heterocyclic compounds, methyl-chloroformates etc. are the most frequently used cheap reagent preparing lsothiocyanates, but due to the high toxicity of such reagent, and equipment is corrosive, produce and transport on security and convenience issue and produce the reasons such as a large amount of acid waste gas, its use is restricted day by day.Therefore, the various reagent preparing lsothiocyanates constantly occurs in recent years, particularly the technique study of commercial introduction can receive attention gradually.
The one of earlier report is two replaces dibromide, by India scholar design and synthesis (Kavala as the conversion reagent DPTBE in organic synthesis, V., Naik, S., Patel, B.K., Anewrecyclableditribromidereagentforefficientbromination undersolventfreecondition.J.Org.Chem.2005,70 (11), 4267-4271.), but the required intermediate DPDBE of the preparation process of this reagent is liquid, and be very difficult to purification process, bring a lot of trouble can to especially the recovery of this reagent.
Summary of the invention
The object of the present invention is to provide a kind of two three bromo 1,3-bis-pyridine alkali propane and preparation method thereof, using method, recovery method and application, the method raw material is easy to get, mild condition, and reaction process is simple to operate; Products obtained therefrom can not only use as brominated reagent, can also use, improve reaction efficiency simultaneously as organic synthesis intermediate, reclaims convenient and can recycle.
In order to achieve the above object, two three bromo 1, the 3-bis-pyridine alkali propane structures of the present invention have disubstituted pyridinium salt structure, and chemical structural formula is:
Two three bromos 1, the preparation method of 3-bis-pyridine alkali propane, by 1,3-bipyridyl bromo propane water dissolution, then add Potassium Bromide, after Potassium Bromide dissolves, add the potassium hydrogen persulfate composite salts aqueous solution again and be made into settled solution, then at-10 DEG C ~ 0 DEG C stirring reaction until separate out solid, isolate solid, obtain two three bromo 1,3-bis-pyridine alkali propane; Wherein, in 1,3-bipyridyl bromo propane, the potassium hydrogen persulfate composite salts aqueous solution, the mol ratio of potassium hydrogen persulfate composite salts and Potassium Bromide is 1:1:(4 ~ 5).
The described process isolating precipitation is: after reaction terminates, and is left standstill, then filters out solid by the reaction solution obtained, use recrystallized from acetonitrile by after solid drying in ice bath.
The preparation method of 1,3-described bipyridyl bromo propane is the one in following three kinds of methods:
First method: back flow reaction after pyridine and the mixing of 1,3-dibromopropane, until generate solid, by solid washed with ether, is obtained 1,3-bipyridyl bromo propane; Wherein, the mol ratio of pyridine and 1,3-dibromopropane is (2 ~ 2.5): 1;
Second method: by 1, after 3 dibromopropanes, pyridine and methanol mixed in normal temperature to reflux temperature under reaction until separate out solid, then suction filtration, the solid obtained with washed with diethylether suction filtration, obtains 1,3-bipyridyl bromo propane; Wherein, the mol ratio of pyridine and 1,3-dibromopropane is (2 ~ 2.5): 1;
The third method: by 1, after the mixing of 3 dibromopropanes, pyridine and ethanol, stirring at normal temperature, until separate out solid, then suction filtration, with washed with diethylether, obtains 1,3-bipyridyl bromo propane; Wherein, the mol ratio of pyridine and 1,3-dibromopropane is (2 ~ 2.5): 1.
Two three bromo 1,3-bis-pyridine alkali propane are preparing the application as conversion reagent in lsothiocyanates, aromatic series thiocarbamide or Acetanilide.
Described lsothiocyanates is aromatic series lsothiocyanates or aliphatics lsothiocyanates, and aromatic series lsothiocyanates is PITC, halogenophenyl lsothiocyanates, 4-aminomethyl phenyl lsothiocyanates, 4-tert-butyl-phenyl lsothiocyanates, 4-p-methoxy-phenyl lsothiocyanates, 3-trifluoromethyl lsothiocyanates, 3-ethynyl phenyl lsothiocyanates, 3-nitro phenylisothiocyanate, 2-trifluoromethyl lsothiocyanates, 2, 6-3,5-dimethylphenyl lsothiocyanates, 3-chloro-4-aminomethyl phenyl lsothiocyanates, 3-isopropyl phenyl lsothiocyanates, 2-methyl-3-chlorophenyl isothiocyanate or 3-trifluoromethyl-4-chlorophenyl lsothiocyanates, aliphatics lsothiocyanates is methylisothiocyanate ethyl ester, ethyl ethyl mustard oil, propyl group ethyl mustard oil or tert.-butyl isothiocyanate.
Described halogenophenyl lsothiocyanates is 4-chlorophenyl isothiocyanate, 4-bromophenyl lsothiocyanates, 4-fluorophenylisothiocyanate, 3-chlorophenyl isothiocyanate, 3-bromophenyl lsothiocyanates, 2-chlorophenyl isothiocyanate, 2-fluorophenylisothiocyanate, 2,6-dichlorophenyl lsothiocyanates or 3,4-difluorophenyl lsothiocyanates.
Described aromatic series phenylthiourea is phenylthiourea, 4-aminomethyl phenyl thiocarbamide or 3-nitrophenyl thiocarbamide.
The using method of two three bromo 1,3-bis-pyridine alkali propane, comprises the one in following three kinds of using method:
The first using method: by organic ammonium salt, acetonitrile and triethylamine-5 DEG C ~ 0 DEG C stirring, two three bromos 1 are added in whipping process, 3-bis-pyridine alkali propane, is incubated 30 ~ 60min after adding at-5 DEG C ~ 0 DEG C, then rises to stirring at room temperature reaction, complete by TLC detection reaction in reaction process, then suction filtration, the filter cake obtained reclaims, and the filtrate obtained concentrates, filtrate after concentrated is carried out column chromatography, obtains lsothiocyanates; Wherein, the mol ratio of organic ammonium salt, triethylamine and two three bromo 1,3-bis-pyridine alkali propane is 1:(2 ~ 3): 0.5; And organic ammonium salt is the ammonium salt of primary aromatic amine or the ammonium salt of Armeen;
The second using method: by organic ammonium salt, water and acetonitrile-5 DEG C ~ 0 DEG C stirring, the ammoniacal liquor that mass concentration is 25% is dripped in the process stirred, reaction 0.5h-1h, then under the stirring of-5 DEG C ~ 0 DEG C, add two three bromos 1,3-bis-pyridine alkali propane, at-5 DEG C ~ 0 DEG C, 1h ~ 1.5h is incubated after adding, then room temperature is risen to and stirring reaction, complete by TLC detection reaction in reaction process, then suction filtration, the filter cake obtained reclaims, and the filtrate obtained concentrates, filtrate after concentrated is carried out column chromatography, obtains aromatic series thiocarbamide; Wherein, the NH in organic ammonium salt, ammoniacal liquor 3and the mol ratio of two three bromo 1,3-bis-pyridine alkali propane is 1:(1 ~ 2): 0.5, organic ammonium salt is the triethylene diammonium salt of the triethylammonium salts of aniline, the triethylammonium salts of 4-monomethylaniline or 3-N-methyl-p-nitroaniline.
The third using method: by aniline, two three bromos 1, back flow reaction after the mixing of 3-bis-pyridine alkali propane, diacetyl oxide and acetonitrile, complete by TLC detection reaction in reaction process, then suction filtration, the filter cake obtained reclaims, the filtrate obtained concentrates, and the filtrate after concentrated is carried out column chromatography, obtains Acetanilide; Wherein, the mol ratio of aniline, two three bromo 1,3-bis-pyridine alkali propane and diacetyl oxide is 1:(0.05 ~ 0.1): 1.
A kind of two three bromos 1, the recovery method of 3-bis-pyridine alkali propane, based on using method, be dissolved in water in the filter cake reclaimed, then add KBr, stirring makes KBr dissolve, then add the potassium hydrogen persulfate composite salts aqueous solution, then at-10 DEG C ~ 0 DEG C stirring reaction until separate out solid, isolate solid, obtain two three bromo 1,3-bis-pyridine alkali propane; Wherein, the mol ratio of 1,3-bipyridyl bromo propane, the potassium hydrogen persulfate composite salts aqueous solution and Potassium Bromide is 1:1:(4 ~ 5).
Compared with prior art, beneficial effect of the present invention is:
Two three bromo 1,3-bis-pyridine alkali propane that the present invention proposes, as a kind of new brominated reagent, can not only be used for bromo-reaction, but also can as conversion reagent for the preparation of lsothiocyanates, aromatic series thiocarbamide or Acetanilide.Preparing lsothiocyanates, in the process of aromatic series thiocarbamide or Acetanilide, two three bromos 1, 3-bis-pyridine alkali propane is reduced into 1 in the reaction, 3-bipyridyl bromo propane (DPDBP), due to DPDBP well water-soluble that reduction generates, fat-soluble difference, and the DPTBP generated is fat-soluble good, poorly water-soluble, can settle out from water so reaction terminates rear DPDBP, then by filtering, collect filter cake just DPDBP to be reclaimed out, then DPDBP is oxidized through potassium hydrogen persulfate composite salts, regenerate two three bromos 1, 3-bis-pyridine alkali propane, achieve two three bromos 1, recycling of 3-bis-pyridine alkali propane, be conducive to environmental protection.
In addition, two three bromo 1, the 3-bis-pyridine alkali propane of the present invention add Potassium Bromide by after 1,3-bipyridyl bromo propane water dissolution, adds that potassium hydrogen persulfate composite salts reactant aqueous solution obtains after Potassium Bromide dissolves again.Therefore, by two three bromos 1,3-bis-pyridine alkali propane is applied in the process preparing lsothiocyanates, aromatic series thiocarbamide or Acetanilide, and the actual reagent be consumed is not bromine, but Potassium Bromide and potassium hydrogen persulfate composite salts (chemical formula: 2KHSO 5kHSO 4k 2sO 4, also known as Oxone), therefore, the present invention avoids using the larger reagent of toxicity as methyl-chloroformate, bromine; Oxygen in Oxone can provide a kind of highly effective non-oxychlorination effect, aftertreatment is very safe, the synthesis industrialization of this oxygenant, commercially available reagent, cheap, be widely used in acidic oxidation agent, sterilizing agent, oil, plating, weaving print, dye auxiliary agent, papermaking bleaching, wool shrinkproof, noble metal refinement, the numerous areas that polyreaction initiation etc. are relevant, and Oxone stable in properties, the plurality of advantages such as process is simple, has nontoxic, inexpensive.Meanwhile, preparation and the use procedure Raw of two three bromo 1, the 3-bis-pyridine alkali propane of the present invention are easy to get, and mild condition, reaction process is simple to operate, and agents useful for same is cheaply easy to get, and can also improve reaction efficiency.
Embodiment
Two three bromo 1,3-bis-pyridine alkali propane structures provided by the present invention have disubstituted pyridinium salt structure, and chemical structural formula is such as formula 1) shown in:
(1) embodiment of the preparation method of two three bromo 1,3-bis-pyridine alkali propane
Embodiment 1:
1) preparation of 1,3-bipyridyl bromo propane:
By the pyridine of 100mmol and 1 of 50.0mmol, 3-dibromopropane adds in the mono-neck bottle of 100mL, heating reflux reaction 0.5 hour, the internal temperature now reacted reaches the boiling point (bp:167 DEG C) of 1,3-dibromopropane, react complete and obtain the large blocks of solid of shallow white, by solid washed with ether twice, each ether consumption is 20.0mL, obtains 1,3-bipyridyl bromo propane (productive rate 99.0%), reaction scheme is shown in formula 2);
2) preparation of two three bromo 1,3-bis-pyridine alkali propane:
By 1 of 50mmol, 3-bipyridyl bromo propane 50mL water dissolution, then Potassium Bromide is added, after 225mmol Potassium Bromide dissolves, adding 50mmol mass concentration is again that the potassium hydrogen persulfate composite salts aqueous solution of 0.2mol/L is made into settled solution, then at 0 DEG C of stirring reaction 10min, now separate out solid, the reaction solution obtained is left standstill in ice bath, then suction filtration, the solid gone out by suction filtration is again dry in vacuum drier, and use 2mL recrystallized from acetonitrile, obtain two three bromos 1, 3-bis-pyridine alkali propane (productive rate 80%), reaction scheme is shown in formula 3), wherein, the mol ratio of 1,3-bipyridyl bromo propane, the potassium hydrogen persulfate composite salts aqueous solution and Potassium Bromide is 1:1:5, dissolves 1, the 3-bipyridyl bromo propane of 1mol in every premium on currency, two three bromo 1,3-bis-pyridine alkali propane prepared by the present embodiment: m.p.74 ~ 75 DEG C .UV (CH3CN) 254nm. 1hNMR (400MHz, DMSO) δ 9.09 (d, 4H, 2,6-pyridyl-CH), 8.66 (t, 2H, 4-pyridyl-CH), 8.22 (t, 4H, 3,5-pyridyl-CH), 4.73 (t, 4H, CH 2cH 2cH 2), 2.69 ~ 2.64 (m, 2H, CH 2cH 2cH 2), 13cNMR (100MHz, DMSO) δ 145.98 (2C, 3-Cofpyridine), 145.45 (4C, 2,6-Cofpyridine), 128.55 (4C, 3,5-Cofpyridine), 58.0 (2C, CH 2cH 2cH 2), 32.23 (1C, CH 2cH 2cH 2).
Embodiment 2:
1) preparation of 1,3-bipyridyl bromo propane:
By the pyridine of 125mmol and 1 of 50.0mmol, 3-dibromopropane adds in the mono-neck bottle of 100mL, heating reflux reaction 1.0 hours, the internal temperature now reacted reaches the boiling point (bp:167 DEG C) of 1,3-dibromopropane, reacts complete and obtains the large blocks of solid of shallow white, by solid washed with ether twice, each ether consumption is 20.0mL, obtains 1,3-bipyridyl bromo propane; Reaction scheme is shown in formula 2);
2) preparation of two three bromo 1,3-bis-pyridine alkali propane:
By 1 of 50mmol, 3-bipyridyl bromo propane 50mL water dissolution, then Potassium Bromide is added, after 200mmol Potassium Bromide dissolves, adding 50mmol mass concentration is again that the potassium hydrogen persulfate composite salts aqueous solution of 0.2mol/L is made into settled solution, then at-5 DEG C of stirring reaction 10min, now separate out solid, the reaction solution obtained is left standstill in ice bath, then suction filtration, then the solid gone out by suction filtration is dry in vacuum drier, and use 2mL recrystallized from acetonitrile, obtain two three bromo 1,3-bis-pyridine alkali propane, reaction scheme is shown in formula 3).
Embodiment 3:
1) preparation of 1,3-bipyridyl bromo propane:
By the pyridine of 120mmol and 1 of 50.0mmol, 3-dibromopropane adds in the mono-neck bottle of 100mL, heating reflux reaction 0.8 hour, the internal temperature now reacted reaches the boiling point (bp:167 DEG C) of 1,3-dibromopropane, reacts complete and obtains the large blocks of solid of shallow white, by solid washed with ether twice, each ether consumption is 20.0mL, obtains 1,3-bipyridyl bromo propane; Reaction scheme is shown in formula 2);
2) preparation of two three bromo 1,3-bis-pyridine alkali propane:
By 1 of 50mmol, 3-bipyridyl bromo propane 50mL water dissolution, then Potassium Bromide is added, after 250mmol Potassium Bromide dissolves, adding 50mmol mass concentration is again that the potassium hydrogen persulfate composite salts aqueous solution of 0.2mol/L is made into settled solution, then at-10 DEG C of stirring reaction 10min, now separate out solid, the reaction solution obtained is left standstill in ice bath, then suction filtration, then the solid gone out by suction filtration is dry in vacuum drier, and use 2mL recrystallized from acetonitrile, obtain two three bromo 1,3-bis-pyridine alkali propane.Reaction scheme is shown in formula 3).
Embodiment 4:
1) preparation of 1,3-bipyridyl bromo propane (DPDBP):
By 50.0mmol1,3-dibromopropane mixes in the methyl alcohol of 2.00mL with 100mmol pyridine, backflow 24h, now separate out solid, then suction filtration, the filter cake ether obtained is washed three times, each ether consumption is 5.00mL, obtain white solid i.e. 1,3-bipyridyl bromo propane (73.3%), reaction scheme is shown in formula 2).
2) identical with embodiment 3 step.
Embodiment 5:
1) preparation of 1,3-bipyridyl bromo propane (DPDBP):
By 50.0mmol1,3-dibromopropane mixes in the methyl alcohol of 2.00mL with 125mmol pyridine, backflow 24h, now separate out solid, then suction filtration, the filter cake ether obtained is washed three times, each ether consumption is 5.00mL, obtain white solid i.e. 1,3-bipyridyl bromo propane (73.3%), reaction scheme is shown in formula 2).
2) identical with embodiment 3 step.
Embodiment 6:
1) preparation of 1,3-bipyridyl bromo propane (DPDBP):
50.0mmol1,3-dibromopropane is mixed in the methyl alcohol of 2.00mL with 120mmol pyridine, backflow 24h, now separate out solid, then suction filtration, the filter cake ether obtained is washed three times, each ether consumption is 5.00mL, obtains white solid i.e. 1,3-bipyridyl bromo propane; Reaction scheme is shown in formula 2).
2) identical with embodiment 3 step.
Embodiment 7:
1) preparation of 1,3-bipyridyl bromo propane (DPDBP):
By 50.0mmol1,3-dibromopropane mixes in 2.00mL ethanol with 100mmol pyridine, solid is separated out after stirring at normal temperature 24h, then suction filtration, divide the solid washing suction filtration and obtain for three times with ether, the consumption of each ether is 5.00mL, obtain white solid, i.e. 1,3-bipyridyl bromo propane (11.2g, 32.9%); Reaction scheme is shown in formula 2).
2) identical with embodiment 3 step.
Embodiment 8:
1) preparation of 1,3-bipyridyl bromo propane (DPDBP):
By 50.0mmol1,3-dibromopropane mixes in 2.00mL ethanol with 120mmol pyridine, solid is separated out after 35 DEG C of stirring 24h, then suction filtration, divide the solid washing suction filtration and obtain for three times with ether, the consumption of each ether is 5.00mL, obtains white solid, i.e. 1,3-bipyridyl bromo propane; Reaction scheme is shown in formula 2).
2) identical with embodiment 3 step.
Embodiment 9:
1) preparation of 1,3-bipyridyl bromo propane (DPDBP):
By 50.0mmol1,3-dibromopropane mixes in 2.00mL ethanol with 125mmol pyridine, solid is separated out after stirring at normal temperature 24h, then suction filtration, divide the solid washing suction filtration and obtain for three times with ether, the consumption of each ether is 5.00mL, obtains white solid, i.e. 1,3-bipyridyl bromo propane; Reaction scheme is shown in formula 2).
2) identical with embodiment 3 step.
(2) two three bromos 1,3-bis-pyridine alkali propane is preparing the application as conversion reagent in lsothiocyanates, aromatic series thiocarbamide or Acetanilide, two three bromos 1 of its concrete use, 3-bis-pyridine alkali propane is prepared shown in the following embodiment of method of lsothiocyanates, aromatic series thiocarbamide or Acetanilide, and following embodiment knowledge is explanation of the invention instead of restriction.
Note 1: embodiment 1 to embodiment 26 is for preparing the method for lsothiocyanates, and embodiment 25 to embodiment is to embodiment 27 for preparing the method for phenylthiourea, and embodiment 28 is for preparing the method for Acetanilide.
Note 2: the preparation method of the intermediate adopted in embodiment 1 to embodiment 27 is reference preparation (OgataM, WatanabeTawaraK.Phenylisothiocyanatederivativesandtheirp roduction [P] .US4248869.1981-2-3.).
Embodiment 1:
1) 25.0mmol aniline, 50mmol triethylamine are joined in 100mL eggplant-shape bottle, then add 15.0mL ether, and at room temperature start stirring, drip the CS of 3.80mL simultaneously 2, then stirring at room temperature 10h, suction filtration, the solid obtained by suction filtration dries naturally, obtains yellow powder phenyl dithiocarbonic acid triethylammonium salts (6.04g, 89.0%); Reaction scheme is shown in formula 4).
2) 2.00mmol phenyl dithiocarbonic acid triethylammonium salts is joined 50mL eggplant-shape bottle, add 8.00mL acetonitrile successively, 4.0mmol triethylamine, then 0 DEG C of stirring, add two three bromos 1 of 1.00mmol in whipping process in batches, 3-bis-pyridine alkali propane, at 0 DEG C, 30min is incubated after adding, rise to stirring at room temperature reaction again, with TLC (thin-layer chromatography in reaction process, developping agent: sherwood oil) detection reaction is complete, react 16 constantly little, TLC detects discovery and reacts completely, then suction filtration, (recovery method is see two three bromos 1 in the filter cake recovery obtained, the recovery embodiment of 3-bis-pyridine alkali propane), the filtrate obtained concentrates, filtrate after concentrated is carried out column chromatography, obtain the PITC (0.135g of yellow oil, 50.0%), reaction scheme is shown in formula 5), IR (KBr): 2061 (ν n=C=S) cm -1, 1594cm -1, 1489 [ν c=C (phenyl ring carbon skeleton)] cm -1), 1hNMR (400MHz, CDCl 3) δ: 7.21-7.37 (m, 5H, Ar-H). 13cNMR (100MHz, CDCl 3) δ: 125.8 (2C), 127.4,129.6 (2C), 131.3,135.3 (N=C=S). wherein, the silica gel adopted during column chromatography is 300-400 order, and eluent is sherwood oil.
Embodiment 2:
1) by embodiment 1 step 1) in aniline replace with 4-monomethylaniline, other conditions are identical, the 4-aminomethyl phenyl dithiocarbonic acid triethylammonium salts (4.20g, 59.1%) of obtained yellow powder, and reaction scheme is shown in formula 6).
2) 0.666mmol4-aminomethyl phenyl dithiocarbonic acid triethylammonium salts is joined 50mL eggplant-shape bottle, add 8.00mL acetonitrile successively, 1.50mmol triethylamine, then 0 DEG C of stirring, add two three bromos 1 of 0.333mmol in whipping process in batches, 3-bis-pyridine alkali propane, at 0 DEG C, 30min is incubated after adding, rise to stirring at room temperature reaction again, with TLC (thin-layer chromatography in reaction process, developping agent: sherwood oil) detection reaction is complete, react 16 constantly little, TLC detects discovery and reacts completely, then suction filtration, (recovery method is see two three bromos 1 in the filter cake recovery obtained, the recovery embodiment of 3-bis-pyridine alkali propane), the filtrate obtained concentrates, filtrate after concentrated is carried out column chromatography, obtain the PITC ((0.089g of white solid thing, 90.0%), reaction scheme is shown in formula 7), m.p.=25-26 DEG C, (document: 25-26 DEG C) (Prakash, L., JournalofFluorineChemistry1988,41 (3), 303-310).IR (KBr): 2010 (ν n=C=S) cm -1, 1500 [ν c=C (phenyl ring carbon skeleton)] cm -1); Wherein, the silica gel adopted during column chromatography is 300-400 order, and eluent is sherwood oil.
Embodiment 3:
1) by embodiment 1 step 1) in aniline replace with 4-anisidine, other conditions are identical, the 4-p-methoxy-phenyl dithiocarbonic acid triethylammonium salts (4.00g, 53.3%) of obtained yellow powder; Reaction scheme is shown in formula 8).
2) by embodiment 2 step 2) in 4-aminomethyl phenyl dithiocarbonic acid triethylammonium salts replace with 4-p-methoxy-phenyl dithiocarbonic acid triethylammonium salts, the add-on 1.5mmol of triethylamine is replaced with 1.33mmol, other conditions are identical, prepare white solid 4-p-methoxy-phenyl lsothiocyanates (0.100g, 90.9%); Reaction scheme is shown in formula 9).M.p.=21-22 DEG C, (document: 21-22 DEG C) (Cymerman-Craig, J.; AustralianJournalofChemistry1960,13,341-346).(KBr): 2110 (ν n=C=S) cm -1, 1504 [ν c=C (phenyl ring carbon skeleton)] cm -1, 2930 (ν c-H (methyl)) cm -1, 1250 (ν= c-O-C) cm -1.
Embodiment 4:
1) by embodiment 1 step 1) in 25.0mmol aniline replace with 22.4mmol4-chloroaniline, other conditions are identical, obtain the 4-chloro-phenyl-dithiocarbonic acid triethylammonium salts (5.88g, 77.2%) of yellow powder; Reaction scheme is shown in formula 10).
2) by embodiment 2 step 2) in 4-aminomethyl phenyl dithiocarbonic acid triethylammonium salts replace with 4-chloro-phenyl-dithiocarbonic acid triethylammonium salts, other conditions are identical, obtain the 4-chlorophenyl isothiocyanate (0.110g, 98.2%) of white solid; Reaction scheme is shown in formula 11), m.p.=41-42 DEG C, (document: 42 DEG C) (Bian, Gaofeng; Phosphorus, SulfurandSiliconandtheRelatedElements2007,182 (3), 503-508).IR (KBr): 2044 (ν n=C=S) cm -1, 1504cm -1, 1482 [ν c=C (phenyl ring carbon frame)] cm -1, 1hNMR (400MHz, CDCl 3) δ: 7.12-7.18 (m, 2H), 7.31-7.36 (m, 2H).
Embodiment 5:
1) by embodiment 1 step 1) in aniline replace with 2-chloroaniline, other conditions are identical, obtain the 2-chloro-phenyl-dithiocarbonic acid triethylammonium salts (1.46g, 19.1%) of yellow powder; Reaction scheme is shown in formula 12).
2) by embodiment 1 step 2) in phenyl dithiocarbonic acid triethylammonium salts replace with 2-chloro-phenyl-dithiocarbonic acid triethylammonium salts, other conditions are identical, preparation yellow oil 2-chlorophenyl isothiocyanate (0.230 g, 67.8%); Reaction scheme is shown in formula 13), IR (KBr): 2050 (ν n=C=S) cm -1, 1474cm -1, 1442 [ν c=C (phenyl ring carbon skeleton)] cm -1.
Embodiment 6:
1) 40.0mmol3-chloroaniline, 100mmol triethylamine are joined in 100mL eggplant-shape bottle, then add 20.0mL ether, and at room temperature start stirring, drip 7.5mLCS simultaneously 2, then stirring at room temperature 10h, suction filtration, the solid that suction filtration obtains dries naturally, obtains yellow powder 3-chloro-phenyl-dithiocarbonic acid triethylammonium salts (8.11g, 66.8%); Reaction scheme is shown in formula 14).
2) by embodiment 1 step 2) in phenyl dithiocarbonic acid triethylammonium salts replace with 3-chloro-phenyl-dithiocarbonic acid triethylammonium salts, other conditions are identical, preparation yellow oil 3-chlorophenyl isothiocyanate (0.257g, 80.3%); Reaction scheme is shown in formula 15), IR (KBr): 2040 (ν n=C=S) cm -1, 1588cm -1, 1574 [ν c=C (phenyl ring carbon skeleton)] cm -1.
Embodiment 7:
1) by embodiment 1 step 1) in aniline replace with 4-bromaniline, other conditions are identical, prepare the 4-bromophenyl dithiocarbonic acid triethylammonium salts (7.37g, 84.4%) of yellow powder; Reaction scheme is shown in formula 16).
2) by embodiment 1 step 2) in phenyl dithiocarbonic acid triethylammonium salts replace with 4-bromophenyl dithiocarbonic acid triethylammonium salts, other conditions are identical, obtain off-white color solid 4-bromophenyl lsothiocyanates (0.371g, 86.7%); Reaction scheme is shown in formula 17); M.p.=51 ~ 52 DEG C, (document: 51-53 DEG C (Kokorev, G.I.; ZhurnalObshcheiKhimii1988,58 (4), 829-836).IR (KBr): 2043 (ν n=C=S) cm -1, 1581cm -1, 1479 [ν c=C (phenyl ring carbon skeleton)] cm -1.
Embodiment 8:
1) by embodiment 1 step 1) in aniline to replace with other conditions of 3-bromaniline identical, prepare the 3-bromophenyl dithiocarbonic acid triethylammonium salts (7.07g, 81.0%) of yellow powder; Reaction scheme is shown in formula 18).
2) by embodiment 1 step 2) in phenyl dithiocarbonic acid triethylammonium salts replace with 3-bromophenyl dithiocarbonic acid triethylammonium salts, other conditions are identical, preparation yellow oil 3-bromophenyl lsothiocyanates (0.420g, 98.1%); Reaction scheme is shown in formula 19).IR (KBr): 2010 (ν n=C=S) cm -1, 1600cm -1, 1450 [ν c=C (phenyl ring carbon skeleton)] cm -1.
Embodiment 9:
1) by embodiment 1 step 1) in aniline replace with 4-fluoroaniline, other conditions are identical, obtain the 4-fluorophenyl dithiocarbonic acid triethylammonium salts (6.84g, 94.8%) of yellow powder; Reaction scheme is shown in formula 20).
2) by embodiment 1 step 2) in phenyl dithiocarbonic acid triethylammonium salts replace with 4-fluorophenyl dithiocarbonic acid triethylammonium salts, other conditions are identical, prepare yellow oil 4-fluorophenylisothiocyanate (0.442g, 43.8%); Reaction scheme is shown in formula 21); IR (KBr): 2922 (ν n=C=S) cm -1, 1465cm -1, 1458 [ν c=c (phenyl ring carbon skeleton)] cm -1.
Embodiment 10:
1) by embodiment 1 step 1) in aniline replace with 2-fluoroaniline, other conditions are identical, prepare the 2-fluorophenyl dithiocarbonic acid triethylammonium salts (3.93g, 45.7%) of yellow powder; Reaction scheme is shown in formula 22).
2) by embodiment 1 step 2) in phenyl dithiocarbonic acid triethylammonium salts replace with 2-fluorophenyl dithiocarbonic acid triethylammonium salts, other conditions are identical, preparation yellow oil 2-fluorophenylisothiocyanate (0.171g, 55.9%), reaction scheme is shown in formula 23); IR (KBr): 2000 (ν n=C=S) cm -1, 1500cm -1, 1450 [ν c=C (phenyl ring carbon skeleton)] cm -1.
Embodiment 11:
1) by embodiment 1 step 1) in aniline replace with 3-5-trifluoromethylaniline, other conditions are identical, prepare yellow powder 3-fluorophenyl dithiocarbonic acid triethylammonium salts (4.01g, 47.4%); Reaction scheme is shown in formula 24).
2) by embodiment 1 step 2) in phenyl dithiocarbonic acid triethylammonium salts replace with yellow oil 3-trifluoromethyl lsothiocyanates (0.430g, 65.4%), reaction scheme is shown in formula 25); IR (KBr): 2359 (ν n=C=S) cm -1, 1650cm -1, 1400 [ν c=C (phenyl ring carbon skeleton)] cm -1.
Embodiment 12:
1) the 3-acetylenylaniline of 14.2mmol, 28.0mmol triethylamine are joined in 50mL eggplant-shape bottle, then add 8.00mL ether, and at room temperature start stirring, drip 2.13mL, CS simultaneously 2, then stirring at room temperature 10h, suction filtration, the solid that suction filtration obtains dries naturally, and obtain lark powder 3-ethynyl phenyl dithiocarbonic acid triethylammonium salts (4.05g, 97.1%), reaction scheme is shown in formula 26).
2) by embodiment 1 step 2) in phenyl dithiocarbonic acid triethylammonium salts replace with 3-ethynyl phenyl dithiocarbonic acid triethylammonium salts, other conditions are identical, obtain yellow oil 3-ethynyl phenyl lsothiocyanates (0.153g, 47.8%), reaction scheme is shown in formula 27), IR (KBr): 2010 (ν n=C=S) cm -1, 1650cm -1, 1400 [ν c=C (phenyl ring carbon skeleton)] cm -1, 3295 (ν ≡ CH) cm -1.
Embodiment 13:
1) 30.0mmol2-5-trifluoromethylaniline, 10.0mmol triethylene diamine are joined in 50mL eggplant-shape bottle, then add 15.0mL toluene, and at room temperature start stirring, drip 1.80mLCS simultaneously 2, then stirring at room temperature 10h, suction filtration, the solid that suction filtration obtains dries to obtain yellow powder 2-trifluoromethyl dithiocarbonic acid triethylammonium salts (1.32g, 12.6%) naturally, and reaction scheme is shown in formula 28).
2) 3.88mmol2-trifluoromethyl lsothiocyanates is joined 50mL eggplant-shape bottle, add 16.0mL acetonitrile successively, 7.90mmol triethylamine, then 0 DEG C of stirring, add two three bromos 1 of 2.00mmol in whipping process in batches, 3-bis-pyridine alkali propane, at 0 DEG C, 30min is incubated after adding, rise to stirring at room temperature reaction again, with TLC (thin-layer chromatography in reaction process, developping agent: sherwood oil) detection reaction is complete, react 16 constantly little, TLC detects discovery and reacts completely, then suction filtration, (recovery method is see two three bromos 1 in the filter cake recovery obtained, the recovery embodiment of 3-bis-pyridine alkali propane), the filtrate obtained concentrates, filtrate after concentrated is carried out column chromatography, obtain the 2-trifluoromethyl lsothiocyanates (0.063g of yellow oil, 7.75%), reaction scheme is shown in formula 29).IR (KBr): 2028 (ν n=C=S) cm -1, 1579cm -1, 1471 [ν c=C (phenyl ring carbon skeleton)] cm -1.
Embodiment 14:
1) by embodiment 13 step 1) in 2-5-trifluoromethylaniline replace with 2,6-DCA, other conditions are identical, prepare 2,6-dichlorophenyl dithiocarbonic acid triethylammonium salts (14,1.82g of yellow powder, 17.3%), reaction scheme is shown in formula 30).
2) by embodiment 1 step 2) in phenyl dithiocarbonic acid triethylammonium salts replace with 2,6-dichlorophenyl dithiocarbonic acid triethylammonium salts, other conditions are identical, obtain yellow solid 2,6-dichlorophenyl lsothiocyanates (0.129g, 29.5%), reaction scheme is shown in formula 31), m.p.=40-41 DEG C, (document: 42-43 DEG C) (FR, 15282491968) IR (KBr): 2358 (ν n=C=S) cm -1, 1600cm -1, 1500 [ν c=C (phenyl ring carbon skeleton)] cm -1.
Embodiment 15:
1) by embodiment 1 step 1) in aniline replace with 4-tertiary butyl aniline, other conditions are identical, and obtain yellow powder 4-tertiary butyl dithiocarbonic acid triethylammonium salts (7.51g, 97%), reaction scheme is shown in formula 32).
2) by embodiment 1 step 2) in phenyl dithiocarbonic acid triethylammonium salts replace with 4-tertiary butyl dithiocarbonic acid triethylammonium salts, other conditions are identical, prepare white solid 4-tert-butyl-phenyl lsothiocyanates (0.314g, 82%), reaction scheme is shown in formula 33).M.p.32-35 DEG C of (document: 38 DEG C) (Quast, Helmut; EuropeanJournalofOrganicChemistry2009, (23), P3940-3952, S3940/1-S3940/57) IR (KBr): 2100 (ν n=C=S) cm -1, 1500cm -1, 1400 [ν c=C (phenyl ring carbon frame)] cm -1, 2980 [ν c-H (methyl)] cm -1, 1380cm -1, 1370 [ν c-C (tertiary butyl)] cm -1.
Embodiment 16:
1) by embodiment 1 step 1) in aniline replace with 2,6-xylidine, other conditions are identical, and prepare yellow powder 2,6-3,5-dimethylphenyl dithiocarbonic acid triethylammonium salts (7.07g, 95%), reaction scheme is shown in formula 34).
2) by 4.00mmol2, 6-3,5-dimethylphenyl dithiocarbonic acid triethylammonium salts joins 50mL eggplant-shape bottle, add 16.0mL acetonitrile successively, 8.0mmol triethylamine, then 0 DEG C of stirring, add two three bromos 1 of 2.00mmol in whipping process in batches, 3-bis-pyridine alkali propane, at 0 DEG C, 30min is incubated after adding, rise to stirring at room temperature reaction again, with TLC (thin-layer chromatography in reaction process, developping agent: sherwood oil) detection reaction is complete, react 16 constantly little, TLC detects discovery and reacts completely, then suction filtration, (recovery method is see two three bromos 1 in the filter cake recovery obtained, the recovery embodiment of 3-bis-pyridine alkali propane), the filtrate obtained concentrates, filtrate after concentrated is carried out column chromatography, obtain light yellow solid 2, 6-3,5-dimethylphenyl lsothiocyanates (0.601g, 92%), reaction scheme is shown in formula 35).IR (KBr): 2100 (ν n=C=S) cm -1, 1600cm -1, 1495 [ν c=C (phenyl ring carbon skeleton)] cm -1, 2900 [ν c-H (methyl)] cm -1.
Embodiment 17:
1) by embodiment 1 step 1) in aniline replace with 3,4-difluoroaniline, other conditions are identical, and obtain yellow powder 3,4-difluoro dithiocarbonic acid triethylammonium salts (6.32g, 83%), reaction scheme is shown in formula 36).
2) by embodiment 1 step 2) in phenyl dithiocarbonic acid triethylammonium salts replace with 3,4-difluoro dithiocarbonic acid triethylammonium salts, other conditions are identical, prepare pale yellowish oil liquid 3,4-difluorophenyl lsothiocyanates (0.095g, 27%), reaction scheme is shown in formula 37).IR (KBr): 2300 (ν n=C=S) cm -1, 1600cm -1, 1500 [ν c=C (phenyl ring carbon skeleton)] cm -1.
Embodiment 18:
1) chloro-for 30.0mmol3-4-monomethylaniline, 9.26mmol triethylamine are joined in 50mL eggplant-shape bottle, then add 15.0mL ether, and at room temperature start stirring, drip 7.5mLCS simultaneously 2, then stirring at room temperature 10h, suction filtration, the solid that suction filtration obtains dries to obtain yellow powder 3-chloro-4-aminomethyl phenyl dithiocarbonic acid triethylammonium salts (7.90g, 99%) naturally, and reaction scheme is shown in formula 38).
2) by embodiment 1 step 2) in phenyl dithiocarbonic acid triethylammonium salts replace with 3-chloro-4-aminomethyl phenyl dithiocarbonic acid triethylene diammonium salt, other conditions are identical, prepare pale yellowish oil liquid 3-chloro-4-aminomethyl phenyl lsothiocyanates (0.255g, 69%), reaction scheme is shown in formula 39).IR (KBr): 2100 (ν n=C=S) cm -1, 1600cm -1, 1500 [ν c=C (phenyl ring carbon skeleton)] cm -1, 2910 [ν c-H (methyl)] cm -1.
Embodiment 19:
1) 30.0mmol3-isopropyl aniline, 60.0mmol triethylamine are joined in 100mL eggplant-shape bottle, then add 15.0mL ether, and at room temperature start stirring, drip 3.80mLCS simultaneously 2, then stirring at room temperature 10h, suction filtration, the solid that suction filtration obtains dries naturally, and obtain yellow powder 3-isopropyl phenyl dithiocarbonic acid triethylammonium salts (7.41g, 95%), reaction scheme is shown in formula 40).
2) by embodiment 1 step 2) in phenyl dithiocarbonic acid triethylammonium salts replace with 3-isopropyl phenyl dithiocarbonic acid triethylammonium salts, other conditions are identical, prepare pale yellowish oil liquid 3-isopropyl phenyl lsothiocyanates (0.239g, 68%), reaction scheme is shown in formula 41).IR (KBr): 2100 (ν n=C=S) cm -1, 1600cm -1, 1550 [ν c=C (phenyl ring carbon skeleton)] cm -1, 2980 [ν c-H (methyl)] cm -1.
Embodiment 20:
1) 30.0mmol2-methyl-3-chloroaniline, 9.26mmol triethylene diamine are joined in 50mL eggplant-shape bottle, then add 15.0mL toluene, and at room temperature start stirring, drip the CS of 1.80mL simultaneously 2then stirring at room temperature 10h, suction filtration, the solid that suction filtration obtains dries to obtain yellow powder 2-methyl-3-chloro-phenyl-dithiocarbonic acid triethylene diammonium salt (4.48g, 68.2%) naturally, and reaction scheme is shown in formula 42).
2) by embodiment 1 step 2) in phenyl dithiocarbonic acid triethylammonium salts replace with 2-methyl-3-chloro-phenyl-dithiocarbonic acid triethylene diammonium salt, other conditions are identical, preparation yellow oil 2-methyl-3-chlorophenyl isothiocyanate (0.179g, 49%), reaction scheme is shown in formula 43) 1hNMR (400MHz, CDCl 3) δ: 7.01 (m, 1H, Ar-H), 7.41 (t, 1H, Ar-H), 7.71 (m, 1H, Ar-H). 13cNMR (100MHz, CDCl 3) δ: 125.8 (2C), 127.4,129.6 (2C), 131.3,135.3 (N=C=S).
Embodiment 21:
1) by embodiment 20 step 1) in 2-methyl-3-chloroaniline replace with 3-trifluoromethyl-4-chlorobenzene, other conditions are identical, prepare yellow powder 3-trifluoromethyl-4-chlorophenyl dithiocarbonic acid triethylene diammonium salt (4.28g, 37.2%), reaction scheme is shown in formula 44).
2) by embodiment 1 step 2) in embodiment 1 step 2) in phenyl dithiocarbonic acid triethylammonium salts replace with 3-trifluoromethyl-4-chlorophenyl dithiocarbonic acid triethylene diammonium salt, other conditions are identical, preparation light yellow oil 3-trifluoromethyl-4-chlorophenyl lsothiocyanates (0.294g, 53.7%), reaction scheme is shown in formula 45) 1hNMR (400MHz, CDCl 3) δ: 7.31-7.34 (m, 1H), 7.42-7.54 (m, 2H).
Embodiment 22:
1) 15.0mmol3-N-methyl-p-nitroaniline, 4.62mmol triethylene diamine are joined in 50mL eggplant-shape bottle, then add 10.0mL toluene, and at room temperature start stirring, drip 0.90mLCS simultaneously 2, then stirring at room temperature 10h, suction filtration, the solid that suction filtration obtains dries naturally, and obtain obtaining yellow powder 3-nitrophenyl dithiocarbonic acid triethylene diammonium salt (3.15g, 64.7%), reaction scheme is shown in formula 46).
2) by embodiment 1 step 2) in phenyl dithiocarbonic acid triethylammonium salts replace with 3-nitrophenyl dithiocarbonic acid triethylene diammonium salt, other conditions are identical, prepare white solid 3-nitro phenylisothiocyanate (0.295g, 82%), reaction scheme is shown in formula 47).M.p.54-55 DEG C of (document: 50-60 DEG C) (Sah, PeterP.T.; JournaloftheChineseChemicalSociety (Peking) 1934,2,153-158).
Embodiment 23:
1) by embodiment 1 step 1) in aniline replace with methylamine, other conditions are identical, and prepare methyl dithiocarbonic acid triethylammonium salts (4.78g, 91.7%), reaction scheme is shown in 48)
2) by embodiment 1 step 2) in phenyl dithiocarbonic acid triethylammonium salts replace with methyl dithiocarbonic acid triethylammonium salts, other conditions are identical, prepare Trapex (0.095g, 65%). 1hNMR (CDCl 3) δ: 3.32 (s, 3H). reaction scheme is shown in formula 49)
Embodiment 24:
1) by embodiment 1) step 1) in aniline replace with ethamine, other conditions are identical, and prepare ethyl dithiocarbonic acid triethylammonium salts (4.78g, 91.7%), reaction scheme is shown in formula 50).
2) by embodiment 1 step 2) in phenyl dithiocarbonic acid triethylammonium salts replace with ethyl dithiocarbonic acid triethylammonium salts, other conditions are identical, prepare ethyl mustard oil (0.115g, 66%). 1hNMR (CDCl 3) δ: 3.58 (q, 2H), 1.42 (t, 3H). reaction scheme is shown in formula 51).
Embodiment 25:
1) by embodiment 1) step 1) in aniline replace with propylamine, other conditions are identical, and prepare propyl disulfide for triethylammonium formate salt (4.78g, 91.7%), reaction scheme is shown in formula 52).
2) by embodiment 1) step 2) in phenyl dithiocarbonic acid triethylammonium salts replace with propyl disulfide for triethylammonium formate salt, other conditions are identical, prepare propyl isothiocyanide (0.154g, 76.2%). 1hNMR (CDCl 3) δ: 3.44 (t, 2H) .1.70 (s, 2H), 1.01 (t, 3H). reaction scheme is shown in formula 53).
Embodiment 26:
1) by embodiment 1) step 1) in aniline replace with tert-butylamine, other conditions are identical, and prepare tertiary butyl dithiocarbonic acid triethylammonium salts (5.51g, 82.5%), reaction scheme is shown in formula 54).
2) by embodiment 1) step 2) in phenyl dithiocarbonic acid triethylammonium salts replace with tertiary butyl dithiocarbonic acid triethylammonium salts, other conditions are identical, prepare tert.-butyl isothiocyanate (0.152g, 66%)., 2077 (ν n=C=S) cm -1, 2982 [ν c-H (methyl)] cm -1. 1hNMR (400MHz, CDCl 3) δ: 1.44 (s, 9H, t-Bu), reaction scheme is shown in formula 55).
Embodiment 27:
1) 100mmol aniline, 200mmol triethylamine are joined in 250mL eggplant-shape bottle, then add 100mL ether, at room temperature start stirring, drip 15.2mLCS simultaneously 2, then stirring at room temperature 10h, suction filtration, the solid that suction filtration obtains dries naturally, and obtain yellow powder phenyl dithiocarbonic acid triethylammonium salts (26.7g, 98.0%), reaction scheme is shown in formula 56).
2) 20mmol phenyl dithiocarbonic acid triethylammonium salts is joined in 250mL eggplant-shape bottle, add 60mL water, 15mL acetonitrile successively, 0 DEG C of stirring, in whipping process, drip the ammoniacal liquor that mass concentration is 25%, and NH in ammoniacal liquor 3be 1:1 with the mol ratio of phenyl dithiocarbonic acid triethylammonium salts, reaction 0.5h, then under the stirring of 0 DEG C, add two three bromos 1 of 10.0mmol in batches, 3-bis-pyridine alkali propane, at 0 DEG C of reaction 1h after adding, then room temperature reaction 5h is risen to, with TLC detection reaction complete (developping agent of TLC is volume ratio is the sherwood oil of 2:1 and the mixed solvent of ethyl acetate) in reaction process, then suction filtration, the filter cake obtained reclaims, the filtrate obtained concentrates, filtrate after concentrated is carried out column chromatography, obtain white solid phenylthiourea (1.29g, 42%), reaction scheme is shown in formula 57).M.p.156-158 DEG C of (document: 153-154 DEG C) (Katritzky, A.R.; Kirichenko, N.; Rogovoy, B.V.; Kister, J.; Tao, H., Synthesis2004,2004 (11), 1799-1805.)
Embodiment 28:
1) 50mmol4-monomethylaniline, 100mmol triethylamine are joined in 100mL eggplant-shape bottle, then add 30mL ether, at room temperature start stirring, drip 7.6mLCS simultaneously 2, then stirring at room temperature 10h, suction filtration, the solid that suction filtration obtains dries naturally, and obtain yellow powder 4-aminomethyl phenyl dithiocarbonic acid triethylammonium salts (13.9g, 98%), reaction scheme is shown in formula 58).
2) by embodiment 27 step 2) in phenyl dithiocarbonic acid triethylammonium salts replace with 4-aminomethyl phenyl dithiocarbonic acid triethylammonium salts, other conditions are identical, obtain white solid 4-aminomethyl phenyl thiocarbamide (0.210g, 6.0%).M.p.188-189 DEG C of (document: 188 DEG C) (Tisler, M.; Vrbaski, Z., J.Org.Chem.1960,25 (5), 770-773.), reaction scheme is shown in formula 59).
Embodiment 29:
1) 15.0mmol3-N-methyl-p-nitroaniline, 4.62mmol triethylene diamine are joined in 50mL eggplant-shape bottle, then add 10.0mL toluene, at room temperature start stirring, drip 0.90mLCS simultaneously 2, then stirring at room temperature 10h, suction filtration, the solid that suction filtration obtains dries naturally, and obtain yellow powder 3-nitrophenyl dithiocarbonic acid triethylene diammonium salt (3.15g, 64.7%), reaction scheme is shown in formula 60).
2) 1.00mmol3-nitrophenyl dithiocarbonic acid triethylene diammonium salt is joined in 50mL eggplant-shape bottle, add 3.00mL water, 2.00mL acetonitrile successively, 0 DEG C of stirring, in whipping process, drip the ammoniacal liquor that mass concentration is 25%, and NH in ammoniacal liquor 3be 1:2 with the mol ratio of phenyl dithiocarbonic acid triethylammonium salts, reaction 0.5h, then under the stirring of 0 DEG C, add two three bromos 1 of 0.50mmol in batches, 3-bis-pyridine alkali propane, at 0 DEG C of reaction 1h after adding, then room temperature reaction 5h is risen to, with TLC detection reaction complete (developping agent of TLC is volume ratio is the sherwood oil of 2:1 and the mixed solvent of ethyl acetate) in reaction process, then suction filtration, the filter cake obtained reclaims, the filtrate obtained concentrates, filtrate after concentrated is carried out column chromatography, obtain white solid 3-nitrophenyl thiocarbamide (0.053g, 27%), reaction scheme is shown in formula 61).M.p.150-151 DEG C of (document: 153-154 DEG C) (Hay, M.P.; Turcotte, S.; Flanagan, J.U.; Bonnet, M.; Chan, D.A.; Sutphin, P.D.; Nguyen, P.; Giaccia, A.J.; Denny, W.A., JournalofMedicinalChemistry2009,53 (2), 787-797.)
Embodiment 30:
1) with the step 1 of embodiment 29) identical;
2) by embodiment 30 step 2) in 0 DEG C replace with-2 DEG C; By NH in ammoniacal liquor 3be that 1:2 replaces to NH in ammoniacal liquor with the mol ratio of phenyl dithiocarbonic acid triethylammonium salts 3be 1:1.8 with the mol ratio of phenyl dithiocarbonic acid triethylammonium salts, other conditions are identical.
Embodiment 31:
1) with the step 1 of embodiment 29) identical;
2) by embodiment 29 step 2) in 0 DEG C replace with-5 DEG C; By NH in ammoniacal liquor 3be that 1:2 replaces to NH in ammoniacal liquor with the mol ratio of phenyl dithiocarbonic acid triethylammonium salts 3be 1:1.2 with the mol ratio of phenyl dithiocarbonic acid triethylammonium salts, other conditions are identical.
Embodiment 32:
10.0mmol aniline is joined 50mL eggplant type bottle, add two three bromos 1 of 0.500mmol more successively, 3-bis-pyridine alkali propane, 10.0mL acetonitrile and 10.0mmol diacetyl oxide, then 90 DEG C of backflow 2h are warming up to, with TLC detection reaction complete (developping agent is volume ratio is the sherwood oil of 3:1 and the mixed solvent of ethyl acetate) in reaction process, then suction filtration, the filter cake obtained reclaims, the filtrate obtained concentrates, filtrate after concentrated is carried out column chromatography, obtain white solid Acetanilide (1.02g, 76%), reaction scheme is shown in formula 62).M.p.114-115 DEG C of (document: 114-115 DEG C) (Buchi, G.; JournaloftheAmericanChemicalSociety1956, V78, P689-90). wherein, the silica gel that column chromatography adopts is 300-400 order, and the eluent of column chromatography is volume ratio is the sherwood oil of 3:1 and the mixed solvent of ethyl acetate.
Embodiment 33: two for 0.500mmol in embodiment 32 three bromo 1,3-bis-pyridine alkali propane are replaced with two three bromo 1, the 3-bis-pyridine alkali propane of 1.00mmol and replaces, other conditions are identical.
Embodiment 33: two for 0.500mmol in embodiment 32 three bromo 1,3-bis-pyridine alkali propane are replaced with two three bromo 1, the 3-bis-pyridine alkali propane of 0.8mmol and replaces, other conditions are identical.
(3) recovery method of two three bromo 1,3-bis-pyridine alkali propane
No matter prepare lsothiocyanates, prepare aromatic series thiocarbamide or prepare Acetanilide, the volume filter cake that final suction filtration obtains is pale precipitation, this pale precipitation is two three bromos 1, reduzate 1,3-bipyridyl bromo propane (DPDBP) of 3-bis-pyridine alkali propane (DPTBP).
By 1,3-bipyridyl bromo propane drying is placed in eggplant-shape bottle also by water dissolution, add KBr again, stirring makes KBr dissolve, then add the potassium hydrogen persulfate composite salts aqueous solution, then at-10 DEG C ~ 0 DEG C stirring reaction until separate out solid, isolate solid, obtain two three bromo 1,3-bis-pyridine alkali propane; Wherein, the mol ratio of 1,3-bipyridyl bromo propane, the potassium hydrogen persulfate composite salts aqueous solution and Potassium Bromide is 1:1:(4 ~ 5), reaction scheme is shown in formula 66).
Two three bromos 1 prepared by the present invention, 3-bis-pyridine alkali propane fusing point is relatively high, stable in properties, can standing storage, the by product generated by this novel agent in reaction process can directly be precipitated out from reaction system, can be separated by simple filtration washing with principal product, operating process is simplified greatly, purity and the productive rate of product lsothiocyanates increase, and can reduce the preparation cost of lsothiocyanates, enhance competitiveness.On the other hand, after separation the by product of gained again by the reagent Oxone that is easy to get with business and Potassium Bromide by simple water react, again this reagent of recovery is transformed due to water-soluble poor, again can from aqueous phase precipitation out, by this reagent can be obtained again after simple filtration washing, the conversion that this reagent should prepared by this recovery method can be used successfully to again, and can repeatedly apply mechanically by circulation and stress, experiment proves, the preparation that reagent after repeatedly reclaiming still can be used successfully to, the reagent that removal process consumes is all nontoxic.

Claims (6)

1. pair three bromo 1,3-bis-pyridine alkali propane, it is characterized in that, its structure has disubstituted pyridinium salt structure, and chemical structural formula is:
2. two three bromo 1,3-bis-pyridine alkali propane according to claim 1 are preparing the application as conversion reagent in lsothiocyanates, aromatic series thiocarbamide or Acetanilide.
3. application according to claim 2, is characterized in that, described lsothiocyanates is aromatic series lsothiocyanates or aliphatics lsothiocyanates, and aromatic series lsothiocyanates is PITC, halogenophenyl lsothiocyanates, 4-aminomethyl phenyl lsothiocyanates, 4-tert-butyl-phenyl lsothiocyanates, 4-p-methoxy-phenyl lsothiocyanates, 3-trifluoromethyl lsothiocyanates, 3-ethynyl phenyl lsothiocyanates, 3-nitro phenylisothiocyanate, 2-trifluoromethyl lsothiocyanates, 2, 6-3,5-dimethylphenyl lsothiocyanates, 3-chloro-4-aminomethyl phenyl lsothiocyanates, 3-isopropyl phenyl lsothiocyanates, 2-methyl-3-chlorophenyl isothiocyanate or 3-trifluoromethyl-4-chlorophenyl lsothiocyanates, aliphatics lsothiocyanates is Trapex, ethyl mustard oil, propyl isothiocyanide or tert.-butyl isothiocyanate.
4. application according to claim 2, it is characterized in that: described halogenophenyl lsothiocyanates is 4-chlorophenyl isothiocyanate, 4-bromophenyl lsothiocyanates, 4-fluorophenylisothiocyanate, 3-chlorophenyl isothiocyanate, 3-bromophenyl lsothiocyanates, 2-chlorophenyl isothiocyanate, 2-fluorophenylisothiocyanate, 2,6-dichlorophenyl lsothiocyanates or 3,4-difluorophenyl lsothiocyanates.
5. application according to claim 2, is characterized in that: described aromatic series phenylthiourea is phenylthiourea, 4-aminomethyl phenyl thiocarbamide or 3-nitrophenyl thiocarbamide.
6. the using method of two three bromo 1,3-bis-pyridine alkali propane as claimed in claim 1, is characterized in that, comprise the one in following three kinds of using method:
The first using method: by organic ammonium salt, acetonitrile and triethylamine-5 DEG C ~ 0 DEG C stirring, two three bromos 1 are added in whipping process, 3-bis-pyridine alkali propane, is incubated 30 ~ 60min after adding at-5 DEG C ~ 0 DEG C, then rises to stirring at room temperature reaction, complete by TLC detection reaction in reaction process, then suction filtration, the filter cake obtained reclaims, and the filtrate obtained concentrates, filtrate after concentrated is carried out column chromatography, obtains lsothiocyanates; Wherein, the mol ratio of organic ammonium salt, triethylamine and two three bromo 1,3-bis-pyridine alkali propane is 1:(2 ~ 3): 0.5; And organic ammonium salt is the ammonium salt of primary aromatic amine or the ammonium salt of Armeen;
The second using method: by organic ammonium salt, water and acetonitrile-5 DEG C ~ 0 DEG C stirring, the ammoniacal liquor that mass concentration is 25% is dripped in the process stirred, reaction 0.5h-1h, then under the stirring of-5 DEG C ~ 0 DEG C, add two three bromos 1,3-bis-pyridine alkali propane, at-5 DEG C ~ 0 DEG C, 1h ~ 1.5h is incubated after adding, then room temperature is risen to and stirring reaction, complete by TLC detection reaction in reaction process, then suction filtration, the filter cake obtained reclaims, and the filtrate obtained concentrates, filtrate after concentrated is carried out column chromatography, obtains aromatic series thiocarbamide; Wherein, the NH in organic ammonium salt, ammoniacal liquor 3and the mol ratio of two three bromo 1,3-bis-pyridine alkali propane is 1:(1 ~ 2): 0.5, organic ammonium salt is the triethylene diammonium salt of the triethylammonium salts of aniline, the triethylammonium salts of 4-monomethylaniline or 3-N-methyl-p-nitroaniline;
The third using method: by aniline, two three bromos 1, back flow reaction after the mixing of 3-bis-pyridine alkali propane, diacetyl oxide and acetonitrile, complete by TLC detection reaction in reaction process, then suction filtration, the filter cake obtained reclaims, the filtrate obtained concentrates, and the filtrate after concentrated is carried out column chromatography, obtains Acetanilide; Wherein, the mol ratio of aniline, two three bromo 1,3-bis-pyridine alkali propane and diacetyl oxide is 1:(0.05 ~ 0.1): 1.
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