CN103483242A - Preparation methods of 4-(2'-pyridyl)benzyl hydrazine and its intermediate - Google Patents
Preparation methods of 4-(2'-pyridyl)benzyl hydrazine and its intermediate Download PDFInfo
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- CN103483242A CN103483242A CN201210197328.8A CN201210197328A CN103483242A CN 103483242 A CN103483242 A CN 103483242A CN 201210197328 A CN201210197328 A CN 201210197328A CN 103483242 A CN103483242 A CN 103483242A
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- 0 *Cc(cc1)ccc1-c1ncccc1 Chemical compound *Cc(cc1)ccc1-c1ncccc1 0.000 description 3
- CCMRFUCSFRRPNT-UHFFFAOYSA-N N#Cc(cc1)ccc1-c1ncccc1 Chemical compound N#Cc(cc1)ccc1-c1ncccc1 CCMRFUCSFRRPNT-UHFFFAOYSA-N 0.000 description 2
- NMLYGLCBSFKJFI-UHFFFAOYSA-N O=Cc(cc1)ccc1-c1ncccc1 Chemical compound O=Cc(cc1)ccc1-c1ncccc1 NMLYGLCBSFKJFI-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/42—Radicals substituted by singly-bound nitrogen atoms having hetero atoms attached to the substituent nitrogen atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
- C07D213/46—Oxygen atoms
- C07D213/48—Aldehydo radicals
Abstract
The invention relates to a preparation method of 4-(2'-pyridyl)benzyl hydrazine (I). The method comprises the following steps: reducing a cyan group of an initial raw material 4-(2'-pyridyl)benzonitrile (II) in the presence of hydrazine (IV) to obtain aldehyde hydrazone of formula (III), and reducing the aldehyde hydrazone of formula (III) to form the above compound of formula (I). R in the formula (IV) can be a C1-4 alkoxycarbonyl group, a C1-4 alkanoyl group or a benzoyl group; and preferably, R is a tert-butyloxycarbonyl group, the cyan group in the formula II can be reduced through Raney nickel-catalyzed hydrogenation to obtain the aldehyde hydrazone of formula (III), and the aldehyde hydrazone of formula (III) can be reduced through palladium-carbon-catalyzed transfer hydrogenation to form the 4-(2'-pyridyl)benzyl hydrazine (I). The invention also provides a preparation method of the 4-(2'-pyridyl)benzyl hydrazine (I) through a one-pot process, and a preparation method of 4-(2'-pyridyl)benzaldehyde (V). The preparation methods have the advantages of ingenious design, cheap and easily available initial raw material, simple process flow, no need of a Grid reaction or an expensive catalyst, and substantially reduced production cost, is in favor of the industrialized production, and is suitable for the large-scale popularized application.
Description
Technical field
The present invention relates to anti-AIDS drug Reyataz R intermediate technical field, particularly 4-(2 '-pyridyl) benzyl hydrazine technical field, specifically refer to the preparation method of 4-(2 '-pyridyl) benzyl hydrazine and intermediate thereof.
Background technology
Reyataz R (Atazanavir) is novel azepine peptides HIV-1-1 proteinase inhibitor, is the active drug for the treatment of acquired immune deficiency syndrome (AIDS), and 2-[4-(2 '-pyridyl) benzyl] hydrazine (I) is the important intermediate of synthetic Reyataz R.
The synthetic method of relevant 4-(2 '-pyridyl) benzyl hydrazine (I), known preparation method is with 4-(2 '-pyridyl) phenyl aldehyde (V) and the condensation of hydrazine carboxylic acid's tert-butyl ester, again the resulting aldehyde hydrazone of condensation reaction (III) reduction is obtained to target product, but the technical process of starting raw material 4-(2 '-pyridyl) phenyl aldehyde (V) of the method is long, high (the J.Med.Chem of preparation cost, 1998,41 (18), 3387-3401, US2002022730A1, US6765097B1 and WO2010149356A1, shown in synthetic route 1)
Particularly linked reaction need to adopt Ni (DPPP)
2, Pd (PPh
3)
4etc. expensive catalyzer, and grignard reaction has relatively high expectations to technological operation, is unfavorable for suitability for industrialized production.
Therefore, need to provide a kind of 4-(2 '-pyridyl) preparation method of benzyl hydrazine, its technical process is simple, and does not need to adopt grignard reaction and expensive catalyst, can reduce production costs greatly, is conducive to suitability for industrialized production.
Summary of the invention
The objective of the invention is to have overcome above-mentioned shortcoming of the prior art, the preparation method of a kind of 4-(2 '-pyridyl) benzyl hydrazine and intermediate thereof is provided, design ingenious, starting raw material cheaply is easy to get, technical process is simple, and does not need to adopt grignard reaction and expensive catalyst, can greatly reduce production costs, be conducive to suitability for industrialized production, be suitable for large-scale promotion application.
To achieve these goals, in a first aspect of the present invention, the method of a kind of 4-of preparation (2 '-pyridyl) benzyl hydrazine (I) is provided, be characterized in, 4-(2 '-pyridyl) cyanophenyl (II) of take is starting raw material, under hydrazine (IV) exists, first the cyano reduction of formula (II) is obtained to the aldehyde hydrazone of formula (III), then the reduction of the aldehyde hydrazone of formula (III) is obtained to formula (I) compound
Wherein, R is C
1-4carbalkoxy, C
1-4alkyloyl or benzoyl, in particular for tertbutyloxycarbonyl.
Preferably, by raney ni catalysis hydrogenation, the cyano reduction of formula (II) is obtained to the aldehyde hydrazone of formula (III).
Better, add acetic acid in the reaction of raney ni catalysis hydrogenation.
Preferably, by palladium carbon catalytic transfer hydrogenation, the aldehyde hydrazone of formula (III) is reduced to 4-(2 '-pyridyl) benzyl hydrazine (I).
Better, take formic acid or the ammonium formiate transfer hydrogenation reagent in palladium carbon catalytic transfer hydrogenation.
In a second aspect of the present invention, the method of a kind of 4-of preparation (2 '-pyridyl) benzyl hydrazine (I) is provided, be characterized in, 4-(2 '-pyridyl) cyanophenyl (II) of take is starting raw material, under hydrazine (IV) exists, the diazanyl thing that is formula (I) by the cyano group direct-reduction of formula (II), thus one kettle way prepares 4-(2 '-pyridyl) benzyl hydrazine (I)
Wherein, R is C
1-4carbalkoxy, C
1-4alkyloyl or benzoyl, in particular for tertbutyloxycarbonyl.
Preferably, the diazanyl thing that is formula (I) by palladium carbon catalytic hydrogenation by the cyano group direct-reduction of formula (II).
In a third aspect of the present invention, the method of a kind of 4-of preparation (2 '-pyridyl) phenyl aldehyde (V) is provided, has been characterized in, 4-(2 '-pyridyl) cyanophenyl (II) of take is starting raw material, become aldehyde to obtain formula (V) compound the cyano reduction of formula (II)
Preferably, by raney ni catalysis hydrogenation, the cyano reduction of formula (II) is become to the aldehyde of formula (V).
Better, add aqueous acetic acid in raney ni catalysis hydrogenation.
Beneficial effect of the present invention specifically is:
1, the method for the 4-of preparation of the present invention (2 '-pyridyl) benzyl hydrazine (I) is that to take 4-(2 '-pyridyl) cyanophenyl (II) be starting raw material, under hydrazine (IV) exists, first the cyano reduction of formula (II) is obtained to the aldehyde hydrazone of formula (III), then the reduction of the aldehyde hydrazone of formula (III) is obtained to formula (I) compound, design ingenious, starting raw material cheaply is easy to get, technical process is simple, and do not need to adopt grignard reaction and expensive catalyst, can greatly reduce production costs, be conducive to suitability for industrialized production, be suitable for large-scale promotion application.
2, the method for the 4-of preparation of the present invention (2 '-pyridyl) benzyl hydrazine (I) is that to take 4-(2 '-pyridyl) cyanophenyl (II) be starting raw material, under hydrazine (IV) exists, the diazanyl thing that is formula (I) by the cyano group direct-reduction of formula (II), thereby one kettle way prepares 4-(2 '-pyridyl) benzyl hydrazine (I), design ingenious, starting raw material cheaply is easy to get, technical process is simple, and do not need to adopt grignard reaction and expensive catalyst, can greatly reduce production costs, be conducive to suitability for industrialized production, be suitable for large-scale promotion application.
Embodiment
Cyano compound, under the existence of hydrazine, can be reduced into the aldehyde hydrazone by selecting suitable processing condition.The industrial raw material of 4-(2 '-pyridyl) cyanophenyl for cheaply being easy to get, industrial preparation method, generally to adopt 4-(2 '-pyridyl) benzoic ether to transform, perhaps with 2-chloropyridine and 4-6-chlorophenyl nitrile, coupling under cheap nickel catalyzator catalysis obtains, as adopt Nickel Bromide-2,2 '-dipyridyl catalytic coupling.
It is starting raw material that the inventor be take 4-(2 '-pyridyl) cyanophenyl (II) cheaply be easy to get, under hydrazine (IV) exists, first the cyano reduction of formula (II) is obtained to the aldehyde hydrazone of formula (III), then the reduction of the aldehyde hydrazone of formula (III) is obtained to 4-(2 '-pyridyl) benzyl hydrazine (I) (synthetic route 2).
Wherein, R is C
1-4carbalkoxy, C
1-4alkyloyl or benzoyl, particularly tertbutyloxycarbonyl.
Formula (IV) compound is selected from the hydrazine with protecting group, and protecting group is preferably C
1-4carbalkoxy, C
1-4alkyloyl or benzoyl, more preferably tertbutyloxycarbonyl.
Under the existence of above-mentioned hydrazine (IV), the method of the aldehyde hydrazone that is formula (III) by the cyano reduction of 4-(2 '-pyridyl) cyanophenyl (II), adopt catalytic hydrogenation or catalytic transfer hydrogenation reaction, the preferred catalytic method for hydrogenation is the aldehyde hydrazone by cyano reduction.The catalyzer of catalytic hydrogenation is selected from the Raney's nickel cheaply be easy to get, and in reaction, adds acetic acid with the catalyst deactivation activity, with the over reduction of avoiding cyano group, becomes amino.
The aldehyde hydrazone of formula (III) is further reduced to the hydrazine of an accepted way of doing sth (I), can adopt known method, as palladium carbon catalytic hydrogenation, borohydride reduction etc., the inventor adopts the method reduction aldehyde hydrazone of palladium carbon catalytic transfer hydrogenation, take formic acid or ammonium formiate as hydrogen source, the reaction conditions gentleness, product is easy to purify.
More than pass through two step reduction reactions and formula (II) cyano group is converted into to the diazanyl thing of formula (I), also can be prepared by one kettle way (synthetic route 3).4-(2 '-pyridyl) cyanophenyl (II) of take is starting raw material, under hydrazine (IV) exists, the diazanyl thing that is formula (I) by the cyano group direct-reduction of formula (II), adopt palladium carbon catalytic hydrogenation, take acetic acid as solvent, and one kettle way prepares 4-(2 '-pyridyl) benzyl hydrazine (I).
The invention still further relates to the preparation method of a kind of 4-(2 '-pyridyl) phenyl aldehyde (V), 4-(2 '-pyridyl) cyanophenyl (II) of take is starting raw material, become aldehyde to obtain 4-(2 '-pyridyl) phenyl aldehyde (V) (synthetic route 4) cyano reduction of formula (II), the cyano group of formula (II) by raney ni catalysis hydrogenation after direct hydrolysis obtain the aldehyde of formula (V), reduction reaction is preferably carried out in aqueous acetic acid.Formula (V) compound can, by known method, obtain formula (I) compound with hydrazine condensation, reduction reaction successively.
The present invention prepares 4-(2 '-pyridyl) phenyl aldehyde (V) with 4-(2 '-pyridyl) cyanophenyl (II) cheaply be easy to get like this, also can be docked with existing technique, with synthetic 4-(2 '-pyridyl) phenyl aldehyde (V) of novel method, directly utilize existing explained hereafter 4-(2 '-pyridyl) benzyl hydrazine (I).
In order more clearly to understand technology contents of the present invention, especially exemplified by following examples, describe in detail.
Embodiment 1:2-[4-(2 '-pyridyl) benzylidene] preparation of diazanyl carboxylic acid tert-butyl ester (1-2)
Under the protection of nitrogen; by 4-(2 '-pyridyl) cyanophenyl (1-1) (Shanghai Jun Yi Pharmaceutical Technology Co., Ltd; content 98%) 91.3g, tertbutyloxycarbonyl hydrazine (Suzhou Highfine Biotech Co., Ltd.; content 99%) 67.3g joins in the reaction flask of the 5L drying that contains 900g acetic acid, and then adds Raney's nickel 45g.System hydrogen exchange 3 times, normal-temperature reaction 5 hours, until the TLC monitoring is to reacting completely.Filter, and use the ethyl acetate rinsing, reclaim Raney's nickel, filtrate is slowly poured in the water of 5L, then extracts three times by the 4L ethyl acetate, and the organic phase of merging is water, salt water washing successively, anhydrous sodium sulfate drying, filter, and removes solvent under reduced pressure, obtain about 160g crude product, with sherwood oil, pull an oar again, suction filtration, 50 degree are dried, obtain sterling 2-[4-(2 '-pyridyl) benzylidene] hydrazine carboxylic acid's tert-butyl ester (1-2) 121g, productive rate: 80.3%.
1H?NMR(CDCl
3,500Hz)δ8.70(m,1H),8.02-8.00(m,3H),7.87(s,1H),7.80-7.75(m,4H),7.23(m,1H),1.55(s,9H);MS(ESI)m/z=298(M
++1).
Embodiment 2:2-[4-(2 '-pyridyl) benzyl] preparation of diazanyl carboxylic acid tert-butyl ester (2-1)
Under the protection of nitrogen; by 2-[4-(2 '-pyridyl) benzylidene] diazanyl carboxylic acid tert-butyl ester (1-2) 121g, ammonium formiate 129g and 10% palladium carbon 12.1g join in 1200g methyl alcohol; this mixture is heated to reflux (80 ° of C); reaction 2-3 hour, until the TLC monitoring is to reacting completely.Filtered and recycled palladium carbon, filtrate is concentrated into dry, then adds 1L ethyl acetate and the layering of 1L water dissolution, with the extraction of 0.5L ethyl acetate once, the organic phase of merging is water, salt water washing successively, anhydrous sodium sulfate drying for water, filter, remove solvent under reduced pressure, obtain crude product 122.3g, then pull an oar with sherwood oil, suction filtration, 50 degree are dried, and obtain sterling 2-[4-(2 '-pyridyl) benzyl] diazanyl carboxylic acid tert-butyl ester (2-1) 98.7g, productive rate: 81.0%.
1H?NMR(CDCl
3,500Hz)δ8.69(1H,m);7.96(d,J=8Hz,2H);7.76-7.71(m,2H);7.45(d,J=8Hz,2H);7.22(m,1H);6.21(br,1H);4,12(br,1H);4.06(s,2H);1.47(s,9H);MS(EI)m/z=300(M
++1).
Embodiment 3:2-[4-(2 '-pyridyl) benzyl] preparation of diazanyl carboxylic acid tert-butyl ester (2-1)
Under the protection of nitrogen; by 2-[4-(2 '-pyridyl) benzylidene] diazanyl carboxylic acid tert-butyl ester (1-2) 121g, formic acid (70%) 120mL and 10% palladium carbon 12.1g join in 1.0L methyl alcohol; this mixture is heated to reflux (80 ° of C); reaction 2-3 hour, until the TLC monitoring is to reacting completely.Filtered and recycled palladium carbon, filtrate is concentrated into dry, then adds 1L ethyl acetate and the layering of 1L water dissolution, with the extraction of 0.5L ethyl acetate once, the organic phase of merging is water, salt water washing successively, anhydrous sodium sulfate drying for water, filter, remove solvent under reduced pressure, obtain crude product 115g, then pull an oar with sherwood oil, suction filtration, 50 degree are dried, and obtain sterling 2-[4-(2 '-pyridyl) benzyl] diazanyl carboxylic acid tert-butyl ester (2-1) 92.3g, productive rate: 75.7%.Nuclear-magnetism and mass-spectrometric data are referring to embodiment 2.
Embodiment 4:2-[4-(2 '-pyridyl) benzylidene] preparation of diazanyl acetic ester (4-1)
Under the protection of nitrogen; by 4-(2 '-pyridyl) cyanophenyl (1-1) (Shanghai Jun Yi Pharmaceutical Technology Co., Ltd; content 98%) 91.3g, acethydrazide (Suzhou Highfine Biotech Co., Ltd.; content 99%) 37.5g joins in the reaction flask of the 5L drying that contains 900g acetic acid, and then adds Raney's nickel 40g.System hydrogen exchange 3 times, normal-temperature reaction 5 hours, until the TLC monitoring is to reacting completely.Filter, and use the ethyl acetate rinsing, reclaim Raney's nickel, filtrate is slowly poured in the water of 5L, then extracts three times by the 4L ethyl acetate, organic phase water, the salt water washing successively merged, anhydrous sodium sulfate drying, filter, and removes solvent under reduced pressure, obtain 2-[4-(2 '-pyridyl) benzylidene] hydrazine acetic ester (4-1) 101g, productive rate: 83.2%.
1H?NMR(CDCl
3,500Hz)δ8.72(m,1H),8.07-8.04(m,3H),7.91(s,1H),7.82-7.78(m,4H),7.24(m,1H),2.05(s,3H);MS(ESI)m/z=240(M
++1).
Embodiment 5:2-[4-(2 '-pyridyl) benzyl] preparation of diazanyl acetic ester (5-1)
Under the protection of nitrogen; by 2-[4-(2 '-pyridyl) benzylidene] diazanyl acetic ester (3-1) 101g, ammonium formiate 133g and 10% palladium carbon 10g join in 1200g methyl alcohol; this mixture is heated to reflux (80 ° of C); reaction 2-3 hour, until the TLC monitoring is to reacting completely.Filtered and recycled palladium carbon, filtrate is concentrated into dry, then adds 1L ethyl acetate and the layering of 1L water dissolution, water with the extraction of 0.5L ethyl acetate once, organic phase water, the salt water washing successively merged, anhydrous sodium sulfate drying, filter, remove solvent under reduced pressure, with the sherwood oil making beating, suction filtration, dry again, obtain product 2-[4-(2 '-pyridyl) benzyl] diazanyl carboxylic acid tert-butyl ester (5-1) 85.1g, productive rate: 83.7%.
1H?NMR(CDCl
3,500Hz)δ8.72(1H,m);7.99(d,J=8Hz,2H);7.79-7.75(m,2H);7.48(d,J=8Hz,2H);7.23(m,1H);6.24(br,1H);4,13(br,1H);4.07(s,2H);2.07(s,3H);MS(ESI)m/z=242(M
++1).
Embodiment 6:2-[4-(2 '-pyridyl) benzyl] preparation of diazanyl carboxylic acid tert-butyl ester (2-1)
Under the protection of nitrogen; by 4-(2 '-pyridyl) cyanophenyl (1-1) (Shanghai Jun Yi Pharmaceutical Technology Co., Ltd; content 98%) 91.3g, tertbutyloxycarbonyl hydrazine (Suzhou Highfine Biotech Co., Ltd.; content 99%) 67.3g joins in the reaction flask of the 5L drying that contains 900g acetic acid, and then adds palladium carbon 9.1g.System hydrogen exchange 3 times, normal temperature and pressure hydrogenation 24 hours, until the TLC monitoring is to reacting completely.Filtered and recycled palladium carbon, filtrate is slowly poured in the water of 5L, then extract three times by the 4L ethyl acetate, the organic phase of merging is water, salt water washing successively, anhydrous sodium sulfate drying, filter, remove solvent under reduced pressure, the crude product of gained is pulled an oar with sherwood oil again, suction filtration, 50 degree are dried, and obtain sterling 2-[4-(2 '-pyridyl) benzyl] diazanyl carboxylic acid tert-butyl ester (2-1) 120g, productive rate: 79.1%.Nuclear-magnetism and mass-spectrometric data are referring to embodiment 2.
The preparation of embodiment 7:4-(2 '-pyridyl) phenyl aldehyde (7-1)
By 4-(2 '-pyridyl) cyanophenyl (1-1) (Shanghai Jun Yi Pharmaceutical Technology Co., Ltd, content 98%) 10g, Raney's nickel 4g join in 150g methyl alcohol, add again acetic acid 20g, this mixture is heated to reflux (80 ° of C), react 2 hours, until the TLC monitoring is to reacting completely.Solids removed by filtration, filtrate is concentrated into dry, adds the 2mL acetic acid ethyl dissolution, water, salt water washing successively again, anhydrous sodium sulfate drying, filter, remove solvent under reduced pressure, obtain oily liquids 4-(2 '-pyridyl) phenyl aldehyde (7-1) 8.0g, productive rate: 78.7%.
1H?NMR(CDCl
3,500Hz)δ10.1(s,1H),8.77(d,1H),8.20(d,2H),8.00(d,2H),7.81(m,2H),7.31(dd,1H).
Therefore, it is raw material that the inventor be take 4-(2 '-pyridyl) cyanophenyl cheaply be easy to get, and (refer to synthetic route 5, wherein, R is C to design new synthetic route
1-4carbalkoxy, C
1-4alkyloyl or benzoyl); only need by two step reduction (or one kettle way); very easy 4-(2 '-pyridyl) benzyl hydrazine (I) that synthesized; technical process is simple; starting raw material cheaply is easy to get; without adopting expensive catalyzer, avoided the grignard reaction operation simultaneously, be applicable to suitability for industrialized production.
To sum up, the preparation method of 4-of the present invention (2 '-pyridyl) benzyl hydrazine and intermediate thereof, design ingenious, technical process is simple, and does not need to adopt grignard reaction and expensive catalyst, can reduce production costs greatly, be conducive to suitability for industrialized production, be suitable for large-scale promotion application.
In this specification sheets, the present invention is described with reference to its specific embodiment.But, still can make various modifications and conversion obviously and not deviate from the spirit and scope of the present invention.Therefore, specification sheets is regarded in an illustrative, rather than a restrictive.
Claims (10)
1. a method for preparing 4-(2 '-pyridyl) benzyl hydrazine (I), it is characterized in that, 4-(2 '-pyridyl) cyanophenyl (II) of take is starting raw material, under hydrazine (IV) exists, first the cyano reduction of formula (II) is obtained to the aldehyde hydrazone of formula (III), then the reduction of the aldehyde hydrazone of formula (III) is obtained to formula (I) compound
Wherein, R is C
1-4carbalkoxy, C
1-4alkyloyl or benzoyl, particularly tertbutyloxycarbonyl.
2. method according to claim 1, is characterized in that, the aldehyde hydrazone that is formula (III) by the cyano reduction of formula (II) by raney ni catalysis hydrogenation.
3. method according to claim 2, is characterized in that, in the reaction of raney ni catalysis hydrogenation, adds acetic acid.
4. method according to claim 1, is characterized in that, by palladium carbon catalytic transfer hydrogenation, the aldehyde hydrazone of formula (III) is reduced to 4-(2 '-pyridyl) benzyl hydrazine (I).
5. method according to claim 4, is characterized in that, take formic acid or the ammonium formiate transfer hydrogenation reagent in palladium carbon catalytic transfer hydrogenation.
6. a method for preparing 4-(2 '-pyridyl) benzyl hydrazine (I), it is characterized in that, 4-(2 '-pyridyl) cyanophenyl (II) of take is starting raw material, under hydrazine (IV) exists, the diazanyl thing that is formula (I) by the cyano group direct-reduction of formula (II), thereby one kettle way prepares 4-(2 '-pyridyl) benzyl hydrazine (I)
Wherein, R is C
1-4carbalkoxy, C
1-4alkyloyl or benzoyl, particularly tertbutyloxycarbonyl.
7. method according to claim 6, is characterized in that, the diazanyl thing that is formula (I) by the cyano group direct-reduction of formula (II) by palladium carbon catalytic hydrogenation.
8. a method for preparing 4-(2 '-pyridyl) phenyl aldehyde (V), is characterized in that, 4-(2 '-pyridyl) cyanophenyl (II) of take is starting raw material, becomes aldehyde to obtain formula (V) compound the cyano reduction of formula (II),
9. method according to claim 8, is characterized in that, the aldehyde that is formula (V) by the cyano reduction of formula (II) by raney ni catalysis hydrogenation.
10. method according to claim 9, is characterized in that, in raney ni catalysis hydrogenation, adds aqueous acetic acid.
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| CN106543073A (en) * | 2015-09-17 | 2017-03-29 | 宁波杰尔盛化工有限公司 | 2-[4-（2- pyridine radicals）Benzyl]-hydrazine carboxylic acid's tert-butyl ester preparation method |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106543073A (en) * | 2015-09-17 | 2017-03-29 | 宁波杰尔盛化工有限公司 | 2-[4-（2- pyridine radicals）Benzyl]-hydrazine carboxylic acid's tert-butyl ester preparation method |
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