TW381070B - Process for the amination of mononuclear, aromatic compounds and polynuclear compounds containing at least one aromatic ring in the presence of a palladium complex catalyst - Google Patents

Abstract

The present invention provides a novel process for the amination of mononuclear, aromatic compounds and polynuclear compounds containing at least one aromatic ring, which process permits simple isolation of the aminated mononuclear, aromatic compound or of the aminated, polynuclear compound containing at last one aromatic ring from the reaction mixture and recovery of the catalyst system used. This process comprises the reaction of the mononuclear, aromatic compound or of the polynuclear compound containing at least one aromatic ring with primary or secondary amines in the presence of water, of a base and of a palladium complex catalyst which contains organic, water-soluble phosphine ligands.

Description

_ Amination with fluorene, in the presence of tin. A7 ____B7 V. Description of the invention (1) The present invention relates to amination of mononuclear aromatic compounds and polynuclear compounds containing at least j-aromatic rings in the presence of palladium-containing composite rhenium. Transition metal-catalyzed nucleophilic substitutes in aromatic compounds have some importance in the synthesis of organic chemistry. It is known to carry out aromatic I .. compounds in homogeneous organic ta. Nickel and palladium catalyze C-C coupling reactions in compounds.

Synlett 1997, 329-340 further revealed that the amination of aryl or amines in the organic phase can be carried out in the CN coupling using tri (o-tolyl) amine or Xf (diphenylphosphine). Ferrocene, as the ligand of the palladium complex catalyst. J. aJq. Chem. Soc 1 " 6,11 8, 721 5-7216 revealed that for the amination of aryl compounds, 2,2 >- Bis (diphenylphosphino) -1, UINAP as the palladium {Please read the note on the back first and then fill in this page-35) System composite catalyst. Sodium terbutyrate is used as a catalyst in these reactions. Separating the product and recovering the organic reaction mixture contains considerable complexity. For example, the purpose of the present invention in these cases is to provide a novel method for the amination of a mononuclear aromatic compound with an aromatic ring, in which the reaction produces Both catalysts can be recovered in a simple manner. This purpose can be achieved in a simple manner by using a mononuclear f-group compound and a ring polynuclear compound. This method allows the aromatic compound to be combined with an aromatic ring polynuclear compound and a primary amine or Secondary amines are reacted in the presence of a medium, wherein the program is performed in the presence of water. The medium contains organic water-soluble phosphine ligands, and is a molble excess of palladium. The mononuclear aromatic compound usable in the method of the present invention includes Compound catalyst, distillation. At least one product is separated and the reaction is continued. Contains at least one aromatic compound and at least one base and palladium complex contact, and palladium complex contact 0 Contains an aryl group of formula I > > Order a 7-line compound:-1-1 paper size applies Chinese National Standards (CNS) Λ4 specification (2i〇X297 public trend) V. Description of the invention (2 R2 A7 B7 R1 R3

X R4 R5 where X is halogen,-(S02-CF3) or-(S02-C6H, Han 1, so that, 4 or 5 are the same or different, are hydrogen, fluorine, unsubstituted or substituted phenyl, CVCe alkyl, non-terminal C = C double bond (: 3-C6 alkenyl, C3-C6 alkynyl with non-terminal 煸 bC triple bond, or -OR6 group, where R6 is hydrogen, -p-CH3), And (please read the notes on the back before filling out this page)-Packing unsubstituted or substituted phenyl, C ^ -C6 alkyl, or 0000 0 c2-c 0 alkenyl, (: 6 aromatic , Or -CN, alkenyl, not printed by the Central Bureau of Standards of the Ministry of Economic Affairs, printed by -COH, -OCR7, -COR7, -CR7, -CN (R where R7 is the same or different, is Ci-Ce: alkane Group, C2-C < substituted or substituted phenyl group. X is preferably chlorine, bromine or iodine. I hate 1, 2, 3, 4, the same or different for citrus, can be 0: 1- <: 1 terminal c = c double bond c3-c6 alkenyl, c3-c, alkynyl with non-terminal triple bond, each is straight or branched, cyclic or non-cyclic.] ^, R2, R3, R4, R5 to 0 〇II 7 II 7 -CR7, -C-OR7 or CsN is preferred. The benzene ring can be substituted in 1 ^, 112, 1 ^, 4,115, 116, 117 if necessary. Description of formula II: an alkyl group having a non statements 2 - This applies China National Standard Paper Scale (CNS) Λ4 size (210X297 mm) B7 V. invention is described in (3) B7

R1

II Alkyl, C2-C, where 11 *, feet 9, 1 °, hat 11, and hat 12 are the same or different, and are 0: 1- € alkenyl, phenyl, or benzyl. Compounds, which are other mononuclear aromatic pyridine compounds of formula III which can be successfully used in the preparation method of the present invention: R14 R13

X The Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs printed J " CH3), and substituted alkenyl, gas, alkenyl, e 0 Ce II CN (R18, h, or e2'ceene,

III where X is halogen,-(so2-cf3) or-(S02-C6h r13, r14, r15, r16 are the same or different, and are hydrogen, fluorine, or

Phenyl, Ci-Ce alkyl, I with non-terminal C = c double bond

^ 3-C C3-C6 alkynyl group, -OR17 group with non-terminal CsC triple bond, R17 unsubstituted or substituted phenyl group, Ci-Ce alkyl group, c aryl group, or 〇 〇 〇 0

II II, 11 II -COH, -OCR18, -COR18, -CR18, -CN, where R18 is the same or different and is Cl_c6 alkyl, —3 — This paper size applies to China National Standard (CNS) Λ4 specification (2IOX 297 male犮) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 51 A7 ___B7 V. Description of the invention (4) Unsubstituted or substituted phenyl. X is preferably chlorine, bromine or iodine. Han 13 ^ 14 氺 15 沭 16 are the same or different, and can be (: 1_ (: terminal C = C double bond C3-C6 alkenyl, non-terminal cs (alkynyl, each is straight or branched, cyclic or Non-cyclic type, preferably hydrogen, Ο 0 || II * -CR18, -C-OR18 or CeN. If necessary, phenyl can be represented by the following formula IV: R19 r20

R ’alkyl, c3-c6 13 r16 with non triple bond

IV where anti 19, rule 2 °, 1121, 1122, 1 ^ are the same or different, and are (: 1 丨 (: 4 alkyl, (: 2-c4 alkenyl, phenyl, or benzyl). The new method can be used to contain at least Amination of polynuclear compounds of an aromatic ring. The amidine of formula V can be particularly successfully aminated:

R30 〇 X

RJ R 25 -4 This paper size is applicable to China National Standard Music (CNS) Λ4 specification (210X297) »-»-: -------- install -------- r order 1 ---- --- 线 {ί (Please read the precautions before filling this page)

V Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 ____B7 V. Description of Invention (5) where X is _ prime,-(so2-cf3) or-(so2-c6h, hate 24, 1125, 1126, hate 27, hate 28, hate 29, hate 3 () are the same or different, are unsubstituted or substituted phenyl, alkyl, Cs-C6 alkenyl with non-terminal c = c taking bond, C3-C6 with non-terminal Cd triple bond Alkynyl, -OR • .., where R31 is hydrogen, unsubstituted or substituted phenyl, c2-c6canyl, c6aryl, or ο ο 〇〇〇〇ⅡII 32 II II II • COH, -OCR32, -COR32, -CR32, _CN (R32) 2, R32 are the same or different, and are Kβ alkyl, (: 2-(: 6 alkenyl substituted phenyl. X is preferably chlorine, bromine or iodine. R24 , R25, R26, R27, R28, R29, R3e are the same or different alkyl groups, c3-c6 alkenyl groups with a non-terminal c = c double bond, and c3-c6 alkynyl groups with a triple bond, each of which is straight or branched, Ringed or acyclic R24, R25, R26, R27, R2S, R29, R3. Hydrogen, 0-CR32, -1-0R3 C = N is preferred. If necessary, the benzene ring can be at r24, r25, r26 , R | 7, r28, r29, R3, r31, r32 are substituted, and R 33 R 3 4 can be represented by the following formula VI

5 R; p-ch3), and Fluorine, Chlorine, Cι-Ce base: ¾ -CN, which is unsubstituted or can be CrC6 has non-terminal csc 0 chlorine or

VI (Please read the notes on the back before filling in this I). Packing;; 1T travel paper size applies Chinese National Standards (CNS) Λ4 specifications (210X297 cm) A7 B7 5. Description of the invention (6) Of which 33 are less 34, Gen 35, Na 36, Na 37 are the same or different and are oc4canyl, phenyl or phenyl. In the present invention, amine compounds of VII can be used. C4, C2-

R

H-N

R 3 9 wherein R38 and R39 are the same or different and are hydrogen, unsubstituted or C ^ -Ct. Alkyl, C3-C10 with non-terminal CdC double bond, Cs-Ci with terminal C5C triple bond. Alkynyl, b (or40) 2 Si (R4 °) 3, R4 ° are the same or different, and are K4 alkenyl,

Wave VII replaces benzene ring, fluorenyl group, non-'Sn (R4e) 3 or phenyl or benzyl group. C1-C10 alkyl in R38 and / or R39, C3-Clit alkenyl with non-terminal C = C double bond, and C with non-terminal CsC triple bond are straight or branched, cyclic or non-cyclic, and C1-C6 courtyard-C1. 0 block 'coke group is preferred, and the benzene ring in R38 and / or R39 may have a substitute. In this case, as shown in the above Π, the Rs-R12 group in the benzene ring is preferably a methyl group, a phenyl group, or a benzyl group. Other amines available are compounds of the formula VIII: R4 ^ \

R 44 ---: ---; ----- install ---- T--, order --------- Μ-ί (please read the precautions of the West first, then fill in this page ) (C) Printed by the Consumers' Cooperative of the Shao Central Bureau of Standards

H-N (C)

R R4〆 R46 where C 41 is Ci-Ci❶ alkyl, C3-C, which has a non-terminal C = C double group and a non-terminal 嫱 CsC triple bond. Base and oxygen 1142 is C ^ -Cw alkyl group, with non-terminal c = c slave bond -6-This paper size applies to China National Standard (CNS) Λ4 specification (210X297 mm)

C3lC1 () ene or NR42 of VIII bond, in which C 3 · c 1 alkoxide, A7 __H7 V. Description of the invention (7) C3-C10 alkynyl group with non-terminal C = C triple bond, and the anorexia 43, 44 Rule 451 ^ Same or different, is hydrogen, unsubstituted or substituted benzene ring, C3-Cle alkenyl with non-terminal C = c double bond in the base, non-C-C triple bond with non-terminal CbC three-bond employee consumer cooperative The printed C3-C1 () alkynyl, B (OR47h, Sn (R47) 3, or Si (R) are the same or different, and are alkyl, phenyl, or benzyl. IMCI and / or jCI-CIO within 42 Alkyl, C3-C! With double bonds. Alkenyl, and those with true non-terminal CSC triple bonds are straight-chain branched, cyclic or acyclic. R43, R44, R45 and / or R46 alkyl groups C = C3-Ch > alkenyl with C double bond, with non-terminal CsC triple group, can be linear or branched, cyclic or acyclic. ^^-R43, R ", R45 and / or R46 benzene The ring may be substituted as shown in the above formula II, and the R8-R12 group in the benzene ring of formula II is benzyl. The palladium compound used may be palladium acetate, Pd (dba: PdBr2, Pdl2, or Pd (acac) 2, where (dba ) Is bis (ijl benzyl) acetone, and (acac) is acetaldehyde Pyruvate. For example, a sulfonated triaryl group of formula IX can be used as a water-soluble phosphine ligand for a palladium compound:

) 3, where R 4 7 has a non-terminal C = C C3-Cie alkynyl group, and a non-terminal bond of 〇3-(: 10 alkyne_C < radical is preferred, in the case of * methyl, phenyl or 2, PdCl2 (Please read the notes on the back to complete this page).

、 1T line 7 This paper size is applicable to China National Standard (CNS) A4 specification (21〇297297 t) 5. Description of invention (8) Α? Β7

Αγ- (S03M) ni (Yi) m, (S03M) n2 (Y2 > m2 (S03M) n3 (Y3) m3, where Ari, Ar2, Ar3 are the same or not, it is the same or different phenyl or leaf group jAJ [蕴Or branch C, -C4 courtyard, C, -C4 烺

IX, Υ ,, Υζ, Υ; phase oxygen, halogen Λ sugar, or -nr48r49 -CN'-NOr-OH'-O-sugar 'printed by the Central Laboratories of the Ministry of Economic Affairs, where the sugar is a monosaccharide or Double base, in which R48 and H49 are the same or different, are linear or branched alkyl, M is hydrogen, ammonium ion, quaternary ammonium ion, monovalent metal or multivalent mi, m 卩 and ιη3. It is a relative integer, Songs 0 to 5 are the same or different integers, from 0 to 3, η, n2, or n3 or greater. Phosphine of formula IX, in which Ari, Ar2, and Ar3 are phenyl hydrogen, formamidine, ethyl, formamyl, lithoxy, or chlorogen containing sodium, potassium, calcium, barium, and ammonium cations, or Methylammonium, tetrapropylammonium or tetrabutylammonium ions, integers mi, m2, m3g, meat 0 to 3. It is particularly preferred that Απ, ΑιίΑι ^ is phenyl, mi, m2, kun—a metal equivalent, at least one of ηι n2 and n3 is equal to, YhYiYs is a child, and M is selected from the group consisting of ammonium and tetraethyl. Different is equal to 0, pu, —IJ —-- Ί —--- -I--n --i order --- * --- line i {(Jing first read the notes on the back and fill in this education) Paper size applies Chinese National Standard (CNS) Λ4 specification (210X 297g t) 5. Description of invention (9) n2, i »3 is 0 or 1 'ηι + n2 + n3 total 1 to 3' S (sulfophenyl ) Sodium, potassium, calcium, barium, tetramethylammonium and tetraethylammonium of diphenylphosphine and diphenylphenyl benzylphosphine membranes g ° The sulfonated dihydrazones of formula X are also suitable for coordination Base: M0 03M in the meta β III (named base) is particularly suitable for progress

(CH2) r PArf (CH2) r-PAr 丨 Php .Php

X (Please read the precautions below and then write this page) Metal, or polyvalent 0, 1, or 2, benzylphosphinomethyl) Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs, India and India mo3s where Ar1 is a period C6H4S03M, M is one equivalent of hydrogen, ammonium, and monovalent metal, Ph is phenyl, p is the same or different, is the same or the same, and is 0 minus 1. The sulfonated dimers of formula X are sulfonated_bis (bis-1,1-binaphalene (8 to 8)), or sulfonated 2,2'-bis (diphenyl) -binaphalene (BINAP). BINAS 6 is preferred, where sodium P is 0.00 in formulas IX and X, and M is a rhenium metal, an alkaline earth metal, or a quaternary phosphonium ion of formula n (r5 ° r51r52r53). 4 is the same or different and is linear Or branched CrCU alkyl group. Sulfonated di-ferrocene ferrocene can also be used as the en position. —9 — This paper size is applicable to the Chinese National Standard (CNS) Λ4 Regulation (210X297) 犮, Bell, Cu, Cu R50R51RS2R53 must use the upstream step of purification and ammoniation. One of the compounds to be ammoniated is this. Phosphine components can also be used as the polymer of the Ammonia Consumer Central Cooperative Standards Consumer Polymer Copolymer and the excessive catalyst system. Mononuclear aromatic primary or secondary amines. The component, that is, the introduction of ammoniated anti-organic water-soluble phosphine components when palladium) makes the amount of molybdenum for palladium to be mononuclear aromatic Λ7 B7 V. Description of the invention (1〇 ) In the ammonium system, the phosphine ligands of formulae IX and X are not. For example, the sulfonation of JT with sulfonation and / or sulfonation mixtures with no 靣 _ 鸯 can be thrown. The formation of a palladium catalyst system containing a phosphine ligand can be performed in situ during a J .. step or ammoniation. The formation of a catalyst system upstream of the ammoniation can be carried out in a subsequent reaction tank or reaction chamber, but it can also be performed in a separate reaction vessel. In the upstream production of this palladium catalyst system, the above-mentioned palladiumization and the above-mentioned one or more phosphines are used as a complex ligand combination. Use as an aqueous solution. In addition, an organic solvent is preferably added, followed by a solvent. The use of methanol has proven to be particularly useful. As a result, oxygen blue became a water-soluble absolute Ji compound, which contained organic water-soluble phosphine ligands. These palladium are compounded with phosphine to obtain a catalyst system. If the solution is produced in another device, it can be moved to the ammoniation reactor, and other raw material compounds or polynuclear compounds containing at least one aromatic ring can be added to destroy the catalyst system if it is produced in situ in the ammoniation reaction. Compounds and organic water-soluble phosphine ligands can be used in the same reactor as the raw materials. In the formation and use of the catalyst system, it has been proven that palladium and non-stoichiometric ratio (that is, according to the formation of palladium complex is appropriate, but excess phosphine is used. Here, the earing ratio of the phosphine complex is (2-200 ): 1, preferably (3-200): 1, palladium group compounds or polynuclear compounds containing at least one aromatic ring ^ 0.001 ~ 25 Mo—10 This paper size applies to Chinese national standards (CNS > A4 specifications (210X297)漦) I m-", I 丨 · 'I ^ 衣 IJI *, 1T: J ί' I (Jing first read the back and pay attention to the items before writing this page) A7 ____B7 V. Description of the invention (Η) Ear%, preferably from 0.00 to 20 mole%, and from 0.1 to 5 mole%; ^:% is particularly preferred. In addition to the organic water-soluble phosphine ligand, the palladium complex P may contain other ligands, Such as halogen, chlorine, bromine, and iodine are preferred, -0c, bis (dibenzylidene) propanium, ethanopyruvate-aromatic compounds, or π-olefins. Mononuclear aromatic compounds or containing at least one Amination of aromatic ring polyamine compounds is carried out in the presence of M (liquid hydrazone solution or solid g can be added to the reaction system) at a reaction temperature of 20-160 ° C, more preferably 50-120 eC. 17〇 minutes to hours, 1J-96 hours with an appropriate amide jian jian for example alkali metal and earth metal methide, ethyl compound, compound tert-butyl acetate wash Η

CO 'NO PF; scandium compounds, scandium hydroxides, carbohydrates, carbonates. Lithium, sodium, potassium, magnesium, calcium, barium hydroxide, lithium, sodium (please read the precautions on the back before filling this page) -pack.

: 1T The consumer cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs printed ¾ potassium methylate, ethylate and t-butylate, sodium salt, potassium carbonate, and sodium acetate are preferred. A method of 3-15% strength is performed in the presence of water. In addition, suitable organic solvents may be, for example, methanol, ethanol, n-propanol, alcohol, isobutanol, t-butanol, tetrahydrofuran, di-n-butyl ether monobutanone, dimethylformamide, dioxane, toluene , Dimethyl ether, ethyl acetate, pentane, hexane, heptane, octane, and potassium bicarbonate in water. Organic solvents are present. Isopropanol, n-butyl 2-butanol, 2 benzene, ethylene glycol, alkane, or a mixture of two or more of these solvents. Preferred mixtures of the two organic solvents are: (a) methanol or ethanol, and (b) toluene, xylene, ethylene glycol dioxane, pentane, hexane, heptane, and octane. If ammoniation is in water and pentane, hexane, heptane, octyl ether, ethyl acetate, di-n-butyl ether, n-butanol, isobutyrate, di-n-butyl ether, alkane, toluene, di-butane Alcohol and travel paper standards are in accordance with Chinese national standard (CNS) Λ4 specification (210X297 gong) Printed by the Ministry of Economic Affairs Central Standard Employee Consumer Cooperative A7 H7 V. Description of the invention (12) 2-Butanone or dioxane , There is a two-phase system of water phase / organic phase (case A). On the other hand, if the procedure is performed in the presence of water and methanol, ethanol, n-propanol, isopropanol, tert-butanol, ethylene glycol, dimethylformamide, or tetrahydrofuran, a homogeneous reaction system (case » -. B). In the process of the present invention, the reaction mixture may be exposed to ultrasound to achieve optimal mixing of the solvents. At the end of the reaction time, the reaction mixture of Case A was separated by simple phase addition. In case B, toluene, diethyl ether, ethyl acetate, di-n-butyl ether or dioxane are first added to make a two-phase system. In both cases, the catalyst system can be easily separated from the reaction products and unconverted materials in this way. The palladium-containing composite catalyst can be recovered from the aqueous phase or recycled to the reaction tank in a continuous reaction *. Aminated mononuclear aromatic compounds or ammoniated polynuclear compounds with one less aromatic ring, ie, separated from the organic phase. The new method opens up high-brightness and light fastness onion sink dyes to pull first-class synthetic pathways. In case A, the procedure should be carried out in a two-phase system with an aqueous / organic phase, especially a water / 2-butanol mixture. According to the new law, F-substituted 1,5-diphenylamine fluorene can also be used. It is known that the reaction of α-chloro- or α-bromoonium stilbene with aniline in the presence of copper and copper acetate can give aniline alloquinone (Just us Annalen der Chemie, 1911, Vol. 3 80 Vol. 3 1 7-3 3 page 5 (J. Org. Chem. USSR / English translation, 1989, pp. 1740-1744). The new method allows simple separation of reaction products and recovery of composite catalysts from the reaction mixture and avoids the generation of metal-containing residues. Example 1 Manufacture of 1- (4-methylaniline phenyl) -1-acetamidine (3) -12-This paper size is applicable to China National Standard (CNS) Λ4 specification (210X29? Mm) Please read The first note to write another

1II Printed by the Consumer Standards Cooperative of the Central Standards Bureau of the Ministry of Line Economy A7 B7 V. Description of the invention (13) 〇Hfi \ = / * / ΝΗ Μ «ΟΗΗζ〇HtC 75 -C. 72 h 1 2 κ > -〇3 ca CHrPA, ^ 0〇rcw NaO) S Ar = m-SChNa-phenyl All operations were performed under an inert gas and in a degassed solvent. Take 25 mg (0. ΐ millimolar) of Pd (0Ac) 2, 6 ml (0.84 millimolar) of BINAS-6 aqueous solution, and ml of ethanol, and simmer at room temperature for 5 minutes. Add 400 mg (mmol) of 4-bromoacetophenone (1), 285 mg (2.65 mmol) of N-methylbenzene limb (2), and 0.4 ml of 71 ^^ 011 (2.8 mmol) ). The solution was reheated to 75V and stirred at this temperature for 72 hours. During the treatment, the reaction solution can be recovered from the aqueous phase by extracting the rho catalyst several times with diethyl ether. The organic phase was dehydrated on silica gel 60 using hexane / ethyl acetate ratios of 10: 1 and 4: 1 hexane / ethyl acetate. This gave 270 mg (1.2 mmol) of 1- (4-methylanilidephenyl)-1-acetone (3) (60% yield for 4-bromoacetophenone). In addition, unconverted N-methylaniline (2) (108 mg; 10 mmol) can be recovered > The same reaction is performed, after 24 hours at 75 ° C, = product (3), yield 4S% . -13 — This paper size is in accordance with Chinese National Standard (CNS) A4 specification (210X297mm) 碕 First news Φ Page binding line

I A7 B7 V. Description of the invention (14) 1- (4-methylaniline phenyl)-1-Ethyl _ (3): Material: 0 2 12 CH3 7 9

H3C 5 15 13

N 14 11 6 3 8 10 iH-NMR (300 MHz), δ (ρριη) multiplicity intensity designation in CDC13 7.78-7.75 m 2 aromatic fluorene 2,4 7.37-7.32 m 2 aromatic fluorene 9,1 0 7.19- 7.14 m 2 Aromatic Η 7,8,11 6.89-6.69 m 2 Aromatic Η 1,3 3.3 1 s 3 ch3 12 2.44 s 3 ch3 6 (Please read the precautions on the back before filling this page)-Pack.

'-ir «J 13C-NMR (75 MHz) printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs, 14 within CDC13 This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X 297g t) V. Description of the invention (15 ) A7 B7 δ (ρριη) Specified 196.27 C 5 152.70 C 13 147.30 C 14 130.16 C 2 129.84 C 9 127.25 C 15 126.05 C 1 125.60 C 1 1 113.64 C 7 4 0.18 C 12 26.02 C 6 Mass spectrum (EI) --- Γ--Γ ---- install ------ order——I-^ ---- line!-(Please read the notes on the back before filling this page) Cooperative printed m / ζ Relative Strength Fragment 225 63.64 M + 210 83.5 1 M Eleven CH3 (15) 167 12.71 210-CH3CO (43) 77 100 c6h5 + -15-This paper size applies to China National Standard (CNS) Λ4 specifications (210X297 metric t) Printed by the Ministry of Standards and Consumer Cooperatives Λ7 B7 V. Description of the invention (16) Example 2 Manufacturing Hao 丨 1- (4-methylanilide phenyl)-1_ ethyl ketone-all work in inert gas Down into the degassing solvent f? ° NaTPPTS is 3,3,, 3 " —phosphine triyl tris (benzenesulfonate Take 25 mg (0.11 mmol) of Pd (OAc) 2, 765_0 mg (1.35 mmol) of NaTPPTS in 5 ml of water and 10 ml of methanol, stir at room temperature for 5 minutes, and add 398.0 mg (2.00) to this solution. Mmol) 4 monobromoacetophenone, 258 mg (2.40 mmol) N-methylaniline, and 269 mg (2.80 mmol) sodium tert-butylate. The reaction mixture was heated to boiling for 3.5 hours. After the solution was cooled, 5.0 mL of diethyl ether and 1.0 mL of water were added, and the ether phase was separated. The remaining catalyst solution was extracted with 5.0 ml of ether. The ether phases were combined, washed with water and dried over magnesium sulfate. Crude j was refined using a color mold tube to obtain 183.7 mg (0.82 mmol) 1 1 (4-methylanilide phenyl> -1 1 ethyl ketone (41% of theory) 0 Examples 3-13 All The operations are performed under an inert gas and in a degassing solvent. The meanings of the halogenated aromatic la-d, halogenated pyridines 5a, 5b and amines 2a -C are shown in Figure 1. Table 1 shows the aromatic aromatic or α-halopyridine And amines, as well as the solvents and bases used in the examples, the amounts of Pd (OAc) 2 and BINAS-6 are also shown in Table 1. All examples were performed using the following general experimental method. X mole% Pd (parahalogen Aromatic or α-halopylide), Pd (OAc) 2 type, y molar equivalent BINAS-6 in 0.5 ml of aqueous solution, and 5 ml of methanol (except for Examples 9 and 11), stirred at room temperature 5 minutes. Add 2.00 millimolar halo aromatic or α-halo-16-piridine to this solution, 2.40 millimeters. The paper size is applicable to the Chinese National Standard (CNS) Λ4 specification (210 × 297 mm) Please read the notes on the back first Order

I

This page ^^ Printed by the Central Standards Bureau of the Ministry of Economic Affairs, Shellfish Consumer Cooperative, printed A7 ____ B7 V. Description of the invention (17) Mole amine and 2.80 millimoles, the reaction mixture was heated to solution cooling, then 5.0 ml of diethyl ether And 1.0 ml of water. The remaining methanol solution was extracted with 5.0 ml of ether. , Washed with water, and dried over magnesium sulfate. The crude product is refined using the color mold analysis method. 1- (4-methylanilide) was obtained in A%. Boiling for t hours. Separate the ether phase & the ether phase is divided into 1-ethyl ketone by a ring color layer, (please read the precautions on the back before filling this page). Pack. • ίτ 17 This paper size applies to China National Standard (CNS) ) A4 specification (2 丨 0X297 mm) V. Description of the invention (18) A7 Η 7 払 5 6 7 8 9 10 11 12 13 la lb lb 1 c 1 c 1 c 1 c 1 e 1 e ΙΛΡ3 5 b Pan, α ITnFF 2b 2a 2b 2b 2b 2c • 2 b 2b 2b 2c 2c 0 2 5 10 pd (OAC) 2 〔x MW times Pd, 1¾¾ Bing Pan, α | Huize 334 (Please read the notes on the back first Please fill in this page again) 7 7! · 7 7 5 7 7 7 5 5 ^ aoffi ISiaO ttdu > iaO twu NaO twu ISiaOH Liow? OH? OH 2; aoH 2; aoffi ^ aoffi BINAS-6 〔< MW 鸸 岫蹿 pdaiIll] Printed by the Consumer Cooperatives of the Central Bureau of Standards, Ministry of Economic Affairs

Meow, K20 Meow, H20 Me〇w, ffi20 Meow, ffi20 Me〇H, H20 Me〇w, ffi20 H2O Me〇H, ffi20 ffi20 Me〇w, ffi20 Meow, ffi20 OS OOUl ^ J ^ OOOOOOLf!

Gnoo »— * 一 OnOnIO — This paper size applies to the Chinese National Standard (CNS) Λ4 specification (210X 297 mm) 璲 bp 18 V. Description of the invention (19)

A7 B7 U-d -XB-UMnosc Ibxl-HSOMC IcX 丨 Br.nscoMC ΞΧΙηί: 0020 At

B2AS6 AT-

NaTPPTS S03N_ά r 户 so3? 2 ·? Σ1 = H, R2 * s-3 4a RncoMC. RrMC. R2Bph lob R rMe. RKJ-ph -lb RnoF.70ΙΑ6 = 3 > 2 «~ 2b R 一 " Produce R2 * ph 4c RWOMC. R rMC, RKJ = ph 4d R-CGMc. R rpKR2 »l I2 + b > ase \ HKJ 2-a-

UC

o— ^ OII two a-d t R!

1.1 ^-^ ----- installation ---- 7- — ten orders one ^ ----- line II (please read the notes on the back first # ball write this page) · staff of the Central Standards Bureau of the Ministry of Economic Affairs Printed by Consumer Cooperatives 9 This paper size is applicable to China National Standards (CNS) A4 (2 丨 OX297 mm) Ministry of Economic Affairs t Central Standard% bei Printed by Consumer Cooperatives Λ7 B7 V. Description of Invention (20) Example 14a All operations for making phenyl (2-pyridyl) amine are performed under an inert gas and in a degassing solvent. Take 2 mg of palladium acetate (8.9 μmol) and dissolve in 0.5 ml of BINAS-6 aqueous solution (69.5 μmol) and a solvent mixture containing 6 ml of water and 1.5 ml of methanol. After stirring for about 5 minutes, 158 mg of α-bromopyridine (1.0 mmol), 0.12 ml of aniline (1.3 mmol), and 0.2 ml of a 7 M NaOH solution were added to the reaction mixture. Reflux at 80 ° C for 6 hours.俟 After the reaction solution was cooled to room temperature, a yellow solid precipitated. After filtration, washing with water, the solid was extracted with ethyl acetate, dried over magnesium sulfate, and the solvent was stripped to obtain 77 mg of phenyl (2-pyridyl) amine (0.45 millimolar = 45%). Example 14B Production of phenyl (2-pyridyl) amine The procedure was the same as in Example 14a, except that α-bromopyridine was changed to α-chloropyridine. Phenyl (2-pyridyl) amine was obtained in a yield of 21%. Example 1 5-21 All operations were performed under an inert gas and using a degassed solvent. The examples were carried out according to the following general working methods 2 and 3. The resulting reaction is processed in batches using general methods C and D. General work method 2 (GWM2): In a nitrogen flask that is boiled and flushed with hydrogen, add 0.50 ml (70 · 0 μmol) of 2.5 mg (11_0 μmol) of Pd (OAc) 8 to 5-6 people Aqueous solution, 3.00 ml of water and 2.00 ml of 2-butanol are stirred for 5-10 minutes until Pd (OAc) 2S is completely dissolved. Dissolve in yellow two-phase reaction -20-This paper size applies Chinese National Standard (CNS) Λ4 specification (210X297 cm). Please read the note on the back first. Preparation of A7 B7 V. Description of the invention (21) Add 1.0 millimolar halogenated onion marks and the following amine amount to the solution. After adding 0.26 ml (1.3 mmol) of 5M NaOH aqueous solution, the reaction mixture was refluxed for the listed time while stirring. General Work Method 3 (GWM3): In a nitrogen flask that was boiled and flushed with hydrogen, 0.50 ml (70 · 0 μmol) of BIN AS-6 was added to 2.5 mg (11.μmol) of Pd (OAc) 2. Aqueous solution, * 3.00 ml of water and 4.00 ml of 2-butanol, stir for 5-10 minutes until Pd (OAc) 2 is completely dissolved. To the yellow two-phase reaction solution was added 1.0 millimolar halogenated shallots and the following amount of amine. After 0.26 ml (1.3 mmol) of 5M NaOH aqueous solution was added by hand, the reaction mixture was refluxed for the listed time while stirring. Treatment method C: After the reaction mixture was cooled, the solid was separated and washed with 10 ml of water. The crude product was dried in a vacuum generated by an oil pump, and then purified on a silica gel 60 by column chromatography. The eluent used was 5: 1 petroleum ether 40-60 / ethyl acetate. After removing the solvent, it was dried in the vacuum generated by the oil pump. Treatment method D: After the reaction mixture was cooled, the solid was separated and washed with 10 ml of water. The crude product was dried in a vacuum generated by an oil pump and purified on a silica gel 60 by column chromatography. The eluent used was toluene. After removing the solvent, it is dried in the vacuum generated by the oil pump. The lower circle 2 indicates the significance of the haloquinone and amine used. Table 2 shows the hafnium halides and amines used and the amounts. The reaction time and reaction temperature are also shown in Table 2. In addition, instruct each of the examples to study -21 — According to the general operation, the paper size applies the Chinese National Standard (CNS) Λ4 specification (210X 297 gong). The sample in the Ministry of Economics is accurate. Member X Cooperative printed A7 B7 V. Description of the invention (22 ) Method 2 or 3, or batchwise according to the reaction of treatment method C or D. Example 21 Production of 1,5-bis (m-toluidine) onion quinone 7h 1. In the use of the genus Jf Ying JD Yan Gailong five nitrogen roasted dragon horn, at 2.5 mg (ΙΙ.ΟμΜ_) Pd (OAch, Add 0.50 ml (70.0 μmol) of BINAS-6 aqueous solution, 3.00 ml of water and 4.00 ml of 2-butanol, and stir for 5-10 minutes until Pd (OAc); 2 is completely dissolved. Add 1 to ( M-Toluidine) —7-Chlorothion 7g to produce 87 mg of crude crude product, and 0.06 ml (0.55 mmol) m-toluidine. Add 0.13 ml (0.65 mmol) of 5M NaOH After the aqueous solution, the reaction mixture was refluxed with stirring for 12 hours. The cooled reaction mixture was extracted 5 times with 2 ml of toluene, the organic phase was evaporated to dryness in a rotary evaporator, and then completely dried in a vacuum generated by an oil pump. Wash with toluene. The extract was subjected to column chromatography on silica gel 60 and evaporated to dryness to obtain a deep red 7h. —2 2 A paper size applies to the Chinese National Standard (CNS) Λ4 specification (210X297 total) Reading the back-to-back precautions f. Note (23) A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 6a H = H 2c RrH, 7a zi, Rrffi 6b unnl 2d 11- = ¾ -OK3 7b z = ffi, R.- = splash-nffi3 2e ^ r ^ -ca3 7c ZNH, Rr ^ -cffi3 2f ϋ ^ g 7d ZArRrM 铖 _ 2g R .- = ia1 -OH3 7e z = 01, R ^ = ffi 7f Z = Xunhegang, R.rH 7WZN2, B ^ ufig -CK3 7h i Han-ffl Thank you M, Rr Han-c?

P G. Cl R.1 〇 ΝΗ β (Please read the precautions on the back before writing this page) This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X 297 mm) 5. Description of the invention (24)

MmMm7e neck > ^ μ · §π7γμ # 7% * 2 笤 躏 雒 ^ ±. ± §: 万 # > Viewed # 砘 望 砘 A7B7 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs ls > 〇to ι-k ·: Example fl {Me σ \ On Qs Pi 〇 \ ο m to 0Q-to 〇to to Λ α * ο — t— * 1— * N— · — — Cao He — U) o Ο 1— * u > 〇s— / t—Λ oo H—1 oo ►— * oo ο ο > — * ο ο »-» ο ο »—» i— * o > — »p l > —1 — o I —Ι ο Η > < > 1— · ο 1 1— »ο 2mm Xiangji 1 \ 〇Ό o ν〇00 Ον w Han 〇 > 'Λ / —N Cl ο Ρ3 严' stuffed to to o 〇 \ 00 00 in to to 浒 bf · Check Ό a σ η η 〇 Broken m N) Please read the precautions of% Back Λ first% Gutter on this page-24-This paper size applies to Chinese national standards (CNS) Α4 specification (210X 297 mm)

Claims (1)

8 Π 10 A8 B8 C8 D8 1. The scope of patent application for amination method of a mononuclear aromatic compound and a polynuclear compound containing at least one aromatic ring, which consists of a mononuclear aromatic compound and a polynuclear compound containing a primary amine or The secondary amine compound is reacted in the presence of tritium, and the procedure is performed in the presence of water and a palladium composite catalyst containing organic water-soluble palladium as a molar excess. 2. The method according to item i of the patent application, wherein the compound is an aryl compound of the formula I: at least one aromatic ring and a palladium complex catalytic phosphine ligand pair for the mononuclear aromatic R-R1 R3 X- ----- * ----- Install ------ Order (Please read the notes on the back before filling out this page) 4-p-CH3), and replace or be replaced by the Central Bureau of Standards of the Ministry of Economic Affairs Employee consumer cooperatives print s alkenyl or 0: 6 aryl) 2, or -CN, Canki, not taken R5 where X is halogen,-(S〇2-CF3) or-(s〇2_c6H 1 ^, 1 ^, 3,114,115 are the same or different, and are hydrogen, fluorine, non-base, K6 alkyl, <: 3-c6 alkenyl with non-terminal C = C double bond, C3 with non-terminal ChC triple bond -Ce alkynyl, -0R6, where R6 is hydrogen unsubstituted or substituted phenyl, Cl-c6 alkyl, c2-c group 'or 0 0 0 〇n II II 7 I! II I -COH, -OCR7, -COR7, -CR7, -CN (R where R7 is the same or different, is (^-(: 6 alkyl, c2_c6 generation or substituted phenyl. 3. If the method of the second item of the patent application, Its # r1r2, r3, r4, -25-This paper size is applicable to China and Central European Countries (CNS) Α4 said (210 × 297 (Mm) A8 B8 C8 D8 VI. The scope of patent application shows that the benzene ring in the R5, R6, R7 group has a substitution, and the following II table r! R9 R 10 II wherein 8, 8, 9 and 1 and 11 are the same or different, and are (: 1_ (: alkenyl, phenyl, or benzyl). 4. If the method of the first item of the patent scope, Wherein the compound is a compound of the general formula II: alkyl, C2-C, the mononuclear aromatic RR used X III Central Consumers Bureau, Ministry of Economic Affairs, Consumer Cooperatives, printed 4-p-CH3), but substituted or substituted 6 alkenyl, R17 is hydrogen, alkenyl, C6 aromatic where X is halogen,-(so2-cf3) Or-(s〇2_c6h r13, r14, r15, r16 are the same or different, are hydrogen, fluorine, unphenyl, Ci-Ce alkyl, C3-C6 alkyne with non-terminal C = c and non-terminal CsC triple bond Group, -OR17 group, its unsubstituted or substituted phenyl group, Ci-G alkyl group, c2_c -26-Private paper applies Chinese National Standard (CNS) A4 ^ (2 丨 GX297 mm) 8 8 8 8 ABCD 6 The scope of the patent application, or C} 〇〇〇〇II II 18 II Ig «18 -COH, -OCR18, -COR18, -CR18, -CN, where R18 is the same or different, is Ci-Ce; alkyl is not Those who are substituted or substituted with phenyl. 5. If the method of the fourth scope of the patent application, the benzene ring in R165R17, R18 has a substitute, can be represented by Formula IV ^: N (R18) 2, or C'2 -C 6 Chanky, r13, r14, r15: Shows: R1 R 20 R21 IV R23 R22, where ruler 19, 112 ° ^ 21, 1122, ruler 23 is the same or different, and is <: 1_ (: 4 alkyl, (: 2-C4 alkenyl, phenyl, or benzyl. 6. For example, the method of applying for item 1 of the patent scope, in which the polynuclear compound containing at least one aromatic ring is an onion quinone compound of the general formula V: (Please read the precautions on the back before filling this page) Staff Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Printed 9 2 R 2 R Where X is halogen,-(so2, cf3) or-(so2-c6h r24, r25, r26, r27, r2S, r29, r3 ° are the same or different, which is -27-the Chinese standard (CNS) A4 is not applicable for paper scale Specifications (210X297 mm) V -p-CH3), while hydrogen, fluorine, chlorine, Α8 Β8 C8 D8 C ^ C6 alkylΐ > 0 ... υ 4 'ϋ 6. The scope of patent application is not substituted or substituted Phenyl, C ^ -Ce alkyl, C3-C6 alkenyl with terminal C = C double bond, c3-c6 block with non-terminal CeC triple bond, -OR31, where R31 is hydrogen, unsubstituted or substituted Substituted phenyl c2-c6 alkenyl, c6 aryl, or 0 0 0 0 0 II II 32 丨 丨 32 1 丨 32 \\ 32, -COH, -OCR32, -COR32, -CR32, -CN (R32) 2 , Or _CN, where R: is the same or different, is Ci-C6 courtyard, C2-C «s alkenyl, unsubstituted or substituted phenyl. 7. If the method of the 6th scope of the patent application, the CU R24 R25 R26 R, R, R29, R3e, R31, R32 has a substituted benzene ring; as shown in the following formula VI: (Please read the first Please fill in this page again)-Pack. R 3 3 R: R R R 3 5 VI-Ordered by a spring. Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs where ^^^^ is the same or different, C4 alkenyl, benzene or even benzyl. 8. The method according to item 1 of the scope of patent application, in which the amine compound: C4 fluorenyl, C2- Use formula 28 of Table VII. Paper size applies to Chinese National Standard (CNS) A4 specification (210X297 mm) υ A8 Β8 C8 D8, Patent application scope R 3 8 HN VII R 3 9 wherein R3 * and R39 are the same or different, and are hydrogen, unsubstituted or Cl-Cl ° fluorenyl group, having C3-Cu terminal CsC triple bond with non-terminal C = c double fluorene C3_Cl. Alkynyl, b (〇r4〇) 2 SUR4 °) 3, R4〇 is the same or different, is Ci_c4 alkyl, is 9. The method of item 1 in the scope of patent application, wherein the compound: Base, non-Sn (R4 °) 3 or base or benzyl. Use amine as formula VIII (please read the precautions on the back before filling out this page)-Install R43 R \ (C / HN R \ (c) r ^ 44 'Order-VIII R 46 Employees of Central Bureau of Economics, Ministry of Economic Affairs Printed by a consumer cooperative, where R is Ci-Ciq, with non-terminal c = c double radical, C3-C1Q alkynyl with non-terminal CsC triple bond, oxygen 1142 is alkyl, and non-terminal C = C with non-terminal OC double bond The Cs-Ci of the triple bond. The alkynyl group, while R43 is the same or different, is hydrogen, an unsubstituted or substituted benzene ring, a C3-C! With a non-terminal C = CX2 bond. An alkenyl group, a non-c3-c1 ( ) Alkynyl, B (OR47) 2, Sn (R47) 3 or Si (R -29-the paper size applies to the Chinese National Standard (CNS) A4 size (210X297 mm) bond C3-C10 · or NR42, where C $ -Ci. Chanji, R44, R45, R46 Phase C1-C1 〇 House, terminal, CsC three-button 47) 3, of which R47 is printed by the Ministry of Economic Affairs t Consumer Employees Cooperative Cooperative A8 and Ug8 VI. Patent Application The ranges are the same or different, and are C ^ -C: 4 alkyl, phenyl or benzyl. 0. The method according to item 1 of the patent application, wherein the palladium compound used is palladium acetate, Pd (d ba) 2, PdCl2, PdBr2, Pd]: 2 or Pd (acac) 2. 11 _ As in the method of applying patent scope 申请 1, wherein the organic water-soluble phosphine ligand of the palladium complex catalyst uses the formula IX Sulfonated triaryl: · (S03M) m ΑΓ1 / ^^ (YOnn / ^^ * (S03M) n2 Ρ Αγ2 \, IX \ ^^-(Y2) m2 ^^^ (S〇3M) n3 Ar3, ^^ (Y3) m3 wherein Αη, Αι ^, Αι ^ are the same or different, are phenyl or naphthyl, Υ "Υ2, Υ3 are the same or different, are straight or branched alkyl, alkoxy, halogen, -CN,- N02, -0H, -0-sugar, where the sugar is a monosaccharide or polysaccharide or -nr48r49, where R48 and R49 are the same or different, and are straight or branched (: 1-C 4 courtyard, M is hydrogen, ammonium ion Quaternary ammonium ion, monovalent metal or polyvalent metal equivalent, ΠM, π2, ιη3 are the same or different integers, from 0 to 5, η !, η2, η3 are the same or different integers, from 0 to 3, m, At least one of n2 or n3 is equal to or greater than 30. — Chinese paper standard (CNS) A4g (210 X 297 mm) for wood and paper scales. Please read the precautions before installing ir spring A8 B8 C8 D8 4 〇 Application Lee range sulfonated diphosphine 1, or of the general formula X: mo3s (CH2) r - pa〆 (CH2) r _ PAr '2 - pPhp X 2 - pPhp mo3s (Please read the notes on the back before filling out this page) Same or different, printed lead, zinc or copper R50R51R52R53 organic water-soluble phosphine 1 for the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs, using palladium to account for 0.1 to 5 of the nuclear compounds Mol where Ar1 is m-CsHiSC ^ M, M is one of hydrogen, ammonium v quaternary ion, monovalent or polyvalent metal equivalent, Ph is phenyl, p-phase 0, 1 or 2, Γ is the same or different, as 〇 or 1 12. The method according to item 11 of the scope of patent application, wherein M in formulae IX and X is a metal ion, especially a sodium ion, or a soil metal ion, or a quaternary ammonium ion of formula N (R5 () R51R52R53) +, Among them, the same or different ones are straight-chain or branched-chain alkyl groups. 13. The method according to item 1 of the patent application range, wherein the molar ratio to palladium is (2 ~ 200): 1, especially (3 ~ 200): mononuclear aromatic compound or as many as containing at least one aromatic ring 0.00% to 25 mole%, preferably 0.001 to 20 mole%, and% is particularly preferred, using a reaction temperature of 20 to 160. (: It is better to be 50 ~ 120 ° C, the reaction time is 10 minutes to 170 hours, and 1 2 to 96 hours is the best. —3 1 The paper size is applicable to China National Standards (CNS) A4 specifications (210X297 mm) Class I U70 A8 B8 C8 D8, patent application scope 14. The method according to item 1 of the patent scope, wherein the organic solvent is methanol, ethanol, n-propanol, isopropanol, n-butanol, Tetrahydrofuran, dibutyl ether, 2-butanol methyl formamide, diethyl ether, ethyl acetate, dioxane, methyl ethylene glycol, pentane, hexane, heptane, and octane, two of which are mixtures. In addition, there are alcohol, isobutanol, 2-butanone, diphenyl, xylene, or more solvents -----------------------, a ' 5J I (Please read the notes on the back before filling out this page) Printed by the Consumer Standards Cooperative of the Central Bureau of Standards, Ministry of Economic Affairs 32 This paper size is in Chinese National Standard (CNS) A4 (210X 297 mm)