CN1173955C - Process for preparing ketone condensate of L-(+)-2-amino-1-p-nitrophenyl-1,3-propanediol - Google Patents
Process for preparing ketone condensate of L-(+)-2-amino-1-p-nitrophenyl-1,3-propanediol Download PDFInfo
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- CN1173955C CN1173955C CNB001143468A CN00114346A CN1173955C CN 1173955 C CN1173955 C CN 1173955C CN B001143468 A CNB001143468 A CN B001143468A CN 00114346 A CN00114346 A CN 00114346A CN 1173955 C CN1173955 C CN 1173955C
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- nitrophenyl
- amino
- ammediol
- ketone
- propanediol
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Abstract
The present invention discloses a novel method for preparing the ketone condensate of L-(+)-2-amino-1-p-nitrophenyl-1, 3-propanediol from industrial L-(+)-2-amino-1-p-nitrophenyl-1, 3-propanediol. In the method, the ketone condensate of crystalline-(+)-2-amino-1-p-nitrophenyl-1, 3-propanediol is directly prepared from purified L-(+)-2-amino-1-p-nitrophenyl-1, 3-propanediol and ketone by condensation in a proper arylhydrocarbon medium under the conditions of atmospheric pressure or higher pressure and no existence of catalysts, or a condensate crystal is prepared from condensed reaction liquid by treatment.
Description
The present invention relates to a kind of preparation L-(+)-2-amino-1-p-nitrophenyl-1, the method for ammediol ketone condensate belongs to the heterogeneous ring compound preparing technical field.
L-(+)-2-amino-1-p-nitrophenyl-1, ammediol is the by product of production of chloramphenicol.Owing to contain a plurality of functional groups in its molecule, so can carry out widely molecular modification, obtain polytype chiral heterocycle compound.These heterogeneous ring compounds can be used as resolving agent in the fractionation of racemic compound, be used as chiral material, chiral induction agent etc. in asymmetric synthesis.
The before existing researchs of L-(+)-2-amino-1-p-nitrophenyl-1, ammediol and reactive ketone.1956, Bergmann, E.D. and Resnick, H. report L-(+)-2-amino-1-p-nitrophenyl-1, ammediol and pimelinketone or propione azeotropic distillation in benzene obtains the condenses (J.Chem.Soc., 1956,1662) that fusing point is respectively 107-108 ℃ or 124-125 ℃; In this simultaneously, Pedrazzdi, A. and Tricerri, S. have also reported racemize 2-amino-1-p-nitrophenyl-1, ammediol and the acetone condensation reaction in benzene under Catalyzed by p-Toluenesulfonic Acid (Helv.Chim.Acta, 1956,39,965).But the two report is the oxazolidine derivative of different types.1987, Werner, people such as W. made L-(+)-2-amino-1-p-nitrophenyl-1 under acetic acid catalysis, and ammediol and pimelinketone, acetone, propione or 2-butanone reaction obtain multiple condensation product (J.Prakt.Chem., 1987,329 (6), 1031); Afterwards, Darabantu, people such as M. were by L-(+)-2-amino-1-p-nitrophenyl-1, and ammediol and acetone synthesize 1.3-diox (Rev.Rom.Chim., 1995,40 (5), 453).But the applicant finds, experimentizes according to their program, or is difficult to obtain crystalline products, or condenses productive rate lower (having only 50～60% usually), or do not match with their result.
Purpose of the present invention just provides L-(+)-2-amino-1-p-nitrophenyl-1, the new system of ammediol and ketone condensation and crystalline products make things convenient for separation method.
For realizing that the technical scheme that purpose of the present invention is taked is:
Industrial by-products L-(+)-2-amino-1-p-nitrophenyl-1 of paraxin will be produced, after the ammediol crude product is purified, in the inertia aromatic hydrocarbon medium, carry out condensation with ketone, azeotropic dehydration under 1-5 normal atmosphere, after cooling, directly separate out crystalline products, perhaps after removing volatilizable thing, evaporation extracts, by obtaining the condenses crystal in the extraction liquid with appropriate solvent.
According to the present invention, pure L-(+)-2-amino-1-p-nitrophenyl-1, the preparation procedure of ammediol is: industrial L-(+)-2-amino-1-p-nitrophenyl-1, ammediol is handled with concentrated hydrochloric acid, removes acid non-soluble substance, by telling L-(+)-2-amino-1-p-nitrophenyl-1 in the solution, ammediol hydrochloride crystal, use alkaline purification again, the L-(+) that dissociates-2-amino-1-p-nitrophenyl-1, ammediol.
According to the present invention, by L-(+)-2-amino-1-p-nitrophenyl-1, L-(+)-2-amino-1-p-nitrophenyl-1 that dissociates in the ammediol hydrochloride crystal, the used alkali of ammediol is selected from sodium hydroxide, calcium hydroxide, sodium bicarbonate, yellow soda ash, solution of potassium carbonate or ammoniacal liquor.
According to the present invention, with L-(+)-2-amino-1-p-nitrophenyl-1, the ketone of ammediol condensation is alkyl ketone R
1R
2CO or alicyclic ketone (CH
2)
nCO.
According to the present invention, with L-(+)-2-amino-1-p-nitrophenyl-1, the alkyl ketone R of ammediol condensation
1R
2R among the CO
1, R
2Be methyl, ethyl, propyl group, butyl, sec.-propyl, isobutyl-; Alicyclic ketone (CH
2)
nN among the CO is 4,5.
According to the present invention, L-(+)-2-amino-1-p-nitrophenyl-1, the used inertia aromatic hydrocarbon medium of ammediol and ketone azeotropic dehydration is by benzene, and toluene is selected in the dimethylbenzene.
According to the present invention, L-(+)-2-amino-1-p-nitrophenyl-1, ammediol and ketone azeotropic dehydration carry out under the 1-5 normal atmosphere.
According to the present invention, L-(+)-2-amino-1-p-nitrophenyl-1, the condenses of ammediol and some ketone is directly separated out with crystalline products after the reaction solution cooling.
According to the present invention, when L-(+)-2-amino-1-p-nitrophenyl-1, the condenses of ammediol and some ketone can not separate out with crystalline products after the reaction solution cooling, can evaporate and remove volatilizable thing, resistates extracts with appropriate solvent, by getting pure condensation product in the extraction liquid.
According to the present invention, the used solvent of the resistates behind the extracting, evaporating reaction solution is by selecting in ether, the ethyl acetate.
According to the present invention, by obtain in the extraction liquid that crystalline products is taked extraction liquid suitably concentrated or solution after concentrating in add the way of this condenses crystal seed.
Compared with the prior art, adopt technical scheme of the present invention to have following several distinguishing feature:
Adopt method of the present invention simple, mild condition, the very convenient condenses that obtains crystalline state, and also its yield is high, can reach more than 90% usually; Method of the present invention has been opened up the new reaction system of a class; Method of the present invention need not any catalyzer.Therefore, technical scheme of the present invention in the fractionation of racemic compound, asymmetric synthesis has important use aspect medium and is worth.
Below in conjunction with specific embodiment technical scheme of the present invention is further described:
Embodiment 1
In inert atmosphere (nitrogen or argon gas), in flask at the bottom of the 250mL exsiccant garden, add L-(+)-2-amino-1-p-nitrophenyl-1 that 12.72 gram purifying are crossed, ammediol (60mmol), 6 gram pimelinketone (61.2mmol) and 100mL toluene; The stirrer of packing into is also installed water-and-oil separator, reflux condensing tube in succession and is had the oily bubbler of piston; Reflux under induction stirring distillates the water of generation rapidly; After 3 hours, stop heating; Use the rare gas element equilibrium pressure, remove water-and-oil separator, reflux condensing tube and have the oily bubbler of piston, change the water distilling apparatus distillation or on rotatory evaporator, evaporate; Resistates extracts with 40mL (20mL * 2) anhydrous diethyl ether; Tell extraction liquid and be concentrated into the about 1/4th of original volume, room temperature is placed, and separates out the faint yellow bulk crystals A of 13.5 grams, M.P 70-72 ℃; Ultimate analysis: C, 61.67; H, 7.12; N, 9.66%.C
15H
20N
2O
4Calculated value: C, 61.63; H, 6.90; N, 9.59%.The mother liquor reconcentration, similar again crystal.Total recovery is higher than 80%.
Gained crystal thermosol is chilled to room temperature behind dimethylbenzene, almost quantitatively separates out L-(+)-2-amino-1-p-nitrophenyl-1 that contains 0.5 mole of dimethylbenzene, ammediol pimelinketone condenses, analytical data is seen embodiment 3.
Embodiment 2
16.96 L-(+)-2-amino-1-p-nitrophenyl-1 that the gram purifying is crossed, ammediol (80mmol), 8 the gram pimelinketone (81.6mmol) in the 120mL toluene as embodiment 1 azeotropic dehydration, evaporation reaction liquid then, extract with the 40mL anhydrous diethyl ether, the crystal that adding embodiment 1 obtains after suitably concentrating is a small amount of, place, obtain the faint yellow bulk crystals of 21.6 grams, yield 92%.Analytical results is with embodiment 1.
Embodiment 3
Replace toluene with dimethylbenzene, make 8.48 gram L-(+)-2-amino-1-p-nitrophenyls-1, ammediol (40mmol) and 4 gram pimelinketone (40.8mmol) condensations under refluxad 3 hours are chilled to room temperature, separate out the yellow needle-like crystal of 12.5 grams.M.P.54-56℃。Ultimate analysis: C, 65.62; H, 7.26; N, 2.81%.C
15H
20N
2O
40.5C
6H
4(CH
3)
2Calculated value: C, 66.06; H, 7.30; N, 8.11%.IR：3404m，3276m，sh(ν
N-H+ν
O-H)；2996s，2858ms(ν
C-H)；1601m(ν
C-C-C)；1520vs，1348vs(ν
N02)；1056s(ν
AS C-O-C)；848s(δ
Ph-H)。MS(EI)：292(M
+)，263(M
+-C
2H
5)，249(M
+-C
3H
7)，195(M
+-C
6H
11N)，177(M
+-C
6H
13NO)，141(M
+-C
7H
5NO
3)，140(M
+-C
7H
6NO
3)，123(M
+-C
8H
13N)，106(M
+ tolene)，91(M
+ tolene-CH
3)。
Embodiment 4
In inert atmosphere (nitrogen or argon gas), in flask at the bottom of the 100mL exsiccant garden, add L-(+)-2-amino-1-p-nitrophenyl-1 that 4.24 gram purifying are crossed, ammediol (20mmol), 4mL acetone (about 3.2 grams, 55.1mmol) and 60mL toluene, the stirrer of packing into is also installed water-and-oil separator, reflux condensing tube and pressure buffer device in succession; Reflux under induction stirring, along with the growth in reaction times, solid-state reactants is dissolved gradually; After 3 hours, stop heating; Remove on the reaction flask and install; Make reactant be chilled to room temperature, separate out colourless acicular crystal; Filter; Collect solid; Dry; Weigh 4.5 grams, yield 75.34%.MP.40-42℃。Ultimate analysis: C, 61.97; H, 6.69; N, 9.30%, C
12H
16N
2O
40.5C
6H
5CH
3Calculated value: C, 62.40; H, 6.76; N, 9.39%.IR：3404sh，3261m，3209sh(ν
N-H+ν
O-H)；2980m，2920m，2880m，2860m(ν
C-H)；1603m(ν
C-C-C)；1522vs，1350vs(ν
N02)；1047s(ν
AS C-O-C)；854s(δ
Ph-H)。Long-time decompression is found time under room temperature, can lose bonded toluene, and fusing point is increased to 76-78 ℃.Mother liquor suitably concentrates the back and places, colourless acicular crystal again, total recovery about 90%.
Claims (6)
1. one kind by industrial L-(+)-2-amino-1-p-nitrophenyl-1, ammediol prepares L-(+)-2-amino-1-p-nitrophenyl-1, the method of the ketone condensate of ammediol, it is characterized in that: the L-(+) that purifying is crossed-2-amino-1-p-nitrophenyl-1, ammediol and ketone are in the inertia aromatic hydrocarbon medium, azeotropic dehydration under 1-5 the normal atmosphere, to directly separate out after the reaction solution cooling then with crystalline products, perhaps in the time can not separating out with crystalline products after the reaction solution cooling, volatile matter is removed in evaporation, the resistates solvent extraction, from extraction liquid, obtain crystalline state 2-amino-1-p-nitrophenyl-1 again, the ketone condensate of ammediol.
2. method according to claim 1, it is characterized in that industrial L-(+)-2-amino-1-p-nitrophenyl-1, the purge process of ammediol is: industrial L-(+)-2-amino-1-p-nitrophenyl-1, ammediol is handled with concentrated hydrochloric acid, removes acid non-soluble substance, by telling L-(+)-2-amino-1-p-nitrophenyl-1 in the solution, ammediol hydrochloride crystal, use alkaline purification again, the L-(+) that dissociates-2-amino-1-p-nitrophenyl-1, ammediol.
3. method according to claim 2, it is characterized in that: from L-(+)-2-amino-1-p-nitrophenyl-1, L-(+)-2-amino-1-p-nitrophenyl-1 that dissociates in the ammediol hydrochloride crystal, the used alkali of ammediol are selected from a kind of in sodium hydroxide, calcium hydroxide, sodium bicarbonate, yellow soda ash, solution of potassium carbonate or the ammoniacal liquor.
4. method according to claim 1 is characterized in that: described and L-(+)-2-amino-1-p-nitrophenyl-1, the ketone of ammediol condensation is alkyl ketone R
1R
2CO or alicyclic ketone (CH
2)
nCO; Wherein, R
1, R
2Be methyl, ethyl, propyl group, butyl, sec.-propyl or isobutyl-; Alicyclic ketone (CH
2)
nN among the CO is 4 or 5.
5. method according to claim 1 is characterized in that described inertia aromatic hydrocarbon medium by benzene, and toluene is selected in the dimethylbenzene.
6. method according to claim 1 is characterized in that: the used solvent of the resistates behind the extracting, evaporating reaction solution is by selecting in ether, the ethyl acetate; By obtain in the extraction liquid that crystalline products is taked extraction liquid suitably concentrated or solution after concentrating in add the way of this condenses crystal seed.
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|---|---|---|---|
| CNB001143468A CN1173955C (en) | 2000-01-27 | 2000-01-27 | Process for preparing ketone condensate of L-(+)-2-amino-1-p-nitrophenyl-1,3-propanediol |
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|---|---|---|---|
| CNB001143468A CN1173955C (en) | 2000-01-27 | 2000-01-27 | Process for preparing ketone condensate of L-(+)-2-amino-1-p-nitrophenyl-1,3-propanediol |
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|---|---|
| CN1266847A CN1266847A (en) | 2000-09-20 |
| CN1173955C true CN1173955C (en) | 2004-11-03 |
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