CN103159699B - N-formyl phenothiazine 1, 3-diaminourea bis-schiff base and preparation method thereof - Google Patents
N-formyl phenothiazine 1, 3-diaminourea bis-schiff base and preparation method thereof Download PDFInfo
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- CN103159699B CN103159699B CN201310100576.0A CN201310100576A CN103159699B CN 103159699 B CN103159699 B CN 103159699B CN 201310100576 A CN201310100576 A CN 201310100576A CN 103159699 B CN103159699 B CN 103159699B
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Abstract
The invention discloses an N-formyl phenothiazine 1, 3-diaminourea bis-schiff base and a preparation method thereof. The structural formula of the N-formyl phenothiazine 1, 3-diaminourea bis-schiff base is shown in the specification, wherein R is O or S; and the preparation method comprises the following steps of: adding A mol of N-formyl phenothiazine and B mol of 1, 3-diaminourea compound to a reaction container, then adding absolute ethyl alcohol, heating to 50-80 DEG C for reaction, monitoring by using TLC (Thin Layer Chromatography) in the reaction process, and stopping reaction till the raw material point of the 1, 3-diaminourea compound disappears, thus obtaining a reaction liquid, wherein the ratio of A to B is (2.0-2.2): 1; and cooling the reaction liquid to room temperature, carrying out suction filtering, washing filter cakes, drying and recrystallizing, thus obtaining the N-formyl phenothiazine 1, 3-diaminourea bis-schiff base. The preparation method is simple in operation, mild in reaction conditions, short in reaction time and high in yield; and the prepared N-formyl phenothiazine 1, 3-diaminourea bis-schiff base has good antibacterial activity.
Description
Technical field
The invention belongs to the field of chemical synthesis, particularly a kind of N-formyl phenothiazine 1, two Schiff's base of 3-diamino ureas and preparation method thereof.
Background technology
Schiff's base mainly refers to a class organic compound that contains imines or azomethine characteristic group (RC=N-), is widely used in medicine, catalysis, analytical chemistry, corrosion and the field such as photochromic.The Schiff's base that wherein contains urea groups or thioureido is the important compound of a class, has antibacterial, sterilization, unique medicinal effect such as antitumor and antiviral, enjoys investigator's concern.
Thiodiphenylamine is a kind of heterogeneous ring compound of nitrogenous, sulphur, its derivative is widely used in the auxiliary agent of agricultural chemicals (fruit tree insecticide), medicine (tranquilizer), dyestuff and synthetic materials, also can be applicable to the photoelectric fields such as nonlinear optics, electroluminescent and semiconducter device, there is good development prospect.
Summary of the invention
The object of the present invention is to provide a kind of N-formyl phenothiazine 1, two Schiff's base of 3-diamino ureas and preparation method thereof, the method is simple to operate, reaction conditions is gentle, productive rate is high.
For achieving the above object, technical scheme of the present invention is:
N-formyl phenothiazine 1, the two Schiff's base of 3-diamino ureas, its structural formula as the formula (1):
Wherein R=O or S.
N-formyl phenothiazine 1, the preparation method of the two Schiff's base of 3-diamino ureas, comprises the following steps:
The first step, by A mol N-formyl phenothiazine and B mol1,3-diaminourea compounds adds in reaction vessel, add again dehydrated alcohol, be heated to 50～80 DEG C and react, in reaction process, monitor with TLC, until 1, stopped reaction when the raw material point of 3-diaminourea compounds disappears, obtains reaction solution, wherein A:B=(2.0～2.2): 1;
Second step, is cooled to room temperature by reaction solution, and suction filtration is by filter cake washing, dry, then uses dehydrated alcohol recrystallization, obtains N-formyl phenothiazine 1, the two Schiff's base of 3-diamino ureas.
Described 1,3-diaminourea compounds is 1,3-diaminourea or 1,3-diamino thiocarbamide.
In the described the first step, the consumption of dehydrated alcohol is C mL, 500B≤C≤800B.
The developping agent of described TLC is that volume ratio is 1:(5～7) ethyl acetate and the mixed solvent of sherwood oil.
In described second step, filter cake is used to D mL absolute ethanol washing, 100B≤D≤200B.
Described N-formyl phenothiazine 1, the two Schiff's base of 3-diamino ureas are as the application of anti-gram-bacteria or yeast medicine.
Described gram-bacteria is intestinal bacteria, streptococcus aureus or actinomycetes.
Described N-formyl phenothiazine 1, the application of the two Schiff's base of 3-diamino ureas in the anti-gram-bacteria of preparation or yeast medicine.
Described gram-bacteria is intestinal bacteria, streptococcus aureus or actinomycetes.
With respect to prior art, beneficial effect of the present invention is:
N-formyl phenothiazine 1 provided by the invention; the preparation method of the two Schiff's base of 3-diamino ureas; taking dehydrated alcohol as solvent; by N-formyl phenothiazine and 1; 3-diaminourea compounds is dissolved in dehydrated alcohol, is then heated to 50～80 DEG C and reacts, and prepares N-formyl phenothiazine 1; the two Schiff's base of 3-diamino ureas, the present invention is simple to operate, raw material is easy to get relatively, reaction conditions gentleness, reaction times are shorter, convenient post-treatment, productive rate are high.
The N-formyl phenothiazine 1 that the present invention prepares; in the structure of the two Schiff's base of 3-diamino ureas, contain thiophene piperazine group and Schiff's base group simultaneously; there is good bacteriostatic activity; gram-bacteria and yeast are all had to good bacteriostatic action; can serve as anti-gram-bacteria or yeast medicinal application; or apply in the anti-gram-bacteria of preparation or yeast medicine, have a good application prospect.
Embodiment
The present invention is taking dehydrated alcohol as solvent; by N-formyl phenothiazine and 1; 3-diaminourea compounds is dissolved in dehydrated alcohol; then being heated to 50～80 DEG C reacts; TLC(thin layer chromatography) monitoring; obtain N-formyl phenothiazine 1, the two Schiff's base of 3-diamino ureas, its reaction formula be its reaction formula as the formula (2):
Wherein R=O or S.
In the time of R=O, 1,3-diaminourea compounds is 1,3-diaminourea; In the time of R=S, 1,3-diaminourea compounds is 1,3-diamino thiocarbamide.
N-formyl phenothiazine 1 provided by the invention, the two Schiff's base of 3-diamino ureas, its structural formula as the formula (1):
Wherein R=O or S.
In the time of R=O, N-formyl phenothiazine 1 provided by the invention, the two Schiff's base of 3-diamino ureas are N-formyl phenothiazine 1, the two Schiff's base of 3-diaminourea, its structural formula as the formula (3):
In the time of R=S, N-formyl phenothiazine 1 provided by the invention, the two Schiff's base of 3-diamino ureas are N-formyl phenothiazine 1, the two Schiff's base of 3-diamino thiocarbamide, its structural formula as the formula (4):
Below in conjunction with embodiment, the present invention is described in further detail.
Embodiment 1
The first step, by 0.020mol N-formyl phenothiazine and 0.010mol1,3-diamino thiocarbamide adds in dry reaction flask, then adds wherein 7mL dehydrated alcohol, is heated to 70 DEG C, reaction 5h, in reaction process with TLC monitoring, until stopped reaction when the disappearance of the raw material point of 1,3-diamino thiocarbamide, obtain reaction solution, wherein the developping agent of TLC is that volume ratio is the ethyl acetate of 1:5 and the mixed solvent of sherwood oil;
Second step, is cooled to room temperature by reaction solution, and suction filtration by dry after filter cake use 1mL absolute ethanol washing, then is used dehydrated alcohol recrystallization, and the 4.74g rice white crystal obtaining is N-formyl phenothiazine 1, the two Schiff's base of 3-diamino thiocarbamide, and productive rate is 90.46%.
IR（cm
-1,KBr）：3309，3089，1643，1593，1309，741。
1HNMR（CDCl
3,400MHZ）:10.80(s,2H,NH)，8.67(s,2H,CH=N)，6.92～7.39(m,16H,ArH)。
Embodiment 2
The first step, by 0.022mol N-formyl phenothiazine and 0.010mol1,3-diamino thiocarbamide adds in dry reaction flask, then adds wherein 8mL dehydrated alcohol, is heated to 80 DEG C, reaction 4h, in reaction process with TLC monitoring, until stopped reaction when the disappearance of the raw material point of 1,3-diamino thiocarbamide, obtain reaction solution, wherein the developping agent of TLC is that volume ratio is the ethyl acetate of 1:6 and the mixed solvent of sherwood oil;
Second step, is cooled to room temperature by reaction solution, and suction filtration by dry after filter cake use 2mL absolute ethanol washing, then is used dehydrated alcohol recrystallization, and the 4.73g rice white crystal obtaining is N-formyl phenothiazine 1, the two Schiff's base of 3-diamino thiocarbamide, and productive rate is 90.27%.
Embodiment 3
The first step, by 0.042mol N-formyl phenothiazine and 0.020mol1,3-diamino thiocarbamide adds in dry reaction flask, then adds wherein 10mL dehydrated alcohol, is heated to 50 DEG C, reaction 6h, in reaction process with TLC monitoring, until stopped reaction when the disappearance of the raw material point of 1,3-diamino thiocarbamide, obtain reaction solution, wherein the developping agent of TLC is that volume ratio is the ethyl acetate of 1:7 and the mixed solvent of sherwood oil;
Second step, is cooled to room temperature by reaction solution, and suction filtration by dry after filter cake use 3mL absolute ethanol washing, then is used dehydrated alcohol recrystallization, and the 9.46g rice white crystal obtaining is N-formyl phenothiazine 1, the two Schiff's base of 3-diamino thiocarbamide, and productive rate is 90.26%.
Embodiment 4
The first step, by 0.022mol N-formyl phenothiazine and 0.010mol1,3-diaminourea adds in dry reaction flask, then adds wherein 6mL dehydrated alcohol, is heated to 50 DEG C, reaction 6h, in reaction process with TLC monitoring, until stopped reaction when the disappearance of the raw material point of 1,3-diaminourea, obtain reaction solution, wherein the developping agent of TLC is that volume ratio is the ethyl acetate of 1:6 and the mixed solvent of sherwood oil;
Second step, is cooled to room temperature by reaction solution, and suction filtration by dry after filter cake use 2mL absolute ethanol washing, then is used dehydrated alcohol recrystallization, and the 4.58g white crystal obtaining is N-formyl phenothiazine 1, the two Schiff's base of 3-diaminourea, and productive rate is 90.16%.
IR（cm
-1,KBr）：3310，3059，1643，1578，1309，741。
1HNMR（CDCl
3,400MHZ）:10.81(s,2H,NH)，7.50(s,2H,CH=N)，6.92～7.39(m,16H,ArH)。
Embodiment 5
The first step, by 0.021mol N-formyl phenothiazine and 0.010mol1,3-diaminourea adds in dry reaction flask, then adds wherein 5mL dehydrated alcohol, is heated to 65 DEG C, reaction 5h, in reaction process with TLC monitoring, until stopped reaction when the disappearance of the raw material point of 1,3-diaminourea, obtain reaction solution, wherein the developping agent of TLC is that volume ratio is the ethyl acetate of 1:7 and the mixed solvent of sherwood oil;
Second step, is cooled to room temperature by reaction solution, and suction filtration by dry after filter cake use 1.5mL absolute ethanol washing, then is used dehydrated alcohol recrystallization, and the 4.59g white crystal obtaining is N-formyl phenothiazine 1, the two Schiff's base of 3-diaminourea, and productive rate is 90.33%.
Embodiment 6
The first step, by 0.040mol N-formyl phenothiazine and 0.020mol1,3-diaminourea adds in dry reaction flask, then adds wherein 16mL dehydrated alcohol, is heated to 80 DEG C, reaction 4h, in reaction process with TLC monitoring, until stopped reaction when the disappearance of the raw material point of 1,3-diaminourea, obtain reaction solution, wherein the developping agent of TLC is that volume ratio is the ethyl acetate of 1:5 and the mixed solvent of sherwood oil;
Second step, is cooled to room temperature by reaction solution, and suction filtration by dry after filter cake use 1mL absolute ethanol washing, then is used dehydrated alcohol recrystallization, and the 9.15g white crystal obtaining is N-formyl phenothiazine 1, the two Schiff's base of 3-diaminourea, and productive rate is 90.08%.
Bacteriostatic test:
The N-formyl phenothiazine 1 that adopts filter paper method to prepare the present invention; the two Schiff's base of 3-diamino thiocarbamide and N-formyl phenothiazine 1; the two Schiff's base of 3-diaminourea carry out bacteriostatic activity test; select pure acetone solution as blank; the bacterial classification of selecting is respectively intestinal bacteria, streptococcus aureus, actinomycetes and yeast, by agar culture dish in 37 DEG C of constant temperature culture 48h.The streptococcus aureus of wherein selecting in bacteriostatic test and actinomyces are in gram-positive microorganism; Intestinal bacteria belong to Gram-negative bacteria; Saccharomycodes is in fungi.Gram-bacteria comprises Gram-negative bacteria and gram-positive microorganism.
Test result is N-formyl phenothiazine 1, and the two Schiff's base of 3-diamino thiocarbamide are respectively 7mm to intestinal bacteria, streptococcus aureus, actinomycetes and saccharomycetic antibacterial circle diameter, 5mm, 4mm and 6mm; N-formyl phenothiazine 1, the two Schiff's base of 3-diaminourea are respectively 6mm to intestinal bacteria, streptococcus aureus, actinomycetes and saccharomycetic antibacterial circle diameter, 5mm, 5mm and 7mm.Experimental result shows; N-formyl phenothiazine 1 prepared by the present invention; the two Schiff's base of 3-diamino ureas have good bacteriostatic activity; gram-bacteria and yeast are all had to good bacteriostatic action; can serve as anti-gram-bacteria or yeast medicinal application; or apply in the anti-gram-bacteria of preparation or yeast medicine, have a good application prospect.
Claims (7)
1.N-formyl phenothiazine 1, the two Schiff's base of 3-diamino ureas, is characterized in that, its structural formula is suc as formula shown in (1):
Wherein R=O or S.
2.N-formyl phenothiazine 1, the preparation method of the two Schiff's base of 3-diamino ureas, is characterized in that, comprises the following steps:
The first step, by A mol N-formyl phenothiazine and B mol1,3-diaminourea compounds adds in reaction vessel, add again dehydrated alcohol, be heated to 50～80 DEG C and react, in reaction process, monitor with TLC, until 1, stopped reaction when the raw material point of 3-diaminourea compounds disappears, obtains reaction solution, wherein A:B=(2.0～2.2): 1; Described 1,3-diaminourea compounds is 1,3-diaminourea or 1,3-diamino thiocarbamide;
Second step, is cooled to room temperature by reaction solution, and suction filtration is by filter cake washing, dry, then uses dehydrated alcohol recrystallization, obtains N-formyl phenothiazine 1, the two Schiff's base of 3-diamino ureas.
3. N-formyl phenothiazine 1 according to claim 2, the preparation method of the two Schiff's base of 3-diamino ureas, is characterized in that: in the described the first step, the consumption of dehydrated alcohol is C mL, 500B≤C≤800B.
4. N-formyl phenothiazine 1 according to claim 2, the preparation method of the two Schiff's base of 3-diamino ureas, is characterized in that: the developping agent of described TLC is that volume ratio is 1:(5～7) ethyl acetate and the mixed solvent of sherwood oil.
5. N-formyl phenothiazine 1 according to claim 2, the preparation method of the two Schiff's base of 3-diamino ureas, is characterized in that: in described second step, filter cake is used to D mL absolute ethanol washing, 100B≤D≤200B.
6. N-formyl phenothiazine 1 claimed in claim 1, the application of the two Schiff's base of 3-diamino ureas in the anti-gram-bacteria of preparation or yeast medicine.
7. N-formyl phenothiazine 1 according to claim 6, the application of the two Schiff's base of 3-diamino ureas in the anti-gram-bacteria of preparation or yeast medicine, is characterized in that: described gram-bacteria is intestinal bacteria, streptococcus aureus or actinomycetes.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3719671A (en) * | 1971-05-27 | 1973-03-06 | Mead Johnson & Co | 10-imidoylphenothiazines |
| DE102004040212A1 (en) * | 2004-08-19 | 2006-03-02 | Icfs Gmbh | New N,N-diacylamine derivatives are useful in the preparation of aromatic and hetero-cyclic aldehydes and useful as acylating or formylating agents |
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2013
- 2013-03-26 CN CN201310100576.0A patent/CN103159699B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3719671A (en) * | 1971-05-27 | 1973-03-06 | Mead Johnson & Co | 10-imidoylphenothiazines |
| DE102004040212A1 (en) * | 2004-08-19 | 2006-03-02 | Icfs Gmbh | New N,N-diacylamine derivatives are useful in the preparation of aromatic and hetero-cyclic aldehydes and useful as acylating or formylating agents |
Non-Patent Citations (8)
| Title |
|---|
| A series of schiffs bases and secondary amine derivatives from 3-formyl-10-methylphenothiazine;W.kremers 等;《 Canad journal of chemistry》;19671231;第45卷(第7期);745-749 * |
| Preparation of 3-substituted 10-methylphenothiazines;Soren Ebdrup;《J.chem.soc》;19981231;1147-1150 * |
| Soren Ebdrup.Preparation of 3-substituted 10-methylphenothiazines.《J.chem.soc》.1998, |
| W.kremers 等.A series of schiffs bases and secondary amine derivatives from 3-formyl-10-methylphenothiazine.《 Canad journal of chemistry》.1967,第45卷(第7期), |
| 吩噻嗪及其衍生物的合成与应用;蒋云涛等;《染料与染色》;20100630;第47卷(第3期);35-39 * |
| 吩噻嗪和三环类药物对结核菌的抑菌作用研究;王金河等;《中国实验诊断学》;20080331;第12卷(第3期);381-382 * |
| 王金河等.吩噻嗪和三环类药物对结核菌的抑菌作用研究.《中国实验诊断学》.2008,第12卷(第3期), |
| 蒋云涛等.吩噻嗪及其衍生物的合成与应用.《染料与染色》.2010,第47卷(第3期), |
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