CN103159698B - N-formyl phenothiazine 1, 3-diaminourea compound and preparation method thereof - Google Patents
N-formyl phenothiazine 1, 3-diaminourea compound and preparation method thereof Download PDFInfo
- Publication number
- CN103159698B CN103159698B CN201310100025.4A CN201310100025A CN103159698B CN 103159698 B CN103159698 B CN 103159698B CN 201310100025 A CN201310100025 A CN 201310100025A CN 103159698 B CN103159698 B CN 103159698B
- Authority
- CN
- China
- Prior art keywords
- diaminourea
- contracting
- formyl phenothiazine
- reaction
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Abstract
The invention discloses an N-formyl phenothiazine 1, 3-diaminourea compound and a preparation method thereof. The structural formula of the N-formyl phenothiazine 1, 3-diaminourea compound is shown in the specification, wherein R is O or S; and the preparation method comprises the following steps of: adding N-formyl phenothiazine and a 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; 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 compound. 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 compound is an important intermediate of a synthetic drug and has good antibacterial activity.
Description
Technical field
The invention belongs to the field of chemical synthesis, particularly a kind of N-formyl phenothiazine contracting 1,3-diaminourea compounds and preparation method thereof.
Background technology
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.
Taking Urea,amino-and thiosemicarbazide compound as raw material, synthetic thiadiazoles, triazole and the diazthines derivative with pharmacologically active become one of study hotspot of current organic synthesis, these derivatives suppressing Gram-negative bacteria and gram-positive microorganism, anti-inflammatory, the aspect such as antitumor shows higher activity.
Summary of the invention
The object of the present invention is to provide a kind of N-formyl phenothiazine contracting 1,3-diaminourea compounds 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 contracting 1,3-diaminourea compounds, its structural formula as the formula (1):
Wherein R=O or S.
The preparation method of N-formyl phenothiazine contracting 1,3-diaminourea compounds, 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=(1.0～1.2): 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 contracting 1,3-diaminourea compounds.
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, 50B≤D≤200B.
Described N-formyl phenothiazine contracting 1,3-diaminourea compounds is as the application of anti-gram-bacteria medicine.
Described gram-bacteria is intestinal bacteria, streptococcus aureus or actinomycetes.
The application of described N-formyl phenothiazine contracting 1,3-diaminourea compounds in the anti-gram-bacteria medicine of preparation.
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 contracting 1 provided by the invention; the preparation method of 3-diaminourea compounds; make solvent with dehydrated alcohol; 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 contracting 1; 3-diaminourea compounds, 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 contracting 1 that the present invention prepares; in the structure of 3-diaminourea compounds, contain thiophene piperazine group simultaneously; there is good bacteriostatic activity; gram-bacteria is had to good bacteriostatic action; can serve as anti-gram-bacteria medicinal application; or apply in the anti-gram-bacteria medicine of preparation, have a good application prospect.
Embodiment
The present invention makes solvent with dehydrated alcohol; by N-formyl phenothiazine and 1; 3-diaminourea compounds is dissolved in dehydrated alcohol; then being heated to 50～80 DEG C reacts; use TLC(thin layer chromatography) monitoring; obtain N-formyl phenothiazine contracting 1,3-diaminourea compounds, 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 provided by the invention contracting 1,3-diaminourea compounds, its structural formula as the formula (1):
Wherein R=O or S.
In the time of R=O, N-formyl phenothiazine provided by the invention contracting 1,3-diaminourea compounds is N-formyl phenothiazine contracting 1,3-diaminourea, its structural formula as the formula (3):
In the time of R=S, N-formyl phenothiazine provided by the invention contracting 1,3-diaminourea compounds is N-formyl phenothiazine contracting 1,3-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 0.010mol N-formyl phenothiazine and 0.010mol1,3-diamino thiocarbamide adds in dry reaction flask, then adds wherein 6mL 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 2.86g rice white crystal obtaining is N-formyl phenothiazine contracting 1,3-diamino thiocarbamide, and productive rate is 90.8%.
IR(cm
-1,KBr)：3339，3053，1643，1595，1307，739。
1HNMR（DMSO-d
6,400MHZ）7.80(s,1H,NH)，7.50(s,1H,CH=N)，6.97～7.51(m,8H,ArH),2.0(s,1H,NH),3.50(s,2H,NH
2)。
Embodiment 2
The first step, by 0.012mol N-formyl phenothiazine and 0.010mol1,3-diamino thiocarbamide adds in dry reaction flask, then adds wherein 8mL 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 1:6 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 2.88g rice white crystal obtaining is N-formyl phenothiazine contracting 1,3-diamino thiocarbamide, and productive rate is 91.4%.
Embodiment 3
The first step, by 0.022mol N-formyl phenothiazine and 0.020mol1,3-diamino thiocarbamide adds in dry reaction flask, then adds wherein 10mL 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 1:7 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 1mL absolute ethanol washing, then is used dehydrated alcohol recrystallization, and the 5.74g rice white crystal obtaining is N-formyl phenothiazine contracting 1,3-diamino thiocarbamide, and productive rate is 91.1%.
Embodiment 4
The first step, by 0.012mol N-formyl phenothiazine and 0.010mol1,3-diaminourea adds in dry reaction flask, then adds wherein 8mL 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 1:7 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 2.72g white crystal obtaining is N-formyl phenothiazine contracting 1,3-diaminourea, and productive rate is 91.0%.
IR(cm
-1,KBr)：3339，3053，1643，1595，1307，739。
1HNMR（DMSO-d
6,400MHZ）7.10(s,1H,NH)，7.62(s,1H,CH=N)，6.94～7.51(m,8H,ArH),6.30(s,1H,NH),3.50(s,2H,NH
2)。
Embodiment 5
The first step, by 0.011mol N-formyl phenothiazine and 0.010mol1,3-diaminourea adds in dry reaction flask, then adds wherein 5mL 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 1:6 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 2.71g white crystal obtaining is N-formyl phenothiazine contracting 1,3-diaminourea, and productive rate is 90.6%.
Embodiment 6
The first step, by 0.020mol N-formyl phenothiazine and 0.020mol1,3-diaminourea adds in dry reaction flask, then adds wherein 14mL dehydrated alcohol, is heated to 60 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 1:5 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 5.43g white crystal obtaining is N-formyl phenothiazine contracting 1,3-diaminourea, and productive rate is 90.8%.
Bacteriostatic test:
The N-formyl phenothiazine contracting 1 that adopts filter paper method to prepare the present invention; 3-diaminourea and N-formyl phenothiazine contracting 1; 3-diamino thiocarbamide carries out bacteriostatic activity test; select pure acetone solution as blank; the bacterial classification of selecting is respectively intestinal bacteria, streptococcus aureus and actinomycetes, by agar culture dish in 37 DEG C of constant temperature culture 48h.The intestinal bacteria of wherein selecting in bacteriostatic test belong to Gram-negative bacteria; Streptococcus aureus and actinomyces are in gram-positive microorganism; Gram-bacteria comprises Gram-negative bacteria and gram-positive microorganism.
Test result is that N-formyl phenothiazine contracting 1,3-diamino thiocarbamide is respectively 5mm to intestinal bacteria, streptococcus aureus and actinomycetic antibacterial circle diameter, 4mm and 6mm; N-formyl phenothiazine contracting 1,3-diaminourea is respectively 7mm to intestinal bacteria, streptococcus aureus and actinomycetic antibacterial circle diameter, 5mm and 6mm.Experimental result shows; N-formyl phenothiazine contracting 1 prepared by the present invention; 3-diaminourea compounds has good bacteriostatic activity; gram-bacteria is had to good bacteriostatic action; can serve as anti-gram-bacteria medicinal application; or apply in the anti-gram-bacteria medicine of preparation, have a good application prospect.
In addition, N-formyl phenothiazine prepared by the present invention contracting 1,3-diaminourea compounds also can be used as nucleophilic reagent and aromatic acid or aromatic aldehyde and reacts and obtain having thiadiazoles and the triazole analog derivative of pharmaceutical activity, has higher researching value.
Claims (7)
1.N-formyl phenothiazine contracting 1,3-diaminourea compounds, is characterized in that, its structural formula is suc as formula shown in (1):
Wherein R=O or S.
The preparation method of 2.N-formyl phenothiazine contracting 1,3-diaminourea compounds, 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=(1.0～1.2): 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 contracting 1,3-diaminourea compounds.
3. the preparation method of N-formyl phenothiazine contracting according to claim 21,3-diaminourea compounds, is characterized in that: in the described the first step, the consumption of dehydrated alcohol is C mL, 500B≤C≤800B.
4. the preparation method of N-formyl phenothiazine according to claim 2 contracting 1,3-diaminourea compounds, 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. the preparation method of N-formyl phenothiazine contracting according to claim 21,3-diaminourea compounds, is characterized in that: in described second step, filter cake is used to D mL absolute ethanol washing, 50B≤D≤200B.
6. the application of N-formyl phenothiazine contracting claimed in claim 11,3-diaminourea compounds in the anti-gram-bacteria medicine of preparation.
7. the application of N-formyl phenothiazine contracting according to claim 61,3-diaminourea compounds in the anti-gram-bacteria medicine of preparation, is characterized in that: described gram-bacteria is intestinal bacteria, streptococcus aureus or actinomycetes.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310100025.4A CN103159698B (en) | 2013-03-26 | 2013-03-26 | N-formyl phenothiazine 1, 3-diaminourea compound and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310100025.4A CN103159698B (en) | 2013-03-26 | 2013-03-26 | N-formyl phenothiazine 1, 3-diaminourea compound and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103159698A CN103159698A (en) | 2013-06-19 |
| CN103159698B true CN103159698B (en) | 2014-12-03 |
Family
ID=48583265
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310100025.4A Expired - Fee Related CN103159698B (en) | 2013-03-26 | 2013-03-26 | N-formyl phenothiazine 1, 3-diaminourea compound and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103159698B (en) |
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 |
-
2013
- 2013-03-26 CN CN201310100025.4A patent/CN103159698B/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), * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103159698A (en) | 2013-06-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106256824A (en) | A kind of preparation method of high-purity De Lasha star meglumine salt | |
| CN104098548A (en) | Delafloxacin purifying method | |
| CN103159698B (en) | N-formyl phenothiazine 1, 3-diaminourea compound and preparation method thereof | |
| CN102276555A (en) | Thiadiazole Mannich alkali as well as preparation method and application thereof | |
| CN104193674A (en) | Synthesis method of flunixin meglumine | |
| CN106631885A (en) | 4-formaldoxime benzoate derivative preparation method | |
| CN103288816B (en) | Containing phenothiazinyl and 1,3,4-thiadiazolyl group Mannich alkaloid compound and its preparation method and application | |
| Mohan et al. | Synthesis and antimicrobial screening of some novel substituted thiophenes | |
| CN103159699B (en) | N-formyl phenothiazine 1, 3-diaminourea bis-schiff base and preparation method thereof | |
| CN112079819B (en) | Improved voriconazole racemate preparation method | |
| CN104086525A (en) | Spiro[tetralone-tetrahydrothiophene] derivative having antibiosis activity, and synthetic method and application thereof | |
| CN107353245A (en) | A kind of synthetic method of quinolines | |
| CN109293616B (en) | Coumarin-containing chalcone derivatives, and preparation method and application thereof | |
| CN102060804B (en) | Method for preparing 1,3,4-thiadiazole derivatives | |
| CN106008653B (en) | Enoxolone acylhydrazone and its preparation method and application | |
| CN103242259B (en) | 2-(carbonyl-N-phenothiazinyl)-benzoic acid and preparation method thereof | |
| CN105418520B (en) | A kind of synthetic method of 3- methyl -2- (2- sodium sulfonates phenylethylene keto) quinoxaline -1,4- dioxide (quinocetone sodium sulfonate) | |
| CN111217805B (en) | (E)2- (2- (9-alkyl) carbazole-3-) vinyl-5-amino-1, 3, 4-thiadiazole | |
| WO2019165810A1 (en) | Method for preparing thiazoloquinazolinone derivative | |
| CN110885313B (en) | Antibacterial active tetraphenylpyrazole compound and preparation method and application thereof | |
| CN103554074B (en) | Preparation method of 3-trifluoromethyl coumarin derivative | |
| CN103204884B (en) | Containing phenothiazinyl and ferrocenyl double-core Mannich base and its preparation method and application | |
| CN108658981A (en) | A kind of synthetic method of the bromo- 4- methoxyl groups hydrogen of 6--pyrazoles [1,5-a] pyridine -3- formonitrile HCNs | |
| CN103172591B (en) | Phenothiazinyl-containing Schiff base compound as well as preparation method and application thereof | |
| CN117886812B (en) | Heterocyclic mercapto triazole Schiff base compound with antibacterial property and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20141203 Termination date: 20210326 |