Synthesis of New Heterocyclic Compounds Derived From 5,10- dihydrophenophosphazine

Synthesis of New Heterocyclic Compounds Derived From 5,10- dihydrophenophosphazine
Suad M. Al – Araji., Moayad abood Gban*
Department of Chemistry, College of Science, University of Baghdad, Baghdad, Iraq.
*Email:moayad.kban@yahoo.com
Iraqi Journal of Science, 2015, Vol 56, No.1A, pp: 12-24
http://www.iasj.net/iasj?func=fulltext&aId=99208

Iraqi Journal of Science

المجلة العراقية للعلوم

 

 




Abstract:
This work comprises the synthesis of 18 new N- substituted 5,10- dihydrophenophosphazine.The diphenylamine was chosen as the starting material , which was reacted with phosphorus trichloride at elevated temperature (200-220)0C for 6 hrs, followed by treating the reaction mixture with water to yield 5,10- dihydrophenophosphazine-10-oxide(1), this was reacted with ethylchloroacetat to obtain ethyl(5,10-dihydrophenophosphazine-10- oxide)acetate(2). Compound (2) was converted to acid hydrazide by treating with hydrazine hydrate( 98% ) to obtain 5-(5,10-dihydrophenophosphazine) acetohydrazide-10-oxide (3). The acid hydrazid was used to react with phenylisocyanat , phenylthioisocyanat to give (4,7) respectively which were used to prepare different heterocyclic compounds. Compound (5) was performed by the intramolecular cyclization of (4) in the presence of NaOH(2N).Compound (8) was synthesized by interaction of (7) with NaOH(2N).Compound (6) and (9) were obtaind upon the reaction of semicarbazide (4) and thiosemicarbazide (7) with phosphoric acid at 1200C. Compound (3) undergoes the character condensation reaction with different aromatic aldehyde in ethanol gave the shiff bases (10-18).
5-N-Ethyl (5, 10-dihydrophenophosphazine-10-oxide) acetate (2)
Amixture of 5,10-dihydrophenophosphazine-10-oxide(1),(5g,0.027mol) ethylchloroacetate (3.5ml,0.027 mol) in dry acetone (5 ml) and anhydrous K2CO3 (0.5 g) was refluxed for 24 h, then cooled ,filtered and solvent removed under reduced pressure. The resulting solid was monitored by (T.L.C) and recrystallized from ethanol.

Result and discussion
5,10-dihydrophenophosphazine-10-oxide(1) was prepared by the reaction of diphenylamine and phosphorus trichloride at 2200C followed by hydrolysis of the mixture with hot water [11] show figure 1.Compound(1) was treated with ethylchloroacetate to give N- ethyl(5,10dihydrophenophosphazine- 10-oxide)acetate(2)which was characterized by T.L.C, m.p , 1HNMR and FTIR spectrum figure 2 showed stretching bands at (3186- 3093) cm -1 for aromatic (C-H)., 2977 cm-1 for aliphatic (C-H) ., 2322 cm-1 (P-H).,1751cm-1 for ester(C=O).,(1612-1591-1520) cm-1 for (C=C) aromatic and bending band at 1465 cm-1 for (N-H) [12-14] see table2.

 

 

Iraqi Journal of Science

المجلة العراقية للعلوم

University of Baghdad, College of Science, Department of Chemistry, Karada, Baghdad,








KARADA

A view above karrada - view is taken to Baghdad's Karrada over from a military plane,

- منظر ماخوذ لبغداد من فوق الكرادة من طائرة عسكرية

///////

EDOXABAN INTERMEDIATE, 2-amino-5-methyl-4,5,6,7-tetrahydro thiazolone [5,4-c] pyridine

ENDOXABAN





2-amino-5-methyl-4,5,6,7-tetrahydro thiazolone [5,4-c] pyridine 

(Reference Example 1)　2-amino-5-methyl-4,5,6,7-tetrahydro thiazolone [5,4-c] pyridine (1-n) (The method described in WO 2005/047296 Pamphlet )

[0091]

[Of 35] 　in 2-PrOH (1.44L) solution was heated to 50 ℃ 1- methyl-4-piperidone (180.0g), 2-PrOH (360mL) solution of cyanamide (67.0g), and sulfur powder (51.0 g) it was added. Pyrrolidine (13.3mL) was added to the reaction mixture, after stirring for 2 hours at 50 ℃, followed by stirring overnight and allowed to cool to room temperature. 　The reaction mixture was cooled to 10 ℃ less in an ice water bath and stirred for 1 hour at the same temperature. Is filtered and the precipitated crystals were washed with 2-PrOH (540mL), the title compound was dried under reduced pressure at 40 ℃ (209.9g, 78%) was obtained.

[0092]

¹ H-NMR (CDCl ₃ ) ppm: 4.86 (Br, 2H), 3.47-3.46 (t, 2H, J = 1.9 Hz), 2.78-2.71 (M, 2H), 2.71-2.65 (M, 2H), 2.47 . (s, 3H)
MS (FAB) M / z: 170 (M + H) ⁺
elemental analysis: C ₇ H ₁₁ N ₃ as S,
　theoretical value: C, 49.68; H, 6.55; N, 24.83; S, 18.95
　measured value: C, 49.70; H, 6.39; N, 24.91; S, 19.00.




 

DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO .....FOR BLOG HOME CLICK HERE

Join me on Linkedin

Join me on Facebook FACEBOOK

Join me on twitter     

Join me on google plus Googleplus

 amcrasto@gmail.com

LIONEL MY SON

He was only in first standard in school when I was hit by a deadly one in a million spine stroke called acute transverse mylitis, it made me 90% paralysed and bound to a wheel chair, Now I keep him as my source of inspiration and helping millions, thanks to millions of my readers who keep me going and help me to keep my son happy

/////////

methyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propanoate 

Compound 2.15b was synthesized using General Procedure 1 and purified by flash chromatography on silica gel to afford a colorless oil;

1H NMR (500 MHz, CDCl3) δ 3.63 (s, 3H), 2.42 (t, J = .5 Hz, 2H), 1.22 (s, 12H), 1.00 (t, J = 7.5 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 1 5.14, 83.30, 51.56, 2 . 6, 28.6 , 24.82;


11B NMR (160 MHz, CDCl3): δ 33.36;


IR (NaCl) 2 80, 1 40, 1381, 131 , 1144, 0, 84 cm-1 ;


HRMS (ESI+): Calcd for C10H20BO4 [M+H]: 215.1455, Found: 215.1447;
Calcd for C10H19BNaO4 [M+Na]: 237.1274, Found: 237.1268.

methyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propanoate
	Molecular Formula: C10H19BO4
	Molecular Weight: 214.069 g/mol
	Cas Number: 1150561-77-5
	InChIKey: SWDXLJYTYJQFJI-UHFFFAOYSA-N
	Melting Point: n/a
	Boiling Point: n/a
	Density: n/a
	Refractive Index: n/a
Synthesis Reference(s) for methyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propanoate
1) Journal of Organic Chemistry, 2011, vol. 76, №10, p. 3997-4007 2) Organic Letters, 2009, vol. 11, №15, p. 3478-3481 3) Organic Letters, 2008, vol. 10, №9, p. 1795-1798
Synonym Chemical Name(s) for methyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propanoate
methyl 3-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolan-2-yl)propanoate

Activation of diboron reagents: The development of mild ...

scholar.lib.vt.edu/theses/available/etd.../Thorpe_SB_D_2012.pdf

by SB Thorpe - ‎2012

Mar 23, 2012 - B NMR, and solvent kinetic isotope experiments were employed to gain...... Interestingly, Tavaborole exhibits a different mechanism of action.

////

(5,7-Dimethyl-4,6-dioxo-4,5,6,7-tetrahydro[1,2]thiazolo[3,4-(/]pyrimidin-3- yl)acetic acid

(5,7-Dimethyl-4,6-dioxo-4,5,6,7-tetrahydro[1,2]thiazolo[3,4-(i]pyrimidin-3-yl)acetic acid

Step 1 : Methyl 6-amino-l,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5- carbodithioate: 
¹H NMR (300 MHz, CF₃COOD) δ 2.73 (s, 3H), 3.51 (s, 3H), 3.62 (s, 3H).

Step 2: 5,7-Dimethyl-3-(methylsulfanyl)[1,2]thiazolo[3,4-ύT|pyrimidine-4,6(5H,7H)- dione: 

¹H NMR (300 MHz, DMSO-^₆) δ 2.67 (s, 3H), 3.18 (s, 3H), 3.40 (s, 3H). 

Step 3: 5,7-Dimethyl-3-(methylsulfonyl)[1,2]thiazolo[3,4-(/]pyrimidine-4,6(5H,7H)- dione:  

 ¹H NMR (300 MHz, DMSO-(Z₆) δ 3.26 (s, 3H), 3.49 (s, 3H), 3.71 (s, 3H).

Step 4: Diethyl (5,7-dimethyl-4,6-dioxo-4,5,6,7-tetrahydro[1,2]thiazolo[3,4-d]pyrimidin- 3-yl)propanedioate:  ¹H NMR (300 MHz, DMSO-(Z₆) δ 1.32 (t, J = 7.2 Hz, 6H), 3.40 (s, 3H), 3.64 (s, 3H), 4.24-4.37 (m, 4H), 6.05 (s, 1H).

Step 5: Ethyl (5,7-dimethyl-4,6-dioxo-4,5,6,7-tetrahydro[1,2]thiazolo[3,4-d]pyrimidin-3- yl)acetate:; ¹H NMR (300 MHz, DMSCM₆) δ 1.34 (t, J = 6.9 Hz, 3H), 3.40 (s, 3H), 3.63 (s, 3H), 4.30 (q, J= 6.9 Hz, 2H), 4.50 (s, 2H)

Step 6: (5,7-Dimethyl-4,6-dioxo-4,5,6,7-tetrahydro[1,2]thiazolo[3,4-(/]pyrimidin-3- yl)acetic acid: The title compound was prepared according to same procedure as described for Intermediate 1, Step 5 by using above Step 5 intermediate (9.0 g, 31.8 mmol), 6 N H₂SO₄ (80 ml) and dioxane (80 ml) to give 5.8 g of the product as yellow solid; 

 ¹H NMR (300 MHz, DMSO-^₆)
δ 3.22 (s, 3H),
3.46 (s, 3H),
4.51 (s, 2H),
13.45 (br s, 1H).  -0H

Interpretation

 

http://www.google.com/patents/EP2411397A1?cl=en 

(5,7-Dimethyl-4,6-dioxo-4,5,6,7-tetrahydro[1,2]thiazolo[5,4-(i]pyrimidin-3-yl)acetic acid

 

¹H NMR (300 MHz, DMSO-<4) δ 3.22 (s, 3H), 3.46 (s, 3H), 3.96 (s, 2H), 12.57 (br s, 1H).

2-(5,7-Dimethyl-4,6-dioxo-4,5,6,7-tetrahydro[1,2]thiazolo[3,4-ύT|pyrimidin-3-yl)-N-{4- [3 -fluoro-4-(trifluoromethyl)phenyl] - 1 ,3 -thiazol-2-yl } acetamide

 ¹H ΝMR (300 MHz, DMSO-^₆) δ 3.23 (s, 3H), 3.48 (s, 3H), 4.83 (s, 2H), 7.86-8.07 (m, 4H), 12.96 (br s, 1H); APCI-MS (m/z) 500.06 (M+H)⁺.

2-(5,7-Dimethyl-4,6-dioxo-4,5,6,7-tetrahydro[1,2]thiazolo[3,4-ύT|pyrimidin-3-yl)-N-{4- [3 -(trifluoromethy l)pheny 1] -1,3 -thiazol-2 -y 1 } acetamide

 ¹H NMR (300 MHz, DMSO-^₆) δ 3.23 (s, 3H), 3.48 (s, 3H), 4.82 (s, 2H), 7.67- 7.72 (m, 2H), 7.96 (s, 1H), 8.20-8.26 (m, 2H), 12.93 (br s, 1H); APCI-MS (m/z) 482.07 (M+H)⁺.

Ethyl (5,7-dimethyl-4,6-dioxo-4,5,6,7-tetrahydro[1,2]thiazolo[5,4-ύT|pyrimidin-3- yl)acetate

 ¹H NMR (300 MHz, CDCl₃) 
δ 1.28 (t, J= 7.2 Hz, 3H), -CH2CH3
3.39 (s, 3H), 
3.56 (s, 3H), 
4.12 (s, 2H), -CH2CH3
4.21 (q, J= 6.9 Hz, 2H).