Synthesis and Investigation of (Five, Six, Seven and Eight)–Membered Rings Containing Di Nitrogen Atoms.

 

Dr. Nagham Mahmood Aljamali1* , Dr. Shireen Ridha Rasool 2, Rana Neama Atiya3

1Assist. Professor, Dept of Chem., Educt. College, Kufa Univ., Iraq

2Lecturer, Dept of Chem., Science College, Babylon Univ., Iraq

3M.Sc., College of Pharmacy, Univ. Kufa, Iraq

*Corresponding Author E-mail: dr.Nagham_mj@yahoo.com

 

ABSTRACT:

In this paper , series of cyclic compounds containing di nitrogen atoms in their structure were synthesized by condensation reactions which involved reaction between di amine compounds with ketone compounds to yield (5, 6, 7 and  8) –membered rings like (diazepine compounds , amide cycles , imine cycles ) ,some of them  via   aldol  reaction  like compounds [1-8 ]   and  other  reaction  via  cycloaddition like  compounds [9-12 ]

 

All formatted compounds [1-12] were characterized by spectroscopic methods [ FT.IR –spectra , H.NMR –spectra , elemental analysis (C.H.N)] and measurement their melting points .

 

KEYWORDS: amide cycle, imine cycle , diazepine , diazepame , eight membered, diazocine.

 

INTRODUCTION:

The compounds containing di amine are used as starting material in synthesis of a number of compounds via condensation reaction , cyclo addition , ring closure and replacement reaction (1-3) .The cycles containing di nitrogen atoms are one of the most important classes of heterocyclic compounds with variety of microbial activity from the literature survey cycles containing di aze  in there structures were found to be having biological activity(4) like diazepam drugs(3) , analgesic(5) , anti de present , anti cancer(6) , anti fungal(7)antiviral, numerous drugs(8)and they have wide applications(9,10) in others fields .diazepine derivative introduced in 1965 for use in the relief of the psychoneuroses characterized by anaxity and tension.,it is non-homologous seven member ring that contains two heteroatoms of ( nitrogen) .,diazepine is awhite solid substance , stable when heated , low solubility in water , has low vapor pressure , can be dissolved in several organic solvents.

 

The importance of these compounds ( diazepines  and all di nitrogen cycles) in nature product chemistry and pharmacology constantly drive the search for new methods for synthesis of various heterocycles(11,12) .

 

EXPERIMENTAL:               

All chemicals used (purity 99.98 %) , FT.IR- spectr :  were recorded on Shimadzu 8300, KBr-disc, H.NMR-spectra were recorded on Varian 300 MHz spectrometer using DMSO-Solvent and elemental analysis (C.H.N)–elemental (analysis  system, GmbH)–Germany Vario EL.  III, in Kashan University in Tahran. The melting points were determined in open capillary tubes by electro thermal 9300 LTD, U.K .

 

Synthesis of Compounds [1,2] :

(0.1 mole, 4.5 ml) of hydrazine was reacted with one of [(0.2 mole, 27.2 gm of 4–hydroxyacetophenone)or (0.2 mole, 39.2 gm of 1,2–di phenyl ethanone)] with mechanical stirrer for (0.5 hrs) in presence of iodine to produce five–membered ring (89, 87)% from compounds [1,2] respectively.

 

Synthesis of Compounds [3,4] :

A mixture of methylene di amine (0.1 mole , 4.6 gm) with one of [(0.2 mole, 27.2 gm of 4– hydroxyacetophenone )or (0.2 mole, 39.2 gm of 1,2–di phenyl ethanone)] were reacted with mechanical stirrer for (1hrs)  in presence of iodine to produce six–membered ring (88, 89)% from compounds [3,4] respectively.

 

Synthesis of Compounds [5,6] :

A mixture of ethylene di amine (0.1 mole , 6 gm) with one of [(0.2 mole, 27.2 gm of 4–hydroxyacetophenone) , (0.2 mole, 39.2 gm of 1,2 –di phenyl ethanone)] were reacted with mechanical stirrer for (1hrs)  in presence of iodine to produce seven–membered ring (87, 89)% from compounds [5,6] respectively.

 

Synthesis of Compounds [7,8] :

A mixture of phenylene di amine (0.1 mole , 10.8 gm) with one of [(0.2 mole , 27.2 gm of 4– hydroxyacetophenone), (0.2 mole, 39.2 gm of 1,2–di phenyl ethanone)] were reacted with mechanical stirr for (1.5hrs) in presence of iodine to produce seven–membered ring (88 , 86 )% from compounds [7,8] respectively.

Synthesis of Compounds [9-12] :

This reactions proceed according to well known    procedure(3), a mixture of equimolar amounts of phenylene di amine (0.01 mol, 1.80 gm) with one of [(1.6 gm of di ethyl malonate), (1.18 gm of succinic acid), (1.66 gm of phthalic acid), (1.86 gm of 1,5–dione–hexane)] were reacted in presence of absolute ethanol to yield (88, 85, 84, 82) % of compounds [9-12] respectively .

 

 

Scheme (1) :Synthesis of compounds [1-8]

Scheme (2) :Synthesis of compounds [9-12]

 

RESULTS AND DISCUSSIONS :

In this paper , the synthesis and characterization of cyclic compounds of diaze through reaction of di amine compounds (hydrazine , methylene di amine , ethylene di amine, phenylene di amine ) with di carbonyl compounds (4–hydroxyacetophenone, di phenyl ethanone, di ethyl malonate, succinic acid, phthalic acid, 1,5–dione hexane ) via cyclization reaction to yield diaze (5, 6, 7 and  8)–membered rings .

All synthesized compounds [1-12] have been characterized by spectroscopic methods (FT.IR, H.NMR, (C.H.N)–analysis).

 

Their FT.IR–spectrum showed an absorption bands at (1534–1595)cm-1and (3290–3380) cm-1 which were assigned(3,9-12) to (C=N) endocycle and (-NH )respectively in compounds [1-8], beside this, the spectrum also showed band at (3440–3479) cm-1 due to (OH) of phenol(16,17) in compounds [1,3,5,7], other bands at (1692–1698 ) cm-1 due to ( -CO–NH) carbonyl of amide(9-12)in compounds [9-11] , and other data of functional groups(9-15) in table (1) and figures (1-4).

 

 

Table (1): (FT.IR) –data (cm-1) of compounds [1-12] .

Comp.

No.

I.R(KBr)( Important Groups )

[1]

(-NH ) of hydrazine : 3290 , (OH) of phenol : 3440 , (C=N) endocycle : 1595 ,   (C–H ) aliphatic : 2900 .

[2]

(-NH ) of hydrazine : 3317 , (C–H ) aliphatic : 2908 , (C=N) endocycle:1577 .

[3]

(-NH ) of amine : 3365 , (OH) of phenol : 3460 , (C–H ) aliphatic : 2950 , (C=N ) endocycle : 1520 .

[4]

(-NH ) of amine : 3355 , (C=N) endocycle: 1562 , (C–H ) aliphatic : 2930

[5]

(-NH ) of amine : 3380 , (C=N) endocycle: 1570 , (C–H ) aliphatic : 2920 , (OH) of phenol : 3455 .

[6]

(-NH ) of amine : 3320 , (C=N) endocycle: 1566 , (C–H ) aliphatic : 2950

[7]

(-NH ) of amine : 3312 , (C=N) endocycle: 1554 , (OH) of phenol : 3479 , (C=C) aromatic : 1560 .

[8]

(-NH ) of amine : 3317 , (C=N) endocycle: 1534 , (C=C) aromatic : 1537 .

[9]

(-CO-) carbonyl of amide : 1695 , (C–H ) aliphatic : 2920 .

[10]

(-CO-) carbonyl of amide : 1692 , (C–H ) aliphatic : 2945 .

[11]

(-CO-)  carbonyl of amide : 1698 , (C=C) aromatic : 1577 .

[12]

(C=N) endocycle: 1565 , (C–H ) aliphatic : 2956 .

 

Fig (1) : FT.IR  of  Compound [1 ]

Fig (2) :FT.IR of Compound [2 ]

Fig (3) : FT.IR  of  Compound [7 ]

Fig (4) : FT.IR  of  Compound [8 ]

 

H.NMR –spectrum of these compounds showed peaks at [ ɓ  (4.54 – 6.15) ,  ɓ  (6.39 – 7.82 ) and ɓ  (0.72 – 1.68 )] due to [ (NH)(3) ,  phenyl rings(13)and ( -CH-) methylene group] , respectively in compounds [1-8]  .,the spectrum also showed peaks at  ɓ  (10.42 –11.14) due to (OH) of phenol in compounds [1,3,5,7] .,while spectrum of compounds [9-12] showed peaks at ɓ (9.63 -9.79 ) due to (CO –NH -) proton of amide(3) in compounds [9-11] , other peaks at  ɓ  (0.98 – 3.87) due to (N-CH2-N,N-CH2–CH2-N, CH3)(9) in compounds [9,10,12 ] respectively , other peaks at  ɓ  (7.11 –7.38 ) due to  protons of phenyl rings in compounds [9-12] , and other data of functional groups shown in the following , table (2) and figures (5-8) .

 

Their (C.H.N)- analysis andphysical properties , it was found from compared the calculated data with experimentally data of these compounds ,the results were compactable , the data of analysis , M.F and melting points are listed in table (3)

 

Fig (5) : 1H.NMR  of  Compound [2 ]

Fig (6) : 1H.NMR  of  Compound [3 ]

Fig (7) : 1H.NMR  of  Compound [7 ]

Fig (8) : 1H.NMR  of  Compound [10 ]

 

 

Table (2) : H.NMR –data (δppm) of compounds [1-12] .

Comp. No.

H.NMR                                                           (Importance Peaks )

[1]

5.96 (NH) proton of hydrazine, 11.58 (OH) proton of phenol, 1.09 (CH3) protons of methyl group, 0.72 (CH2) protons of methylene group 6.77 -7.82 (Ph-) protons of phenyl rings.

[2]

5.54 (NH) proton of hydrazine, 0.98 (CH2) protons of methylene , 0.91 (-CH-) proton of methylene . 

[3]

6.64 (NH) proton of amine, 3.39 (CH2 –N) , 11.14 (OH) proton of phenol , 0.96 (CH2 ) , 1.08 (CH3) , 6.26 – 7.72 (Ph-) protons of phenyl groups .

[4]

5.04 (NH) proton of amine, 3.6 (CH2 –N ) , 0.87 (CH-) , 0.98 (-CH2 -) , 6.39 – 7.32 (Ph-) protons of phenyl rings . 

[5]

5.07 (NH) proton of amine, 3.2 , 3.5 (CH2-CH2-N) , 11.56 (OH) of phenol , 0.97 (CH2 ) , 0.81 (CH3) , 6.73 – 7.45 (Ph-) protons of phenyl rings .

[6]

5.23 (NH) proton of amine, 3.19 , 3.34 (CH2-CH2-N) , 1.07 (CH-) , 0.941 (CH2 ) , 6.82– 7.52 (Ph-) protons of phenyl rings .

[7]

6.15 (NH) proton of amine, 10.42 (OH) of phenol , 1.18 (CH3) , 1.01 (CH), 6.77 – 7.82 (Ph-) protons of phenyl rings .

[8]

5.65 (NH) proton of amine, 0.973 (CH3) , 1.2 (CH) , 6.57 – 7.52 (Ph-) protons of phenyl rings .

[9]

9.79 (NH–CO) proton of amine, 2.41 (-CH2-) , 7.23 (Ph-) protons of phenyl group .

[10]

9.63 (NH–CO ) proton of amine, 2.47 , 3.87 (CH2 –CH2) , 7.131 (Ph-) protons of phenyl group .  

[11]

9.38 (NH –CO ) proton of amine, 6.84 – 7.46 (Ph-) protons of phenyl rings .

[12]

1.86 (CH3) ; 1.98 , 2.18 (CH2 –CH2) ; 7.11 – 7.38 (Ph-) protons of phenyl rings .


.

Table (3): physical properties and (C.H.N) –analysis of compounds [1-12] .

Comp. NO.

M.F

m.p(Cₒ )

Name of compounds

Calc./ Found.

C%

H%

N%

[1]

C16H16O2N2

194

3,5–bis (4- -hydroxy phenyl )-3 –methyl -1,2 –diazoledine .

72.18

72.07

6.01

6.00

10.52

10.41

[2]

C28H24N2

213

3–benzayl-3,4,5–Tri phenyl-1,2 - diazoledine .

86.59

86.47

6.18
6.03

7.21

7.14

[3]

C17H18N2O2

224

4,6 –bis (4- -hydroxy phenyl )-4 –methyl -1,3 –diazine .

72.34

72.26

6.38

6.30

9.92

9.90

[4]

C29H26N2

236

4 –benzayl -3,4,5–Tri phenyl-1,3 - diazine .

86.56

86.42

6.46

6.33

6.96

6.88

[5]

C18H20N2O2

249

5,7 –bis (4- -hydroxy phenyl )-5 –methyl -1,4 –diazepine .

72.97

72.80

6.75

6.61

9.45

9.31

[6]

C30H28N2

260

5 –benzayl -5,6,7–Tri phenyl-1,4 - diazepine .

86.53

86.33

6.73

6.55

6.73

6.56

[7]

C22H20N2O2

278

5,7–bis(4- -hydroxy phenyl )-5 –methyl-1,4 –benzodiazepine .

76.74

76.59

5.81

5.66

8.13

8.02

[8]

C34H28N2

296

5–benzayl -5,6,7–Tri phenyl-1,4–benzodiazepine .

87.93

87.77

6.03

5.96

6.03

6.00

[9]

C9H8N2O2

208

2,4–dione–6,7-benzo diazepane .

61.36

61.24

4.54

4.47

15.90

15.85

[10]

C10H10N2O2

168

2,5–dione–7,8-benzo diazocane.

63.15

63.08

5.26

5.19

14.73

14.61

[11]

C14H10N2O2

190

2,5 –dione –3,4,7,8-di benzodiazocane  .

70.58

70.49

4.20

4.11

11.76

11.63

[12]

C12H14N2

177

2,5–di methyl -1,6–benzodiazocine .

77.41

77.33

7.52

7.47

15.05

15.00

 

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Received on 09.08.2014          Accepted on 24.08.2014        

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Asian J. Pharm. Tech.  2014; Vol. 4: Issue 3, Pg 141-146