environmentally benign synthesis

ENVIRONMENTALLY BENIGN SYNTHESIS, CHARACTERISATION AND EVALUATION OF ANTIBACTERIAL ACTIVITY OF TRANSITION

METAL (II) COMPLEXES OF SUBSTITUTED QUINAZOLINONE

Krishna P. Srivastava

¹

, Om Prakash Putul

²

1Presently Principal, N.L.S. College, Jaitpur- Daudpur, Saran, Bihar (India)

2 Department of Chemistry, Jai Prakash University, Chapra, Saran, Bihar, (India)

ABSTRACT

A facile, fast, simplistic, highly efficient, environmentally safe and economical method for the synthesis of the ligand 3-amino-2-methyl-4-oxo-1,2,3,4-tetrahydroquinazoline-2-carboxylic acid (L) by using the cyclization of o-ABH with pyruvic acid. The transition metal complexes of L have been prepared in an environmentally benign microwave protocol and characterized by elemental analysis, conductivity measurements, magnetic moment, spectral and thermogravimetric analysis. Physico-chemical studies reveal that, the ligand loses carboxylic group upon complexation and gets coordinated through nitrogen of the amine and ring carbonyl oxygen. The ligand behaves as a neutral bidentate donor (O & N) yielding six coordinated transition metal complexes with octahedral geometry around the central metal ion. The plausible mechanisms have been deduced for the formation of tetrahydroquinazolinone and for the decarboxylation of the tetrahydroquinazolinone upon complexation. Antimicrobial data suggests that the metal complexes are better antibacterial agents as compared to their ligand.

Keywords: Environmentally Benign, Coordination Complexes, Quinazoline-2-Carboxylic Acid, Anti-Bacterial Activity, Transition Metals

I. INTRODUCTION

In recent years, the use of hazardous and toxic solvents in chemical laboratories, chemical industry has been considered a very serious problem for the health, safety of workers, and environmental pollution. For these purposes, the emerging area of green chemistry plays an important role into the development of synthetic strategies [1-2].A grinding technique, which is reacting under solvent-free conditions, is one of the green synthetic routes that has gained popularity towards designing the structure of new molecules [3-6]. Eco-friendly techniques have been increasingly used in organic synthesis as compared to traditional methods [7-9], because these reactions are not only of interest from an economical point of view, but also in many cases they offer considerable advantages in terms of yield, selectivity, and simplicity of reaction procedure with high atom

efficiency. Many well-known reactions have been reported under non-hazardous solvent environments using the eco-friendly technique [10-17].

Many quinazolines and tetrahydroquinazolines are biologically active [18] and derivatives of these are of interest as dihydrofolate reductase inhibitors, anticonvulasant [19-21], antitubercular [22] and antibacterial agents [23]. Now, there are numerous data on 1,2,3,4-tetrahydroquinazolin-4-ones which are proved to be physiologically active compounds [24-25]. Recently 1,2,3,4-tetrahydroquinazolin-4-ones were synthesized by the use of anthranilic acid mesyl hydrazide and spiro derivatives of these were prepared from o-amino benzoyl hydrazide (o-ABH) with the use of cyclic ketones under organic-solvent free conditions [26].

So, because of these reasons much attention is being paid for the synthesis of quinazoline derivatives. Looking at the biological significance of quinazoline nucleus it was thought to design and synthesize new quinazoline derivatives and screen them for their antibacterial activity. As part of our ongoing program to develop more efficient and environmentally benign methods for organic / inorganic syntheses using economic and eco-friendly materials/methods [27-30], we have presented the synthesis of new substituted 1,2,3,4-tetrahydroquinazolin-4- one (L) with the use of o-amino benzoyl hydrazide(o-ABH) and pyruvic acid. Transition metal (II) complexes of (L) have been synthesized, characterized and screened them for their antibacterial activity in this research article.

II. EXPERIMENTAL 2.1 Materials and Methods

All the chemicals were obtained from commercial and used without further purification. The melting points of the synthesized compounds were taken in open capillary and are uncorrected. IR spectra were recorded in KBr on a Shimadzu FT-IR 8400 spectrophotometer. ¹H NMR spectra were obtained using AMX-400 liquid state spectrometer at 400MHz in CDCl₃ using TMS as internal standard. Mass spectra were recorded on GCMS solution. Elemental analysis (C, H, N) of these newly synthesized compounds were performed on a Carlo Erba- 1108 elemental analyzer. Microwave assisted synthesis were carried out in open glass vessel on a modified microwave oven model 2001 ETB with rotating tray and a power source 230 V, at output energy of 800W and 2450 MHz frequency. A thermocouple device was used to monitor the temperature inside the vessel of the microwave. The microwave reactions were performed using on/off cycling to control the temperature.

2.2 Synthesis of 3-amino-2-methyl-4-oxo-1,2,3,4-tetrahydroquinazoline-2-carboxylic acid(L):

Pyruvic acid (0.71 g, 10 mmol) was added to o- ABH (1.51 g, 10 mmol) and the mixture was dissolved in DMSO and stirred for 4 h at room temperature to yield a bright yellow solid (Scheme-1). Completion of the reaction was verified by TLC. The residue was washed with cold methanol and dried in air. Recrystallization from hot methanol yielded yellow crystals of the L.

2.3 General Procedure for the Synthesis of Mn(II), Co(II), Ni(II) and Cu(II) [C

1

, C

2

, C

3

, and C

4

]

complexes of L

Ligand L (0.356g, 1 mmol) was mixed with transition metal(II) chlorides (1mmol) in DMSO medium. The reaction mixtures were then refluxed for about 12-14 min. in microwave oven. Except copper, all the complexes were precipitated. The solid residue was filtered under suction and washed with methanol and air dried. The green solution of copper complex (C₄) was left overnight for gradual cooling and the complex was obtained as green shiny crystals (Scheme-3).The physical parameters of L and its metal complexes are presented in Table- 1.

2.4 Biological Evaluation

The synthesized ligand L and its complexes (C1-C4) were screened for their in vitro antimicrobial activity against two Gram-positive [Staphylococcus aureus (SA), Enterococcus faecalis (EF)] and two Gram-negative bacterial strains [Escherichia coli (EC), Streptococcus mutans (SM)] by disc diffusion method [31] using nutrient agar as medium. The in-vitro antimicrobial activity of L and its metal complexes (C1-C4) was measured in comparison with ciprofloxacin (Table-4) as standards to reveal the potency of synthesized derivatives. Each test was performed in triplicate in individual experiments and the average is reported.

III. RESULTS AND DISCUSSION

The hydrazones derived from the reaction of o-ABH and aromatic ketones are well documented in the literature [32-33]. There are no reports in the literature on the reactivity of α-keto acids with o-ABH, but it is reported that the reaction of o-amino benzamide with phenyl pyruvic acid resulted in the formation quinazoline. The synthesis of 3-amino-2-methyl-4-oxo-1,2,3,4-tetrahydroquinazoline-2- carboxylic acid (L) was achieved by the equimolar condensation of o-ABH and pyruvic acid (Scheme-1).

Scheme-1: Synthesis of Ligand (L)

The reaction of pyruvic acid with o-ABH was expected to yield the corresponding hydrazone; instead, tetrahydroquinazolinone product was obtained in single step. The plausible mechanism for the formation of L is given in the Scheme-2.

Scheme-2: Mechanism of the formation of L

o-ABH reacts with pyruvic acid to form the intermediate hydrazone (A) which could not be isolated as it undergoes cyclization in situ to form a stable six membered quinazolinone ring (L) under the given reaction conditions. The plausible mechanism for the formation of the quinazolinone ring from the hydrazone intermediate formed by the hydrazide and pyruvic acid was thought to proceed via four steps.

In the first step, electrophilicity of the azomethine carbon of hydrazone (A) leads to intramolecular nucleophilic attack of aromatic −NH₂ on the azomethine carbon to form an intermediate 7-membered triazepine ring (B). In the second step proton shift occurs from N₁ to N₃ and that leads to the formation of C. In the third step, cleavage of N₃−C1 bond and formation of N₂−C1 bond (C) in the said step afford D with six membered ring. Finally in the forth step, deprotonation of D leads to the formation of stable six membered quinazolinone product (L).

The prepared quinazolinone (L) has many coordinating sites and is a suitable candidate to prepare metal complexes of biologically important metal ions. Interestingly the complexes (C-1 to C-4) were formed with the loss of carboxylic group present at second position in the ligand. This was confirmed by physico-chemical studies. The plausible mechanism for the oxidative decarboxylation is shown in the Scheme-3.

Scheme-3: Mechanism for the formation of complexes (C-1-4) via oxidative decarboxylation Carboxylic function being the sterically hindered, tertiary group in the ligand L tends to undergo decarboxylation in presence of acidic condition to afford the thermodynamically stable compound. It is known fact that, during complexation the reaction mixture is generally acidic in nature and facilitates the acidic media for oxidative decarboxylation.

The reaction of L with metal chlorides forms the intermediate A, wherein the oxygen of carboxylic OH has coordinated to the metal ion via deprotonation. This makes the sterically hindered carbon (C¹) adjacent to the carboxylic group electrophilic. To fulfill the electron deficiency of C¹ carbon, the elimination of NH proton and formation of double bond between N₁and C¹ occurs. This probably favors the oxidative decarboxylation and forms thermodynamically stable 3- amino-2-methylquinazolin-4(3H)-one (B), which is further reacted with metal chlorides to yield the corresponding complexes (C-1 to C-4).

The elemental analyses of prepared compounds are given in Table-1 and these are in good agreement with the proposed formula. Elemental and thermal analyses of the complexes C-1 to C-4 reveal 1:2 metal to ligand stoichiometry. Except copper all the complexes are insoluble in common organic solvents but soluble in DMF and DMSO. The Cu(II) complex is soluble in methanol, ethanol and chloroform. The lower molar conductance value in DMF solution indicates non-electrolytic nature of the complexes.

Table-1: Analytical and physico-chemical data of L and its metal complexes (C-1to C-4)

Compound

(Colour)

Mol. Formula Yield (%)

mp (⁰C)

Elemental analysis Found (Calcd)(%)

Mol.

Cond.

(Λ) μeff (BM)

λmax (nm)

C H N M Cl

L light yellow

C₁₀H₁₁N₃O₃ 95 220 53.97 (54.29)

5.11 (5.01)

19.25 (19.00)

-- --

-- --

^325,

353

C-1 green

[Mn(C₁₈H₁₈N₆O₂)Cl₂] 75 ˃300 45.43 (45.40)

3.88 (3.81)

17.66 (17.65)

11.44 (11.54)

14.87 (14.89)

0.93 5.13 431, 536 C-2

parrot green

[Co(C₁₈H₁₈N₆O₂)Cl₂] 80 ˃300 45.05 (45.02)

3.77 (3.78)

17.43 (17.50)

12.22 (12.27)

14.74 (14.77)

0.31 4.31 459, 676

C-3 green

[Ni(C₁₈H₁₈N₆O₂)Cl₂] 85 ˃300 45.06 (45.04)

3.73 (3.78)

17.47 (17.51)

12.28 (12.23)

14.72 (14.77)

2.39 2.86 432, 643, 893 C-4

dark green

[Cu₂(C₁₈H₁₈N₆O₂) Cl₄(CH₃OH)₂]

93 ˃300 35.11 (35.15)

3.80 (3.83)

12.38 (12.30)

18.66 (18.60)

20.72 (20.75)

7.80 1.71 290- 630 Λ in Ω^-1cm² mol^-1

3.1 IR spectral studies

The diagnostic IR bands of L and its complexes are presented in Table-2. The bands corresponding to ν(O-H) and ν(C=O) of carboxylic group are observed at 3495 and 1706 cm^-1 respectively. These bands are absent in IR spectra of all the metal complexes supporting the loss of carboxylic group upon complexation. A strong intensity band around 3104 cm^-1 is assigned to N−H stretching vibrations of quinazolinone ring L. The absence of this N−H band and appearance of new band due to ν(C=N) in all the complexes in the region 1564-1590 cm^-1 validates the formation of double band between N₁ and C₁. This leads to the attainment of the complete aromaticity in the pyrimidine ring. The characteristic frequency for ν(C=O) of quinazolinone ring in L appeared at 1642 cm^-1. The shift of this band to lower frequency in all the complexes by 12-22 cm^-1 indicates the involvement of carbonyl oxygen in coordination. The asymmetric and symmetric bands for ν(NH2) were observed at 3315 and 3247 cm^-1 respectively in the ligand. The bands due to NH₂ appeared in the higher frequency region compared to ligand at 3449-3235 cm^-1 in all the complexes. The coordination of NH₂ towards metal ions is difficult to define as there is a hydrogen bonding between NH₂ and methyl group present at second position of the quinazolinone ring. This is validated in the crystal structure of the Cu(II) complex. The series of bands due to ν(CH₃) have appeared in ligand as well as complexes between 2835 and 3062 cm^-1. Thus from IR data it is clear that L loses its carboxylic group present at second position upon complexation and attains planarity due to double bond formation between N¹ and C¹. Because of the formation of this double bond, the sp³ hybridised carbon (C1) is transformed to sp²hybridization and makes the ring planar. Perhaps the formation of stabilized planar ring structure is the driving force for oxidative decarboxylation. The intermediate (Scheme- 3, structure B) planar structure generated in-situ further reacts with metal ions to form stable complexes. The

ligand coordinates to metal ions in bidentate fashion through nitrogen atom of tertiary amine and carbonyl oxygen of quinazolinone ring.

Table-2: Diagnostic IR bands (cm

^-1

) of L and its metal complexes (C-1 to C-4)

Compound ν(O-H) ν(N-H) ν(NH2) δ(NH2) ν(C=O)^b ν(C=O)^a ν(C=N) ν(CH3)

L 3495m 3104s 3315m,

3247m

1615s 1706s 1642s -- 3062, 3010,

2944m

C-1 n.o. n.o. 3387s,

3297m

1618s n.o. 1622s 1562s 2926, 2835m

C-2 n.o. n.o. 3449br,

3306m

-- n.o. 1620s 1567m 3005, 2943m

C-3 n.o. n.o. 3393m,

3303m

-- n.o. 1621s 1564s 2954, 2926,

2848m C-4 3533br n.o. 3418b,

3235s

1613s n.o. 1630s 1590m 2935, 2916m

a =Quinazolinone ring, b = Carboxyl ic group, s = strong, br = broad, w = weak, m = medium, n.o. = not observed

3.2 NMR Spectral Studies

The ¹H and ¹³C NMR spectral data of L and its Mn(II) complex (C-1) obtained in DMSO-d₆ are given in Table- 3 and numbering for the assignment of carbons and the corresponding protons is shown in Figure-1. The ¹H and

13C NMR spectra of L are depicted in Figure-2. The ¹H and ¹³C spectra of complex C-1 obtained in DMSO-d₆ are presented in Figure-3. The spectral assignments were made based on the comparison with NMR assignments of o-ABH and pyruvic acid [34].

Figure-1: Numbering scheme for L

Figure-2:

¹

H and

¹³

C NMR Spectra of L

Figure-3:

¹

H and

¹³

C NMR Spectra of C-1complex

The ¹H NMR spectral data of both L and C-1 are in good agreement with proposed structures. In the ¹H NMR spectrum of L, proton signals due to N¹H of quinazolinone ring and O₁H of carboxylic group are resonated as singlets at 7.43 and 12.19 ppm respectively. Proton signals of N¹H and O¹H are devoid of directly attached carbon atoms. These signals are absent in the ¹H NMR spectrum of C-1 supporting the formation of double bond between N¹−C¹ and decarboxylation of L upon complexation. The singlets due to C₁₀H (methyl) and N₃H₂ are observed at 1.72 and 3.46 ppm respectively. The N³H₂ protons resonates downfield in Mn(II) complex at 4.20 ppm indicating the involvement of nitrogen of amine group in coordination. The C¹⁰H (methyl) protons resonated at 2.26 ppm in Mn(II) complex. The conversion of hybridization from sp³ to sp² upon complexation increases the electronegativity of the carbon atom (C¹) adjacent to methyl group (C¹⁰H³). The increased electronegativity of C¹ carbon is responsible for the downfield shift of C¹⁰H³ methyl protons due to inductive effect. In L7the aromatic protons were observed in the region 6.69 to 7.60 ppm. The C⁴H appeared as doublet at 7.60 ppm and C⁶H resonated as triplet at 7.24 ppm. The signals due to C⁵H andC₇H appeared as multiplet at 6.69 ppm integrating for two protons. The signals due to aromatic protons in C-1 complex show variation in the chemical shifts but with same multiplicity of the signals as compared to the ligand.

13C NMR spectrum is consistent with ¹H NMR analysis in demonstrating the architecture of the ligand L and C- 1 complex. The peak at 76.20 ppm in ¹³C NMR spectrum of L is assigned to sp³ hybridized carbon (C¹), which confirms the formation of tetrahydroquinazolinone. The C² (ring carbonyl carbon) and C⁹ (carboxylic group) signals are observed at 164.44 and 173.04 ppm respectively in the L. The C² signal has shifted to downfield in

the spectrum of C-1 indicating the participation of carbonyl oxygen of quinazolinone ring in coordination with the metal ion. The disappearance of signal due to C⁹ carbon in C-1 complex confirms the decarboxylation upon complexation. The methyl carbon (C¹⁰) appeared at 22.25 ppm in the C-1 complex. The aromatic carbons have appeared in the expected region in the ligand and are unaltered upon complexation. Thus, from the NMR data it is clear that the ligand is coordinated to metal through nitrogen atom of the amine group and ring carbonyl oxygen. NMR spectral study also proves the loss of carboxylic group during complex formation.

Table-3:

¹

H and

¹³

C NMR chemical shifts of L and its Mn(II) complex (C-1)

Position L C-1

13C ¹H ¹³C ¹H

C¹ 76.20 -- 76.58 --

C² 164.44 -- 165.71 --

C³ 113.60 -- 113.72 --

C⁴ 113.60 7.60 (d, J = 10 Hz,

1H)

133.93 7.63 (d, J = 9.3 Hz, 1H)

C⁵ 113.55 6.69 (m, 2H) 113.28 6.66 (m, 2H)

C⁶ 127.09 7.24 (t, J = 7.5 Hz,

1H)

127.11 7.10 (t, J = 7.6 Hz, 1H)

C⁷ 117.30 6.69 (m, 2H) 117.33 6.71 (m, 2H)

C⁸ 145.31 -- 145.38 --

C⁹ 173.04 -- -- --

C¹⁰ 23.42 1.72 (s, 3H). 22.25 2.26 (s, 3H)

O¹H -- 12.19 (s, 1H) -- --

N¹H -- 7.43 (s, 1H) -- --

N³H2 -- 3.46 (s, 2H) -- 4.20 (s, 2H)

m = multiplet, d = doublet, s = singlet

3.3 Electronic spectral and magnetic susceptibility studies

Electronic spectra of the compounds in DMF were scanned in the region 200-1000 nm region. Electronic spectra of L and its complexes [(C-1) Mn(II), (C-2) Co(II), (C-3) Ni(II), (C-4) Cu(II)] are depicted in Figure-4. The electronic spectrum of the synthesized ligand in DMF showed two absorption bands, the band at 355 nm represents the π→π* transition while the second at 353 nm corresponds to the n→π* transition.

The electronic spectrum of the Mn(II) complex (C-1) exhibit two bands at 431 and 536 nm assignable to ⁶A_1g →

4T_2g and ⁶A_1g → ⁴T_1g transitions, respectively, corresponding to an octahedral geometry [35]. This is supported by its magnetic moment value of 5.13. The Co(II) complex (C-2) exhibit two bands at 459 and 676 nm assignable to the ⁴T_1g(F) → 4T_1g(P) (υ3) and ⁴T_1g → ⁴A_2g(F) (υ2) transitions as expected for an octahedral Co(II) complex [36]. The electronic spectrum of the Ni(II) complex (C-3) show three bands in the region 893, 643 and 432 nm attributable to³A_2g(F) → ³T_2g(F) (υ1), ³A_2g(F) → ³T_1g(F) (υ2), and ³A_2g(F) → ³T_1g(P) (υ3) transitions, respectively, suggesting an octahedral geometry around the Nil(II) atom [36]. The high spin octahedral Co(II) and Ni(II) complexes exhibit magnetic moment values around 4.31and 2.86 B. M. respectively. The Cu(II)

complex (C-4) with μeff = 1.71 corresponds to its spin only value and exhibit a broad absorption centered at 290- 630 nm which could be assigned to ²E_g → ²T_2g transition suggesting a distorted octahedral geometry [37].

Figure-4: Electronic spectra of L and its complexes [(C-1), (C-2), (C-3) & (C-4)]

3.4 EPR Spectral Studies

The EPR spectra of the Cu(II) complex (C-4) both at 300 and 77 K show a broad absorption band, which is isotropic due to the tumbling motion of the molecules. The ‘giso’ values at 300 and 77 K are 2.0021 and 2.0017 respectively.

3.5 Thermal Studies

Thermogravimetric (TG) analysis of the reported metal(II) complexes have been carried out so as to corroborate the information obtained from their spectral and molar conductance. From the TG we can account for the presence of solvent molecules present in these complexes, as well as to know their general decomposition patterns. The thermal decomposition was recorded in the temperature range of 25–1000 °C.

The TG curves of the reported complexes show that, all complexes have a similar decomposition patterns. From the thermograms it can be observed that, the complexes decompose in two stages. The complexes are thermally stable up to 119–233 °C, which indicates the absence of lattice held or coordinated water molecules. The complex C-3 has followed the two step decomposition pattern. The first weight loss of 13.98 % (14.72 %) at 195–280 °C corresponds to the loss of two coordinated chlorides. The second weight loss of 88.63 % (88.44 %) at 281–693°C corresponding to the loss of two ligand molecules. The plateau obtained above 693 °C corresponds to the formation of stable nickel oxide. Metal content calculated (14.93 %) from this residue, is in good agreement with the metal analysis (14.58 %). The thermogram of C-4 shows similar two-step decomposition. The first weight loss of 30.11 % (29.99 %) in the temperature range of 119-263°C corresponds to the loss of two coordinated chlorides and two coordinated methanol molecules. Second weight loss of 61.06

% (61.78 %) in the temperature range of 264-817 °C corresponds to the loss of two ligand molecules. After 817

°C a plateau was observed and this corresponds to the formation of stable CuO. The complexes C-1 and C-2 have also followed the same decomposition and the values are given in the Table-4.

Table-4: Thermal decomposition details of the complexes

Compound Temp.

(⁰C)

Weight loss corresponds to

Mass % of metal content calculated from MO Calcd. TG Calcd. Expt.

C-1 195–280 two coordinated chlorides

14.72 13.98

281–693 two ligand molecule

88.44 88.63

>693 14.93 14.58

C-2 209–295 two coordinated chlorides

14.60 14.35

296–726 two ligand molecule

87.70 87.19

>726 15.64 14.94

C-3 233-257 two coordinated chlorides

14.63 14.57

258-510 two ligand molecule

87.88 88.09

>510 15.47 15.68

C-4 119-263 two methanol+

four coordinated

chlorides

29.99 30.11

264-817 two ligand molecule

61.78 61.06

>817 11.66 12.34

IV. PROPOSED STRUCTURES

On the basis of the above observations, it is tentatively suggested that transition metal(II) investigated complexes show an octahedral geometry [Figure-10] in which the ligand acts as a neutral bidentate [N & O donor] ligand.

Figure-10: Tentative Structures for Investigated Complexes

4.1 Anti-bacterial Activity

The difference in anti-bacterial activities of the investigated complexes and ligand with the standard were studied and the results are presented in table-5.

Table-5: In vitro anti-bacterial activities of L and its metal complexes (C-1 to C-4)

Compound Gram Positive Gram Positive

SA EF EC SM

L 25 50 25 12.5

C-1 12.5 25 12.5 6.25

C-2 6.25 12.5 6.25 12.5

C-3 8.50 6.25 3.125 3.125

C-4 3.125 1.6 0.8 6.25

Ciprofloxacin 0.006 0.006 0.00125 0.00125

The synthesized complexes were found to be more active compared with their respective free ligands against the same microorganisms and under the identical experimental conditions. The increase in biological activity of the metal chelates may be due to the effect of the metal ion on the normal cell process. A possible mode of toxicity increase may be considered in the light of Tweedy’s chelation theory [38]. Chelation considerably reduces the polarity of the metal ion because of partial sharing of its positive charge with the donor group and possible p- electron delocalization within the whole chelate ring system that is formed during coordination. Such chelation could enhance the lipophilic character of the central metal atom and hence increase the hydrophobic character and liposolubility of the complex favoring its permeation through the lipid layers of the cell membrane. This enhances the rate of uptake or entrance and thus the antimicrobial activity of the testing compounds.

Accordingly, the antimicrobial activity of the complexes present in this investigation can be referred to the increase of their lipophilic character which in turn deactivates enzymes responsible for respiration processes and probably other cellular enzymes, which play a vital role in various metabolic pathways of the tested micro- organisms.

The activity study evidences that the complexation with copper enhances the antimicrobial activity of the ligands against some of the tested organism. Since copper chelates have an enhanced antimicrobial activity, in comparison to their analogous containing Mn(II) Co(II) and Ni(II) chelates. The metal seems to play a relevant role in the activity of these compounds [39].

The cursory view of the data indicates the following trend in antibacterial activity of the substances under investigation:

Cu(II)-complex ˃ Ni(II)-complex ˃ Co(II)-complex ˃ Mn(II)-complex ˃ Ligand

V. CONCLUSIONS

This paper presents the unusual cyclization of o-ABH when treated with pyruvic acid to produce the ligand 3- amino-2-methyl-4-oxo-1,2,3,4-ntetrahydroquinazoline-2-carboxylic acid (L). The transition metal complexes of L have been prepared in an environmentally benign microwave protocol and characterized by elemental analysis, conductivity measurements, magnetic moment, spectral and thermogravimetric analysis. Physico- chemical studies reveal that, the ligand loses carboxylic group upon complexation and gets coordinated through nitrogen of the amine and ring carbonyl oxygen. The ligand behaves as a neutral bidentate donor (O & N) yielding six coordinated transition metal complexes with octahedral geometry around the central metal ion. The plausible mechanisms have been deduced for the formation of tetrahydroquinazolinone and for the decarboxylation of the tetrahydroquinazolinone upon complexation. Antimicrobial data suggests that the metal complexes are better antibacterial agents as compared to their ligand.

Present methodology offers very attractive features such as simple experimental procedure, higher yields and economic viability, when compared with other method as well as with other catalysts, and will have wide scope in organic/inorganic syntheses.

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