SYNTHESIS AND ANTIMICROBIAL EVALUATION OF SOME NOVEL

SUBSTITUTED VANILLIN DERIVATIVES

DISSERTATION PROTOCOL

Submitted to the

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA

BY
HEMANTH .S, M.Pharm, Part- I

DEPARTMENT OF PHARMACEUTICAL CHEMISTRY

UNDER THE GUIDANCE OF

Mr. M. GURUMURTHY, M.Pharm

Assistant Professor

Department Of Pharmaceutical Chemistry

Dr.H.L.T College of Pharmacy,

Kengal, Channapatna-571502

2008

Rajiv Gandhi University of Health Sciences, Bangalore

Karnataka

AnneXUre II

Proforma for Registration of subjects for Dissertation

1. / Name of the Candidate and
Address (in Block Letters) /

HEMANTH.S. M. Pharm, Part-I

DEPARTMENT OF PHARMACEUTICAL CHEMISTRY.
Dr. H. L. T.COLLEGE OF PHARMACY.
KENGAL, CHANNAPATNA-571502
BANGALORE (RURAL), KARNATAKA.
2 / Name of the Institution / Dr. H. L. T. College of Pharmacy
Kengal, Channapatna, - 571 502
Bangalore Rural.
3 / Course of the Study and Subject /

Master of Pharmacy in Pharmaceutical Chemistry.

4 / Date of Admission to the Course / 16/06/2008
5 /

Title of the Topic

/ “SYNTHESIS AND ANTIMICROBIAL EVALUATION OF SOME NOVEL SUBSTITUTED VANILLIN DERIVATIVES”

6  BRIEF RESUME OF THE INTENDED WORK

6.1  NEED FOR THE STUDY

The deterioration of human population due to enhanced prevalence of infectious diseases is becoming a worldwide problem. Significant research efforts continued towards the development and marketing of novel antimicrobial agents. Since the discovery of substituted vanillins in pharmaceutical industries have produced number of synthetic or semisynthetic antimicrobial agents to combact a wide variety of microbial infections. However in the past several years of extensive use or misuse of antimicrobial agents has generated a rapid emergence of resistance.

Among many promising compounds vanillin and its derivatives exhibit broad spectrum of antimicrobial and various pharmacological activities.

Some novel substituted vanillin derivatives such as ethyl vanillin (3-ethoxy 4-hydroxy benzaldehyde, iso vanillin (3-hydroxy 4-methoxy benzaldehyde) and these compounds used in treatment of bronchial asthma, as an antidepressant.

Vanillin and its derivatives exhibit a broad spectrum of antimicrobial activity including Gram positive such as S. subfava and B. megaterium. Gram negative bacteria E. aerogenes and C. frundii.

The present investigation includes synthesis of substituted vanillin derivatives and exploring more antimicrobial activities of such molecules through structural modification.

6.2. REVIEW OF LITERATURE

The review of various published works related to the subject and objective of the studies have revealed the following.

1.  Preparation of vanillin, from wood derivatives, see (a) Lampman, G.M; Andrews, J.; Bratz, W,; Hanssen, O.; Kelley, K.; Perry, D. Ridgeway, A.J. Chem. Educ. 1977, 54, 776. (b) Hocking, M.B.J. Chem. Educ. 1997, 74,1055.

2.  Li, K.; Frost, J.W. J. Am. Chem. Soc. 1998, 120, 10545.

3.  Van den Heuvel, R.H.H.; Fraaije, M.W.; Laane, C.; van Berkel, W.J.H.J. Agric. Food Chem. 2001, 49, 2954.

4.  (a) For the original report of this preparation of vanillin, see Nobel, D. J. Chem. Soc., Chem. Commun. 1993, 419. (b) For a variation on the Cu-mediated methoxide coupling, see Capdevielle, P.; Maumy, M. Tetrahedron Lett. 1993, 34, 1007.

5.  Alfred Burgers, Medicinal Chemistry and Drug discovery, vol. 1, 419, 420.

6.  Alfred Burgers, Medicinal Chemistry and Drug discovery, vol. 2, 314, 315.

7.  Bentley and Drivers, Text book of pharmaceutical chemistry, 553, 557.

6.3.  MAIN OBJECTIVES OF THE STUDY

In this present investigation, we propose:

·  To synthesize novel substituted vanillin derivatives by using guaicol, formaldehyde, sodium hydroxide, phenyl ammonium hydroxide, concentrated nitric acid, concentrated sulphuric acid, bromine, ammonia.

·  Characterize the synthesized compounds by Spectroscopic studies like UV, IR, NMR and Mass Spectroscopy. Melting point, Boiling point. Chromatographic studies etc.,

·  Screen active compounds for antimicrobial activities using Gram +ve and Gram –ve bacteria, fungus, microbes etc.,

7. MATERIALS AND METHODS

7.1 SOURCE OF DATA

The preliminary data required for the experimental study was obtained from CD-Rom search available at National Center for Scientific Information (NCSI). Chemical Abstract.

Scientific Journals.Dr. H.L.T. college of Pharmacy Library, Indian institution of sciences (IISC). Bangalore, Internet Source

7. 2. METHODS OF COLLECTION OF DATA

A)  Synthetic Studies:

As per literature review the Newer Vanillin will be synthesized and progress of reaction as follows: -

Guaicol + Formaldehyde Sodium 3-methoxy 4-hydroxy

Hydroxide Benzyl alcohol

Electrophilic Substitution

5-substituted 3-methoxy

4-hydroxy benzyl alcohol

Phenyl ammonium hydroxyide

Protonation

5-substituted 5-substituted 3-methoxy

Vanillin 4-phenyl imine benzaldehyde

7.3 Does the study required any investigation are interventions to be conducted on patients

or other humans or animals? if so please describe briefly

The study does not require any investigation on patients or humans are animals

7.4. Has ethical clearance been obtained from your institution in care of 7.3

7.5 ……………. Not Applicable …………………..

7.  LIST OF REFERENCES

  1. Preparations of vanillin, from wood derivatives, see (a) Lampman, G. M.; Adrews, J.; Bratz, W.; Hanssen, O.; Kelley, K.; Prerry, D; Ridgeway, A.J. Chem. Educ. 1977, 5, 776. (b) Hocking, M.B.J. Chem. Educ. 1997, 120, 10545.
  2. Li, K.; Frost, J. W. J. Am. Chem. Soc. 1998, 120m 10545
  3. Van den Heuvel, R.H. H.; Fraaije, M. W.; Laane, C.; van Berkel, W.J.H. J. Afric. Food Chem. 2001, 49, 2954

4.  (a) For the original report of this preparation of vanillin, see Nobel, D.J. Chem. Soc., Chem.Commun. 1993, 419. (b) For variation on the C9-mediated methozide coupling, see Capdevielle, P.; Maumy, M. Tetrahedron Lett. 1933, 34, 1007.

5.  Taber, D.F.; Wange,Y.; Liehr, S.J. Chem. Ed. 1996. 73, 1042-1043

6.  K.Y. Lau, A. Mayr. K.K. Cheung, Inorg. Chim. Acta 285 (1999) 223.

7.  A.S. Shawali, N.M.S. Harb, K.O. Badahdan, J. Heterocyclic Chem. 22 (1985) 1397.

8.  N. Raman, V. Muthuraj, S. Ravichandran, A. Kulandaisamy, Proc. Ind. Acad. Sci. 115 (2003).

9.  S.K. Sridhar, A. Ramesh, Ind. J. Chem. Soc. 41 (2002) 668.

  1. Z. Wei, C.Qiong, H. Chao-gang, Hruazhong Shifan Daxue. Xuebao Zirankexue ban 36 (2002).
  2. Y. Dong-Dong, J. Yan Lan, S. Lu, Chinese J. Chem. 19 (2001) 1136.
  3. P. Piotr, B. Bogumil, Biopolymers 67 (2002) 61.
  4. Rh. Miao, Li. Shuolions, Y. Rudong, V.L.Y. Welbing, Ind. J. Chem. 42 (2003) 318.
  5. Z. Yuxia, Z. Tao, M. Wanshan, Z. Haibin, C. Suifeng, Hauxue Shiji 24 (2002) 117.
  6. M.A. Gawad, Y.M. Issa, S.M. Abd-Alhamid, Egypt J. Pharm. Sci 34 (1993) 219.
  7. V.V. Mulwad, J.M. Shirodkar, Ind. J. Hetrocyclic Chem. 11 (2002) 199
  8. N. Sari, S. Arslan, E. Logoglu, I. Sariyan, G.U.J. Sci 16 (2003) 199.
  9. S. Rao, A.S. Mitra, J. Ind. Chem. Soc. 55 (1978) 420
  10. S.A. Khan, A.A. Siddiqui, B. Shibeer, Asian J. Chem. 15 (2002) 117
  11. A. Marchetti. C. Preti. M. Tagliazucchi, L. Tassil, G. Tosi, J. Chem. Eng. Data 36 (1991) 360.

9 / Signature of the candidate
10 / Remarks of the Guide / Topic selected for Dissertation work is satisfactory. This can be carried out in our Laboratory.
11 / Name and Designation of
(In Block Letters)
11.1  Guide
11.2  Signature / Mr. M. GURUMURTHY, M. Pharm
ASSISTANT PROFESSOR
DEPT. OF PHARMACEUTICAL CHEMISTRY.
Dr. H. L. T. COLLEGE OF PHARMACY,
KENGAL, CHANNAPATNA-571 502
BANGALORE (RURAL), KARANATAKA.
11.3  Co – Guide
(If any)
11.4  Signature
11.5  Head of the Department
11.6 Signature / Mr. M. GURUMURTHY.M. Pharm
ASSISTANT PROFESSOR
DEPT. OF PHARMACEUTICAL CHEMISTRY.
Dr. H. L. T. COLLEGE OF PHARMACY,
KENGAL, CHANNAPATNA-571 502
BANGALORE (RURAL), KARANATAKA.
12 / 12.1  Remarks of the Chairman and Principal
12.2  Signature / The above mentioned information is correct and recommend the same for approval.

From

HEMANTH .S, M.Pharm,

Department of Pharmaceutical Chemistry,

Dr.H.L.T College of Pharmacy,

Kengal, Channapatna-571 502

Bangalore Rural.

To

The Registrar (Evaluation),

Rajiv Gandhi University of Health Sciences,

4th ‘‘T’’ Block, Jayanagar,

Bangalore-560 041

(Through Proper Channel)

Respected Sir,

Sub: Submission of Synopsis of Dissertation

Herewith, I am submitting synopsis of dissertation work “SYNTHESIS AND ANTIMICROBIAL EVALUATION OF SOME NOVEL SUBSTITUTED VANILLIN DERIVATIVES” for registration in M.Pharm (Pharmaceutical chemistry) of Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka.

Kindly accept the same and oblige.

Thanking you,

Yours faithfully,

Place: Channapatna (HEMANTH .S)

Date:

Guide:

Mr. M.GURUMUTHY, M.Pharm PRINCIPAL

ASSISTANT PROFESSOR Dr. H.L.T.College of Pharmacy,

DEPT. OF PHARMACEUTICAL CHEMISTRY Kengal, Channapatna – 571 502

Dr. H.L.T.College of Pharmacy, Bangalore (Rural).

Kengal, Channapatna-571 502

Bangalore (Rural).

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