The Simple and Efficient Method of Synthesis of Amino Pyrimidine and Their Derivatives

Sirsat Shivraj; Bobade Dnyaneshwar; Shinde Sainath

doi:doi:10.11648/j.ajhc.20220801.11

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The Simple and Efficient Method of Synthesis of Amino Pyrimidine and Their Derivatives

Sirsat Shivraj, Bobade Dnyaneshwar, Shinde Sainath

Published in American Journal of Heterocyclic Chemistry (Volume 8, Issue 1)

Received: 22 March 2022 Accepted: 21 April 2022 Published: 31 May 2022

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Abstract

In the literature survey others reported a variety of synthesis of Pyrimido pyrimidine and their derivatives that have been potential bioactive molecules. Hence, they have to drag considerable attention in the synthesis of biologically active molecule and advanced organic chemistry. In the group of heterocyclic compounds nitrogen containing heterocycles are an important class of compounds in the medicinal chemistry and also contributed to the society from biological, industrial and pharmacological applications such as anticonvulsant, antihypertensive aactivity, analgesic, anti-depressive, antipyretic, anti-inflammatory, Chemotherapeutic agents, antiviral, anti-HIV, antimicrobial and anti-tumour activities. Therefore, the present study aim to investigate the chemistry of heterocycles incorporating 4,11-diimino-2,9-bis(methylthio)-6-hydroxy-7,11-dihydro-4H,6H-dipyrimido[1,2-a:1',2'-c]pyrimidine-3,10-dicarbonitrile skeletons and their derivatives. The simple and efficient synthesis of amino pyrimidine have been demonstrated by using Michael addition reaction, Michael acceptor ethylecyano acetate and Michael donor guanidine nitrate. The resulting compound 2,6 diamino 4-hydroxy pyrimidine was further reacted with 2-[bis (methylthio)methylene]malononitrile in the presence of catalytic amount of K₂CO₃ in DMF under reflux condition that offered substituted amino pyrimidine. In the compound of amino pyrimidine have replaceable methylthio group, This group are substituted by various nucleophiles such as various substituted aromatic amines, aromatic phenols, heteryl amines and active methylene compounds. The structure and formula of all the synthesized compounds were characterized by spectral data. Some of the synthesized compounds were evaluated for their biological activities. The compounds of this class of heterocycles containing a significant characteristic scaffold and possessing a wide range of biological characteristic.

Published in	American Journal of Heterocyclic Chemistry (Volume 8, Issue 1)
DOI	10.11648/j.ajhc.20220801.11
Page(s)	1-6
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2022. Published by Science Publishing Group

Keywords

Michael Reaction, 2-[bis(methylthio)methylene]malononitrile, Guanidine Nitrate

References

[1]	S. B. Sirsat, A. G. Jadhav, N. B. Chavhan, D. R. Bobade, Simple and Efficient Synthesis Of Fused Hydroxy Pyrimido Pyrimidine Dinitrile Heterocycles and Its Derivatives, Journal of Emerging Technologies and Innovative Research, 2021, Volume 9, Issue 7, PP 56-60.
[2]	Kappe, C. O. 4-Aryldihydropyrimidines via the Biginelli condensation: Aza-analogs of nifedipine-type calcium channel modulators. Molecules 1998, 3, 1.
[3]	S. Hawser, S. Lociuro, and K. Islam, “Dihydrofolate reductase inhibitors as antibacterial agents,” Biochemical Pharmacology, 2006, vol. 71, no. 7, pp. 941–948.
[4]	Y. Ju, D. Kumar, and R. S. Varma, “Revisiting nucleophilicsubstitution reactions: microwave-assisted synthesis of azides, thiocyanates, and sulfones in an aqueous medium,” Journal of Organic Chemistry, vol. 71, no. 17, pp. 6697–6700, 2006.
[5]	P. D. Lokhande, B. Y. Waghamare, and S. S. Sakate, “Regioselectiveone-pot synthesis of 3,5-diarylpyrazoles,” Indian Journal of Chemistry B, vol. 44, no. 11, pp. 2338–2342, 2005.
[6]	D. J. Brown, Comprehensive Heterocyclic Chemistry, vol. 14, Pergamon Press, Oxford, UK, 1984, edited by A. R. Katritzky and C. W. Rees.
[7]	M. Garc´ıa-Valverde and T. Torroba, “Special issue: sulfurnitrogen heterocycles,” Molecules, vol. 10, no. 2, pp. 318–320, 2005.
[8]	D. W. Hopper, A. L. Crombie, J. J. Clemens, and S. Kwon,“Six-membered ring systems: pyridine and benzo derivatives,”Progress in Heterocyclic Chemistry, vol. 21, pp. 330–374, 2009.
[9]	A. Manlove and M. P. Groziak, “Six-membered ring systems: diazines and benzo derivatives,” Progress in Heterocyclic Chemistry, vol. 21, pp. 375 414, 2009.
[10]	O. Prakash, V. Bhardwaj, R. Kumar, P. Tyagi, and K. R. Aneja, “Organoiodine (III) mediated synthesis of 3-aryl/hetryl5,7-dimethyl-1,2,4-triazolo[4,3-a]pyrimidines as antibacterial agents,” European Journal of Medicinal Chemistry, vol. 39, no. 12, pp. 1073–1077, 2004.
[11]	P. Sharma, N. Rane, and V. K. Gurram, “Synthesis and QSAR studies of pyrimido[4,5-d]pyrimidine-2,5-dione derivatives as potential antimicrobial agents,” Bioorganic and Medicinal Chemistry Letters, vol. 14, no. 16, pp. 4185–4190, 2004.
[12]	H. S. Basavaraja, G. M. Sreenivasa, and E. Jayachandran, “Synthesis and biological activity of novel pyrimidino imidazolines,” Indian Journal of Heterocyclic Chemistry, vol. 15, p. 69, 2005.
[13]	V. J. Ram, N. Haque, and P. Y. Guru, “Chemotherapeutic agents XXV: synthesis and leishmanicidal activity of carbazolylpyrimidines,” European Journal of Medicinal Chemistry, vol. 27, no. 8, pp. 851–855, 1992.
[14]	M. Amir, S. A. Javed, and H. Kumar, “Pyrimidine as antiinflammatory agent: a review,” Indian Journal of Pharmaceutical Sciences, vol. 68, p. 337, 2007.
[15]	S. M. Sondhi, S. Jain, A. D. Dwivedi, R. Shukla, and R. Raghubir, “Synthesis of condensed pyrimidines and their evaluation for anti-inflammatory and analgesic activities,” Indian Journal of Chemistry B, vol. 47, no. 1, pp. 136–143, 2008.
[16]	S. Vega, J. Alonso, J. A. Diaz, and F. Junquera, “Synthesis of 3-substituted-4-phenyl-2-thioxo-1,2,3,4,5,6,7,8 octahydrobenzo[4,5]thieno[2,3-d]pyrimidines,” Journal of Heterocyclic Chemistry, vol. 27, no. 2, pp. 269–273, 1990.
[17]	K. Rana, B. Kaur, and B. Kumar, “Synthesis and antihypertensive activity of some dihydropyrimidines,” Indian Journal of Chemistry B, vol. 43, no. 7, pp. 1553–1557, 2004.
[18]	P. A. S. Smith and R. O. Kan, “Cyclization of isothiocyanates as a route to phthalic and homophthalic acid derivatives,” Journal of Organic Chemistry, vol. 29, no. 8, pp. 2261–2265, 1964.
[19]	J. Balzarini and C. McGuigan, “Bicyclic pyrimidine nucleoside analogues (BCNAs) as highly selective and potent inhibitors of varicella-zoster virus replication,” Journal of Antimicrobial Chemotherapy, vol. 50, no. 1, pp. 5–9, 2002.
[20]	P. F. Juby, T. W. Hudyma, M. Brown, J. M. Essery, and R. A. Partyka, “Antiallergy agents. 1. 1,6-dihydro-6-oxo-2phenylpyrimidine-5-carboxylic acids and esters,” Journal of Medicinal Chemistry, vol. 22, no. 3, pp. 263–269, 1979.
[21]	A. K. Gupta, Sanjay, H. P. Kayath, A. Singh, G. Sharma, and K. C. Mishra, “Anticonvulsant activity of pyrimidine thiols,” Indian Journal of Pharmacology, vol. 26, no. 3, pp. 227–228, 1994.
[22]	A. A. Abu-Hashem, M. M. Youssef, and H. A. R. Hussein, “Synthesis, antioxidant, antituomer activities of some new thiazolopyrimidines, pyrrolothiazolopyrimidines and triazolopyrrolothiazolopyrimidines derivatives,” Journal of the Chinese Chemical Society, vol. 58, no. 1, pp. 41–48, 2011.
[23]	A. A. Abu-Hashem, M. F. El-Shehry, and F. A. Badria, “Design and synthesis of novel thiophenecarbohydrazide, thienopyrazole and thienopyrimidine derivatives as antioxidant and antitumor agents,” Acta Pharmaceutica, vol. 60, no. 3, pp. 311– 323, 2010.
[24]	S. A. Rahaman, Y. R. Pasad, P. Kumar, and B. Kumar, “Synthesis and anti-histaminic activity of some novel pyrimidines,” Saudi Pharmaceutical Journal, vol. 17, no. 3, pp. 255–258, 2009.
[25]	J. W. Coe, A. F. J. Fliri, T. Kaneko, and E. R. Larson, “Pyrimidine derivatives enhancing antitumour activity,” U.S. Patent 5, 491, 234, 1996.
[26]	J. Tani, Y. Yamada, T. Oine, T. Ochiai, R. Ishida, and I. Inoue, “Studies on biologically active halogenated compounds. 1.
[27]	Synthesis and central nervous system depressant activity of 2(fluoromethyl)-3-aryl-4(3H)-quinazolinone derivatives,” Journal of Medicinal Chemistry, vol. 22, no. 1, pp. 95–99, 1979.
[28]	B. Kumar, B. Kaur, J. Kaur, A. Parmar, R. D. Anand, and H. Kumar, “Thermal/microwave assisted synthesis of substituted tetrahydropyrimidines as potent calcium channel blockers,” Indian Journal of Chemistry B, vol. 41, no. 7, pp. 1526–1530, 2002.

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APA Style

Sirsat Shivraj, Bobade Dnyaneshwar, Shinde Sainath. (2022). The Simple and Efficient Method of Synthesis of Amino Pyrimidine and Their Derivatives. American Journal of Heterocyclic Chemistry, 8(1), 1-6. https://doi.org/10.11648/j.ajhc.20220801.11

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ACS Style

Sirsat Shivraj; Bobade Dnyaneshwar; Shinde Sainath. The Simple and Efficient Method of Synthesis of Amino Pyrimidine and Their Derivatives. Am. J. Heterocycl. Chem. 2022, 8(1), 1-6. doi: 10.11648/j.ajhc.20220801.11

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AMA Style

Sirsat Shivraj, Bobade Dnyaneshwar, Shinde Sainath. The Simple and Efficient Method of Synthesis of Amino Pyrimidine and Their Derivatives. Am J Heterocycl Chem. 2022;8(1):1-6. doi: 10.11648/j.ajhc.20220801.11

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@article{10.11648/j.ajhc.20220801.11,
  author = {Sirsat Shivraj and Bobade Dnyaneshwar and Shinde Sainath},
  title = {The Simple and Efficient Method of Synthesis of Amino Pyrimidine and Their Derivatives},
  journal = {American Journal of Heterocyclic Chemistry},
  volume = {8},
  number = {1},
  pages = {1-6},
  doi = {10.11648/j.ajhc.20220801.11},
  url = {https://doi.org/10.11648/j.ajhc.20220801.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajhc.20220801.11},
  abstract = {In the literature survey others reported a variety of synthesis of Pyrimido pyrimidine and their derivatives that have been potential bioactive molecules. Hence, they have to drag considerable attention in the synthesis of biologically active molecule and advanced organic chemistry. In the group of heterocyclic compounds nitrogen containing heterocycles are an important class of compounds in the medicinal chemistry and also contributed to the society from biological, industrial and pharmacological applications such as anticonvulsant, antihypertensive aactivity, analgesic, anti-depressive, antipyretic, anti-inflammatory, Chemotherapeutic agents, antiviral, anti-HIV, antimicrobial and anti-tumour activities. Therefore, the present study aim to investigate the chemistry of heterocycles incorporating 4,11-diimino-2,9-bis(methylthio)-6-hydroxy-7,11-dihydro-4H,6H-dipyrimido[1,2-a:1',2'-c]pyrimidine-3,10-dicarbonitrile skeletons and their derivatives. The simple and efficient synthesis of amino pyrimidine have been demonstrated by using Michael addition reaction, Michael acceptor ethylecyano acetate and Michael donor guanidine nitrate. The resulting compound 2,6 diamino 4-hydroxy pyrimidine was further reacted with 2-[bis (methylthio)methylene]malononitrile in the presence of catalytic amount of K2CO3 in DMF under reflux condition that offered substituted amino pyrimidine. In the compound of amino pyrimidine have replaceable methylthio group, This group are substituted by various nucleophiles such as various substituted aromatic amines, aromatic phenols, heteryl amines and active methylene compounds. The structure and formula of all the synthesized compounds were characterized by spectral data. Some of the synthesized compounds were evaluated for their biological activities. The compounds of this class of heterocycles containing a significant characteristic scaffold and possessing a wide range of biological characteristic.},
 year = {2022}
}

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TY  - JOUR
T1  - The Simple and Efficient Method of Synthesis of Amino Pyrimidine and Their Derivatives
AU  - Sirsat Shivraj
AU  - Bobade Dnyaneshwar
AU  - Shinde Sainath
Y1  - 2022/05/31
PY  - 2022
N1  - https://doi.org/10.11648/j.ajhc.20220801.11
DO  - 10.11648/j.ajhc.20220801.11
T2  - American Journal of Heterocyclic Chemistry
JF  - American Journal of Heterocyclic Chemistry
JO  - American Journal of Heterocyclic Chemistry
SP  - 1
EP  - 6
PB  - Science Publishing Group
SN  - 2575-5722
UR  - https://doi.org/10.11648/j.ajhc.20220801.11
AB  - In the literature survey others reported a variety of synthesis of Pyrimido pyrimidine and their derivatives that have been potential bioactive molecules. Hence, they have to drag considerable attention in the synthesis of biologically active molecule and advanced organic chemistry. In the group of heterocyclic compounds nitrogen containing heterocycles are an important class of compounds in the medicinal chemistry and also contributed to the society from biological, industrial and pharmacological applications such as anticonvulsant, antihypertensive aactivity, analgesic, anti-depressive, antipyretic, anti-inflammatory, Chemotherapeutic agents, antiviral, anti-HIV, antimicrobial and anti-tumour activities. Therefore, the present study aim to investigate the chemistry of heterocycles incorporating 4,11-diimino-2,9-bis(methylthio)-6-hydroxy-7,11-dihydro-4H,6H-dipyrimido[1,2-a:1',2'-c]pyrimidine-3,10-dicarbonitrile skeletons and their derivatives. The simple and efficient synthesis of amino pyrimidine have been demonstrated by using Michael addition reaction, Michael acceptor ethylecyano acetate and Michael donor guanidine nitrate. The resulting compound 2,6 diamino 4-hydroxy pyrimidine was further reacted with 2-[bis (methylthio)methylene]malononitrile in the presence of catalytic amount of K2CO3 in DMF under reflux condition that offered substituted amino pyrimidine. In the compound of amino pyrimidine have replaceable methylthio group, This group are substituted by various nucleophiles such as various substituted aromatic amines, aromatic phenols, heteryl amines and active methylene compounds. The structure and formula of all the synthesized compounds were characterized by spectral data. Some of the synthesized compounds were evaluated for their biological activities. The compounds of this class of heterocycles containing a significant characteristic scaffold and possessing a wide range of biological characteristic.
VL  - 8
IS  - 1
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Author Information

Sirsat Shivraj

Department of Chemistry, Yeshwant Mahavidyalaya, Nanded, India
Bobade Dnyaneshwar

Department of Chemistry, Yeshwant Mahavidyalaya, Nanded, India
Shinde Sainath

Department of Chemistry, Yeshwant Mahavidyalaya, Nanded, India

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APA Style

Sirsat Shivraj, Bobade Dnyaneshwar, Shinde Sainath. (2022). The Simple and Efficient Method of Synthesis of Amino Pyrimidine and Their Derivatives. American Journal of Heterocyclic Chemistry, 8(1), 1-6. https://doi.org/10.11648/j.ajhc.20220801.11

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ACS Style

Sirsat Shivraj; Bobade Dnyaneshwar; Shinde Sainath. The Simple and Efficient Method of Synthesis of Amino Pyrimidine and Their Derivatives. Am. J. Heterocycl. Chem. 2022, 8(1), 1-6. doi: 10.11648/j.ajhc.20220801.11

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AMA Style

Sirsat Shivraj, Bobade Dnyaneshwar, Shinde Sainath. The Simple and Efficient Method of Synthesis of Amino Pyrimidine and Their Derivatives. Am J Heterocycl Chem. 2022;8(1):1-6. doi: 10.11648/j.ajhc.20220801.11

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@article{10.11648/j.ajhc.20220801.11,
  author = {Sirsat Shivraj and Bobade Dnyaneshwar and Shinde Sainath},
  title = {The Simple and Efficient Method of Synthesis of Amino Pyrimidine and Their Derivatives},
  journal = {American Journal of Heterocyclic Chemistry},
  volume = {8},
  number = {1},
  pages = {1-6},
  doi = {10.11648/j.ajhc.20220801.11},
  url = {https://doi.org/10.11648/j.ajhc.20220801.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajhc.20220801.11},
  abstract = {In the literature survey others reported a variety of synthesis of Pyrimido pyrimidine and their derivatives that have been potential bioactive molecules. Hence, they have to drag considerable attention in the synthesis of biologically active molecule and advanced organic chemistry. In the group of heterocyclic compounds nitrogen containing heterocycles are an important class of compounds in the medicinal chemistry and also contributed to the society from biological, industrial and pharmacological applications such as anticonvulsant, antihypertensive aactivity, analgesic, anti-depressive, antipyretic, anti-inflammatory, Chemotherapeutic agents, antiviral, anti-HIV, antimicrobial and anti-tumour activities. Therefore, the present study aim to investigate the chemistry of heterocycles incorporating 4,11-diimino-2,9-bis(methylthio)-6-hydroxy-7,11-dihydro-4H,6H-dipyrimido[1,2-a:1',2'-c]pyrimidine-3,10-dicarbonitrile skeletons and their derivatives. The simple and efficient synthesis of amino pyrimidine have been demonstrated by using Michael addition reaction, Michael acceptor ethylecyano acetate and Michael donor guanidine nitrate. The resulting compound 2,6 diamino 4-hydroxy pyrimidine was further reacted with 2-[bis (methylthio)methylene]malononitrile in the presence of catalytic amount of K2CO3 in DMF under reflux condition that offered substituted amino pyrimidine. In the compound of amino pyrimidine have replaceable methylthio group, This group are substituted by various nucleophiles such as various substituted aromatic amines, aromatic phenols, heteryl amines and active methylene compounds. The structure and formula of all the synthesized compounds were characterized by spectral data. Some of the synthesized compounds were evaluated for their biological activities. The compounds of this class of heterocycles containing a significant characteristic scaffold and possessing a wide range of biological characteristic.},
 year = {2022}
}

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TY  - JOUR
T1  - The Simple and Efficient Method of Synthesis of Amino Pyrimidine and Their Derivatives
AU  - Sirsat Shivraj
AU  - Bobade Dnyaneshwar
AU  - Shinde Sainath
Y1  - 2022/05/31
PY  - 2022
N1  - https://doi.org/10.11648/j.ajhc.20220801.11
DO  - 10.11648/j.ajhc.20220801.11
T2  - American Journal of Heterocyclic Chemistry
JF  - American Journal of Heterocyclic Chemistry
JO  - American Journal of Heterocyclic Chemistry
SP  - 1
EP  - 6
PB  - Science Publishing Group
SN  - 2575-5722
UR  - https://doi.org/10.11648/j.ajhc.20220801.11
AB  - In the literature survey others reported a variety of synthesis of Pyrimido pyrimidine and their derivatives that have been potential bioactive molecules. Hence, they have to drag considerable attention in the synthesis of biologically active molecule and advanced organic chemistry. In the group of heterocyclic compounds nitrogen containing heterocycles are an important class of compounds in the medicinal chemistry and also contributed to the society from biological, industrial and pharmacological applications such as anticonvulsant, antihypertensive aactivity, analgesic, anti-depressive, antipyretic, anti-inflammatory, Chemotherapeutic agents, antiviral, anti-HIV, antimicrobial and anti-tumour activities. Therefore, the present study aim to investigate the chemistry of heterocycles incorporating 4,11-diimino-2,9-bis(methylthio)-6-hydroxy-7,11-dihydro-4H,6H-dipyrimido[1,2-a:1',2'-c]pyrimidine-3,10-dicarbonitrile skeletons and their derivatives. The simple and efficient synthesis of amino pyrimidine have been demonstrated by using Michael addition reaction, Michael acceptor ethylecyano acetate and Michael donor guanidine nitrate. The resulting compound 2,6 diamino 4-hydroxy pyrimidine was further reacted with 2-[bis (methylthio)methylene]malononitrile in the presence of catalytic amount of K2CO3 in DMF under reflux condition that offered substituted amino pyrimidine. In the compound of amino pyrimidine have replaceable methylthio group, This group are substituted by various nucleophiles such as various substituted aromatic amines, aromatic phenols, heteryl amines and active methylene compounds. The structure and formula of all the synthesized compounds were characterized by spectral data. Some of the synthesized compounds were evaluated for their biological activities. The compounds of this class of heterocycles containing a significant characteristic scaffold and possessing a wide range of biological characteristic.
VL  - 8
IS  - 1
ER  -

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