Synthesis of Substituted Quinazolinones

Synthesis of Substituted Quinazolinones 6. DISCUSSION Heterocyclic compounds, widely distributed in nature are very essential to life. They play a vital role in the metabolism of all living cells. With their high degree of structural diversities and broad spectrum activities, they have proven to be one of the most economically useful chemotherapeutic agents. Synthesis of novel heterocyclic compounds with more potent activities, better efficacy and lower toxicity is the need of the day to the modern synthetic and medicinal chemists. In the present work, a total of 90 newer therapeutic compounds with heterocyclic rings like quinazolinonyl isoxazole and thiocarbamoyl pyrazolines were synthesized by conventional heating. In the 1st step, a total of 18 substituted quinazolinones were synthesized followed by 18 substituted acetylated quinazolinones in the 2nd step by acetylation of 1st step compounds. Treatment of various substituted acetylated quinazolinones with benzaldehyde lead to 18 substituted quinazolinonyl chalcones respectively. Further, when the chalcones were treated with thiosemicarbazide and NH2OH.HCl lead to synthesis of a total of 36 compounds with complex quinazolinonyl thiocarbamoyl pyrazolines and quinazolinonyl isoxazoles. All the above synthesized compounds were structurally confirmed by the IR, 1HNMR and mass spectral analysis. After structural confirmation by physical and spectral characterizations, they were evaluated for pharmacological activities like antibacterial, antifungal, anthelmintic, analgesic and anti-inflammatory activities. 6.1 Structural characterization of synthesized compounds Reaction of anthranilic acid and its derivatives bromo, iodo anthranilic acids with aromatic amines (aniline, p-chloro aniline, p-bromo aniline, m-chloro aniline, p-fluoro aniline and p-methyl aniline) and carbon disulfide in the presence of potassium hydroxide in methanol under reflux for 3hr afforded the corresponding 3-(un)substituted phenyl-6-(un)substituted-2-thioxo-4(3H)-quinazolinones 1a-r. Absorption bands in the range 3210-3445 cm-1 and 1505-1590 cm-1 in the IR spectrum of the synthesized compounds (1a-r) indicated the presence of N-H and a thioureide group (N-C=S) in the thioxoquinazolinone system. Strong absorption band in the range of 1600-1690 cm-1 and a medium band at 1100-1290 cm-1 were also observed due to C=O stretching and C=S stretching respectively [66]. The absence of any band in the region 2600-2550 cm-1 (characteristic of a thiol group) indicated that the compound exists in the solid state in the thione form. The 1HNMR spectrum of 2-thioxo-quinazolin-4(3H)-one in DMSO-d6 showed a singlet of 1H intensity at ÃŽ ´13 ppm for the proton attached to the nitrogen at position 1, and a complex multiplet of 14 protons between ÃŽ ´ 6.0-8.8 ppm. All the above results correlate and confirm the formation of thioxoquinazolinone ring system in respective compounds 1 a-r. When compounds 1 a-r treated with acetic anhydride, N-acetylation was took place and acetyl group was introduced at 1st position of the thioxo quinazolinone nucleus and gave compounds 2 a-r. Acetylation was confirmed by the appearance of peak at ÃŽ ´ 1.72 ppm and disappearance of a peak corresponding to NH in between ÃŽ ´ 9.7 ppm to ÃŽ ´ 13.0 ppm due to the protons of acetyl group. Claisen-Schmidt condensation of 2 a-r with benzaldehyde in alcoholic alkali gave corresponding quinazolinonyl chalcones 3 a-r. IR spectrum of the quinazolinonyl chalcones showed a peak at 1670 cm-1 characteristic of à ¯Ã‚ Ã‚ ¡, à ¯Ã‚ Ã‚ ¢-unsaturated keto functional group [255] of chalcones. Appearance of doublets in the range of ÃŽ ´ 6.7-6.9 ppm and ÃŽ ´ 7.44-7.56 ppm, disappearance of singlet corresponds to 3 protons of the N- acetyl group confirmed the 2-propen-1-one moiety of the titled compounds 3 a-r. 5-Phenyl-3-[3’-(un) substituted phenyl-6’-(un) substituted-2’-thioxo-4’ (3’H)-quinazolinon-1’-yl]-1-thiocarbamoyl-2-pyrazolines 4 a-r were prepared by refluxing quinazolinonyl chalcones with thiosemicarbazide in the presence of sodium hydroxide. Disappears of peck corresponds to ÃŽ ±, ÃŽ ²-unsaturated keto functional group of chalcones at 1670 cm-1 and appearance of pecks at 709.92 cm-1, 1067.42 cm-1, 1386.89 cm-1,1517 cm-1 and 3239.62 cm-1 confirmed the thiocarbamoyl-2-pyrazoline nucleus. Appearance of singlet at ÃŽ ´ 8.46 ppm indicated the two protons of thiocarbamoyl group (NH2-C=S) at 1st position of 1-thiocarbamoyl-2-pyrazoline ring [256]. Cycloaddition of chalcones with hydroxyl amine hydrochloride (NH2OH.HCl) gave isoxazoles 5 a-r. Absence of C=O band and appearance of new bands in the range of 1210-1270 cm-1, 1560-1610 cm-1 in the IR spectrum of all the compounds indicated -C-O-N- and C=N of isoxazole ring respectively [257, 258]. Appearance of a peek in the range of ÃŽ ´ 5.9-6.9 ppm in 1HNMR spectrum correlates with IR spectrum data and confirms the formation of isoxazole ring in the respective compounds. 6.2 Biological activities 6.2.1 Antibacterial activity All the titled compounds (1 a-r, 2 a-r, 3 a-r, 4 a-r and 5 a-r) were evaluated for antibacterial activity. The results were given in Table 5.29, 5.30, 5.31, 5.32 and 5.33. In all compounds basic skeleton and the electron withdrawing halogens played a key role in pharmacological activities. Compounds with electron withdrawing F, Br, Cl groups at para position of phenyl ring and electron releasing CH3 group at para position of the phenyl ring displayed maximum activity against Bacillus subtilis 6.2.2 Antifungal activity All the titled compounds (1 a-r, 2 a-r, 3 a-r, 4 a-r and 5 a-r) were evaluated for antifungal activity. The results were given in Table 5.34, 5.35, 5.36, 5.37 and 5.38. In all compounds basic skeleton and the electron withdrawing halogens played a key role in pharmacological activities. Compounds with electron withdrawing F, Br, Cl groups at para position of phenyl ring and electron releasing CH3 group at para position of the phenyl ring displayed maximum activity against Candida species. 6.2.3 Anthelmintic activity All the titled compounds (1 a-r, 2 a-r, 3 a-r, 4 a-r and 5 a-r) were evaluated for anthelmintic activity. The results were given in fig 5.1, 5.2, 5.3, 5.4 and 5.5. In all compounds basic skeleton and the electron withdrawing halogens played a key role in pharmacological activities. Compounds with electron withdrawing F, Br, Cl groups at para position of phenyl ring and electron releasing CH3 group at para position of the phenyl ring displayed maximum activity against Perithima posthuma. 6.2.4 Analgesic activity All the titled compounds (1 a-r, 2 a-r, 3 a-r, 4 a-r and 5 a-r) were evaluated for analgesic activity. The results were given in fig 5.6, 5.7, 5.8, 5.9 and 5.10. In all compounds basic skeleton and the electron withdrawing halogens played a key role in pharmacological activities. Compounds with electron withdrawing F, Br, Cl groups at para position of phenyl ring and electron releasing CH3 group at para position of the phenyl ring displayed potent analgesic activity. 6.2.5 Anti-inflammatory activity All the titled compounds (1 a-r, 2 a-r, 3 a-r, 4 a-r and 5 a-r) were evaluated for anti-inflammatory activity. The results were given in fig 5.11, 5.12, 5.13, 5.14 and 5.15. In all compounds basic skeleton and the electron withdrawing halogens played a key role in pharmacological activities. Compounds with electron withdrawing F, Br, Cl groups at para position of phenyl ring and electron releasing CH3 group at para position of the phenyl ring displayed maximum anti inflammatory activity.

Finlands Education System Essay

â€Å"The Finland Phenomenon† a name given to Finland’s admired education system. It is listed as the most surprising school system in the world. Its success is intently watched by other countries. The assigned video â€Å"Finland’s Education Success† was documented by Tom Burridge of BBC World News America on April 6, 2010. Week four Reading Journal for English 101 was a writing assignment asking students if the system could be implemented in the United States. â€Å"Finland’s schools score consistently at the top of the world rankings yet the pupils have the fewest number of class hours in the developed world. The proof is in the results and Finland has an education system other countries should learn from and envy. The transformation of Finland’s education system began 40 years ago as a key component to an economic recovery plan. The educators had no idea it was so successful until the year 2000, when a standardized test was given to fifteen years old students. The results revealed the scores. The Finnish youth came out on top as the best readers in the world. Three years later the youth led the scores in math as well. â€Å"By 2006 Finland was first out of 57 countries. The Finnish answer to standardized testing has been to only give exams to small groups of students and to trust in teachers. In 1991 the National Board of Education closed its inspectorate. â€Å"Teachers in Finland design their own courses using a national curriculum as a guide and spend about eighty percent as much time leading classes as their U. S. counterparts do. † Finnish teachers have sufficient opportunity to plan lessons and collaborate with colleagues. â€Å"Teachers in Finland spend fewer hours at school and less time in the classroom than American teachers. In 1979 reformers decided that every teacher in Finland earn a fifth-year master’s degree in theory and practice at one of the eight state universities. From that time forward teachers were granted equal status with doctors and lawyers. Teaching programs were flooded with applicants not because the salaries were that high, but because respect made the job so attractive. Pasi Sahlberg a former physics teacher points out â€Å"We prepare children to learn how to learn and not how to take a test†. All children- clever or less so- were to be taught in the same classrooms, with lots of special teacher help available to make sure no child would be left behind. † Compulsory school in Finland doesn’t begin until children reach the age of seven. â€Å"Children learn better when they are ready. Why stress them out? † Finnish culture values childhood independence children get themselves to school by either walking or biking. Upon arrival at school, children remove their shoes to maintain a relaxed atmosphere. Finnish children spend far more time playing outside even in the depth of winter. The children can’t learn if they don’t play. The children must play† The Finnish children are provided with seventy-five minutes of recess a day compared to the average of twenty-seven for U. S children. Finnish schools don’t assign homework because it is assumed the task is mastered in the classroom. Children are also mandated to take lots of arts and crafts and learning by doing. This is a far cry from the U. S concentration on testing in reading and math since the enactment of No Child Left Behind in 2002. The focus in Finland is on the individual child. If a child is falling behind, the highly trained staff recognizes and addresses the issues to meet the child’s needs. Nearly thirty percent of the children in Finland receive some kind of special help during their first nine years in school. The true focus on education is â€Å"equal opportunity for all. † Finnish educators have a hard time understanding the United States’ fascination with standardized tests. â€Å"Americans like all these bars and graphs and colored charts. † ‘It’s nonsense. We know far more about the children than these tests can tell us. Finland has a culture of collaboration between schools, not competition. All schools perform at the same level and there is no status in attending a particular facility. Finland has no private schools and all Finland’s schools are publicly funded. It is surprising to know that Finland spends about thirty percent less per student to achieve their far superior educational outcomes. The people in the government agencies running the schools from the national officials to the local officials are educators, not business people, military leaders or career politicians. The United States has muddled along in the middle of the pack for the past decade. Government officials have attempted to introduce competition into public schools. President Obama’s Race to the Top initiative invites states to compete for federal dollars using tests and other methods to measure teachers, a philosophy that goes against everything the Finnish schools stand for. â€Å"If you only measure the statistics, you miss the human aspect. † Fortunately United States Federal policies continue to move away from the rigid certainties of the No Child Left Behind legislation. The law has set an unrealistic target for one hundred percent student proficiency in every school by 2014. I couldn’t agree more with the Finland approach to education. In order for the United States to come close to Finland’s success a major change would need to occur. A change I believe would take decades to complete. â€Å"The Finns have made it clear, that in any country, no matter its size or composition, there is much wisdom to minimizing testing and instead investing in broader curricula, smaller classes, and better training, pay and treatment of teachers. The United States should take heed. †

The Unexplained Puzzle Into Sat Writing Essay Samples

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When Was Barbecue Invented

Because humankind has no doubt been cooking meat since the discovery of  fire, its impossible to point to any one person or culture  that invented the barbecue method of cooking. Neither do we know when, exactly, it was invented. We can look to several countries and cultures, however, from which barbecue likely gets its roots, like the 19th-century United States or the Caribbean.   Cowboy Cookin The trail hands slogging their way across the American West in endless cattle drives were allotted less than perfect cuts of meat as part of their daily rations. But these cowboys were nothing if not industrious, and they soon discovered these cuts, like the stringy brisket, could be much improved with five to seven hours of slow cooking to tenderize. Soon they became adept at other meats and cuts, like pork butt, pork ribs, beef ribs, venison, and goat. Funny, how this invention of necessity would eventually become a mania in some parts of the U.S., but just try to debate the merits of Kansas City over Texas over Low Country styles of barbecue. Youll quickly see how passionate and obstinate their adherents can be. Island Meats and French Treats Although there is hardly a country in the world whose people dont in some way partake in outdoor grilling of some kind, say the word barbecue to most people and they think America. But that doesnt mean it was invented here, cowboys or no cowboys.  For instance, the Arawakan Indians of the  West Indian island of Hispaniola have for over 300 years cooked and dried meat over an apparatus they call a barbacoa—which is just a short linguistic hop to barbecue. And no discussion of culinary history would be complete without the French stepping in to assert their hegemony. Many assert the origin of the word goes back to Medieval France, stemming from an  Old Anglo-Norman word, barbeque,  a contraction of the old-french expression barbe-à  -queue, or, from the beard to the tail, referring to how a whole animal was speared before being cooked, spit-style, over a fire. But this is all conjecture, as no one is really certain of the origin of the word. Charcoal Instead of Wood For centuries, the fuel of choice for cooking has been  wood, and it is  still preferred among barbecue aficionados, including those who compete in the thousands of contests that crop up in the U.S. each year.  In America, in fact, smoking meats with woods like mesquite, apple, cherry, and hickory, thereby adding extra dimensions of flavor, has become a culinary art form.   But modern-day backyard barbecuers have  Ellsworth B. A. Zwoyer of Pennsylvania to thank for making their lives much easier. In 1897, Zwoyer patented a design for charcoal briquettes and even built several plants after World War I to produce these compacted squares of wood pulp. However, his story is overshadowed by that of  Henry Fords, who in the early 1920s was looking for a way to reuse wood scraps and sawdust from his Model T assembly lines. He snagged the technology to start a briquette-manufacturing company, which was run by his buddy Edward G. Kingsford. The rest is history.