Chem 234 Organic Chemistry II Professor Duncan J. Wardrop

2. Topics Covered: Phenol - Bonding, Physical Properties and Reactions Electrophilic Aromatic Substitution: Halogen, Nitration, Nitrosation O- and C-Acylation of Phenols: Fries Rearrangement Kolbe-Schmitt Reaction: Carboxylation of Phenols Preparation and Cleavage of Aryl Alkyl Ethers Claisen Rearrangement of Aryl Allyl Ether Preparation of Quinones

3. Chapter 24Phenols

4. 24.1Nomenclature

5. named on basis of phenol as parent substituents listed in alphabetical order lowest numerical sequence: first point ofdifference rule

7. The importance of dopamine in neural transmission is emphasized by the number of major neurological diseases that are associated with improper dopamine regulation. The earliest indication of this type of defect was the finding that dopamine levels are abnormally low in a particular region of the brain of patients with Parkinsonism, a severe neurological disorder. Attempts to treat such patients with dopamine were futile, because after injection, dopamine does not cross the blood brain barrier. However, the dopamine precursor, dopa, does cross the blood brain barrier. For many individuals with Parkinsonism, daily doses of dopa have provided dramatic clinical improvement. Dopamine is a catecholamine derived from tyrosine. Other catecholamines include epinephrine and norepinephrine. ����������������. ����������������.. ����������������.. ����������������.. ����������������.. Epinephrine, also known as adrenaline, is the principal hormone governing the "fight or flight" response to various stimuli. In addition to stimulating glycogenolysis, the hormone triggers a variety of physiological events, such as increasing depth and frequency of heartbeats. Epinephrine is secreted from the adrenal medulla and binds to specific receptors on muscle cell membranes. Binding of the hormone at the membrane stimulates the synthesis of cAMP by membrane-bound adenylate cyclase, through the action of a G protein, Gs. cAMP in turn activates cAMP-dependent protein kinase, which catalyzes the phosphorylation of phosphorylase b kinase. This kinase in turn catalyzes the phosphorylation of phosphorylase b to a and, hence, the activation of glycogen breakdown, through the action of phosphorylase a. These events explain how the secretion of relatively few molecules of hormone, such as epinephrine, can, within just a few moments, trigger a massive conversion of glycogen to glucose-1-phosphate. The importance of dopamine in neural transmission is emphasized by the number of major neurological diseases that are associated with improper dopamine regulation. The earliest indication of this type of defect was the finding that dopamine levels are abnormally low in a particular region of the brain of patients with Parkinsonism, a severe neurological disorder. Attempts to treat such patients with dopamine were futile, because after injection, dopamine does not cross the blood brain barrier. However, the dopamine precursor, dopa, does cross the blood brain barrier. For many individuals with Parkinsonism, daily doses of dopa have provided dramatic clinical improvement. Dopamine is a catecholamine derived from tyrosine. Other catecholamines include epinephrine and norepinephrine. ����������������. ����������������.. ����������������.. ����������������.. ����������������.. Epinephrine, also known as adrenaline, is the principal hormone governing the "fight or flight" response to various stimuli. In addition to stimulating glycogenolysis, the hormone triggers a variety of physiological events, such as increasing depth and frequency of heartbeats. Epinephrine is secreted from the adrenal medulla and binds to specific receptors on muscle cell membranes. Binding of the hormone at the membrane stimulates the synthesis of cAMP by membrane-bound adenylate cyclase, through the action of a G protein, Gs. cAMP in turn activates cAMP-dependent protein kinase, which catalyzes the phosphorylation of phosphorylase b kinase. This kinase in turn catalyzes the phosphorylation of phosphorylase b to a and, hence, the activation of glycogen breakdown, through the action of phosphorylase a. These events explain how the secretion of relatively few molecules of hormone, such as epinephrine, can, within just a few moments, trigger a massive conversion of glycogen to glucose-1-phosphate.

8. name on basis of benzoic acid as parent higher oxidation states of carbon outrankhydroxyl group

9. 24.2Structure and Bonding Phenol is highly corrosive and moderately toxic. It effects humans by burning the skin and other tissue that it comes into contact with. This gives severe skin burning and if inhaled serious internal corrosion. The skin burning is not initially felt because the phenol has a local anesthetic effect. It can affect the central nervous system, which will at first lead to sweating, weakness, dizziness and twitching but with prolonged exposure leads to nausea, vomiting and coma. If ingested even a small dose can lead to be fatal in humans and therefore care must be taken at all times using phenol-containing products.Phenol is highly corrosive and moderately toxic. It effects humans by burning the skin and other tissue that it comes into contact with. This gives severe skin burning and if inhaled serious internal corrosion. The skin burning is not initially felt because the phenol has a local anesthetic effect. It can affect the central nervous system, which will at first lead to sweating, weakness, dizziness and twitching but with prolonged exposure leads to nausea, vomiting and coma. If ingested even a small dose can lead to be fatal in humans and therefore care must be taken at all times using phenol-containing products.

10. phenol is planar C�O bond distance is 136 pm, which isslightly shorter than that of CH3OH (142 pm)

11. 24.3Physical Properties

14. Joseph Lister (1827-1912) came to Edinburgh in 1853 after graduating in medicine in London. He worked closely with James Syme, the celebrated Professor of Surgery in Edinburgh, becoming his assistant and marrying his daughter. In 1860 he was appointed to the Chair of Surgery in Glasgow, and it was there that he first applied Louis Pasteur�s recent discoveries about the role of airborne bacteria in fermentation to the prevention of infection in surgery. In 1866 he introduced carbolic acid as an antiseptic, to kill airborne bacteria and prevent their transmission into wounds from the air of the operating theatre. In 1869 he returned to Edinburgh as successor to Syme as Professor of Surgery, and continued to develop improved methods of antisepsis and asepsis, with greatly reduced infection rates. In 1877 Lister moved to London to continue the struggle to have his new theories accepted. Lister�s carbolic spray in use during an operation With increasing appreciation of the role of bacteria in infection new techniques replaced carbolic acid, but the advent of safe surgery converted it from an emergency treatment of last resort and widened the scope of planned surgery enormously. Lord Lister achieved international recognition but retained his affection for his old university, and at his death in 1912 bequeathed his portrait and collection of honours and medals to the University of Edinburgh. They are still proudly displayed in a case at the top of the Library Stair in Old College. Joseph Lister (1827-1912) came to Edinburgh in 1853 after graduating in medicine in London. He worked closely with James Syme, the celebrated Professor of Surgery in Edinburgh, becoming his assistant and marrying his daughter. In 1860 he was appointed to the Chair of Surgery in Glasgow, and it was there that he first applied Louis Pasteur�s recent discoveries about the role of airborne bacteria in fermentation to the prevention of infection in surgery. In 1866 he introduced carbolic acid as an antiseptic, to kill airborne bacteria and prevent their transmission into wounds from the air of the operating theatre. In 1869 he returned to Edinburgh as successor to Syme as Professor of Surgery, and continued to develop improved methods of antisepsis and asepsis, with greatly reduced infection rates. In 1877 Lister moved to London to continue the struggle to have his new theories accepted. Lister�s carbolic spray in use during an operation With increasing appreciation of the role of bacteria in infection new techniques replaced carbolic acid, but the advent of safe surgery converted it from an emergency treatment of last resort and widened the scope of planned surgery enormously. Lord Lister achieved international recognition but retained his affection for his old university, and at his death in 1912 bequeathed his portrait and collection of honours and medals to the University of Edinburgh. They are still proudly displayed in a case at the top of the Library Stair in Old College.

15. Joseph Lister (1827-1912) came to Edinburgh in 1853 after graduating in medicine in London. He worked closely with James Syme, the celebrated Professor of Surgery in Edinburgh, becoming his assistant and marrying his daughter. In 1860 he was appointed to the Chair of Surgery in Glasgow, and it was there that he first applied Louis Pasteur�s recent discoveries about the role of airborne bacteria in fermentation to the prevention of infection in surgery. In 1866 he introduced carbolic acid as an antiseptic, to kill airborne bacteria and prevent their transmission into wounds from the air of the operating theatre. In 1869 he returned to Edinburgh as successor to Syme as Professor of Surgery, and continued to develop improved methods of antisepsis and asepsis, with greatly reduced infection rates. In 1877 Lister moved to London to continue the struggle to have his new theories accepted. Lister�s carbolic spray in use during an operation With increasing appreciation of the role of bacteria in infection new techniques replaced carbolic acid, but the advent of safe surgery converted it from an emergency treatment of last resort and widened the scope of planned surgery enormously. Lord Lister achieved international recognition but retained his affection for his old university, and at his death in 1912 bequeathed his portrait and collection of honours and medals to the University of Edinburgh. They are still proudly displayed in a case at the top of the Library Stair in Old College. Joseph Lister pioneered antiseptic techniques in surgery. He used carbolic acid sprays to decontaminate surgical wounds as he worked. The phenol in these sprays irritated surgeon's hands and, to protect themselves from phenol burns, they started wearing rubber gloves. This practice continues today, although it is many years since carbolic acid was sprayed on open wounds. Lister studied the microbiology of air in his attempts to control wound infection associated with surgery. He used urine as a culture medium and noted that bacteria in cultures that were mixed with particular fungi appeared dead when viewed microscopically. He went on to demonstrate that fungal extracts could kill bacteria. Lister used to irrigate wounds with fungal extracts, but he could never isolate enough of the active compound for this approach to cleansing wounds to be truly effective. Phenol is the 'gold standard' for disinfectants and was the first to be used in clinical practice. Joseph Lister used it to prevent infection of his surgical wounds. Surgeons first wore rubber gloves not to prevent wound infections in patients but to stop their hands from being burned by the phenol that was sprayed over the wounds during operations. It acts by causing cell disruption and denaturing proteins. It is highly corrosive and toxic to humans. Because of its undesirable properties, many less toxic derivatives of phenol have been developed. Among the most popular are hexachlorophene and chlorhexidine. Chlorhexidine can be used in an isopropanol solution for skin disinfection, or as an aqueous solution for wound irrigation. It is often used as an antiseptic hand wash. When used regularly it may become mildly irritant. The temptation to use a moisturizing cream after hand-washing and before handling open wounds must be avoided. Hand creams often act as vectors for pathogens that can cause wound infections. A reproduction from a woodcut from Hans Von Gersdorff's Feldtbuch der Wundtarzney, Strassburg, J. Schott, 1517, this is reputed to be the first known picture of an amputation. The four figures are the patient, the operator and his assistant, and probably a priest. (Courtesy of the American College of Surgeons).Joseph Lister (1827-1912) came to Edinburgh in 1853 after graduating in medicine in London. He worked closely with James Syme, the celebrated Professor of Surgery in Edinburgh, becoming his assistant and marrying his daughter. In 1860 he was appointed to the Chair of Surgery in Glasgow, and it was there that he first applied Louis Pasteur�s recent discoveries about the role of airborne bacteria in fermentation to the prevention of infection in surgery. In 1866 he introduced carbolic acid as an antiseptic, to kill airborne bacteria and prevent their transmission into wounds from the air of the operating theatre. In 1869 he returned to Edinburgh as successor to Syme as Professor of Surgery, and continued to develop improved methods of antisepsis and asepsis, with greatly reduced infection rates. In 1877 Lister moved to London to continue the struggle to have his new theories accepted. Lister�s carbolic spray in use during an operation With increasing appreciation of the role of bacteria in infection new techniques replaced carbolic acid, but the advent of safe surgery converted it from an emergency treatment of last resort and widened the scope of planned surgery enormously. Lord Lister achieved international recognition but retained his affection for his old university, and at his death in 1912 bequeathed his portrait and collection of honours and medals to the University of Edinburgh. They are still proudly displayed in a case at the top of the Library Stair in Old College. Joseph Lister pioneered antiseptic techniques in surgery. He used carbolic acid sprays to decontaminate surgical wounds as he worked. The phenol in these sprays irritated surgeon's hands and, to protect themselves from phenol burns, they started wearing rubber gloves. This practice continues today, although it is many years since carbolic acid was sprayed on open wounds. Lister studied the microbiology of air in his attempts to control wound infection associated with surgery. He used urine as a culture medium and noted that bacteria in cultures that were mixed with particular fungi appeared dead when viewed microscopically. He went on to demonstrate that fungal extracts could kill bacteria. Lister used to irrigate wounds with fungal extracts, but he could never isolate enough of the active compound for this approach to cleansing wounds to be truly effective. Phenol is the 'gold standard' for disinfectants and was the first to be used in clinical practice. Joseph Lister used it to prevent infection of his surgical wounds. Surgeons first wore rubber gloves not to prevent wound infections in patients but to stop their hands from being burned by the phenol that was sprayed over the wounds during operations. It acts by causing cell disruption and denaturing proteins. It is highly corrosive and toxic to humans. Because of its undesirable properties, many less toxic derivatives of phenol have been developed. Among the most popular are hexachlorophene and chlorhexidine. Chlorhexidine can be used in an isopropanol solution for skin disinfection, or as an aqueous solution for wound irrigation. It is often used as an antiseptic hand wash. When used regularly it may become mildly irritant. The temptation to use a moisturizing cream after hand-washing and before handling open wounds must be avoided. Hand creams often act as vectors for pathogens that can cause wound infections. A reproduction from a woodcut from Hans Von Gersdorff's Feldtbuch der Wundtarzney, Strassburg, J. Schott, 1517, this is reputed to be the first known picture of an amputation. The four figures are the patient, the operator and his assistant, and probably a priest. (Courtesy of the American College of Surgeons).

20. 24.5Substituent Effectson theAcidity of Phenols

26. Picric acid, a.k.a. 2,4,6-trinitrophenol� pale yellow, odourless crystalline solid that has been used as a military explosive, as a yellow dye, and as an antiseptic. Picric acid (from Greek pikros, �bitter�) was so named by the 19th-century French chemist Jean-Baptiste-Andr� Dumas because of the extremely bitter taste of its yellow aqueous solution. Percussion or rapid heating can cause it (or its salts with heavy metals, such as copper, silver, or lead) to explode. Picric acid was first obtained in 1771 by Peter Woulfe, a British chemist, by treating indigo with nitric acid. It was used as a yellow dye, initially for silk, beginning in 1849. As an explosive, picric acid was formerly of great importance. The French began using it in 1886 as a bursting charge for shells under the name of melinite. By the time of the Russo-Japanese War, picric acid was the most widely used military explosive. Its highly corrosive action on the metal surfaces of shells was a disadvantage, however, and after World War I its use declined. Ammonium picrate, one of the salts of picric acid, is used in modern armour-piercing shells because it is insensitive enough to withstand the severe shock of penetration before detonating. Picric acid has antiseptic and astringent properties. For medical use it is incorporated in a surface anesthetic ointment or solution and in burn ointments. Picric acid is a much stronger acid than phenol; it decomposes carbonates and may be titrated with bases. In a basic medium, lead acetate produces a bright yellow precipitate, lead picrate. Picric acid, a.k.a. 2,4,6-trinitrophenol� pale yellow, odourless crystalline solid that has been used as a military explosive, as a yellow dye, and as an antiseptic. Picric acid (from Greek pikros, �bitter�) was so named by the 19th-century French chemist Jean-Baptiste-Andr� Dumas because of the extremely bitter taste of its yellow aqueous solution. Percussion or rapid heating can cause it (or its salts with heavy metals, such as copper, silver, or lead) to explode. Picric acid was first obtained in 1771 by Peter Woulfe, a British chemist, by treating indigo with nitric acid. It was used as a yellow dye, initially for silk, beginning in 1849. As an explosive, picric acid was formerly of great importance. The French began using it in 1886 as a bursting charge for shells under the name of melinite. By the time of the Russo-Japanese War, picric acid was the most widely used military explosive. Its highly corrosive action on the metal surfaces of shells was a disadvantage, however, and after World War I its use declined. Ammonium picrate, one of the salts of picric acid, is used in modern armour-piercing shells because it is insensitive enough to withstand the severe shock of penetration before detonating. Picric acid has antiseptic and astringent properties. For medical use it is incorporated in a surface anesthetic ointment or solution and in burn ointments. Picric acid is a much stronger acid than phenol; it decomposes carbonates and may be titrated with bases. In a basic medium, lead acetate produces a bright yellow precipitate, lead picrate.

27. 24.6Sources of Phenols

29. Phenol is mainly used as an intermediate in organic synthesis. In this, phenol essentially serves as a raw material for the production of bisphenol A, phenolic resins, alkylphenols and caprolactam. It is also used for salicylic acid, nitrophenols, diphenyl ethers, halogenated phenols and other chemicals. Phenolic resins, or phenol-formaldehyde polymers, were the first completely synthetic polymers to be commercialised. Although moulded products no longer represent their most important application, through their use as adhesives they still represent almost half of the total production of thermosetting polymers.Bisphenol A is a building block for making polycarbonate resins, which are used for structural parts, impact resistant glazing, street-light bulbs, household appliance parts, components of electrical/electronic devices, automotive applications, reusable bottles, and food and drink containers. It is also a building block used to make epoxy resins for coatings, electrical laminants, composites and adhesives. Alkylphenol is mainly used as a stabiliser for rubbers and plastics, as a surfactant, as an industrial detergent, and in the mining and textile industries. Caprolactam is a raw material for the manufacture of some nylons.Phenol is mainly used as an intermediate in organic synthesis. In this, phenol essentially serves as a raw material for the production of bisphenol A, phenolic resins, alkylphenols and caprolactam. It is also used for salicylic acid, nitrophenols, diphenyl ethers, halogenated phenols and other chemicals. Phenolic resins, or phenol-formaldehyde polymers, were the first completely synthetic polymers to be commercialised. Although moulded products no longer represent their most important application, through their use as adhesives they still represent almost half of the total production of thermosetting polymers.Bisphenol A is a building block for making polycarbonate resins, which are used for structural parts, impact resistant glazing, street-light bulbs, household appliance parts, components of electrical/electronic devices, automotive applications, reusable bottles, and food and drink containers. It is also a building block used to make epoxy resins for coatings, electrical laminants, composites and adhesives. Alkylphenol is mainly used as a stabiliser for rubbers and plastics, as a surfactant, as an industrial detergent, and in the mining and textile industries. Caprolactam is a raw material for the manufacture of some nylons.

31. 24.7Naturally Occurring Phenols

32. Thyme is grown in Algeria, China, Israel, Russia, Turkey, Tunisia and the USA. Thyme has been used since the earliest times. Its familiar and pervasive scent is the origin of its name, which derives from the Greek "thymos", which means "to perfume". Thyme was used as an early perfume and incense. Used in religious ceremonies by the Jews, Egyptians and Greeks, it was introduced to Europe by the Romans. It was presented to knights for courage and, during the Middle Ages, was carried by judges into courtrooms. It was believed to protect them from disease.Thyme is grown in Algeria, China, Israel, Russia, Turkey, Tunisia and the USA. Thyme has been used since the earliest times. Its familiar and pervasive scent is the origin of its name, which derives from the Greek "thymos", which means "to perfume". Thyme was used as an early perfume and incense. Used in religious ceremonies by the Jews, Egyptians and Greeks, it was introduced to Europe by the Romans. It was presented to knights for courage and, during the Middle Ages, was carried by judges into courtrooms. It was believed to protect them from disease.

33. RM Willst�tter received the Nobel prize for chemistry in 1915 for his work on plant pigments. He discovered that fruit and flowers that have red, blue or purple colors contain pigment molecules based on cyanidin. When sugars attach to the points on the molecule the molecule is now called an anthocyanin. Higher sugar contents increase the solubility and stability of anthocyanins in water. Anthocyanins are divided into five classes depending on their structure: cyanins, delphinins, malvins, peonins and petunins - did you spot the name of your favorite flower? - this is where their color comes from, the proportions of each anthocyanin will depend on the grape variety. Interestingly if the anthocyanin has mainly hydroxyl (-OH) substituents at the points marked in blue, the color is shifted towards blue, whereas if the substituents are methylated (-OCH3) the color is more red. Malvin is the most red of these compounds and is therefore responsible for most of the red color in a young wine. The anthocyanins complex with sugars in the wine which helps to 'fix' the color, it is only with aging that the anthocyanin complexes start to disassociate and start to join up with tannins to form polymers - this causes a gradual reduction in the intensity of the color. From: http://www.burgundy-report.com/ref/tech.htmlRM Willst�tter received the Nobel prize for chemistry in 1915 for his work on plant pigments. He discovered that fruit and flowers that have red, blue or purple colors contain pigment molecules based on cyanidin. When sugars attach to the points on the molecule the molecule is now called an anthocyanin. Higher sugar contents increase the solubility and stability of anthocyanins in water. Anthocyanins are divided into five classes depending on their structure: cyanins, delphinins, malvins, peonins and petunins - did you spot the name of your favorite flower? - this is where their color comes from, the proportions of each anthocyanin will depend on the grape variety. Interestingly if the anthocyanin has mainly hydroxyl (-OH) substituents at the points marked in blue, the color is shifted towards blue, whereas if the substituents are methylated (-OCH3) the color is more red. Malvin is the most red of these compounds and is therefore responsible for most of the red color in a young wine. The anthocyanins complex with sugars in the wine which helps to 'fix' the color, it is only with aging that the anthocyanin complexes start to disassociate and start to join up with tannins to form polymers - this causes a gradual reduction in the intensity of the color. From: http://www.burgundy-report.com/ref/tech.html

34. Thyroxine - also called 3,5,3�,5�-tetraiodothyronine�, or T4� one of the two major hormones secreted by the thyroid gland (the other is triiodothyronine). Thyroxine's principal function is to stimulate the consumption of oxygen and thus the metabolism of all cells and tissues in the body. Thyroxine is formed by the molecular addition of iodine to the amino acid tyrosine while the latter is bound to the protein thyroglobulin. Excessive secretion of thyroxine in the body is known as hyperthyroidism, and the deficient secretion of it is called hypothyroidism.Thyroxine - also called 3,5,3�,5�-tetraiodothyronine�, or T4� one of the two major hormones secreted by the thyroid gland (the other is triiodothyronine). Thyroxine's principal function is to stimulate the consumption of oxygen and thus the metabolism of all cells and tissues in the body. Thyroxine is formed by the molecular addition of iodine to the amino acid tyrosine while the latter is bound to the protein thyroglobulin. Excessive secretion of thyroxine in the body is known as hyperthyroidism, and the deficient secretion of it is called hypothyroidism.

35. Tetracycline: any of a group of antibiotic compounds that have a common basic structure and are either isolated directly from several species of Streptomyces bacteria or produced semisynthetically from those isolated compounds. These drugs, which include chlortetracycline, oxytetracycline, tetracycline, demeclocycline, methacycline, doxycycline, and minocycline, are �broad spectrum� antibiotics, meaning they are effective against many different bacterial species as well as other types of microorganisms. They act by interfering with a microorganism's ability to produce certain vital proteins; thus they are inhibitors of growth (bacteriostatic) rather than killers of the infectious agent (bacteriocidal) and are only effective against multiplying microorganisms. These drugs are used against a variety of infectious diseases, including those caused by Rickettsia, Chlamydia, and Mycoplasma, as well as respiratory and urinary tract infections. By the late 20th century, concerns arose that the widespread use of tetracyclines was contributing to an increase in the number of tetracycline-resistant organisms, which in turn had rendered certain infections more resilient to treatment. The use of tetracyclines in livestock feed to promote growth was also called into question. Tetracycline: any of a group of antibiotic compounds that have a common basic structure and are either isolated directly from several species of Streptomyces bacteria or produced semisynthetically from those isolated compounds. These drugs, which include chlortetracycline, oxytetracycline, tetracycline, demeclocycline, methacycline, doxycycline, and minocycline, are �broad spectrum� antibiotics, meaning they are effective against many different bacterial species as well as other types of microorganisms. They act by interfering with a microorganism's ability to produce certain vital proteins; thus they are inhibitors of growth (bacteriostatic) rather than killers of the infectious agent (bacteriocidal) and are only effective against multiplying microorganisms. These drugs are used against a variety of infectious diseases, including those caused by Rickettsia, Chlamydia, and Mycoplasma, as well as respiratory and urinary tract infections. By the late 20th century, concerns arose that the widespread use of tetracyclines was contributing to an increase in the number of tetracycline-resistant organisms, which in turn had rendered certain infections more resilient to treatment. The use of tetracyclines in livestock feed to promote growth was also called into question.

36. 24.8Reactions of Phenols:Electrophilic Aromatic Substitution

37. Halogenation Nitration Nitrosation Sulfonation Friedel-Crafts Alkylation Friedel-Crafts Acylation

39. monohalogenation occurs in non-polar solvents(1,2-dichloroethane) TCP as example?TCP as example?

40. multiple halogenation in polar solvent(water)

41. Halogenation Nitration Nitrosation Sulfonation Friedel-Crafts Alkylation Friedel-Crafts Acylation

42. the OH group is more electron donating than the methyl group and consequently controls the regiochemistry of this reaction Para-Red Synthesis? Proparacine Synthesis?Para-Red Synthesis? Proparacine Synthesis?

43. Hydroxyl groups are ortho, para-directing, while carboxylate groups are meta-directing. In this example, these effects reinforce each other and a single product is obtained Para-Red Synthesis? Proparacine Synthesis?Para-Red Synthesis? Proparacine Synthesis?

44. Halogenation Nitration Nitrosation Sulfonation Friedel-Crafts Alkylation Friedel-Crafts Acylation

46. Halogenation Nitration Nitrosation Sulfonation Friedel-Crafts Alkylation Friedel-Crafts Acylation

48. Halogenation Nitration Nitrosation Sulfonation Friedel-Crafts Alkylation Friedel-Crafts Acylation

49. The oxidation of food products involves the addition of an oxygen atom to or the removal of a hydrogen atom from the different chemical molecules found in food. Two principal types of oxidation that contribute to food deterioration are autoxidation of unsaturated fatty acids (i.e., those containing one or more double bonds between the carbon atoms of the hydrocarbon chain) and enzyme-catalyzed oxidation. The autoxidation of unsaturated fatty acids involves a reaction between the carbon-carbon double bonds and molecular oxygen (O2). The products of autoxidation, called free radicals, are highly reactive, producing compounds that cause the off-flavours and off-odours characteristic of oxidative rancidity. Antioxidants that react with the free radicals (called free radical scavengers) can slow the rate of autoxidation. These antioxidants include the naturally occurring tocopherols (vitamin E derivatives) and the synthetic compounds butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and tertiary butylhydroquinone (TBHQ). The oxidation of food products involves the addition of an oxygen atom to or the removal of a hydrogen atom from the different chemical molecules found in food. Two principal types of oxidation that contribute to food deterioration are autoxidation of unsaturated fatty acids (i.e., those containing one or more double bonds between the carbon atoms of the hydrocarbon chain) and enzyme-catalyzed oxidation. The autoxidation of unsaturated fatty acids involves a reaction between the carbon-carbon double bonds and molecular oxygen (O2). The products of autoxidation, called free radicals, are highly reactive, producing compounds that cause the off-flavours and off-odours characteristic of oxidative rancidity. Antioxidants that react with the free radicals (called free radical scavengers) can slow the rate of autoxidation. These antioxidants include the naturally occurring tocopherols (vitamin E derivatives) and the synthetic compounds butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and tertiary butylhydroquinone (TBHQ).

51. Bakelite is the trademark of phenol�formaldehyde resin. It is a synthetic resin formed from the chemical combination of phenols and formaldehydes. Bakelite is a hard, infusible, and chemically resistant plastic whose properties as a nonconductor of electricity have made it exceptionally useful in all sorts of electrical appliances. It is used in many industrial applications as an electrical insulator, in molding and casting operations, as an adhesive, and in paints and baked-enamel coatings. Phenol�formaldehyde resins are indispensable in manufacturing chemical equipment, machine and instrument housings, bottle closures, and many machine and electrical components. The production method for manufacturing this plastic was devised in 1909 by L.H. Baekeland in the United States, and the name Bakelite is a registered trademark of the Union Carbide Corporation. It displaced celluloid for nearly all the latter's applications early in the 20th century. Bakelite is the trademark of phenol�formaldehyde resin. It is a synthetic resin formed from the chemical combination of phenols and formaldehydes. Bakelite is a hard, infusible, and chemically resistant plastic whose properties as a nonconductor of electricity have made it exceptionally useful in all sorts of electrical appliances. It is used in many industrial applications as an electrical insulator, in molding and casting operations, as an adhesive, and in paints and baked-enamel coatings. Phenol�formaldehyde resins are indispensable in manufacturing chemical equipment, machine and instrument housings, bottle closures, and many machine and electrical components. The production method for manufacturing this plastic was devised in 1909 by L.H. Baekeland in the United States, and the name Bakelite is a registered trademark of the Union Carbide Corporation. It displaced celluloid for nearly all the latter's applications early in the 20th century.

52. Halogenation Nitration Nitrosation Sulfonation Friedel-Crafts Alkylation Friedel-Crafts Acylation

53. 24.9Acylation of Phenols

54. Acylation of phenolic compounds can take place either on the ring by electrophilic aromatic substitution or on oxygen by nucleophilic acyl substitution

56. in the absence of AlCl3, acylation of the hydroxyl group occurs (O-acylation)

57. O-Acylation is kinetically controlled process; C-acylation is thermodynamically controlled AlCl3 catalyzes the conversion of the aryl ester to the aryl alkyl ketones; this is called the Fries rearrangement Rearrangement of phenolic esters to o- and/or p-phenolic ketones with Lewis acid catalysts: K. Fries and G. Fink, Ber. 41, 4271 (1908) K. Fries and W. Pfaffendorf ibid. 43, 212 (1910) Blatt, Chem. Reus. 27, 413 (1940) Blatt in Organic Reactions vol. 1, 342 (New York, 1942) Thomas, Anhydrous Aluminum Chloride in Organic Chemistry, p 696 (New York, 1941). Catalysts used: d'Ans, Zimmer, Ber. 85,585 (1952). Review: Gerecs in Olah's Friedel-Craps and Related Reactions, vol. III, part I (New York, 1964), p 499 Jensen, Goldman, ibid. vol. III, part 2, p 1349.Rearrangement of phenolic esters to o- and/or p-phenolic ketones with Lewis acid catalysts: K. Fries and G. Fink, Ber. 41, 4271 (1908) K. Fries and W. Pfaffendorf ibid. 43, 212 (1910) Blatt, Chem. Reus. 27, 413 (1940) Blatt in Organic Reactions vol. 1, 342 (New York, 1942) Thomas, Anhydrous Aluminum Chloride in Organic Chemistry, p 696 (New York, 1941). Catalysts used: d'Ans, Zimmer, Ber. 85,585 (1952). Review: Gerecs in Olah's Friedel-Craps and Related Reactions, vol. III, part I (New York, 1964), p 499 Jensen, Goldman, ibid. vol. III, part 2, p 1349.

58. Use this example in connection with Salbutamol SynthesisUse this example in connection with Salbutamol Synthesis

59. Salbutamol is a specific b2-adrenoceptor receptor agonist. It is used to treat asthma and is a great improvement over its predecessor, isoproterenol; because the activity of isoproterenol is not specific, it acts on b1-adrenoceptors as well as b2-adrenoceptors, resulting in cardiac effects that are unwanted and sometimes dangerous. Salbutamol is a specific b2-adrenoceptor receptor agonist. It is used to treat asthma and is a great improvement over its predecessor, isoproterenol; because the activity of isoproterenol is not specific, it acts on b1-adrenoceptors as well as b2-adrenoceptors, resulting in cardiac effects that are unwanted and sometimes dangerous.

63. 24.10Carboxylation of Phenols 

64. how is salicylic acid prepared?

65. this process is called the Kolbe-Schmitt reaction acidification converts the sodium salt shownabove to salicylic acid Formation of aromatic hydroxy acids by carboxylation of phenolates, mostly in the ortho position, by carbon dioxide Reviews: A. S. Lindsey, H. Jeskey, Chem. Rev. 57, 583 (1957); D. C. Ayres, Carbanions in Synthesis 1966, 168-173; J. L. Hales et al., J. Chem. Soc. 1954, 3145; J. March, Advanced Organic Chemistry (Wiley-Interscience, New York, 4th ed., 1992) p 546.Formation of aromatic hydroxy acids by carboxylation of phenolates, mostly in the ortho position, by carbon dioxide Reviews: A. S. Lindsey, H. Jeskey, Chem. Rev. 57, 583 (1957); D. C. Ayres, Carbanions in Synthesis 1966, 168-173; J. L. Hales et al., J. Chem. Soc. 1954, 3145; J. March, Advanced Organic Chemistry (Wiley-Interscience, New York, 4th ed., 1992) p 546.

66. acid-base considerations provide an explanation:stronger base on left; weaker base on right

67. how does carbon-carbon bond form? recall electron delocalization in phenoxide ion negative charge shared by oxygen and by the ring carbons that are ortho and para to oxygen

72. 24.11Preparation of Aryl Ethers

78. nucleophilic aromatic substitution is effective with nitro-substituted (ortho and/or para) aryl halides Prozac Synthesis would be good exampleProzac Synthesis would be good example

79. with regards to nucleophilic aromatic substitution (SNAr), trifluoromethyl groups function like the nitro groups Prozac Synthesis would be good exampleProzac Synthesis would be good example

80. 24.12Cleavage of Aryl Ethersby Hydrogen Halides

83. 24.13Claisen Rearrangementof Allyl Aryl Ethers

84. Highly stereoselective [3,3]-sigmatropic rearrangement of allyl vinyl or allyl aryl ethers to yield ?dunsaturated carbonyl compounds or o-allyl substituted phenols, respectively. L. Claisen, Ber. 45, 3157 (1912); L. Claisen, E. Tietze, ibid. 58, 275 (1925); 59, 2344 (1926).Highly stereoselective [3,3]-sigmatropic rearrangement of allyl vinyl or allyl aryl ethers to yield ?dunsaturated carbonyl compounds or o-allyl substituted phenols, respectively. L. Claisen, Ber. 45, 3157 (1912); L. Claisen, E. Tietze, ibid. 58, 275 (1925); 59, 2344 (1926).

87. pericyclic reaction A chemical reaction in which concerted reorganization of bonding takes place throughout a cyclic array of continuously bonded atoms. It may be viewed as a reaction proceeding through a fully conjugated cyclic transition state. The number of atoms in the cyclic array is usually six, but other numbers are also possible. The term embraces a variety of processes, including cycloadditions, decarboxylation (retro-ene reactions) and sigmatropic rearrangements pericyclic reaction A chemical reaction in which concerted reorganization of bonding takes place throughout a cyclic array of continuously bonded atoms. It may be viewed as a reaction proceeding through a fully conjugated cyclic transition state. The number of atoms in the cyclic array is usually six, but other numbers are also possible. The term embraces a variety of processes, including cycloadditions, decarboxylation (retro-ene reactions) and sigmatropic rearrangements

88. pericyclic reaction A chemical reaction in which concerted reorganization of bonding takes place throughout a cyclic array of continuously bonded atoms. It may be viewed as a reaction proceeding through a fully conjugated cyclic transition state. The number of atoms in the cyclic array is usually six, but other numbers are also possible. The term embraces a variety of processes, including cycloadditions, decarboxylation (retro-ene reactions) and sigmatropic rearrangements pericyclic reaction A chemical reaction in which concerted reorganization of bonding takes place throughout a cyclic array of continuously bonded atoms. It may be viewed as a reaction proceeding through a fully conjugated cyclic transition state. The number of atoms in the cyclic array is usually six, but other numbers are also possible. The term embraces a variety of processes, including cycloadditions, decarboxylation (retro-ene reactions) and sigmatropic rearrangements

89. 24.14Oxidation of Phenols:Quinones

91. Show Methoxatin - coenzyme from bacteria living on methaneShow Methoxatin - coenzyme from bacteria living on methane

92. Alizarine is a red dye originally obtained from the root of the common madder plant, Rubia tinctorum, in which it occurs combined with the sugars xylose and glucose. The cultivation of madder and the use of its ground root for dyeing by the complicated Turkey red process were known in ancient India, Persia, and Egypt; the use spread to Asia Minor about the 10th century and was introduced into Europe in the 13th. Laboratory methods of preparing alizarin from anthraquinone were discovered in 1868, and, upon commercial introduction of the synthetic dye in 1871, the natural product disappeared from the market for textile dyes, though natural rose madder is still occasionally used, as a lake, for artists' colors. The application of alizarin to cotton, wool, or silk requires prior impregnation of the fiber with a metal oxide, or mordant. The shade produced depends on the metal present: aluminum yields a red; iron, a violet; and chromium, a brownish red. Alizarine is a red dye originally obtained from the root of the common madder plant, Rubia tinctorum, in which it occurs combined with the sugars xylose and glucose. The cultivation of madder and the use of its ground root for dyeing by the complicated Turkey red process were known in ancient India, Persia, and Egypt; the use spread to Asia Minor about the 10th century and was introduced into Europe in the 13th. Laboratory methods of preparing alizarin from anthraquinone were discovered in 1868, and, upon commercial introduction of the synthetic dye in 1871, the natural product disappeared from the market for textile dyes, though natural rose madder is still occasionally used, as a lake, for artists' colors. The application of alizarin to cotton, wool, or silk requires prior impregnation of the fiber with a metal oxide, or mordant. The shade produced depends on the metal present: aluminum yields a red; iron, a violet; and chromium, a brownish red.

93. also called Coenzyme Q, � any of several members of a series of organic compounds belonging to a class called quinones. Widely distributed in plants, animals, and microorganisms, ubiquinones function in conjunction with enzymes in cellular respiration (i.e., oxidation-reduction processes). The naturally occurring ubiquinones differ from each other only slightly in chemical structure, depending on the source, the structures resembling those of the fat-soluble vitamin K and certain derivatives of vitamin E. also called Coenzyme Q, � any of several members of a series of organic compounds belonging to a class called quinones. Widely distributed in plants, animals, and microorganisms, ubiquinones function in conjunction with enzymes in cellular respiration (i.e., oxidation-reduction processes). The naturally occurring ubiquinones differ from each other only slightly in chemical structure, depending on the source, the structures resembling those of the fat-soluble vitamin K and certain derivatives of vitamin E.

94. Worldwide, only a handful of researchers study vitamin K�long known for its critical role in blood clotting. But with the aging of the U.S. population, this vitamin may command a bigger following as its importance to the integrity of bones becomes increasingly clear. Vitamin K is a fat-soluble vitamin. The "K" is derived from the German word "koagulation". Coagulation refers to blood clotting, because vitamin K is essential for the functioning of several proteins involved in blood clotting (1). There are two naturally occurring forms of vitamin K. Plants synthesize phylloquinone, also known as vitamin K1. Bacteria synthesize a range of vitamin K forms, using repeating 5-carbon units in the side chain of the molecule. These forms of vitamin K are designated menaquinone-n (MK-n), where n stands for the number of 5-carbon units. MK-n are collectively referred to as vitamin K2 (2). MK-4 is not produced in significant amounts by bacteria, but appears to be synthesized by animals (including humans) from phylloquinone. MK-4 is found in a number of organs other than the liver at higher concentrations than phylloquinone. This fact, along with the existence of a unique pathway for its synthesis, suggests there is some unique function of MK-4 that is yet to be discovered (3).Worldwide, only a handful of researchers study vitamin K�long known for its critical role in blood clotting. But with the aging of the U.S. population, this vitamin may command a bigger following as its importance to the integrity of bones becomes increasingly clear. Vitamin K is a fat-soluble vitamin. The "K" is derived from the German word "koagulation". Coagulation refers to blood clotting, because vitamin K is essential for the functioning of several proteins involved in blood clotting (1). There are two naturally occurring forms of vitamin K. Plants synthesize phylloquinone, also known as vitamin K1. Bacteria synthesize a range of vitamin K forms, using repeating 5-carbon units in the side chain of the molecule. These forms of vitamin K are designated menaquinone-n (MK-n), where n stands for the number of 5-carbon units. MK-n are collectively referred to as vitamin K2 (2). MK-4 is not produced in significant amounts by bacteria, but appears to be synthesized by animals (including humans) from phylloquinone. MK-4 is found in a number of organs other than the liver at higher concentrations than phylloquinone. This fact, along with the existence of a unique pathway for its synthesis, suggests there is some unique function of MK-4 that is yet to be discovered (3).

95. Topics Covered: Phenols - Bonding, Physical Properties and Reactions Electrophilic Aromatic Substitution: Halogen, Nitration, Nitrosation O- and C-Acylation of Phenols: Fries Rearrangement Kolbe-Schmitt Reaction: Carboxylation of Phenols Preparation and Cleavage of Aryl Alkyl Ethers Claisen Rearrangement of Aryl Allyl Ether Preparation of Quinones