Celanese synthesis
An alternative industrial synthesis developed at Celanese involves direct acylation of phenol with acetic anhydride in the presence of hydrogen fluoride, conversion of the resulting ketone to a ketoxime with hydroxylamine, followed by the acid-catalyzed Beckmann rearrangement. Reactions
4-Aminophenol may be obtained by the amide hydrolysis of paracetamol. This reaction is also used to determine paracetamol in urine samples: After hydrolysis with hydrochloric acid, 4-aminophenol reacts in ammonia solution with a phenol derivate, e.g. salicylic acid, to form an indophenol dye under oxidization by air. History
Acetanilide was the first aniline derivative serendipitously found to possess analgesic as well as antipyretic properties, and was quickly introduced into medical practice under the name of Antifebrin by Cahn & Hepp in 1886. But its unacceptable toxic effects—the most alarming being cyanosis due to methemoglobinemia, an increase of hemoglobin in its ferric [Fe3+] state, called methemoglobin, which cannot bind oxygen, and thus decreases overall carriage of oxygen to tissue—prompted the search for less toxic aniline derivatives. Some reports state that Cahn & Hepp or a French chemist called Charles Gerhardt first synthesized paracetamol in 1852.Harmon Northrop Morse synthesized paracetamol at Johns Hopkins University via the reduction of p-nitrophenol with tin in glacial acetic acid in 1877, but it was not until 1887 that clinical pharmacologist Joseph von Mering tried paracetamol on humans. In 1893, von Mering published a paper reporting on the clinical results of paracetamol with phenacetin, another aniline derivative. Von Mering claimed that, unlike phenacetin, paracetamol had a slight tendency to produce methemoglobinemia.
Coffin–Lowry syndrome is a genetic disorder that is X-linked dominant and which causes severe mental problems sometimes associated with abnormalities of growth, cardiac abnormalities, kyphoscoliosis, as well as auditory and visual abnormalities. Presentation
Symptoms of disease are more severe in males, who are generally diagnosed in early childhood. Children with CLS display cognitive disabilities of varying severity. Additional neuromuscular features include sleep apnea, muscular spasticity, progressive loss of muscle strength and tone leading to paraplegia or partial paralysis. Affected individuals are at elevated risk of stroke. Some patients experience stimulus-induced drop attacks (SIDAs, temporary paralytic episodes without loss of consciousness), triggered by unpredictable environmental stimuli (touch, scents, sounds, etc.). SIDA episodes become more frequent as the disease progresses, and become frequent around adolescence in males. Additional clinical physical features include small, soft hands with tapered fingers. Distinct facial architecture such as a flattened nose, widely separated and downward sloping eyes, a prominent forehead, and a wide mouth with large lips are reported as coincident facial features in patients with the disorder. Some individuals experience hearing loss. Others display kyphoscoliosis (multidirectional curvature of the spine) which can lead to difficulty with breathing and/or pulmonary hypertension. Cardiorespiratory complications may arise, which is why it is recommended that CLS patients undergo regular monitoring for spinal irregularities. Physical exams, CT imaging and X-ray imaging are standard methods of assessment. Causes
The syndrome is caused by mutations in the RPS6KA3 gene. This gene is located on the short arm of the X chromosome (Xp22.2).