Safer way to make diazomethane developed.


Diazomethane is a toxic, explosive reagent prepared as needed in laboratories, where it is commonly used in cyclopropanation, but its explosive nature prevents it being used widely on an industrial scale. Now, scientists in Switzerland have developed a new method of synthesising diazomethane that is much safer and therefore could lead to much wider use.

 

Diazomethane (CH2N2) is a toxic yellow gas at 25 degrees Celsius, and is usually used in solution in ether. It is a useful reagent for many reasons, such as its ability to be converted to carbene, which is used in the synthesis of cyclopropanes. It is usually prepared as needed in the lab by hydrolysis of a precursor such as diazald (N-methyl-N-nitroso-p-toluenesufonamide), but becomes explosive during the processes of purifying and isolating it. Safety precautions such as preparing the chemical in a fume hood or behind a blast shield, avoiding ground glass joints, wearing thick protective gloves, avoiding any sharp edges or scratches on the glassware, and so on, are employed during the synthesis to protect the scientists from potential explosions.

Researchers Erick Carreira and Bill Morandi of the Laboratory of Organic Chemistry at ETH in Zurich have developed a new method for generating diazomethane in situ that uses a catalyst and avoids the need for the dangerous isolation process and generation of large volumes of the explosive chemical. The catalyst is an iron porphyrin complex and is used to catalyze the cyclopropanation of olefins such as styrenes, dienes, and enynes in anaqueous solution of potassium hydroxide (6M, KOH). Since olefins are immiscible with water, they create a safe biphasic environment for the formation of the intermediate, diazomethane, which is constantly generated and immediately consumed in the reaction. The catalyst remains within the olefin phase.

 

The new method is safer for the chemists because there is a much lower risk of explosion since the diazomethane is consumed as soon as it is created, and large volumes do not accumulate. There is also a much lower chance of exposure to the toxic gas.

In the paper, published in Science, Carreira and Morandi suggest the method could also be used in the synthesis of other toxic or explosive reagents, provided they can be prepared in aqueous solutions.

ABSTRACT 
Diazomethane is a common and versatile reagent in organic synthesis whose broader use is generally impeded by its explosiveness and toxicity. Here we report that a simple iron porphyrin complex catalyzes the cyclopropanation of styrenes, enynes, and dienes under the demanding conditions [aqueous 6 molar potassium hydroxide (KOH) solution, open to air] necessary for the in situ generation of diazomethane from a water-soluble diazald derivative. A biphasic reaction medium arising from the immiscibility of the olefin substrates with water appears essential to the overall efficiency of the process. The work we describe highlights an approach to catalysis with untoward reactive intermediates, in which the conditions for their generation under operationally safe regimes dictate catalyst selection.

Source: PhysOrg.com

 

FDA Approves New GERD Treatment .


The FDA has approved a new device to treat symptoms of gastroesophageal reflux disease in patients who have not responded to traditional medical therapy.

The LINX Reflux Management System is a surgically-placed string of magnetic titanium beads that is placed at the lower esophageal sphincter. When a person swallows, the device expands to accommodate the liquid or food. Once the food passes, the device keeps a weak lower esophageal sphincter closed, thus preventing material from flowing back into the esophagus.

Common side effects of the LINX device include difficulty and pain on swallowing, chest pain, vomiting, and nausea. Patients with LINX should not undergo MRI procedures.

Source: FDA news

ADHD Diagnoses Up 66 Percent Since 2000.


According to a new study, the number of children diagnosed with attention deficit hyperactivity disorder (ADHD) has increased by 66 percent over the past 10 years.

Researchers analyzed changes in the diagnosis of youth ADHD and treatment of the disorder from 2000 to 2010. Only youth under the age of 18, and cared for by office-based physicians, were included in the evaluation.

Northwestern University researchers also discovered that specialists, instead of primary care physicians, have begun treating an increasing number of these young patients.

Psychostimulants such as methylphenidate (Ritalin) remain the most common medication prescribed to children with ADHD. Psychostimulants were used in 96 percent of treatments in 2000 and 87 percent in 2010.

“ADHD is now a common diagnosis among children and teens,” said lead author Craig Garfield, M.D. “The magnitude and speed of this shift in one decade is likely due to an increased awareness of ADHD, which may have caused more physicians to recognize symptoms and diagnose the disorder.”

Symptoms of ADHD, such as trouble paying attention and controlling impulsive behaviors and being overly active, can affect children and teens both academically and socially, Garfield said.

In the past decade several important regulatory and clinical changes regarding ADHD and the medications used to treat it have occurred, yet it was unknown how these factors have affected ADHD management, Garfield said.

For the study, Garfield and his team of researchers quantified ADHD diagnosis and treatment patterns among people under 18 using the IMS Health National Disease and Therapeutic Index. This is a nationally representative sample of office-based visits and included 4,300 office-based physicians in 2010.

According to the study, in 2010, 10.4 million children and teens under age 18 were diagnosed with ADHD at physician outpatient visits, versus 6.2 million in 2000.

Investigators were unable to explain the reduction in use of psychostimulants during the decade studied although they did note that there was not an increase in treatment with other, substitute medications.

Although the majority of children and teens with ADHD are still managed by primary physicians, researchers determined a significant shift away from primary doctors and toward specialists, such as pediatric psychiatrists.

“Recently, there’s been more public health advisories issued about problems or side effects of different ADHD medications,” Garfield said. “It may be that general pediatricians are shying away from treating patients themselves and instead rely on their specialist colleagues to provide the treatment and management of these medications.”

Given the short supply of psychiatrists specializing in pediatric ADHD, Garfield said this trend might make it difficult for many children to receive medical treatment for ADHD in the future.

The study will be published in the March/April issue of the journal Academic Pediatrics.

Source: Northwestern University