Safrole, structure

So now that we have all the reagents out of the way let s see how the reaction proceeds. There s the clear- yellow "safrole" sitting in the bottom if the flask and the clear saturated KOH solution is dumped in. The solution is heated to reflux etc. and yes, some brown byproducts and destruction artifacts will appear. Especially if the safrole is not pure. These byproducts should be expected to some extent because concentrated basic (OH) solutions can be as nasty as concentrated acidic solutions. One is mindful that KOH is less intrusive towards the delicate methylenedioxy ring structure of the safrole/isosafrole molecule. 

As part of a research program to develop therapeutically active compounds from raw materials in nature, researchers have synthesized a potentially useful nonsteroidal anti-inflammatory drug (NSAID) structurally similar to sulindac from safrole (Pereira et al., 1989 Barreiro and Lima, 1992). In addition, sassafras itself has been used for relieving eye inflammation (Duke, 1989). 

DERIVATIVES OF ALDEHYDES 694. Safrol is a methylene ether of the structure,—... 

The observation that the urinary metabolite of safrole, 3-piperidyl-l-(3, 4 -methylenedioxyphenyl)-l-propanone is mutagenic and is structurally somewhat reminiscent of certain Piper amides, has led to the suggestion that some of these compounds should, perhaps be considered as potential mutagens or carcinogens [141]. Whether or not this proves to be a problem warranting major concern, it is well to note that mono-N-substituted amides can react with nitrite under acidic conditions, with formation of potentially carcinogenic N-nitroso products [131]. 

Wiseman, R.W., E.C. Miller, J.A. Miller, and A. Liem. 1987. Structure-activity studies of the hepatocarcinogenicities of alkenylbenzene derivatives related to estragole and safrole on administration to preweanUng male C57BL/6J. x C3H/HeJ Fj mice. Cane. Res. 47 (9) 2275-2283. 

Safrole (25) and isosafrole were once important as the flavoring for root beer. These compounds are present in the plant extracts used to make this beverage. By the 1950s, however, most root beer was flavored with synthetically derived safrole. Both safrole and isosafrole were shown to be weakly carcinogenic and now have been banned for this purpose (Fishbein et al., 1967). These compounds have a methylenedioxy structure and are known to inhibit mixed-function oxidase enzymes. Two compounds of similar structure, piperonal (26) (naturally occurring) and piperonyl bu-toxide (27) (synthetic) are mixed function oxidase inhibitors and are used as synergists for insecticides such as pyrethrins, rotenoids, and Sevin (a carbamate insecticide) (Fishbein et al., 1967). 

The structures are characterised by a side group with two oxygen atoms attached to the phenylpropanoid ring as occurs in safrole. 

Myristicin is found in nutmeg and mace—Myristica fragrans (Myristicaceae). It also occurs in black pepper, carrot, parsley and dill. Myristicin is structurally related to safrol and is toxic in high doses. Nutmeg itself exhibits narcotic and intoxicating properties, though it does have medicinal uses in lower doses (Hall 1973). 

The phenolic primary alcohols derived in this way from phenylalanine (Phe, F) and in some systems from tyrosine (Tyr, Y) are incorporated into structural plant materials by linking carbohydrates (Chapter 11) together to form Ugnins. The same alcohols give rise to phenylpropenes, such as eugenol and safrole, which are commonly referred to as essential oils, while further oxidation and double-bond isomerization of p-coumaric acid leads to umbeUiferone (Figure 12.6). 

The odor compounds in wood are usually in a liquid state at room temperature. They can be classified by chemical structure into mono- or sesquiterpenes (e.g., a-pinene, camphor, cedrene), aromatic compounds (e.g., methyl salicylate, safrol), nitrogenous compounds (e.g., pyridine, 3-methylpyrrolidine), and sulfur compounds (e.g., allylsulfide) (35). The latter two groups are rarely formed except as bad-smelling components. The content of these compounds in wood is quite small compared with the major components such as cellulose and lignin, and they are irregularly distributed among species. 

---