Direct patent activity

The intense patent activity in this area attests to the vast interest for implementing nonphosgene technologies to produce organic carbonates [12]. Hence, the state of the art in research for the three chemical routes based on C02 (i.e., transesterification, urea alcoholysis, and direct carbonation) is discussed in the following sections. 

Those wishing to come within a 271(e)(1) exemption should be careful to direct all activities covered by an assay or process patent toward obtaining FDA approval of a therapeutic - i.e. have as its ultimate goal - obtaining an NDA on one or more therapeutics. 

Food apphcations of sorbates expanded rapidly after issuance of the original patents in 1945 (92). The first uses were based on their excellent fungistatic properties and thus involved foods with low pH and/or low water activity in which yeasts and molds are the primary spoilage agents. More recent appHcation research has been directed toward utilizing the bacteriostatic properties of sorbates. 

In order to circumvent this problem, there has been significant activity directed toward the search for a less environmentally toxic and more selective oxidizing agent than chromium. For example, Hoechst has patented a process which uses organorhenium compounds. At a 75% conversion, a mixture of 86% of 2-methyl-l,4-naphthoquinone and 14% 6-methyl-l,4-naphthoquinone was obtained (60). Ceric sulfate (61) and electrochemistry (62,63) have also been used. 

A iD-Corticoids have been important intermediates since it was shown ° that substitution at C-9 enhances anti-inflammatory activity. These olefins are usually obtained from 11a- or 11)5-alcohols, and consequently several refined methods have been devised for effecting this dehydration. It is desirable that such methods be compatible with the presence of A" -3-ketone and 17-hydroxy functions. The first direct procedure for which high yields were claimed was described in a patent issued to Upjohn. According to this method, the alcohol (11a or )5) is treated first with A-bromoacetamide in pyridine, then with sulfur dioxide. Recently it has been claimed " that the A-haloamide/sulfur dioxide method gives results superior to other methods, although the methanesulfonyl chloride/sulfur dioxide procedure (see below) apparently was not compared (see also ref. 94). 

Much research has been carried out into direct amination of aromatic substrates, typified by the direct conversion of benzene to aniline using ammonia and a catalyst. Although there have been many patented routes conversions, are normally low, making them uneconomic. Modem catalysts based on rhodium and iridium, together with nickel oxide (which becomes reduced), have proved more active,and such is the research activity in this area that it is only a matter of time before such processes become widely used. 

The KOCAT Society (no patent reference known by authors), in South Korea, solved the DeNO problem of big burners, by directly injecting oxygenates on the catalyst at the outlet of the burner. This process involves the third function of our model. This example shows that only one model (the present one) for DeNO reaction can be used for either mobile or stationary sources. Pathways are the same what is changing is the nature of the reductant, which has to be activated, through its partial oxidation, at the temperature when N—O bonds (dinitrosyl species) are broken. 

Direct hydrogenation of amino acids to amino alcohols was first examined by Adkins et al. (3) via the esters, and recently studied by Antons and Beitzke in patents (4). Using Ru/C catalysts at high pressures (>14 MPa) and mild temperatures (70-150 °C), Antons demonstrated the conversion of carboxylic acids and amino acids with retention of optical activity in the product alcohols. High yields (>80%) and high enantiomeric purity (>97% in many cases) were achieved. Broadbent et al. had demonstrated earlier that under certain conditions hydrogenation of amino acids can be accompanied by deamination (8). 

Thus, we see that the protection of innovation by means of patents affects the costs of innovating in both directions. However, these costs are also affected by the length of the patent. A long protection period increases the reward for the innovator, and encourages his or her activity. Given that many developments are cumulative, some subsequent innovations depending on their predecessors, the result is increased costs for the remainder or a restriction in terms of time. 

MEOR is an active research area in the oil industry but is not specifically detailed in this book. The patent ( Enhanced oil recovery ) discussed below, W09215771, directly concerns oil production by MEOR, rather than refining. However, as will be described below, the organisms works by excreting lactic acid, which chemically affect certain compounds in oil and most particularly metal compounds. So far, the concept of applying metabolic excretions has not been exploited for oil related chemical reactions. 

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