The chlorination of a series of a,a-unsaturated ketones and esters by CI, in CH,OH, with and without acid scavengers such as N-chlorosuccinimide (NCS), pyridine and 2,6-lutidine, is described. Methyl vinyl ketone and cyclohex-2-enone have also been chlorinated in ethanol. Mixtures of Markovnikov( M) and anti-Markovnikov(AM) methoxy chlorides and dichlorides are formed in most cases; phenyl vinyl ketone gives no M products in the absence of pyridine, M methoxy chloride is not formed with ( E ) -4-chlorobut-3-en-2-one under any conditions, pyridine has n o effect o n the product ratios and methyl 3-chlorobut-2-enoate forms only dichloride. Chlorination of the ketones in the presence of the pyridines results in a significant increase in the M regioisomer (except for methyl isopropenyl ketone and the ketones mentioned), giving M : A M ratios which are similar to the corresponding esters. Ratios for the esters are not affected significantly b y pyridine. We ascribe the effect of the pyridine bases to the elimination of acid and the acid-catalysed mechanism, permitting the chlorination to occur via a carbon-carbon n-bond (chloronium ion) mechanism. The rate of chlorination of methyl vinyl ketone is retarded by pyridine but is still considerably faster than methyl acrylate. NCS, in contrast to N-bromosuccinimide (NBS) reported previously, has no effect o n the M : A M ratio. The chlorination of methyl vinyl ketone with NCS and HCI gives markedly different results from CI , .Recently we reported on the bromination by Br, of a$unsaturated ketones and esters in methanol, in the presence of acid scavengers such as N-bromosuccinimide (NBS) and other bromoamides. This study showed that bromination of the ketones in the presence of an acid scavenger led to a significant increase in the Markovnikov to anti-Markovnikov (M : AM) ratio, probably by eliminating a rapid acid-catalysed addition, and by delivering bromine to the carbon-carbon n-bond as a bromine-bromoamide complex for both ketones and esters. In the present paper, we have extended the investigation to the chlorination of a$-unsaturated ketones and esters by C1, in methanol (and, in certain cases, ethanol), in the presence of potential acid scavengers such as N-chlorosuccinimide (NCS), pyridine and 2,6-lutidine. ResultsChlorination of the Ketones and Esters.-Several a,P-unsaturated esters and ketones were chlorinated by C1, in methanol in the presence of potential acid scavengers, NCS, pyridine (Pyr), and 2,6-lutidine (Lut). The reactions are shown in Scheme 1, and the results are summarized in Tables 1 and 3. R* M AM Dichloride Methoxy chlorides Scheme 1In most cases, mixtures of anti-Markovnikov (AM) and Markovnikov methoxy chlorides (M, methoxy adjacent to the carbonyl group) and dichlorides (DiCI) were formed.

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In previous data (J. Exp. Med. 147:76,1977), we have demonstrated that soluble fibrin/fibrinogen complexes are bound to the plasma membrane of guinea pig peritoneal macrophages. This binding is largely irreversible and is not a result of phagocytosis. We have extended our studies to examine the response in vitro of peritoneal macrophages to soluble fibrin/fibrinogen complexes. Unstimulated mouse macrophages were collected by peritoneal lavage and 5–60 μg of soluble fibrin/fibrinogen complexes placed into tissue culture dishes containing the unstimulated cells. Aliquots of the media were collected at 24, 48 and 72 hours. The cell-free media contained increasing amounts both of plasminogen activator and an enzymatic activity which resulted in fibrin and fibrinogen proteolysis independent of the amount of plasmingoen present. The major proteolytic activity was due to the non-plasminogen dependent enzyme. Similar enzymes were released from peritoneal macrophages stimulated in vivo. The plasminogen activator enzyme had a low molecular weight comparable to that previously reported by Unkeless et al, with in vivo stimulation. Other coagulation moieties, such as plasmin and α-2 macroglobulin plasmin complexes did not result in release of the macrophage proteolytic enzymes. The results suggest that the previously described release of fibrinolytic enzymes after thioglycolate injections, may also result from the more pathophysiological stimulation by soluble fibrin/fibrinogen complexes. Release of these enzymes from phagocytic cells may be important, not only in blood clearance of soluble fibrin/fibrinogen complexes, but as part of thrombus reabsorption and wound healing.

Chlorination of α,β-Unsaturated Ketones and Esters in the Presence of Acid Scavengers.-As a continuation of recently published (1988) work on bromination, now the chlorination of a range of title compounds such as (I), (VI), and (X) is examined (influence of added bases NCS, Py, and 2,6-lutidine on the ratio of anti-Markovnikov, Markovnikov, and dichloride products formed). Some of the products undergo further reactions forced by the reaction medium. -(HEASLEY, V. L.; ELLIOTT, S. L.; ERDMAN, P. E.; FIGUEROA, D. E.; KROSLEY, K. W.; LOUIE, T. J.; MOORE, H. B.; MUDGE, B. P.; NOGALES, D. F.; NORDEEN, J.; OAKES, M. L.; ROSBRUGH, J. W. JUN.; SAUERBREY, A. M.; SHIBUYA, T. Y.; STANLEY, M. S.; STEWART, C. C.; SHELLHAMER, D. F.; HEASLEY, G. E.; J. Chem.