Chloro functional moieties

Recent notable improvements by Knochel and co-workers include iron-catalyzed cross-coupling reactions of various acid chlorides 148 with dialkylzinc reagents (Equation (24))324 as well as the iron-catalyzed arylation of aroyl cyanides 149 with Grignard reagents (Equation (25)).3 5 In the first case Knochel s reaction conditions tolerate ester groups on the organozinc compounds, while in the latter case ester, aryl alkyl ether, cyano, and chloro functionalities on the aromatic moieties are compatibles with the reaction conditions. 

In enzymic assays, 3-acetylpyridine adenine dinucleotide (3-APAD) can replace NAD as substrate. No one has as yet succeeded in the direct bromination to form 3-bromo-APAD, although 3-chloro-APAD has been synthesized. If the ribose of the functional moiety of 3-APAD is replaced by a hydrocarbon chain, the redox potential is altered to —320 mV, a magnitude close to that of NAD+ Compounds of this structure can be easily labeled by using methyl or carbonyl-labeled acetylpyridine for synthesis. 

The imidoyl chloride moiety of 5-chloro-l-alkyl-1,4-benzodiazepin-2-ones participates in Pd-catalyzed, Suzuki crosscoupling reactions, reacting with a range of functionalized aromatic boronic acids to provide an efficient and versatile approach to 5-aryl and 5-heteroaryl compounds (Scheme 19) <2003JOC2844>. This chemistry readily extends to 3-amino-substituted compounds that are orally bioavailable inhibitors of the aspartyl protease 7-secretase <2003BML4143>. 

Functionalization of the carbon radical resulting from cyclization of an aminium radical is an important step for synthetic chemists in order to obtain the desired product directly or to provide a handle for further transformations. Radical reactions of A-chloroalkenylamines (Section III,B) lead to /3-chloro pyrrolidines, which are prone to rearrangement to give piperidines. Reactions of N-nitroso alkenylamines lead to 8-nitroso pyrrolidines and, if an a-hydrogen is present, ultimately to oximes of aldehydes or ketones. Advantages of the latter transformation are the formation of stable substituted pyrrolidines and the utility of the oxime moiety in regard to further transformations. 

Allylic Chloride vs. tert-Chloride Reactivity. There is some question in the literature as to whether the allylic chloride moiety or ferf-chloride group is more responsible for the thermal instability of poly (vinyl chloride) (I, 2). To shed some light on this problem we compared the relative reactivities at 100 °C. in chlorobenzene of 4-chloro-2-pentene and 2-chloro-2-methylbutane with dibutyltin -mercaptopropionate. Data are summarized in Table I. The half-time for the reaction of the allylic chloride with the stabilizer mercaptide group was less than 15 minutes, whereas the half-time for the tert-chloride was nearly 20 times longer. The greater reactivity of the allyl chloride suggests that it is the more important functionality in polymer degradation. However, these results on rates of chlorine substitution are not necessarily an exact measure of thermal instability. 

Since a nitro substituent is more electron-withdrawing than a chloro substituent, it was anticipated by Archer and his colleagues that replacing the p-chloro atom on the cinnamoylamino moiety with a p-nitro group would make the cinnamoylamino function a better Michael acceptor [106]. 5/ -Methyl-14/ -(4-nitrocinnamoylamino)-7,8-dihydromorphinone (MET-CAMO, 55) was found to be an irreversible fi selective antagonist, MET-... 

The design and s)mthesis of the new oxime-functionalized pyrrolidine derivative of gemifloxacin, which bear an alkyloxime substituent in the 4-position and an aminomethyl substituent in the 3-position of the pyrrolidine ring, was first described in Scheme 4.1 starting from step (a) to step (i) in the scheme. Then, the new pyrrolidine derivative moiety was coupled with a certain quinoline carboxylic acid derivative (7-chloro (or fluoro)-l-cyclopropyl-6-fluoro-l,4-dihydro-4-oxo-l,8-naphthyridine-3-carboxylic acid) to form the new fluoroquinolone drug, gemifloxacin as described in Scheme 4.1. 

Summary From catalytic hydrogenation of olefinic silicon-functionalized compounds (chloro-Si, alkoxy-Si, alkyl-Si, and aryl-Si) the saturated products are available in good yield. In general, the chloro- and alkoxy substituents are unaffected and for silaheterocyclic compounds the cyclic or the bicyclic moieties, respectively, remain intact. Thus, the silanorbomenes 1, 2, and 3, compounds containing cyclopentenyl groups 13 and 15, and various carbon vinyl substituted silacyclobutanes 7, 8, and 11 were hydrogenated in a simple apparatus. The reactions were performed in ether and THF as solvents the hydrogenation catalyst Pd/C can be used several times. 

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