Sulfone, chloromethyl phenyl

Also, the observed highly regioselective course in the SnFI substitutions in 2-R-3-nitro-l, 8-naphthyridines (R = FI, OFI, Cl, NFI2, OEt) with the anion of chloromethyl phenyl sulfone was explained by MNDO quantum-chemical calculations showing that, like in the aminations, the interaction of FIOMO of the nucleophile with LUMO of the nitronaphthyridines controls the regioselectivity (91JFIC1075). 

The reaction of 3-methoxy-1,2,4-triazine 1-oxide 20 with the carbanion generated from chloromethyl phenyl sulfone proceeds as the vicarious nucleophilic substitution (VNS) of hydrogen (Scheme 1, path B) via addition of the carbanion at position 5 of the heterocycle. Following base-induced elimination of HCl and protonation, 3-methoxy-5-phenylsulfonyl-1,2,4-triazine 4-oxides 65 result (88LA627). 

At the same time, the reaction of 1,2,4-triazine 4-oxides 55 with the anion of chloromethyl phenyl sulfone affords 5-(l-chloro-l-phenylmethyl)-l,2,4-triazines 66. In this case, autoaromatization of the a -adducts proceeds by the deoxygenative... 

Nitro-, 4-nitro-, 7-nitro-, 5,7-dinitro-, and 6,8-dinitroquinoline react with the carbanion of chloromethyl phenyl sulfone to give products of substitution of hydrogen at positions 4 3 8 6,8 and 5,7 respectively <96LA641>. The base-induced reaction of benzoyl chloride salts of quinoline iV-oxides with carbonitriles to give 2-quinolyldiacylamines as the main products has been reported <96TL(37)69>. 

Control of the regioselectivity of VNS is important. It is governed by three major factors the structure of the nitroarene the nature of the nucleophile, and the reaction conditions, especially solvent and base. The different effect of methoxy and hydroxy groups is interesting the reaction of l-methoxy-2,4-dinitrobenzene with chloromethyl phenyl sulfone proceeds in... 

Trifluoromethyl iodide is a poor substrate for SN2 reactions [28], The increased donativity of the methylene carbon as rendered by the fluorine atoms is reflected in its reluctance to enter a bonding relationship with a nucleophile. Similar reactivity patterns are known for chloromethyl phenyl sulfone [28] and chloromethyltrimethyl-silane. In these latter compounds the reactive center is directly linked to an acceptor group. 

Similarly, chloromethyl phenyl sulfone (197) was coupled with several aromatic aldehydes, 198a-i, again using the trifluoromethylated phase-transfer catalyst 185b... 

Naphthyridine (19) with chloromethyl phenyl sulfone gave 6,7-bisphenylsul-fonyl-6,6a,6b,7-tetrahydro-1 //-azirino [1,2-a] cyclopropa[c]-l,5-naphthyridine... 

Naphthyridine with chloromethyl phenyl sulfone gave 1,7-bisphenylsulfo-nyl-6b,7,7a,7b-tetrahydro-l//-azirino [l,2-a]cyclopropa [h [l,6]-naphthyr-idine (16) (KOH, Me2SO, reactants slowly, 20°C, tic monitored ... 

Naphthyridine with chloromethyl phenyl sulfone gave 5,6-bis(phenylsulfo-nyl)-5,5a,5b,6-tetrahydro-4b//-azirino[l,2-fl]cyclopropa c [l,8 naphthyridine (14) (reactants, KOH, Me2SO, 20°C 66%).803 cf 393... 

In conclusion, all results obtained thus far on this reaction show that it is especially the 4-position in the 3-nitro-l,8-naphthyridines which is strongly favored toward the attack of the carbanion of chloromethyl phenyl sulfone. When position 4 is occupied by a substituent no reaction occurs. This behavior is in accordance with the behavior observed in reactions with liquid ammonia and liquid methylamine. 

OL-Hydroxy aldehydes. A new method for one-carbon homologation of ketones to a-hydroxy aldehydes involves Darzens condensation with chloromethyl phenyl sulfone to give an ex,p-epoxy sulfone followed by ring opening by hydroxide ion. The anhydrous potassium hydroxide obtained by controlled addition of water to potassium /-butoxide (8,... 

When chloromethyl phenyl sulfone (130 Ar = phenyl) was subjected to the Darzens-type reaction with an aldehyde, a thermodynamically stable trans isomer (133) was produced exclusively (equation 32). This is in sharp contrast with the corresponding reaction of chloromethyl phenyl sulfoxide. Tavares proposed that the initial nucleophilic attack of the a-sulfonyl carbanion upon a carbonyl compound is rapidly reversible due to its stability, and that the product-determining step is the ring closure. Thermodynamic equilibrium between the two diastereomers of (132) allows predominant formation of the thermodynamically stable isomer (133) from the preferred transition state. ... 

Chloromethyl phenyl sulfone and related compounds can undergo deprotonation and addition to ketones under a variety of conditions. These procedures appear most prominently as part of one-... 

Aral, S., Shioiri, T. Asymmetric Darzens reaction utilizing chloromethyl phenyl sulfone under phase-transfer catalyzed conditions. Tetrahedron 2002, 58,1407-1413. 

Later, Arai, and coworkers applied their PTC-mediated Darzens reaction conditions to the synthesis of optically active oc, 3-epoxysulfones [43], The reaction of the chloromethyl phenyl sulfone 102 with aromatic aldehydes under PTC conditions (101 (10mol%), KOH-toluene) at room temperature afforded the desired trans-epoxysulfones 103 in good yields and with moderate to good ee values (33-81%) (Scheme 8.35). On the other hand, aliphatic aldehydes gave the Darzens product as the racemates. The use of a Lewis acid additive (Sn(OTf)2) improved the selectivity, but only slightly (up to 32% ee). Under PTC conditions, chloromethylsulfone is transformed into the corresponding carbanion, which then reacts with the... 

Makosza (83TL3277) utilized the carbanion of chloromethyl phenyl sulfone (254) as the nucleophile to prepare substituted triazine 255. The proposed mechanism is given in Scheme 7 and accounts for the necessary presence of the chloride leaving group. 

The electrophilic phosphonylation of chloromethyl phenyl sulfone in the presence of n-BuLi (2 eq) proceeds smoothly at low temperature, probably via the sulfone dianion, to give diethyl 1-lithio-1-chloro-l-(phenylsulfonyl)methylphosphonate. This is treated in situ with aliphatic or aromatic aldehydes and ketones to obtain a-chloro-a,(3-unsaturated ketones by the Homer-Wadsworth-Emmons reaction in good overall yields (76—85%)... 

Another method to introduce a substituent into the 1,2,4-triazine system is vicarious nucleophilic substitution. Here, a carbanion with a leaving group at the carbanionic center reacts with a 1,2,4-triazine replacing protons in the 5-, 3- and 6-position with the carbanionic moiety. The reactivity of the various positions decreases in the order 5 > 3 > 6. This reactivity differs from that toward Grignard reagents. Thus, substitution of the 5-position occurs in the 1,2,4-triazine to afford 15 which undergoes elimination to 16 followed by protonation to yield 17 275,276 Carbanions of the following compounds were used in this reaction nitrones, chloromethyl phenyl sulfones, chloromethanesulfonamides and acetonitriles.274-378... 

To a stirred suspension of powdered KOH (4g) in DMSO (20 mL) a solution of 1,2,4-triazine (810 mg, 10 mmol) and chloromethyl phenyl sulfone (2.1 g, 11 mmol) in DMSO (2-5 mL) was added dropwise at 20 25 C. The mixture was stirred at rt for 1 h, then was poured into ice-water (200 mL) and acidified with HOAc. The precipitated solids were collected by filtration and washed with It20. The crude product was purified by recrystallization (EtOH/H20) yield 940 mg (72%) inp 150-151 °C. 

Reactions of carbonyl compounds and imines. The salt 4 obtained from reaction of cinchonine with m-xylylene dibromide is shown to promote enantioselective transfer of the trifluoromethyl group from Me3SiCF3 to aryl ketones Also obtained from quinidine the salt containing a trifluorobenzyl group (5) promotes the condensation of chloromethyl phenyl sulfones with ArCFlO to give benzenesulfonyl epoxides ... 

Another example for the application of the methodology in the chemistry of nitroarenes is the synthesis of fluorine-containing indoles. It has been shown that substitution of hydrogen H-6 in 3-fluoro-4-/ -substituted nitrobenzenes by the action of vicarious chloromethyl phenyl sulfone proceeds selectively in DMSO in the presence of KOH at room temperature to give 4-/ -3-fluoro-6-(phenylsulfonyl-methyl)nitrobenzenes in 60-70% yields (Scheme 23) [101]. 

However, under the conditions that favor dissociation of the adducts and disfavor p-elimination, namely, a higher temperature and absence of a strong base, the conventional S Ar of fluorine atom can be observed [13]. Interestingly, the reaction of wefa-dinitrobenzene with an excess of this carbanion gave the disubstitution product, whereas with equimolar amounts of reactants only monosubstitution proceeds. It is evident that the anion of 2,4-dinitrobenzyl phenyl sulfone is still sufficiently active electrophile to react with the carbanion of chloromethyl phenyl sulfone (Scheme 3) [14]. 

The effect of substituents on the rate of addition of carbanions to nitroarenes and the rate of p-elimination of HL from the o adducts have also been studied [8, 30, 31]. The former effect is an important parameter, because it is, in fact, a measure of influence of substituents on electrophilic activity of nitroaromatic rings. The effect of substituents on rate of the S Ar reactions of o- and p-halonitrobenzenes has been thoroughly studied [2, 32]. However, since the S Ar of halogen is a secondary process, the obtained data cannot be used as a real measure of electrophilicity of halonitroarenes. We have determined the effects of substituents and the ring structure on the rate of the VNS reactimi of nitroarenes with the carbanion of chloromethyl phenyl sulfone by using competitive experiments under the conditions, which assure a fast p-eUmination of HL from the o adducts [30, 31]. The values of VNS rates obtained under such conditions proved to correlate with those of the addition step. Selected values of the relative rate constants in relation to nitrobenzene as the standard are shown in Fig. 1. 

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