Chloro groups

Some 5-substituted 2-aminothiazoles with alkyl (15, 173, 175, 224, 366, 396), ester (173, 184, 220), aryl (115, 265, 396, 414), a-naphthyl (463), sulfur and sulfones derivatives (329, 373), isonitrosomethyl (772), and chloro groups were synthetized from the corresponding a-haloaldehyde and thiourea in lower yield (Table 11-14). 

Anthraquinone can be sulfonated, nitrated, or halogenated. Sulfonation is of the greatest technical importance because the sulfonic acid group can be readily replaced by an amino or chloro group. Sulfonation with 20—25% oleum at a temperature of 130—135°C produces predominandy anthraquinone-2-sulfonic acid [84-48-0]. By the use of a stronger oleum, disulfonic acids are produced. The second sulfonic acid substituent never enters the same ring a mixture of 2,6- and 2,7-disulfonic acids is formed (Wayne-Armstrong rule). In order to sulfonate in the 1-, 1,5-, or 1,8-positions, mercury or one of its salts must be used as a catalyst. 

The 4-chloro group can be removed selectively when pentachloropyridiae [2176-62-7] (47) is treated with 2iac to form symmetrical 2,3,5,6-tetrachloropyridine (45). 

All lation. Several alkylation reactions are known either the olefin or chloro- group may be involved. The reactions of aEyl chloride with benzene are typical of reactions involving the double bond. In the presence of ferric or zinc chloride, the products are 2-chloropropylbenzene [10304-81-1] and 1,2-diphenylpropane [5814-85-7]. ... 

As with the purines, the replacement of chloro groups by amino groups has been one of the major building blocks of pyridopyrimidine chemistry, being employed in a great variety of reactions too numerous to catalogue fully, particularly in the piromidic and pipemidic acid fields. 

In addition to conversion to chloro compounds, -ones and diones have given thiones with phosphorus pentasulfide, whilst in some cases replacement by amine of alkoxy groups in preference to a chloro group has been observed (68JHC13). 

However, other studies on the nitration of a series of 3-methyl- and 3-ethyl-1,2-benzisoxazoles have shown that a mixture of the 5-nitro and 5,7-dinitro derivatives is formed (77IJC(B)1058, 77IJC(B)1061). The effect of substituents in the benzene ring is also of interest. If the 5-position is blocked, e.g. by a chloro group or by alkyl groups, nitration then occurs at the 4-position. 3-Alkyl-7-chloro and 3,7-dialkyl derivatives result in the formation of the appropriate 5-nitro derivative. The isomeric 3-alkyl-6-chloro- and 3,6-dialkyl-1,2-benzisoxazoles yield a mixture of the 5-nitro and 5,7-dinitro compounds. Both H NMR measurements and alternate syntheses were used in establishing the structures of these substitution products. 

Reductive ring closure with thionyl chloride led to the introduction of a chloro group in the 5-position. When the 5-position was blocked by a substituent, halogen attack occurred in the 7-position. The mechanism is shown in Scheme 177 (67AHC(8)277>. 

The presence of functional groups on the steroid nucleus can affect the course of the epoxidation reaction thus epoxidation of 3/ -chlorocholest-4-ene (11) gives the 4a,5a-epoxide in 97 % yield, whereas the 3a-chloro group hinders (presumably sterically) attack on the 4,5-double bond towards the a-face of the molecule. The 3a-acetoxy function similarly influences the selectivity of the epoxidation of cholest-4-enes, a 53 47 mixture of the respective 4 , 5a- and 4jS, 5jS-epoxides being obtained after exposure of the 3a-acetoxy-4-ene (13) to perbenzoic acid. 

Addition to the 6,7-double bond is also observed with 4-chloro-A -3-ketones (20). Attack at the 1,2-double bond occurs as well to give mainly the la,2a 6, 7j -dimethylene steroids (21) in addition to some la,2a 6a,7a-dimethylene compounds (22). Reaction at the 6,7-double bond in the 4-chlorotrienone series may be promoted by the —I effect of the 4-chloro group resulting in an increased positive character at Methylena-... 

Deep fluorinalion of alkanes, ethers, acid fmlides, esters, alkyl chlorides, most ketones, ketals, orthoesters, and combinations of these functional groups produces principally the perfluonnated analogues (Table 2) Chlorine substituents (or chloro groups) usually survive fluorination... 

A chloro group in the 5-position in a pyrido[4,3-d]p37rimidine proved to be labile, " compound 159 being readily converted into the 5-hydrazino, oxo, ethoxy, and thioxo derivatives. 

It is also interesting to note that quatemization of a chloropyrimi-dine at the nitrogen atom adjacent to the chloro group with methyl iodide results in the easy replacement of the chlorine by iodine, whereas similar salt formation on the remote nitrogen either leaves the chlorine unaffected or replacement occurs only at higher temperatures. A similar reaction occurs between 2-amino-6-chloro-4-methylpyrimidine and dimethyl sulfate in nitrobenzene to give the salt 45 and betaine 46. ... 

Like the chloronitrobenzenes, a chloroquinoline reacts faster with sodium p-tolylsulfide when the chloro group is para to the aza-group than when it is orthoy the factor involved being about 10. However, a strikingly different behavior is noted in the much lower BS-/ BO- ratio which is 2.5 for 4-chloroquinoline ( para isomer) and 0.24 for 2-chloroquinoline ( ortho isomer). For p-chloronitro-benzene this ratio is 38, and for 2,4-dinitrochlorobenzene it is 1950. Thus far there is no case in which the reaction of a chloronitrobenzene derivative with sodium methoxide is faster than that with sodium phenylsulfide. 

The jS-position of pyridine 1-oxide is much less reactive than either the a- or y-position. This is shown for the displacement of the chloro group in structures 39 and 40 the relative rates are indicated (jS = 1) at... 

In 2-substituted dinitrothiophenes, phenylsulfone and p-nitro-phenoxy groups both react faster than the chloro group with pyridine, i.e., in a reverse order with respect to l-substituted-2,4-dinitro-benzenes, although with both substrates the factors involved are small. 

An interesting example of the result of conjugation of substituents is the behavior of 3-methoxy-6-methylsulfonylpyridazine studied in our Laboratories. In 6-chloro-3-methoxypyridazine and in 3,6-dimethoxypyridazine, the methoxy groups are unreactive toward sulfanilamide anion, and the chloro group is deactivated relative to... 

Aryloxy, hydroxy arylsulfonyloxy, and phosphoryloxy. The 4-toluenesulfonyloxy and 4-nitrophenyloxy groups approximate the chloro group in replaceability in benzene derivatives. The former appears to be less reactive than chloro toward hydroxide on quinoline and -phenoxy on pyrimidine is relatively unreactive toward sulfanilamide anion or ammonia. On cinnoline, quinazoline, or quinoline, a 4-phenoxy group is less reactive than a chloro group. 

The replacement of a heterocyclic hydroxyl group (generally in the 0X0 form, Section II,E, 2,e) with thioxo or chloro groups by phosphorus pentasulfide or phosphorus oxychloride presumably proceeds through nucleophilic substitution (frequently acid-catalyzed, 21 and 86) of thiophosphoryloxy and dichlorophosphoryloxy intermediates. The 4-position in pyrimidine is more reactive than the 2-position and, at low temperature, this type of thionation of pyrimidine-2,4-diones is specific for the 4-position. In as-triazine... 

The diazomethyl group in 165, formed from 2,4,6-trichloro-s-triazine and diazomethane, deactivates (relative to chloro) the remaining chloro groups towards diazomethane, ammonia, and methoxide ion. 

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