Haloalkyl

The last group of reactions uses ring opening of carbonyl or 1-hydroxyalkyl substituted cyclopropanes, which operate as a -synthons. d -Synthons, e.g. hydroxide or halides, yield 1,4-disubstituted products (E. Wenkert, 1970 A). (1-Hydroxyalkyl)- and (1-haloalkyl)-cyclopropanes are rearranged to homoallylic halides, e.g. in Julia s method of terpene synthesis (M. Julia, 1961, 1974 S.F. Brady, I968 J.P. McCormick, 1975). 

Each of the following dihaloalkanes gives an N (haloalkyl)phthahmide on reaction with one equivalent of the potassium salt of phthalimide Write the structure of the phthahmide denvative formed m each case and explain the basis for your answer... 

The question as to whether a flame retardant operates mainly by a condensed-phase mechanism or mainly by a vapor-phase mechanism is especially comphcated in the case of the haloalkyl phosphoms esters. A number of these compounds can volatilize undecomposed or undergo some thermal degradation to release volatile halogenated hydrocarbons (37). The intact compounds or these halogenated hydrocarbons are plausible flame inhibitors. At the same time, thek phosphoms content may remain at least in part as relatively nonvolatile phosphoms acids which are plausible condensed-phase flame retardants (38). There is no evidence for the occasionally postulated formation of phosphoms haUdes. Some evidence has been presented that the endothermic vaporization and heat capacity of the intact chloroalkyl phosphates may be a main part of thek action (39,40). 

A critical review of the toxicity of the haloalkyl phosphates and the potential metaboHc products is available (141). The toxicity of flame retardants used in textiles has also been reviewed (142). 

Haloall lation. Haloalkyl groups can be introduced directiy by processes similar to Friedel-Crafts alkylation into aromatic and, to some extent, ahphatic compounds. Because halo alkylations involve bi- or polyfunctional alkylating agents, they must be performed under conditions that promote the initial halo alkylation but not, to any substantial degree, subsequent further alkylations with the initially formed haloalkylated products. 

The most frequentiy used halo alkylating agents are aldehydes and hydrogen haUdes, haloalkyl ethers, haloalkyl sulfides, acetals and hydrogen haUdes, di- and polyhaloalkanes, haloalkenes, haloalcohols, haloalkyl sulfates, haloalkyl -tosylates, and miscellaneous further haloalkyl esters. Haloalkylations include halomethylation, haloethylation, and miscellaneous higher haloalkylations. Under specific conditions, bis- and polyhaloalkylation can also be achieved. 

Haloalkylations are accompanied by further alkylation by the initially formed haloalkylated product, yielding diarylalkanes or cychalkylated products, eg, ben2ene reacts with CCl in the presence of AlCl to give C H CCl and (43). With dichloromethane, the initially formed ben2yl chloride is... 

Cinnamyl—sesamol ethers, eg (35), are useful as insect chemosterilants (111). 3,4-Methylenedioxyphenyl-3-halo-2-propynyl ethers (36, X = halogen) are synergists for carbamate insecticides (112). HaloaLkyl or haloalkenyl ethers, eg (37), show acaricidal and insect juvenile hormone activity (113). The first total synthesis of gibbereUic acid was from 2-methoxy-6-aLkoxyethyl-l,4-benzoquinone, a derivative of hydroxyhydroquinone (114). 

This method is also used with alcohols of the stmcture Cl(CH2) OH (114). HaloaLkyl chlorosulfates are likewise obtained from the reaction of halogenated alkanes with sulfur trioxide or from the chlorination of cycHc sulfites (115,116). Chlorosilanes form chlorosulfate esters when treated with sulfur trioxide or chlorosulfuric acid (117). Another approach to halosulfates is based on the addition of chlorosulfuric or fluorosulfuric acid to alkenes in nonpolar solvents (118). 

Hydroxyalkyl groups attached to pyridopyridazines have been converted to haloalkyl groups by standard methods and the products reacted with amines. Ketones have been converted to hydrazones and oximes and the resulting derivatives deprotected during syntheses. 

Irradiation of the A-bromo- or N- chloro-azetidin-2-ones (71) in the presence of alkenes, alkynes or radical donors induces rearrangement to the /3-haloalkyl isocyanates (72) via a... 

To the best of our knowledge, the hrst paper which mentioned an A-(l-haloalkyl)pyridinium compound appeared 66 years ago in the Chemische Berichte (Krohnke 33CB1386). Tlie author described the reaction of phenacyl pyridinium derivatives 1 with bromine in acetic acid to give the halides 2 (36CB2006 37CB864). Tire addition of bromine to the double bonds of A-vinylpyridinium salts 3 and 4 giving the adducts 5 and 6 has also been reported (51CB399) (Scheme 1). 

Wlieii thiomethoxymethyl hexachloroaiitimoiiate was treated with pyridine, a methylthio derivative 28 was isolated in low yield in addition to the expected chlorinated sulfides (71T4209). Several A, A -haloalkyl-bis-4,4 -pyridiniumethenes 29 have been reported in a Japanese patent (80JAP75479). Tliese compounds are promising candidates for the construction of electrochromic display devices (Scheme 7). 

Many A-(l-haloalkyl)heteroarylium salts 33 have been characterized by their and NMR spectra (Table I) (Scheme 11). 

Selected H- and C-Chemical Shifts (in Parts Per Million) of A -(1-Haloalkyl)Hetarylium Halides 7, 33, and 43... 

Trichloro- and dichloromethane, ether, dioxane, benzene, toluene, chlorobenzene, acetonitrile, or even pyridine itself has been employed to carry out the one-pot syntheses. Tliese solvents allow straightforward preparation of the salts. The temperature range between 0° and 20°C is usually employed and the salts formed are sufficiently soluble. In the case of slow reactions, selection of a solvent with a higher boiling point is prohtable since thermal instability of the A -(l-haloalkyl)heteroarylium halides has not been reported. Addition of water or an aqueous solution of sodium acetate does not cause a rapid decomposition of the salts so that this constitutes a useful step in the optimization of some procedures. 

Not many reactions between A-(l-haloalkyl)heteroarylium halides and anionic nucleophiles are reported in the literature. In trichloromethane or... 

Tliere are few examples for the preparation of imines from A-(l-haloalkyl)azinium halides and primary diamines. Among those reaetions reported, A-(ehlorophenylmethyl)pyridinium ehloride (33k), whieh has not been isolated, reaets with ethane-1,2-diamine and propane-1,3-diamine to afford the eorresponding diimines 72 (Seheme 22, 45-80%) (89JOC4808, 92BSB233). 

A -(l-Haloalkyl)pyridinium halides have been advantageously employed in the Hantzsch multicomponent synthesis, yielding alkyl 1,4-dihydropyri-dine-3,5-dicarboxylates, which are a well-known class of calcium channel modulators (81AGE762). Tire halides readily interact with an excess of an ethyl 3-aminobut-2-enoate 82 (R = H) in dichloromethane at room temperature to afford the heterocycles 83 (R = H) in good to excellent yields (65-95%) (92T1263). Tliis observation has been exploited to perform a quantitative study of the reactivity of the salts (93CB1251).Tlie results have... 

Practical experience enables us to emphasize the simplicity and the efficiency of the activation of aldehydes by their conversion into N- -haloalkyl)heteroarylium halides upon treatment with an azine and a thionyl halide. Preparation of these salts requires a minimum of precautions, and a wide variety of solvents can be used. Special glassware and/or the use of an inert gas is not necessary. Tire salts can be reacted under numerous experimental conditions and, in most cases, it is unnecessary to isolate them. Tire flexibility of the method represents an interesting feature for the study of the reactivity of A-(l-haloalkyl)heteroarylium halides and deserves further investigations in this held. Many elegant compromises can be found in a judicious choice of the precursors and of the experimental conditions, and it is possible to design readily a salt suitable for each individual purpose. 

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