Halides, alkyl from esters

Hoerold, S., Weferling, N., and Breuer, H.-R, Preparation of phosphonic acid esters from alkyl halides and elemental phosphorus, and their use, Ger. DE 19,828,861, 2 Dec. 1999 Chem. Abstr., 132, 12410r, 2000. 

The use of organic halogen compounds as the starting products for the synthesis of other organic chemicals is too immense a field to do more than indicate some of the commercial applications. In his book I4S) on the chemistry of petroleum derivatives, Ellis includes a chapter on the production of alcohols and esters from alkyl halides, and also one on miscellaneous reactions of halo-paraffins and cycloparaffins. The manufacture of amyl alcohols and related products from the chlorides has been well covered 14 ) 1 )-A two-step process for the synthesis of cyclopropane by chlorinating propane from natural gas and dechlorinating with zinc dust was devised in 1936 152). A critical review of syntheses from l,3-dichloro-2-butene was published in Russia in 1950 (1-54). The products obtainable from the allylic chlorides are covered in a number of articles 14If 14 157). 

Formation of monoalkylphosphonic esters from alkyl halides and trialkyl phosphites, via the intermediate phosphonium salt ... 

Section 21 7 The malonic ester synthesis is related to the acetoacetic ester synthesis Alkyl halides (RX) are converted to carboxylic acids of the type RCH2COOH by reaction with the enolate ion derived from diethyl mal onate followed by saponification and decarboxylation... 

This reaction sequence is called the acetoacetic ester synthesis. It is a standard procedure for the preparation of ketones from alkyl halides, as the conversion of 1-bromobutane to 2-heptanone illustrates. 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

Strictly speaking the alkyl halides are esters of the halogen acids, but since they enter into many reactions (e.g., formation of Grignard reagents, reaction with potassium cyanide to yield nitriles, etc.) which cannot be brought about by the other esters, the alkyl halides are usually distinguished from the esters of the other inorganic acids. The preparation of a number of these is described below. 

Organometallic compounds or carbanions undergo a number of reactions in which the carbanion or carbanion-like moiety of the organometallic compound acts as a nucleophilic displacing agent. Examples are the formation of hydrocarbons from alkyl halides, alkyl halides from halogens, and ketones from acid chlorides or esters. The latter two reactions are closely related to the base-catalyzed condensations and are perhaps additions as well as displacement reactions. Related addition reactions are the carbonation of organometallic compounds and the addition to ketones or aldehydes. 

The opposite of the stabilisation of an ester is its activation. If we include in the concept ester the alkyl halides, their Friedel-Crafts reactions provide familiar examples of this phenomenon. An unusual example especially relevant to our present considerations is provided by some results made available to me in advance of publication by Giusti and Andruzzi. Their results [38] on the polymerisation of styrene by iodine and hydrogen iodide can be interpreted in terms of an organic iodide derived from styrene, probably 1-phenylethyl iodide, being activated by the co-ordination of one or two molecules of iodine. This process appears to polarise the C—I bond to such an extent that the normally stable ester becomes activated to a chain-propagating species and induces a pseudocationic polymerisation ... 

Polymeric phosphonium salt-bound carboxylate, benzenesulphinate and phenoxide anions have been used in nucleophilic substitution reactions for the synthesis of carboxylic acid esters, sulphones and C/O alkylation of phenols from alkyl halides. The polymeric reagent seems to increase the nucleophilicity of the anions376 and the yields are higher than those for corresponding polymer phase-transfer catalysis (reaction 273). 

The protected methyl glycoside 3 is converted to the corresponding aldehyde by Swern oxidation using oxalyl chloride activated DMSO. Further reaction with triethyl phosphonoacetate and sodium hydride -known as the Horner-Wadsworth-Emmons reaction - provides selectively the trans et /Tun saturated ester 4 in 72 % yield. This valuable alternative to the Wittig olefination protocol uses phosphonate esters as substrates which are readily available from alkyl halides and trialkyl phosphites via the Arbuzov rearrangement.9 co2Et Reaction of the phosphonate with a suitable base gives the... 

Functional Group Transformations Functional group transformations help us in the conversion of a functional group to an aldehyde or a ketone without affecting the carbon skeleton of the molecule. Aldehydes can be synthesised by the oxidation of primary alcohols, or by the reduction of esters, acid chlorides, or nitriles. Since nitriles can be obtained from alkyl halides, this a way of adding an aldehyde unit (CHO) to an alkyl halide ... 

The target is now cyclopentanol. Alcohols can be prepared from alkyl halides by reaction with hydroxide ion as the nucleophile. Again, however, the combination of a strongly basic nucleophile and a secondary alkyl halide will result in an unacceptable amount of elimination. A better plan is to treat bromocyclopentane with acetate ion in an aprotic solvent such as DM SO. followed by cleavage of the ester to cyclopentanol ... 

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