Methylene dihalides

Instead of formaldehyde, other aldehydes or ketones may be used—aliphatic as well as aromatic recently methylene dihalides have been employed with success. The amine component is often employed as hydrochloride in addition to... 

It has also been suggested to manufacture heliotropin starting from catechol (J. Gen. Chem., USSR, 1938, 8, 1975). This method involves a 3-step process which comprises 1) the preparation of methylenedioxybenzene from catechol, 2) the conversion of methylenedioxybenzene with paraformaldehyde and hydrogen chloride to heliotropyl chloride and 3) the reaction of the latter with hexamethylenetetramine in ethanol to obtain heliotropin with an overall yield of 11—28 % based on catechol. An improvement in the yield of step 1), and thus overall yield, can be obtained by employing a process for preparation of methylenedioxybenzene from catechol as described in U.K. patent specification 1,097,270 which involves the reaction of catechol with a methylene dihalide under alkaline conditions in the presences of a highly polar, aprotic solvent. 

Generally speaking, about stoichiometric quantities of the reactants are employed—that is, about one mole of methylene dihalide and two moles of base per mole of aromatic reactant charged. In some cases, it may be desirable to employ a slight to moderate excess—for example 5-50% excess of the base and/or the methylene halide to insure completion of the reaction. 

Methylene dihalides, A-(CH2)w X, react satisfactorily with pyridine and the picolines, examples with w — 2, 3, 4, 5 and 10 having been reported. Methylene dihalides give only the bis-quaternary salts, but in other cases both bis- and mono-quaternary salts have been isolated oo. 

Synthesis. These macrocycles are prepared from seven-membered ring dinitrile complexes, 84a-84c (Scheme 17), which contain either methylene, sulfur or oxygen in the five position (129). These cyclic dinitriles are synthesized by alkylating maleonitrile dithiolate or derivatives thereof with the corresponding dihalide. The dinitriles 84a-84c can be cyclized in magnesium propoxide to form porphyrazines 85a (33%), 85b (19%), and 85c (27%) (Scheme 17), which can be demetalated with trifluoroacetic to form 86a-86c. Additionally, 86a has been remetalated with nickel (87a, 92%), copper (88a, 95%), and zinc (89a, 94%). The sulfur and oxygen derivatives 85b, 85c, 86b, and 86c are of low solubility and are not suitable for further manipulation. 

Di-iodocyclopropanes are unstable and cannot be isolated readily [133]. Other dihalocyclopropanes rearrange thermally during work up, or in the presence of the base, to produce ring-opened allylic dihalides or vinyl halides [e.g. 15, 81, 87, 96, 100, 103, 152, 157] (Scheme 7.4). Thermal rearrangement of the dihalocarbene adducts from halocycloalkenes leads to ring expanded products or methylene derivatives [e.g. 87], whereas 1, l-dichlorocyclopent-3-enes produce halobenzenes in high yield [96]. 

If small amounts of PhSSPh were deliberately added from the beginning, the more positive reduction potential could be applied from the start. Indirect electrochemical eliminations were also performed in the case of 1,2-dihalides Ringopening reactions by the redox catalytic method were possible in the case of methylene cyclopropanes and epoxides... 

A facile method for the preparation of a variety of stabilized arsonium ylides in good yield has been developed by the action of active methylene compounds with tertiary arsine oxide or tertiary arsine dihalide. Thus triphenyl-arsine dihalides react with a number of active methylene compounds in the presence of a tertiary amine to afford arsonium ylides (6) (40). The reaction of triphenylarsine oxide with active methylene compounds in the presence of either acetic anhydride or triethylamine-phos-phorus pentoxide gave rise to arsonium ylides (6) (32, 36. 65, 67). 

This binuclear photooxidative addition reaction is general for a number of halocarbons (Figure 3). While DCE and 1,2-dibromoethane react cleanly to give the dihalide metal dimers and ethylene, substrates such as bromobenzene or methylene chloride react through an alkyl or aryl intermediate. This intermediate reacts further to yield the dihalide d2-d2 metal complexes. 

A reaction sequence starting with bis[phenyltelluro]mcthane leads to the insertion of a methylene group into the carbon-halogen bond of an alkyl halide. The bis[phenyltelluro] methane is reacted with butyl lithium to yield lithiomethyl phenyl telluride, which combines with an alkyl halide. The resulting alkylmethyl phenyl tellurium is converted to the tellurium dihalide, which in turn decomposes to an alkylmethyl halide when kept under vacuum at 250 6 or heated in DMF in the presence of a sodium halide at 100°7. 

Preparation of the simplest diamine, ethylene diamine, by ammonolysis of the dihalide is accompanied by the formation of diethylenediamine and triethylenetetramine other methods for its preparation are more suitable. Only the higher homologs of /3-dialkylaminoethyl bromide respond favorably to this treatment. Thus, di-n-butylaminoethyl bromide is converted to the diamine in 55% yield whereas the dimethylaminoethyl bromide undergoes extensive dimerization. Triniethylene bromide reacts with liquid ammonia to form trimethylenediamine (50%) however, experimental details are lacking. When the two halogens in the dihalide approach one another in space as in tetra- and penta-methylene dibromides, then nitrogen spiranes are the main products. ... 

The two most common methods of synthesis of methylene-1,3-dithietanes are the reaction of 1,1-dihalides or their equivalents with salts of 1,1-dimercapto-... 

In the reactions of 1,1-dihalides, tin salts of 1,1-dimercaptoalkenes give somewhat better yields (only an 18% yield of 564 is obtained with the disodium salt). The reaction of active methylene compounds with carbon disulfide is a common method for obtaining 1,1-dimercaptoalkene derivatives, as exemplified in the synthesis of 565. The reaction of dimercaptoalkene salts with phosgene yields 2-keto-4-methylene-l,3-dithietanes. 

If the dihalide precursor is o-substituted, reaction with dialkylphosphorus halide or alkylarsenious halide can lead to a complex mixture of products, in addition to products of diheteroatom substitution [122,123]. The novel cyclobutanaphthalene 154 [Eq. (68)] was formed from methylene bis(p-toluenesulfonate) and the di-Grignard reagent 153 formed from 1,8-dibromonaphthalene [124] dihalomethanes failed in this reaction. 

Other phosphorus compounds, e.g. PBrs, mixtures of PBrs and Br or PCI3/CI2 and phenyltetra-chlorophosphorane (PhPCU) have been used to convert amides to imidoyl halides. The formation of imidoyl halides proceeds under mild conditions by action of triphenylphosphine/CCU or triphenylphos-phine dihalides on secondary amides or ketoximes. The work-up procedure can be facilitated by use of polymer-supported triphenylphosphine/CCU. By the action of POCI3, phenyl- or methyl-phos-phonic acid dichloride on aminocarboxylic acid thiol esters in the presence of triethylamine the imidoyl chlorides (205 equation 114) are formed in moderate to good yields. The mechanism of this reaction has not been established. The methylene dialkylchlorophosphorane (206 equation 115) allows the conversion of secondary aromatic amides to imidoyl chlorides under very mild conditions. ... 

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