Bromoform, reaction with base

The 6,7-dihydro-5/f -1,4-dioxepin (266) has been prepared (54CR(38)982). and more recently it has been shown that the 2,3-dihydro-5jF/-l,4-dioxepins (263) and (265) can be produced from 1,4-dioxine-halocarbene adducts (264), either by heating under reflux in xylene or by treatment with bases. The allylic chlorine atom in (263) is readily substituted by alkoxide or cyanide ions (77ZC331, 76UKZ968). Saturated rings of type (267) have been prepared by the treatment of cyclic acetals of ethane-1,2-diol with vinyl ethers in the presence of boron trifluoride, and l,4-dioxepan-5-one (268) has been prepared by the reaction of bromoform and silver nitrate with aqueous dioxane (60AG415). 

Dibromocarbene.2 1-Bromobenzocyclobutene can be prepared conveniently by reaction of cycloheptatriene with dibromocarbene generated from bromoform with base in the presence of 18-crown-6. No reaction occurs in the absence of the crown ether. 

Ring expansion of I-methylindenes. Gillespie et al have described a convenient synthesis of phenyl(tribromomethyl)mercury by mixing phenylmercuric chloride, sodium hydride, and bromoform in benzene with methanol as initiator. They have converted l-methyUndenes into 3-bromo-l-methylnaphthalenes by reaction with dibromocarbene generated from this precursor. Reaction of 1-methylindenes with dibromocarbene generated from bromoform with base... 

Carbenes are also formed by reactions of halogenated compounds with bases. If a carbon atom has bonds to at least one hydrogen and to enough halogen atoms to make the hydrogen shghtly acidic, it may be possible to form a carbene. For example, bromoform (CHBr3) reacts with a 50% aqueous solution of potassium hydroxide to form dibromocarbene. 

The idea that dichlorocarbene is an intermediate in the basic hydrolysis of chloroform is now one hundred years old. It was first suggested by Geuther in 1862 to explain the formation of carbon monoxide, in addition to formate ions, in the reaction of chloroform (and similarly, bromoform) with alkali. At the end of the last century Nef interpreted several well-known reactions involving chloroform and a base in terms of the intermediate formation of dichlorocarbene. These reactions included the ring expansion of pyrroles to pyridines and of indoles to quinolines, as well as the Hofmann carbylamine test for primary amines and the Reimer-Tiemann formylation of phenols. 

With the exception of the parent compounds, where the Michael adducts are isolated, acrylic esters [see, e.g. 6,7,31,105,111 ] and nitriles [6,7], and vinyl ketones [26, 113, 115] generally yield the cyclopropanes (Table 7.6) under the standard Makosza conditions with chloroform. Mesityl oxide produces a trichlorocyclopropy-lpropyne in low yield (10%) [7]. When there is no substituent, other than the electron-withdrawing group at the a-position of the alkene, further reaction occurs with the trichloromethyl anion to produce spiro systems (35-48%) (Scheme 7.12) [7, 31]. Under analogous conditions, similar spiro systems are formed with a,p-unsaturated steroidal ketones [39]. Generally, bromoform produces cyclo adducts with all alkenes. Vinyl sulphones are converted into the dichlorocyclopropane derivatives either directly or via the base-catalysed cyclization of intermediate trichloromethyl deriva-... 

As dibromocyclopropanes can easily be synthesized by reacting a cycloalkene with bromoform in the presence of a base [16], this method affords an alternative procedure for cyclopentenone annelation onto cyclic alkenes. It should be noted that in the Pauson-Khand reaction, which is probably the most direct cyclopentenone annelation reaction, the reaction using cyclohexene gives the product only in very low yield [11,17]. Also, the position of the original alkynyl substituent on the product double bond is opposite to that in the present reaction. Thus the two reactions are complementary. 

When a base is used with a methy] ketone, the alpha carbon will become completely halogenated. This trihalo product reacts further with the base to produce a carboxylic acid and a haloform (chloroform, CHCI j bromoform, CHBr, or iodoform, CHIj). This is called the Haloform Reaction. 

A trihalo compound may be formed from the halogenation of a methyl ketone. The electron-withdrawing effect of the trihalomethyl group makes the carbonyl group very sensitive to nucleophilic addition. Consequently, in the presence of a mild base the trihalomethyl compound easily decomposes with the formation of chloroform, bromoform or iodoform, depending on the halogen. The other product of the haloform reaction is a carboxylic acid (Scheme 3.86). 

Because these fire-retardant salts are water-soluble and subject to leaching, several new methods have been developed which provide a water-resistant or permanent treatment for cotton fabrics and cellu-losic materials. Perkin developed a process involving successive treatment with sodium stannate and ammonium sulfate, which precipitates stannic oxide in the cellulose libers. Antimony oxide in combination with vinyl chloride or other chlorinated polymers has also been found effective. A more recent approach to this problem involves application of fire-retardant resin-forming or cross-linking compounds. " These include materials and methods based on the copolymerization of tetrakis(hydroxymethyl)phosphonium chloride and methylol — melamine, the reaction of bromoform and triallyl phosphate to form a cross-linked polymer, and the cross-linking reaction of tris(l-aziridinyl)phosphine oxide with cellulose, or its copolymerization with tetrakis(hydroxymethyl)phosphonium chloride and other materials. ... 

Study carefully the pKgS for the haloform series, CHX3— they may not do what you think they should Chloroform is much more acidic than fluoroform even though fluorine is more electronegative (likewise with bromoform and chloroform). The anion CFamust be slightly destabilized because of some backdonation of electrons. The anion from chloroform and bromoform may also be stabilized by some interaction with the d orbitals (there aren t any on fluorine). The conjugate base anion of bromoform is relatively stable— you will meet this again in the bromoform/iodoform reaction (Chapter 21). 

The most widely used substrates for a-elimination reactions are chloroform and bromoform, but other halides also can undergo a-elimination. For example, allyl chloride undergoes a-elimination when it is treated with a very strong base. 

It is often difficult to make a comparison between the various results obtained for the same polyenes as different reaction conditions (ratio of reactants, temperature, time) were used in each case. The addition of dichlorocarbene (chloroform/base/phase-transfer catalysis) to straight chain and cyclic unconjugated di- and trienes, carried out under identical conditions but varying the catalysts, showed the peculiar properties of tetramethylammonium chloride. Under precisely tailored conditions, either highly selective mono- or polyaddition of dichlorocarbene to the polyenes is possible tetramethylammonium chloride was the most efficient catalyst for monocyclopropanation. (For the unusual properties of tetramethylammonium salts on the phase-transfer catalyzed reaction of chloroform with electrophilic alkenes see Section 1.2.1.4.2.1.8.2. and likewise for the reaction of bromoform with allylic halides, see Section 1.2.1.4.3.1.5.1.). For example, cyclopropanation of 2 with various phase-transfer catalysts to give mixtures of 3, 4, and 5, ° of 6 to give 7 and 8, ° and of 9 to give 10 and 11. °... 

Dibromocarbene undergoes addition to alkenes in a stereospecific manner. The sole case of nonstereospecific dibromocyclopropanation using bromoform/base/phase-transfer catalyst concerns ( )-cyclooctene, and is explained by isomerization of this cycloalkene caused by reversible addition of tribromomethyl or ethoxide anion the latter is formed from the ethanol present in bromoform (see also ref 2 and Houben-Weyl, Vol. El 9b, p 1617 for stereomutation in the reactions of dibromocarbene, generated from organomercury reagents, with low-active alkenes, see Section 1.2.1.4.3.1.5.1. and Vol. E19b, pp 1615 1616). 

This carbanion is capable of leaving because its negative charge is stabilized by the combined inductive effects of the three halogen atoms. It is still a moderately strong base with a pA., in the mid-teens. Proton transfer between this anion and the carboxylic acid gives the final products of the reaction, the salt of the acid and the haloform. bromoform (CHBrs). The same process occurs with trichloro- and triiodo-substituted methyl ketones, to give chloroform and iodoform, respectively. 

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