Processes for converting ethanol and syngas (CO and H2) to isobutanol are disclosed. Syngas and ethanol are reacted in the first reaction zone in the presence of a first heterogeneous catalyst to produce a first reactor effluent comprising a first mixture of alcohols. The first reactor effluent is reacted a second reaction zone in the presence of a second heterogeneous catalyst to produce a second reactor effluent comprising a second mixture of alcohols. The second reactor effluent is separated into an overhead gas stream and a liquid bottom stream. The liquid bottom stream is separated into at least a C1-2 stream, a C3 stream, and a C4+ stream. The isobutanol is recovered from the C4+ stream.
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